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The survival benefit to patients with positive sentinel node melanoma after completion lymph node dissection may be limited to the subgroup with a primary lesion Breslow thickness greater than 1.0 and less than or equal to 4 mm (pT2-pT3). The survival benefit of sentinel node biopsy is still controversial. The aim of our study was to assess the overall survival (OS; calculated both from the date of primary tumor excision and lymph node dissection) data from two large groups of AJCC 2002 stage-III cutaneous melanoma patients-after completion lymph node dissection (CLND after positive sentinel node biopsy) and after therapeutic LND (TLND for clinically/cytologically detected regional lymph node metastases). We analyzed the outcomes for 544 consecutive patients, who underwent CLND (47.4%; 258 patients) or TLND (52.6%; 286 patients) at one institution between December 1994 and January 2005. There were no significant differences between the two groups in terms of age and gender distribution and in the parameters of the primary tumor. Median follow-up time was 36 months (range 6-110 months). We found no significant differences in OS (from the date of primary tumor excision) between CLND and TLND patients in the groups with primary tumor thicknesses of 1.0 mm or less or greater than 4.0 mm (pT1 and pT4); however, in patients with thicknesses greater than 1.0 mm and 4.0 mm or less (in subgroups pT2 and pT3), we found significantly better OS for CLND than for TLND patients-CLND: median OS not reached, 5-year OS was 57.2% (95%CI: 44.4-70.1%); TLND: median OS 42.1 months, 5-year OS was 37.9% (95%CI: 26.5-49.2%) (P = 0.0006). In the entire CLND and TLND groups, the median OS and 5-year OS rates were 60.5 months and 52.5% (95%CI: 45.6-61.5%) and 38.2 months and 39.5% (95%CI: 32.7-46.5%), respectively. Based on multivariate analysis, we have found that in the CLND group the important factors negatively influencing OS (from the date of lymphadenectomy) are: male gender, features of primary tumor (higher Breslow thickness and presence of ulceration) and features of nodal metastases (extracapsular invasion and number of involved nodes). In the TLND group, however, the negative prognostic factors are: male gender and features of nodal metastases (extracapsular invasion and number of involved nodes) without the impact of primary tumor characteristics. The results of the study demonstrate that the survival benefit after positive sentinel node biopsy with subsequent CLND is probably limited only to the subgroup of patients with primary tumor thicknesses not larger than 4 mm and not less than 1 mm when compared with lymph node dissection of palpable nodes. The primary tumor features have no impact on survival after lymphadenectomy performed for clinically involved nodes.

Effectiveness of sinus lift procedures for dental implant rehabilitation: a Cochrane systematic review. Marco Esposito, Pietro Felice and Paul Coulthard are among the authors of four of the included trials, however, they were not involved in the quality assessment of these trials. This review is based on a Cochrane systematic review entitled 'Interventions for replacing missing teeth: augmentation procedures of the maxillary sinus' published in The Cochrane Library (see http:// www.cochrane.org/ for information). Cochrane systematic reviews are regularly updated to include new research and in response to comments and criticisms from readers. If you wish to comment on this review, please send your comments to the Cochrane website or to Marco Esposito. The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane Review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of the review authors, and are not necessarily shared by the Cochrane Collaboration. Insufficient bone volume is a common problem encountered in the rehabilitation of the edentulous posterior maxillae with implant supported prostheses. Bone volume is limited by the presence of the maxillary sinus together with loss of alveolar bone height. Sinus lift procedures increase bone volume by augmenting the sinus cavity with autogenous bone and/or commercially available biomaterials. To test whether and when augmentation of the maxillary sinus is necessary and which are the most effective augmentation techniques for rehabilitating patients with implant-supported prostheses. The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Several dental journals were hand searched. The bibliographies of review articles were checked, and personal references were searched. More than 55 implant manufacturing companies were also contacted. The last electronic search was conducted on 7th January 2010. Randomised controlled trials (RCTs) of different techniques and materials for augmenting the maxillary sinus for rehabilitation with dental implants reporting the outcome of implant therapy at least to abutment connection. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted independently and in duplicate. Authors were contacted for any missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and odds ratios for dichotomous outcomes with 95% confidence intervals. The statistical unit of the analysis was the patient. Ten RCTs out of 29 potentially eligible trials were suitable for inclusion. One trial including 15 patients, evaluated whether 5-mm-long implants with a diameter of 6 mm could be an alternative to sinus lift in bone having a residual height of 4 to 6 mm. Nine trials with 235 patients compared different sinus lift techniques and, of these, four trials (114 patients) evaluated the efficacy of platelet-rich plasma (PRP). Since different techniques were evaluated in different trials, only two meta-analyses evaluating the efficacy of PRP could be performed for implant failures (two trials) and complications (three trials). No statistically significant difference was observed for any of the evaluated interventions. Conclusions are based on few trials, usually underpowered, having short follow-ups, and often judged to be at high risk of bias, therefore they should be viewed as preliminary and interpreted with great caution. It is still unclear when sinus lift procedures are needed. Short implants (5 mm) can be successfully loaded in maxillary bone with a residual height of 4 to 6 mm, but their long-term prognosis is unknown. Elevating the sinus lining in the presence of 1 to 5 mm of residual bone height without the addition of a bone graft may be sufficient to regenerate new bone to allow rehabilitation with implant-supported prostheses. Bone substitutes might be successfully used as replacements for autogenous bone. If the residual alveolar bone height is 3 to 6 mm, a crestal approach to lifting the sinus lining and placing 8 mm implants may lead to less complications than a lateral window approach and placing implants at least 10 mm long. PRP treatment does not seem to improve the clinical outcome of sinus lift procedures with autogenous bone or bone substitutes.

Urban vs. rural factors that affect adult asthma. In this review, our aim was to examine the influence of geographic variations on asthma prevalence and morbidity among adults, which is important for improving our understanding, identifying the burden, and for developing and implementing interventions aimed at reducing asthma morbidity. Asthma is a complex inflammatory disease of multifactorial origin, and is influenced by both environmental and genetic factors. The disparities in asthma prevalence and morbidity among the world's geographic locations are more likely to be associated with environmental exposures than genetic differences. In writing this article, we found that the indoor factors most consistently associated with asthma and asthma-related symptoms in adults included fuel combustion, mold growth, and environmental tobacco smoke in both urban and rural areas. Asthma and asthma-related symptoms occurred more frequently in urban than in rural areas, and that difference correlated with environmental risk exposures, SES, and healthcare access. Environmental risk factors to which urban adults were more frequently exposed than rural adults were dust mites,high levels of vehicle emissions, and a westernized lifestyle.Exposure to indoor biological contaminants in the urban environment is common.The main risk factors for developing asthma in urban areas are atopy and allergy to house dust mites, followed by allergens from animal dander. House dust mite exposure may potentially explain differences in diagnosis of asthma prevalence and morbidity among adults in urban vs. rural areas. In addition, the prevalence of asthma morbidity increases with urbanization. High levels of vehicle emissions,Western lifestyles and degree of urbanization itself, may affect outdoor and thereby indoor air quality. In urban areas, biomass fuels have been widely replaced by cleaner energy sources at home, such as gas and electricity, but in most developing countries, coal is still a major source of fuel for cooking and heating, particularly in winter. Moreover, exposure to ETS is common at home or at work in urban areas.There is evidence that asthma prevalence and morbidity is less common in rural than in urban areas. The possible reasons are that rural residents are exposed early in life to stables and to farm milk production, and such exposures are protective against developing asthma morbidity. Even so, asthma morbidity is disproportionately high among poor inner-city residents and in rural populations. A higher proportion of adult residents of nonmetropolitan areas were characterized as follows:aged 55 years or older, no previous college admission, low household income, no health insurance coverage, and could not see a doctor due to healthcare service availability, etc. In rural areas, biomass fuels meet more than 70% of the rural energy needs. Progress in adopting modern energy sources in rural areas has been slow. The most direct health impact comes from household energy use among the poor, who depend almost entirely on burning biomass fuels in simple cooking devices that are placed in inadequately ventilated spaces. Prospective studies are needed to assess the long-term effects of biomass smoke on lung health among adults in rural areas.Geographic differences in asthma susceptibility exist around the world. The reason for the differences in asthma prevalence in rural and urban areas may be due to the fact that populations have different lifestyles and cultures, as well as different environmental exposures and different genetic backgrounds. Identifying geographic disparities in asthma hospitalizations is critical to implementing prevention strategies,reducing morbidity, and improving healthcare financing for clinical asthma treatment. Although evidence shows that differences in the prevalence of asthma do exist between urban and rural dwellers in many parts of the world, including in developed countries, data are inadequate to evaluate the extent to which different pollutant exposures contribute to asthma morbidity and severity of asthma between urban and rural areas.

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants. Allergies and food reactions are common and may be associated with foods including adapted cow's milk formulas. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance, and have been advocated for prevention of allergy and food intolerance in infants. To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Controlled Trials Register (2003, Issue 1), MEDLINE (1966 - January 2003), EMBASE (1980 - January 2003) and CINAHL (1982 - January 2003) and previous reviews including cross references. Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion. Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each reviewer. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. Eighteen trials met criteria for inclusion. No eligible trials compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to human milk feeding and reported no significant difference in infant allergy or childhood cow's milk allergy (CMA). Two trials compared early, short term hydrolysed formula to cow's milk formula feeding with no significant benefits reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00).Seven studies compared prolonged feeding of hydrolysed formula to cow's milk formula without using co-interventions for allergy prevention. Meta-analysis of 4 studies (386 infants) found a significant reduction in allergy incidence in infancy (typical RR 0.63, 95% CI 0.47, 0.85; RD -0.15, 95% CI -0.25, -0.06). One study reported a significant reduction in allergy incidence in childhood (RR 0.54, 95% CI 0.36, 0.81). Significant reductions were found in asthma prevalence in childhood, eczema incidence in infancy and prevalence in childhood, food allergy prevalence in childhood, and CMA incidence in infancy. All studies enrolled infants at high risk of allergy. Only three trials comparing prolonged hydrolysed formula feeding to cow's milk formula feeding were considered of good methodology. Only one of these trials demonstrated a benefit into childhood (5 years of age). No eligible trials examined the effects of prolonged hydrolysed formula feeding on allergy beyond early childhood. Costs were not reported. Three trials compared prolonged feeding with an extensive to a partially hydrolysed formula and reported no significant difference in allergy incidence in infancy. There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is evidence that prolonged feeding with a hydrolysed compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. Further trials are required to determine if significant clinical benefits persist beyond 5 years of age and if there is any additional benefit from use of an extensive compared to a partially hydrolysed formula. Incremental costs of formula and the effect on compliance should be measured.

Effects of decreased estradiol-17beta on the serum and anterior pituitary IGF-I system in pigs. To further delineate the role of estradiol in the IGF system an experiment was conducted to determine the dosage of the aromatase inhibitor, anastrozole, needed to decreases serum concentrations of estradiol-17beta (E2) in maturing boars. A second experiment was conducted to determine if administration of anastrozole to growing boars decreased serum concentrations of E2 and affected components of the serum and anterior pituitary gland (AP) IGF system vs untreated boars and barrows. In Experiment 1, 12 crossbred boars (292 days, 158 kg) were administered either 0, 1 or 10 mg/day anastrozole (n = 4/group) beginning on day 1. Blood samples were collected every 7-14 days. Mean serum concentrations of E2 were decreased (P < 0.05) in the 10 mg group vs the 0 and 1 mg groups by day 36; however, no difference (P > 0.05) existed between the 0 and 1 mg groups. In Experiment 2, 24 crossbred boars and 12 barrows (101 days, 44 kg) were stratified by litter to one of three treatment groups (n = 12): boars administered 10 mg/day anastrozole, boars administered 0 mg/day, and barrows administered 0 mg/day. Blood samples were collected and pigs were weighed on day 0 and every 14 days thereafter, then killed on day 84 when blood and APs were collected. The 10 mg/day pigs were fed the anastrozole-amended diet beginning on day 1. Mean serum concentrations of E2 did not differ (P > 0.05) between the 10 mg/day pigs and 0 mg/day pigs on day 0; however, on day 15 through to 84 mean serum concentrations of E2 were greater (P < 0.05) in 0 mg/day pigs than in the 10 mg/day pigs. Mean percentage increase in serum concentrations of IGF-I was greater (P < 0.05) in untreated boars than anastrozole-treated boars and barrows from day 58 through to 84. Mean percentage of basal IGF-I increased (P < 0.05) from day 29 through to 84 in untreated boars. Mean relative amounts of AP IGF-binding protein (IGFBP)-2 and -5 were less (P < 0.01) in 10 mg/day pigs than in the 0 mg/day pigs, but each was greater (P < 0.01) than in barrows administered 0 mg/day. These results indicate anastrozole administered at a dosage of 10 mg/day suppresses serum concentrations of E2 in pigs. Administration of anastrozole to boars reduced the percentage increase in serum concentrations of IGF-I and relative amounts of AP IGFBP-2 and -5. These data further support a role for E2 in regulating components of the IGF system in pigs.

Fast-track hip and knee arthroplasty: clinical and organizational aspects. Fast-track hip and knee arthroplasty aims at giving the patients the best available treatment at all times, being a dynamic entity. Fast-track combines evidence-based, clinical features with organizational optimization including a revision of traditions resulting in a streamlined pathway from admission till discharge – and beyond. The goal is to reduce morbidity, mortality and functional convalescence with an earlier achievement of functional milestones including functional discharge criteria with subsequent reduced length of stay and high patient satisfaction. Outcomes are traditionally measured as length of stay; safety aspects in the form of morbidity/mortality; patient satisfaction; and – as a secondary parameter – economic savings. Optimization of the clinical aspects include focusing on analgesia; DVT-prophylaxis; mobilization; care principles including functional discharge criteria; patient-characteristics to predict outcome; and traditions which may be barriers in optimizing outcomes. Patients should be informed and motivated to be active participants and their expectations should be modulated in order to improve satisfaction. Also, organizational aspects need to be analyzed and optimized. New logistical approaches should be implemented; the ward ideally (re)structured to only admit arthroplasties; the staff educated to have a uniform approach; extensive preoperative information given including discharge criteria and intended length of stay. This thesis includes 9 papers on clinical and organizational aspects of fast-track hip and knee arthroplasty (I–IX). A detailed description of the fast-track set-up and its components is provided. Major results include identification of patient characteristics to predict length of stay and satisfaction with different aspects of the hospital stay (I); how to optimize analgesia by using a compression bandage in total knee arthroplasty (II); the clinical and organizational set-up facilitating or acting as barriers for early discharge (III); safety aspects following fast-track in the form of few readmissions in general (IV) and few thromboembolic complications in particular (V); feasibility studies showing excellent outcomes following fast-track bilateral simultaneous total knee arthroplasty (VI) and non-septic revision knee arthroplasty (VII); how acute pain relief in total hip arthroplasty is not enhanced by the use of local infiltration analgesia when multi-modal opioid-sparing analgesia is given (VIII); and a detailed description of which clinical and organizational factors detain patients in hospital following fast-track hip and knee arthroplasty (IX). Economic savings following fast-track hip and knee arthroplasty is also documented in studies, reviews, metaanalyses and Cochrane reviews – including the present fast-track (ANORAK). In conclusion, the published results (I–IX) provide substantial, important new knowledge on clinical and organizational aspects of fast-track hip and knee arthroplasty – with concomitant documented high degrees of safety (morbidity/mortality) and patient satisfaction. Future research strategies are multiple and include both research strategies as efforts to implement the fast-track methodology on a wider basis. Research areas include improvements in pain treatment, blood saving strategies, fluid plans, reduction of complications, avoidance of tourniquet and concomitant blood loss, improved early functional recovery and muscle strengthening. Also, improvements in information and motivation of the patients, preoperative identification of patients needing special attention and detailed economic studies of fast- track are warranted.

13C-, 15N- and 31P-NMR studies of oxidized and reduced low molecular mass thioredoxin reductase and some mutant proteins. Thioredoxin reductase (TrxR) from Escherichia coli, the mutant proteins E159Y and C138S, and the mutant protein C138S treated with phenylmercuric acetate were reconstituted with [U-(13)C(17),U-(15)N(4)]FAD and analysed, in their oxidized and reduced states, by (13)C-, (15)N- and (31)P-NMR spectroscopy. The enzymes studied showed very similar (31)P-NMR spectra in the oxidized state, consisting of two peaks at -9.8 and -11.5 p.p.m. In the reduced state, the two peaks merge into one apparent peak (at -9.8 p.p.m.). The data are compared with published (31)P-NMR data of enzymes closely related to TrxR. (13)C and (15)N-NMR chemical shifts of TrxR and the mutant proteins in the oxidized state provided information about the electronic structure of the protein-bound cofactor and its interactions with the apoproteins. Strong hydrogen bonds exist between protein-bound flavin and the apoproteins at C(2)O, C(4)O, N(1) and N(5). The N(10) atoms in the enzymes are slightly out of the molecular plane of the flavin. Of the ribityl carbon atoms C(10alpha,gamma,delta) are the most affected upon binding to the apoprotein and the large downfield shift of the C(10gamma) atom indicates strong hydrogen bonding with the apoprotein. The hydrogen bonding pattern observed is in excellent agreement with X-ray data, except for the N(1) and the N(3) atoms where a reversed situation was observed. Some chemical shifts observed in C138S deviate considerably from those of the other enzymes. From this it is concluded that C138S is in the FO conformation and the others are in the FR conformation, supporting published data. In the reduced state, strong hydrogen bonding interactions are observed between C(2)O and C(4)O and the apoprotein. As revealed by the (15)N chemical shifts and the N(5)H coupling constant the N(5) and the N(10) atom are highly sp(3) hybridized. The calculation of the endocyclic angles for the N(5) and the N(10) atoms shows the angles to be approximately 109 degrees, in perfect agreement with X-ray data showing that the flavin assumes a bent conformation along the N(10)/N(5) axis of the flavin. In contrast, the N(1) is highly sp(2) hybridized and is protonated, i.e. in the neutral state. Upon reduction of the enzymes, the (13)C chemical shifts of some atoms of the ribityl side chain undergo considerable changes also indicating conformational rearrangements of the side-chain interactions with the apoproteins. The chemical shifts between native TrxR and C138S are now rather similar and differ from those of the two other mutant proteins. This strongly indicates that the former enzymes are in the FO conformation and the other two are in the FR conformation. The data are discussed briefly in the context of published NMR data obtained with a variety of flavoproteins.

A pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin. Management of cardiac intensive care unit (ICU) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. This pilot randomised trial investigated whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis. The main objective of this pilot study was to provide preliminary data on the likely safety and efficacy of a reduced course of antibiotics for the treatment of ICU infections of unknown origin. A pilot, single-centre, open-label randomised trial. This study was carried out in the ICU of a tertiary heart and chest hospital. Patients being treated within the ICU were recruited into the trial if the intensivist was planning to commence antibiotics because of evidence of systemic inflammatory response syndrome and a strong suspicion of infection but there was no actual known source for that infection. Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control). The primary outcome was a composite outcome of the rate of death or initiation of antibiotic therapy after the completion of the treatment schedule allocated at randomisation. Secondary outcomes included the duration of mechanical ventilation and ICU and hospital stay; the incidence of infection with Clostridium difficile (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008; resource utilisation and costs associated with each of the two pilot arms; the ratio of patients screened to patients eligible to patients randomised; the incidence of crossover between groups; and the significance of newer biomarkers for sepsis for predicting patients' need for further antibiotics. A total of 46 patients were recruited into the trial, with 23 randomised to each group. There was no significant difference between the two groups in terms of the composite primary outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11 to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further antibiotics compared with three (13%) in the 7-day group. Four patients died within the trial period and the deaths were not trial related. Patients who died during the trial period received no additional antibiotics in excess of their trial allocation. There were no documented incidences of MRSA or C. difficile infection in either group. No significant differences in adverse events were observed between the groups. Key economic findings were mean antibiotic costs per patient of £168.97 for the 2-day group and £375.86 for the 7-day group. The potential per annum cost saving for the ICU of 2-day treatment was estimated to range from £108,140 to £126,060. Patient screening was considered the biggest barrier to recruitment. There was no crossover between the two randomised groups. Data verification ascertained > 98% accuracy in data collection. Baseline procalcitonin was found to be predictive of the composite outcome (death and needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005). Analysis of baseline procalcitonin also indicated a trend towards it being a predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to 2.02; p = 0.01). Data from this pilot study suggest that there could be significant benefits of reducing broad-spectrum antibiotic use in the ICU without it undermining patient safety, with a potential cost saving in our unit of over £100,000 per year. Evidence from this pilot trial is not definitive but warrants further investigation using a large randomised controlled trial. Current Controlled Trials ISRCTN82694288. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme website for further project information.

Genetics, biomarkers, hereditary cancer syndrome diagnosis, heterogeneity and treatment: a review. Molecular genetic pathways that drive the phenotypic and genotypic heterogeneity of hereditary colorectal cancer also can affect response to chemotherapy and chemoprevention. These mutations also can alter patients' response to therapy. Environmental differences can affect this highly complex conundrum. We will use Lynch syndrome as a model to explore this issue. However, to begin with, after more than a century of documentation, we must ask what is meant by the eponym "Lynch syndrome". Germline mutations may act as drivers of chemoprevention and chemotherapy and therein may act positively or conversely they may have a negative effect in terms of inhibiting the inactivation of cancer-causing germline mutations. A relatively new field of hereditary cancer therapeutics has significantly impacted cancer care, from the standpoint of the sensitivity or resistance to a particular form of chemotherapy and/or chemoprevention. The question for the diagnostician and therapist must always concern what is the best possible management approach for the patient, particularly when he or she harbors a cancer-causing germline mutation, which, in this case, causes Lynch syndrome. Continued molecular genetic research might yield a more tailored effective treatment for Lynch syndrome. The ultimate goal of such hereditary oncologic research is to better understand the mutation's therapeutic task, namely, its potential to benefit the patient in terms of its treatment goal, thereby fulfilling the essence of personalized medicine. However, this goal may be exceedingly complicated. For example, in the natural clinical and molecular genetic history of hereditary forms of cancer, there will be a predominance of early-onset cancers of multiple anatomic sites. In our Lynch syndrome model, these will be most commonly colorectal, endometrial, and ovarian cancer. Attention must initially be focused upon cancer's early age of onset coupled with the tendency to multiple primary cancers so that, in the case of CRC, colonoscopic screening must be initiated by age 20-25 years and repeated every other year until age 40 years and then annually thereafter. However, screening will be of limited efficacy in the gynecologic cancers (endometrial and ovarian) so that once the family is completed, particularly by age 35-40 years, careful attention must be given to the option of prophylactic hysterectomy and bilateral salpingo-oophorectomy. Given issues of tumor heterogeneity, selected Lynch syndrome families may show an excess of urologic cancers or cancers of the small bowel, and highly targeted screening should be given serious consideration for these as well as cancers of other anatomic sites in such high-risk, cancer-prone patients.

Determinants and measures of quality in oral anticoagulation therapy. Anticoagulation management services or clinics have been recommended as the preferred method in the long-term management of oral anticoagulation with vitamin K antagonists and have been shown to increase the time patients spend in the therapeutic range. This surrogate marker of the quality of anticoagulation control is a well accepted predictor of bleeding and thromboembolic events and is generally used as a quality measure. However, the method of calculating the time in the therapeutic range can give different results and there is no consensus on the methodology that should be used or the benchmark targets that should be aimed for. Additionally, the expected rates of bleeding and thromboembolic complications are dependent on the indications for anticoagulation in the patient population being evaluated. These issues need to be taken into account when setting quality standards for anticoagulation clinics. An informal survey and group discussion with anticoagulation clinic personnel attending a workshop at the 9th National Conference on Anticoagulant Therapy was used to generate a list of pragmatic barriers to measuring these quality indicators and to share ideas on other quality markers. A narrative review of selected literature was used throughout the workshop to exemplify potential benchmark rates for therapeutic time in range, bleeding, and thromboembolic complication rates. Approximately 65% of the workshop attendees measure time in range in their anticoagulation clinics, however, only 15% used the linear interpolation method which has a quality measurement target of 65%. Less than half of the attendees measure bleeding or complication rates and very few adjust these rates based on the indication for anticoagulation. There was strong agreement regarding pragmatic barriers to collect this information and difficulties in extrapolating standards from the literature. Several clinics also measure the percent of extremely high International Normalized Ratios (INR) and also track late patients. Using clinical trial bleeding and thromboembolic complication rates to set quality measurement targets for anticoagulation clinics may not be appropriate, given the inherent difference in these patient populations. Additionally, there are pragmatic issues affecting the completeness and accuracy of adverse event gathering outside of a trial scenario that could be misleading. The time in the therapeutic range, however, is relatively easy to calculate and is a well substantiated surrogate marker for complication rates and should be a standard quality indicator. Benchmark targets for time in range are dependent on the methodology used in the calculation and should be adjusted accordingly.

Aim and indications of spinal angiography for spine and spinal cord surgery: Based on a retrospective series of 70 cases. For spinal surgery, computerized tomography (CT scan) and magnetic resonance imaging (MRI) have clear indications and are easily accessible. In contrast, the indications and the use of spinal angiograms (SA) remain unclear, and many centres performing spinal surgery do not have an access to SA. Based on a retrospective study, the role of SA in spinal surgery is assessed and their indications are discussed. A retrospective series of 72 SA in 70 patients is presented. No procedural accident occurred. SA was performed under general anaesthesia in 57 cases (82%). In 61 patients, locating the radiculomedullary arteries (RMA) was obligatory and performed in all cases: for 14 patients (21%), RMA were identified using the forecasted surgical approach (4 patients with degenerative disc disease out of 10 in the entire series were included), and modified. No ischaemic complications were observed in the series. Thirty-nine patients were treated for a tumour that was considered hypervascular (based on a histological hypothesis or the MRI data): 20 of them (51%) were preoperatively embolised and in only 8 cases was the operation considered "haemorrhagic" by the surgeon (among which, 3 intramedullary hemangioblastomas were included). No accident was observed during the embolisations. Thirteen patients presented with a vascular or haemorrhagic lesion (4 arteriovenous malformations, 6 dural arteriovenous fistulas, 3 intramedullary cavernomas): in all these cases, the SA was indispensable for the diagnosis and the decision-making process. Seven patients were treated by embolisation. In the last 8 cases, SA was considered for the diagnosis of a clinical worsening myelopathy with a non-contributive MRI, but it was not useful in providing a positive diagnosis. SAs were performed with different goals: (i) localization of RMA when a surgical approach between T4 and L2 involved the intervertebral foramen, or when an anterior approach was considered in order to avoid severe ischaemic complications (40% of the degenerative disc patients and 33% of the extramedullary tumour patients in this series); (ii) preoperative embolisation in cases of extramedullary tumours probably considered hypervascular (51% of the cases in the series) or in cases of arteriovenous shunt lesions (7 of 13 patients were treated by embolisation); (iii) as a diagnostic tool, SA is indispensable when MRI can reveal vascular abnormalities; it also provides information about the vascularisation as well as the endovascular possibilities in extramedullary tumours. In contrast, SA was not useful for intramedullary tumours because the RMA preoperative localisation is not mandatory (posterior approach), and embolisation seemed ineffective. SA was also not useful for the diagnosis of myelopathy with normal MRI. In the future, angiograms and MR angiography of the spinal cord may be useful in order to avoid general anaesthesia for a diagnostic procedure, but not practical to obtain access for endovascular treatment.

Voluntary intake and digestibility by mature beef cattle and Holstein steer calves consuming alfalfa or orchardgrass hay supplemented with soybean oil and(or) corn. Effects and interactions of corn and soybean oil supplementation and forage source on feed intake and digestibility by mature and growing cattle were determined. Eight mature beef cattle (571 +/- 17 kg initial body weight) were used in two simultaneous 4 x 4 Latin squares. Cattle in each square consumed long-stemmed alfalfa (AL; 16% crude protein, 54% neutral detergent fibre and 6.1% acid detergent lignin) or orchardgrass (OR; 11% crude protein, 71% neutral detergent fibre and 9.4% acid detergent lignin) hay ad libitum for 15 d followed by 6 d of restricted consumption (85% of ad libitum). Supplement treatments were Control, ground corn (C; 0.5% body weight), soybean oil (O; 0.125% body weight), or C + O. Total ad libitum dry matter (DM) intake was greater for AL than for OR (P < 0.05) and with than without C (P < 0.05), and a corn x soybean oil interaction occurred (P = 0.07; 11.8, 14.0, 13.6, 14.2, 8.4, 10.7, 9.3 and 10.3 kg/d); total tract neutral detergent fibre (NDF) digestibility was 66.0, 67.7, 65.8, 68.8, 52.5, 50.6, 55.1 and 59.4% for AL, AL - C, AL - O, AL - C + O, OR, OR - C, OR - O, and OR - C + O, respectively (SE 2.46). Eight Holstein steer calves (83 +/- 5 and 131 +/- 11 kg initial and final body weight, respectively) were subjected to the same dietary treatments, except for higher levels of C (1.0% body weight) and O (0.25% body weight) and periods with 21 d of ad libitum forage intake. Total DM intake was greater (P = 0.06) for AL than for OR, increased (P < 0.05) by C, and decreased (P < 0.05) by O (3.92, 4.17, 3.51, 4.00, 2.53, 2.90, 2.09 and 2.51 kg/d), and total tract NDF digestibility was affected by forage source (P < 0.05) and a corn x soybean oil interaction (P = 0.08; 58.8, 56.9, 60.1, 56.0, 41.9, 44.5, 45.8 and 40.1% for AL, AL - C, AL - O, AL - C + O, OR, OR - C, OR - O and OR - C + O, respectively). In conclusion, effects of supplementation with corn and (or) soybean oil on feed intake and digestibility were similar for AL and OR, which differed in voluntary intake and digestibility, and animal characteristics such as stage of maturity may have influenced effects of soybean oil on feed intake.

Intestinal absorptive surface in mammals of different sizes. The present treatise is primarily concerned with the structural and morphometric parameters of the cecum and large intestine of mammals. Over the past century, numerous accounts have visually presented the variation and diversity of the large intestine of mammals. This includes above all comprehensive works on the macroscopic anatomy. More recently, the microscopic anatomy of various animals at the light, electron, and scanning electron microscopy levels has been covered, especially for rodents and primates. In the past two decades, progress has been made by adding a new dimension to the previous structural studies, namely, the morphometrical analysis of the intestine of various animals and subsequent employment of this data in an analysis based on principles of scaling. The present account follows essentially this outline, but presented in a slightly different order. First, in the introductory section, the scientific aims and general prologue to this field of study are presented. Included in this section is a short, concise literature survey that deals with the major literature available on the subject of the large intestine at the macroscopical and microscopical level, as well as the most recent morphometric analyses of the intestines. The main focus of the present work is on the methodological; a new method is described to measure the intestines of animals ranging in size from the harvest mouse to the horse. This technique may also be applicable to other hollow or tube-like organs. Heretofore, previous techniques have been based on obtaining the area of the surface mucosa by measuring lengths and widths and calculating the area by multiplying the two measurements. Alternatively, some methods have taken probes and made measurements at the light microscopy level and then extrapolated these results to determine the entire area. The former method is inadequate, while the latter possesses the inherent disadvantages of all sampling techniques. The present technique has two levels: (1) obtaining the basal surface area of the entire intestine and (2) accounting for any increase in the mucosal surface area that is due to microscopically visible folds, villi, or other such structures. The former is accomplished by flattening appropriately sized pieces of intestine between two glass plates and tracing the contours onto transparent paper. The entire intestine is processed in this manner, resulting in a basal surface area, the contours having been submitted to analysis on a semi-automatic image analyzer to determine the area in square millimeters. The second-level measurements determine a factor of surface enlargement by calculating a ratio of the distance along the surface contour of the mucosa on a histological section cut perpendicular to the width of the intestine to a second distance (reference line) drawn straight beneath the mucosa but not tracing the enlargements. The measurements obtained at both levels are multiplied to give a final surface area. In addition to a detailed description of the technique complete with a flow sheet and pictorial diagram, the various aspects of proper fixation, tissue embedding, shrinkage, and determination of sampling sites (for the second level of measurement) are discussed. A pilot experiment to determine the surface enlargement due to microvilli is presented from material taken from the giant pouched rat. This was performed by measuring video sequences of microvilli taken from electron microscopy images. Cecal microvilli increase the surface area 15-fold, while in the colon the increase is approximately 19- to 20-fold. In the discussion, the choice of using three animals per group is discussed, based on simple statistical tests. Section 3 is entitled "Morphology of the Mammalian Cecum." Chronologically, it marks the onset of the entire investigation. Before having developed the method described in Sect. 2, these morphological investigations at the light, electron and scanning electron microscopy

Ecological principles of World Ocean monitoring. Anthropogenic effect on the World Ocean in the course of exploiting its resources has led to a significant contamination of some ocean areas in the latest decades and to diminution of the natural capacity of marine ecosystems to reproduction and self-regulation. Thus, the most urgent problem of today has become evident: the problem of the World Ocean pollution and its negative ecological effects.Local pollutions and their ecological effects on the World Ocean go on acquiring large-scale regional and even global character since the elements of ocean ecosystems and the ocean properties are interrelated and interconditioned. Looking into pollutant transfer and transformation in the marine environment we can distinguish four subsystems: ocean-land, ocean-atmosphere, and water-bottom sediments interfaces as well as ocean water mass. Ocean-atmosphere and water-floor subsystems require special consideration since their coefficients of pollutant accumulation are much greater than that of the water mass. Besides water exchange, the processes of pollutant transfer in the water mass effect the interference between the solute and suspended matter on the one hand, and water mass-biota interaction on the other. Atmospheric transport and deposition of chemical toxicants are considerable sources of the World Ocean pollution; their share in the total balance of the anthropogenic pollution influx into marine environment is commensurable with the river runoff.The most dangerous, among various pollutants entering the World Ocean, are oil, hydrocarbon chlorides (pesticides, polychloride bifenyls), toxic metals (mercury, cadmium, lead), i.e. globally occurring chemical compounds continuously entering the marine environment and effecting marine organisms and their populations. Still new and new pollutants are being discovered now in the oceans: chloride and polychloride terpenes, nitrosamines, chlordane, etc. The problems of eutrophication and microbiological contamination of the inland seas and ocean coastal zones are becoming still more urgent. Accumulation of aromatic polycyclic carcinogenous hydrocarbons. BaP in particular, is pregnant with unexpected ecological effects. The highest PAH concentrations have been observed in the sea coast areas and in the zones of intensive navigation. Rather high coefficients (10(2)-10(4)) of BaP accumulation in the sea biota and bottom sediments are marked.Ecological and biological effects of changes in the chemical composition of the ocean make up the chain of interrelated reactions; transformation of natural biogeocenoses, disturbance of the cycle of carbon, nitrogen, sulphur and other elements, reduction of biological productivity and cell genome affection present the most essential effects of these reactions. Stresses in the abiotic component of the ecosystem are expressed through disturbances in the chemical balance, changes in the evaporation from the sea surface, oil aggregate formation (floatable biocenoses), disturbances in reducing reactions of biogenous elements, salinity and temperature variation, and so on. Population-biocenotic effects of the man-made impact, actually important for the level of ecosystem stability, include the following processes of the structural and functional character: - alteration of the mean biomass of plankton and benthos populations, in particular in semi-enclosed seas and off-shore ocean areas; - alteration of the number of higher taxons-genera or families of the sea organisms, in particular replacement of the dominant populations of mass species, and emergence of hydrobionts new for the marine environment; - alteration of the relations between the numbers of some taxonomic groups of hydrobionts and abundant development of indicator species of the sea biota, e.g. BaP and PCB oxidizing microorganisms; - disturbances in production/destruction processes of organic substances; - energy flux changes in the marine ecosystem. Analysis of the current knowledge on the ocean environment pollution and its negative effects has enabled to formulate the main directions of the World Ocean ecological monitoring. Investigations of the biogeochemical cycles of pollutants and elements in the marine environment, identification of the effect of pollutants abundant in the ocean on the Earth's climate and hydrochemical regime as well as major geophysical processes in the ocean and atmosphere make up integral parts of the ocean monitoring together with the studies of pollutant impact on the ocean biota which leads to biological regime alterations and affection of the sea organisms genofond.

Spatial and temporal patterns of water flow generated by suction-feeding bluegill sunfish Lepomis macrochirus resolved by Particle Image Velocimetry. The suction-feeding fish generates a flow field external to its head in order to draw prey into the mouth. To date there are very few empirical measurements that characterize the fluid mechanics of suction feeding, particularly the temporal and spatial patterns of water velocity in front of the fish. To characterize the flow in front of suction-feeding bluegill sunfish Lepomis macrochirus, measurements with high spatial (<1 mm) and temporal (500 Hz) resolution were taken using Particle Image Velocimetry (PIV). In an analysis separate from the PIV, high-speed video sequences were used for a novel method of visually tracking every seed particle for the duration of each feeding in order to determine directly the total parcel of water that the fish ingests. PIV measurements and particle tracking show that water is drawn from all around the mouth. Fluid velocity decreases rapidly with distance from the mouth and is only significant (>5% of speed at the mouth) within roughly 1 mouth diameter of the fish. Suction feeders gain little in terms of extending this flow field by even substantial increases in the fluid speed at the mouth opening. Instead, the chief advantage of increased flow speed at the mouth may be the increased magnitude of generated forces within the space very close to the mouth. After scaling of the velocity field based on size of the mouth opening and the measured fluid speed at a fixed position, the measured velocity profiles for all feedings are very similar to one another, so that a functional relationship for the magnitude of fluid speed as a function of distance from the predator mouth is presented and shown to be accurate over the range of kinematic variables tested. This relationship describes the velocity field both along the centerline of the fish and along transects lying at an angle to the centerline within both the mid-sagittal and frontal planes. Comparison of the time-resolved fluid velocity measurements to gape kinematics demonstrate that peak fluid speed occurs simultaneously with 95% of peak gape, showing that the bluegill maximizes nearly simultaneously both the generated forces and size of the region over which these forces act. The magnitude of peak fluid speed during each strike decreases as a function of increasing time to peak gape (r2 = 0.87), demonstrating a strong relationship between the rate of buccal cavity expansion and maximum generated flow speed.

Introduction: military neurosurgery, past and present. For a physician has the worth of many other warriors, both for the excision of arrows and for the administration of soothing drugs. Homer, Iliad XI.514-515 Ever since armed conflict has been used as a means to settle disputes among men, there have been those who have been tasked to mend the wounds that ravage a soldier's body from the weapons of war. The Iliad portrays the pivotal 10th year of the legendary Trojan War, during which a schism in the Greek leadership prolongs the extended siege of the city of Troy. In the midst of this martial epic come the lines quoted above, quietly attesting to the value of the military physician, even under the crude conditions of the Greek Dark Age. They are uttered by Idomeneus, one of the foremost Greeks, when he is enjoining one of his comrades, Nestor, to rescue the injured Greek physician Machaon and take him back from the line to treat his wounds. He is afraid that Machaon will be captured by the Trojans, a loss far greater than that of any other single warrior. Duty to country has helped shape the careers of many neurosurgeons, including iconic US figures such as Harvey Cushing and Donald Matson. This issue of Neurosurgical Focus celebrates the rich history of military neurosurgery from the wars of yesterday to the conflicts of today. We have been humbled by the tremendous response to this topic. The 25 articles within this issue will provide the reader with both a broad and an in-depth look at the many facets of military neurosurgery. We have attempted to group articles based on their predominant topic. We also encourage our audience to read other recently published articles. The first 8 articles relate to the current conflicts in Afghanistan and Iraq. The lead article, written by Randy Bell and colleagues from the National Naval Medical Center and Walter Reed Army Medical Center, discusses what is arguably one of the most important contributions by military neurosurgeons from these 2 conflicts: the rapid and aggressive use of decompressive craniectomies. This is followed by articles on decompressive craniectomy techniques by Ragel and colleagues and cranioplasty outcomes by Stephens and colleagues. After reading these articles, the reader will come away with an appreciation of the often complex nature of wartime penetrating and closed-head injuries and the remarkable recovery that many injured soldiers make with time.

[Therapy of inflammatory changes in Bartholin's glands]. Bartholin's glands are bilateral structures whose function begins after puberty, so the diseases of these glands are most common during the reproductive period. Management of the inflammatory changes--abscess and cyst can be invasive and conservative, and quite often the changes become chronic, due to the failure of techniques. The aim of the study was to assess efficacy of various therapeutic approaches in the treatment of the inflammatory changes of Bartholin's glands. The study was done at the Department of Obstetrics and Gynecology, Clinical Centre in Novi Sad, during the period 1993-1996, at the Dept. of Inflammatory Gynaecological Diseases. The total of 129 patients was treated. The first two years were analyzed retrospectively while during the years 1995 and 1996 a prospective study was done. The analysis of the therapeutic results was done according to the immediate efficacy of the therapeutic approach, incidence of recurrence, length of hospitalization and use of antibiotics. A total of 129 patients was treated, the mean age was 35.4 years. Cysts were treated in 14.7% and abscess in 85.3% of cases. Therapeutic approaches were different during different years. During 1993 and 1994 in majority of cases incision and complete extirpation of the glands were done, and rarely marsupialization, alone or in combination with silver nitrate (AgNO3). In 1995 and 1996 in a majority of cases incision of the gland was performed, together with the AgNO3 application (94.3% in 1995, 64% in 1996). In 1995 total gland extirpation was performed (5.7%) while in 1996 in 9 cases (36%) incision was done. The length of hospitalization was longer in earlier years, the shortest being when incision and AgNO3 application was performed (3.1/2.4 days). The use of antibiotics was significantly lower in the years when incision and AgNO3 were used. Our results are in concordance with the results of similar studies except for the fact that in our group the changes were seen more often in the age group 30-39 years. The parity was of no significance. The recurrence of the disease when this method is applied is the same as in other studies--around 3%, whereas the complications were rare. The length of hospitalization and the cost of the antibiotic therapy is of great significance as well, and they can be brought to minimum by employment of this method. The therapeutic approach of incision and AgNO3 application in therapy of inflammatory changes of Bartholin's glands is an efficient, safe, simple and cheap method, which can easily be applied in ambulatory conditions.

Magnetic resonance imaging of the brain in patients with pseudoexfoliation syndrome and glaucoma. To evaluate ischemic changes in brain magnetic resonance images in patients with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) and compare them with age- and sex-matched control subjects. This case-control study involved 16 consecutive patients with PXS, 21 patients with PXG and 18 healthy age- and sex-matched control subjects. Each subject underwent a comprehensive ophthalmological examination. In all participants, an axial T(1)-, T(2)- and proton-density-weighted and coronal cerebral 1.5-tesla magnetic resonance imaging (MRI) scan was made. White matter hyperintensities (WMH) were considered present if these were hyperintense on both proton-density- and T(2)-weighted images and not hypointense on T(1)-weighted images. White matter lesions were classified into two parts as the subcortical and periventricular regions. We used a validated rating scale of subcortical WMH: 0 = absent, 1 = punctuate foci, 2 = beginning confluence of foci and 3 = large confluent areas. Periventricular white matter lesions were classified on a scale of 0 (no white matter lesions), 1 (pencil-thin periventricular lining), 2 (thick lining) or 3 (large confluent white matter lesions). The proportions of persons with WMH were 93.7% for patients with PXS, 95.2% for patients with PXG and 55.5% for control subjects. The numbers of white matter lesions in patients with PXS and PXG were significantly greater than in the control subjects (p < 0.05). White matter lesions at subcortical locations in patients with PXG were significantly more frequent than in the control subjects (80.9 vs. 33.3%; p < 0.05). The proportion of patients with subcortical WMH was 56.2% in PXS; no significant difference was found in subcortical WMH between PXS and controls. The proportions of patients with periventricular WMH were 93% in PXS, 90.4% in PXG and 44.4% in controls. White matter lesions at periventricular locations in patients with PXG and PXS were significantly more frequent than in the control subjects (p < 0.05). The difference between the pseudoexfoliation groups and controls with regard to the size of periventricular and subcortical white matter lesions was statically significant (p < 0.05). When patients with PXS were compared with PXG patients, there was no statistically significant difference in the number, size and scale of white matter lesions. We found a significantly higher prevalence of MRI-defined WMH in patients with a clinical diagnosis of pseudoexfoliation with or without glaucoma versus control subjects. We think that the findings in this study may shed light on a possible link between ischemic brain lesions and pseudoexfoliation, which is not related with the presence of glaucomatous optic neuropathy. Further investigations are required to resolve the underlying associations.

[Prostacyclin (iloprost) as an adjuvant in local surgical therapy of stage IV arterial occlusive disease--is quantification of the therapeutic effect possible with tcPO2 measurements?]. The effect of intravenous therapy with iloprost (average duration 6 weeks) on the prognosis of leg-preserving local surgical treatment and on the transcutaneously measured oxygen pressure (tcPO2) in patients with ischaemic lesions was investigated in a prospective, open, controlled, randomized study. All of the 30 patients recruited to the study suffered from a peripheral arterial occlusive disease Fontaine stage IV with progressive symptoms and arterial occlusions below the knee. 15 patients received iloprost intravenously for 6 hours per day in an individual tolerable dose (mean dose: 1.7 ng/kg/min). 15 patients in the control group received no trial therapy. During the treatment period each patient underwent minor amputation or skin grafting. Wound healing after surgery and tcPO2 were assessed. The long-term efficacy of iloprost was assessed by following the patients for one year. The iloprost treatment was in general well tolerated and all patients completed the study in accordance with the trial protocol. Primary postoperative wound healing as the responder-criterion was observed in 9 patients (60%) of the iloprost group and in 4 patients (27%) of the control group. Patients with iloprost therapy were especially likely to show wound healing if they received the operation approximately in the mid of the treatment phase. The effect of therapy lasted for one year after the end of the treatment in 7 of 9 classified responders of the iloprost group. After one year the responder rate of 47% in the iloprost group was still 20% higher than in the control group. Surgical revisions were necessary in 7 patients (47%) of each group. 2 patients (13%) treated with iloprost and 4 control patients (27%) underwent major amputation. The mortality was 13% = 2 of 15 patients (iloprost) and 7% = 1 of 15 patients (control). Transcutaneous PO2-measurements were very reproducible over a long-term period under standardized conditions. A significant effect of iloprost on the tcPO2 was shown. There was a mean increase of 8.1 mmHg +/- 11.2 (mean +/- SD) in the foot of the affected limb after an average 6-week therapy (p < 0.05). At the same time a significant difference in the tcPO2-changes between responders and nonresponders was demonstrated (p < 0.05). Patients with primary wound healing had a greater increase in tcPO2 than patients whose wounds did not heal. An increase of at least 10 mmHg (6 patients) in tcPO2 during the infusion after 3 weeks of therapy predicted primary post-operative wound healing.

Perimenopause and Menopause Are Associated With High Frequency Headache in Women With Migraine: Results of the American Migraine Prevalence and Prevention Study. To examine the relationship of headache frequency to the stages of the menopausal transition in mid-life women with migraine. Past studies suggest that the perimenopause is associated with an increased prevalence of migraine, particularly in those with a history of premenstrual syndrome. The effect of the menopausal transition on the frequency of headache attacks in women with migraine has not been explored. This was a cross-sectional observational study. Using data from the 2006 American Migraine, Prevalence and Prevention study survey, women meeting modified ICHD-3 beta criteria for migraine between the ages of 35-65 years were included in analyses. Women who had never menstruated or were pregnant, breastfeeding, or using exogenous sex hormones were excluded. The 2006 survey was selected because it included detailed questions on the menstrual cycle. The stages of the menopausal transition were defined based upon the self-reported cycle length and/or duration of amenorrhea. The primary outcome, high vs low headache frequency, was defined using a cut score of ≥10 headache days per month. Binary logistic regression models were used to assess the influence of menopausal stage on headache frequency category using premenopause as the reference group. Adjustments for stage of menopausal transition and sociodemographics (eg, age and income) were included in the first model, while the second model included sociodemographics, depression, body mass index, preventative medications, and medication overuse. The study sample included 3664 women at a mean age of 46 years. Among women who were premenopausal, 8.0% (99/1242) were in the high frequency headache group in comparison with 12.2% (154/1266) of perimenopausal and 12.0% (131/1095) of postmenopausal women. Compared with premenopausal women, the adjusted odds of being in the high frequency headache group was 1.62 (95% CI = 1.23, 2.12) for perimenopausal and 1.76 (95% CI = 1.23, 2.52) for postmenopausal women (Model 1). In model 2, high frequency headache was only increased in perimenopausal women with an OR of 1.42 (95% CI = 1.03, 1.94). The risk of high frequency headache is increased in women during the perimenopause compared to premenopause in the fully adjusted model. The fact that the increased risk of high frequency headache was not statistically significant for menopause in the fully adjusted models suggests that different mechanisms might account for the increased risk for this stage of the menopausal transition. Recognition of the increased risk of high frequency headache during the menopausal transition suggests a need for optimized preventive treatment of migraine during this time of women's life.

Validity of self-reported drug use in chronic pain patients. Previous researchers have reported that in psychiatric populations many patients provide incorrect self-report information on current drug use. Therefore, the purposes of the present study were to determine the percentage of chronic pain patients (CPPs) using illicit drugs (cannabis, cocaine), to determine the percentage of CPPs who provide incorrect self-report drug use information in the psychiatric examination, and to identify some variables that could help in identifying the CPP likely to provide an incorrect drug use history using drug urine toxicologies. DESIGN/SETTING/PARTICIPANTS/OUTCOME MEASURES: Two hundred seventy-four CPP consecutive admissions to a pain facility were psychiatrically examined according to criteria in the Diagnostic and statistical manual of mental disorders (3rd ed., rev; DSM-III-R), with special emphasis on all current drug use. Immediately after the psychiatric examination, all CPPs were asked to consent to urine toxicology. Urine was tested for benzodiazepines, opioids, tricyclics, propoxyphene, cannabinoids, barbiturates, amphetamines, methadone, methaqualone, phencyclidine, alcohol, and cocaine. CPPs were then segregated into three groups: negative toxicology, positive toxicology but concordant with self-report of current drug use, and positive toxicology discordant with self-report of current drug use. These groups were statistically compared with each other with regard to age, gender, race, workers' compensation status, and prevalence of individual DSM-III-R psychoactive substance use disorders. Sensitivities were also calculated for two conditions: accuracy of toxicology and accuracy of self-report. Toxicologies were obtained from 226 (82.5%) of the CPPs. Toxicologies were negative in 121 (53.5%) and positive in 105 (46.5%) of the CPPs. Of the 226 CPPs, 8.4% had illicit drugs in the urine (6.2% cannabis, 2.2% cocaine). Twenty (8.8%) of the CPPs provided incorrect self-report information about current drug use, the incorrect information most frequently about illicit drugs. Drug urine toxicology sensitivity results indicated that a significant percentage of CPPs was claiming to be taking a drug but was not taking it or taking it incorrectly. The psychiatric examination drug self-report sensitivity results indicated that a significant percentage of CPPs was withholding or providing incorrect information on current drug use. Lowest self-report sensitivity results were in reference to illicit drugs. CPPs who were more likely to provide incorrect psychiatric examination self-report information about current drug use were more likely to be younger, to be a workers' compensation CPP, and to have been assigned a DSM-III-R diagnosis of polysubstance abuse in remission. A significant percentage of CPPs appears to provide incorrect information on current illicit drug use. Urine toxicology studies may have a place in the identification of drugs for which incorrect information may be provided by CPPs. There are many possible reasons, such as assay error, that could lead to apparent misinformation. In the clinical setting, these possibilities should be considered if urine toxicology results appear to be incongruent with psychiatric examination drug use self-report.

Patterns of hearing aid usage predict hearing aid use amount (data logged and self-reported) and overreport. Previous studies found that, on average, users overreport their daily amount of hearing aid use compared to objective measures such as data logging. However, the reasons for this are unclear. This study assessed data-logged and self-reported amount of hearing aid use in a clinical sample of hearing aid users. It identified predictors of data-logged hearing aid use, self-reported hearing aid use, and hearing aid use overreport. This observational study recruited adult hearing aid users from 22 private dispensers in the Netherlands and in Denmark. The sample consisted of 228 hearing aid users. Typical participants were over the age of 65 and retired, were fitted binaurally, and had financially contributed to the cost of their hearing aids. Participants had on average a mild-to-severe sloping bilateral hearing impairment. Participants completed a purposefully designed questionnaire regarding hearing aid usage and the International Outcome Inventory-Hearing Aids. Dispensers collected audiometric results and data logging. Multiple linear regression identified predictors of data-logged hearing aid use, self-reported hearing aid use, and hearing aid use overreport when controlling for covariates. Data logging showed on average 10.5 hr of hearing aid use (n = 184), while participants reported on average 11.8 hr of daily hearing aid use (n = 206). In participants for which both data-logged and self-reported hearing aid use data were available (n = 166), the average absolute overreport of daily hearing aid use was 1.2 (1 hr and 11 min). Relative overreport was expressed as a rate of absolute overreport divided by data-logged hearing aid use. A positive rate denotes hearing aid use overreport: the average overreport rate was .38. Cluster analysis identified two data-logged patterns: "Regular," where hearing aids are typically switched on for between 12 and 20 hr before their user powers them off (57% of the sample), and "On-off," where hearing aids are typically switched on for shorter periods of time before being powered off (43% of the sample). In terms of self-report, 77% of the sample described their hearing aid use to be the same every day, while 23% of the sample described their hearing aid use to be different from day to day. Participants for whom data logging showed an On-off pattern or who reported their hearing aid use to be different from day to day had significantly fewer data-logged and self-reported hours of hearing aid use. Having an On-off data-logging pattern or describing hearing aid use as the same every day was associated with a significantly greater hearing aid use overreport. Data-logged and self-reported usage patterns significantly predicted data-logged hearing aid use, self-reported hearing aid use, and overreport when controlling for covariates. The results point to patterns of hearing aid usage as being at least as important a concept as amount of hearing aid use. Dispensers should discuss not only the "how much", but also the "how" of hearing aid usage with their clients.

Effects of systemic endothelin A receptor antagonism in various vascular beds in men: in vivo interactions of the major blood pressure-regulating systems and associations with the GNB3 C825T polymorphism. We used the orally available endothelin A (ETA) receptor antagonist darusentan to characterize interactions between the major blood pressure-regulating systems in healthy men. Mediators of the endothelin system, the sympathetic nervous system, and the renin-angiotensin system act via G protein-coupled receptors with a possible involvement of the G-protein beta3 subunit (GNB3) C825T polymorphism. We studied the influence of this polymorphism on the responses to ETA antagonism in the presence of endothelin 1 (ET-1), norepinephrine (NA), and angiotensin II (ANGII). Thirty-seven individuals were included in a randomized, double-blind, placebo-controlled, crossover trial with 100 mg darusentan. Systemic hemodynamics and plasma ET-1, NA, and ANGII concentrations were assessed. Local studies were performed in the dorsal hand veins (n=18) and skin microcirculation (n=12), respectively. Darusentan lowered systolic and diastolic blood pressure ( P <.001 versus placebo) without any differences according to genotype (mean maximum Delta systolic blood pressure, -7 +/- 2 mmHg for CT/TT versus -5 +/- 3 mmHg for CC, P=.37; mean maximum Delta diastolic blood pressure, -3 +/- 2 mmHg for CT/TT versus -4 +/- 2 mmHg for CC, P=.96). Venoconstriction to ET-1 and NA was not affected by ET A blockade in either group; however, carriers of the 825T allele demonstrated a markedly enhanced venoconstriction to ET-1 and NA (median effective concentration [ED50] for ET-1 after darusentan [placebo]: 2.5 +/- 0.2 pmol/min for CT/TT [2.7 +/- 0.3 pmol/min], P=.42; 3.9 +/- 0.6 pmol/min for CC [4.6 +/- 0.3 pmol/min], P=.42; P=.046 [P=.0005] for CT/TT versus CC) (ED50 for NA after darusentan [placebo]: 5.2 +/- 1.2 ng/min for CT/TT [7.3 +/- 1.2 ng/min], P=.20; 32.9 +/- 7.1 ng/min for CC [19.7 +/- 5.5 ng/min], P=.75; P=.0008 [P=.026] for CT/TT versus CC). Darusentan dilated veins at baseline in CC homozygous subjects (+0.21 +/- 0.05 mm, P=.004 versus placebo). Systemic ET A antagonism inhibited constriction to ET-1 and also to NA and ANGII in the skin microcirculation without differences according to genotype (ET-1, P=.017 for all individuals versus placebo; NA, P=.0005; and ANGII, P=.002). GNB3 C825T allele carrier status did not influence systemic hemodynamic or local vascular responses to ET A blockade with darusentan in young, healthy men. However, it determined venoconstriction to exogenous ET-1 and NA. Darusentan markedly inhibited not only ET-1-induced but also NA-induced and ANGII-induced vasoconstriction in the skin microcirculation. In contrast, it had no effects on either ET-1-mediated or NA-mediated venoconstriction, indicating that, in the presence of high local ET-1 concentrations, constrictive endothelin B receptors may be of greater importance in the venous vasculature than has been recognized so far.

Steer responses to feeding soybean hulls and steroid hormone implantation on toxic tall fescue pasture. Crossbred steers were grazed in the spring and early summer on endophyte-infected (Neotyphodium coenophialum), Kentucky-31 tall fescue (Lolium arundinaceum) pastures to evaluate effects and interactions of feeding pelleted soybean hulls (PSBH) and steroid hormone implants (SHI) on steer performance, serum prolactin, and hair coat ratings (HCR). Steers were stratified by BW for assignment to six 3.0-ha toxic tall fescue pastures. With or without daily PSBH feeding, treatments were assigned randomly to pastures as the main plot treatment in a split-plot design. Pelleted soybean hulls were group-fed to provide 2.3 kg(steer·d(-1)) (as fed). With or without SHI (200 mg of progesterone and 20 mg of estradiol) treatments were randomly assigned as the subplot treatment to 2 steer subgroups within each pasture. Sixty-four steers were grazed for 77 d in 2007, and 60 steers were grazed for 86 d in 2008. Pasture forage mass declined linearly over time, but the rate of decline was greater (P = 0.001) in 2007 than in 2008. Pasture forage mass was never below 2,300 kg of DM/ha in either year. Average daily gain for steers on the combined PSBH and SHI treatments was greater (P < 0.01) than for those on the PSBH-only, SHI-only, and control (no SHI, no PSBH) treatments. Average daily gain for the PSBH-only steers was greater (P < 0.01) than for SHI-only and control steers and tended (P = 0.063) to be greater for SHI-only than for control steers. Steroid implants did not affect (P = 0.826) serum prolactin concentrations; however, prolactin concentrations in PSBH steers, with or without SHI, were increased (P = 0.01) 2-fold over SHI-only and control steers. Feeding PSBH and SHI treatments both reduced (P < 0.05) the percentage of steers with rough HCR, and a greater percentage of steers fed PSBH tended (P < 0.076) to have sleek hair coats. An economic analysis was conducted, which determined that costs of additional ADG with PSBH feeding were below breakeven costs over a wide range of PSBH costs and cattle prices. Breakeven costs for PSBH-only treatment for a range of cattle prices of $1.80 to $2.40/kg of BW were less than $120/t, whereas with PSBH feeding combined with SHI the breakeven cost was less than $240/t. Results indicate that steers grazing endophyte-infected tall fescue can be fed PSBH and implanted with steroid hormones to cost effectively increase ADG and that feeding PSBH can increase serum prolactin concentrations and induce some shedding of rough hair coats.

[Endoscopic sinus surgery in flowing water]. A balloon has been developed that completely fills the choana, preventing water from leaking into the pharynx even when the water is entering into the nasal cavity at a rate of 1000 ml per minute. The balloon enables endoscopic sinus surgery (ESS) to be safely performed in "flowing water". This surgical technique is similar to that used in transurethral resections of the prostate because the tip of the endoscope is kept clean, and blood, debris and resected tissues are continuously removed by the water flow. In addition, the water pressure helps to suppress bleeding. This technique enables ESS to be performed with greater ease and efficiency. We have performed ESS in flowing water on 38 patients with chronic sinusitis under local anaesthesia. No complications, such as water leakage into the pharynx, were encountered, and only a few patients felt discomfort from the insertion of the balloon. Even if the balloon had burst, an emergency could have been easily prevented by withdrawing the endoscope from the nasal cavity and stopping the flow of water. Ultrasonography (USG) was used to examine the water-filled nasal cavity during surgery (SSD-2000 and Micro Tip Radial (ASU-101); Aloka, Ltd., Japan). Using USG, the middle turbinate, the inferior turbinate and the nasal septum could be visualized in a single coronal image. When the sensor was in the posterior ethmoid sinus, the orbit and its optic nerve could also be visualized. Since this surgery is performed under local anesthesia, eye movements can rapidly alter the position of the optic nerve. Thus, visualization of the optic nerve's exact position is extremely important. Unfortunately, USG is not very useful for localizing structures and guiding the surgeon to distant tumors or cysts located behind thick bones, since ultrasound can not penetrate hard masses or bones. In this situation, navigation systems are more reliable than USG. Nevertheless, USG is often useful for depicting surgical sites, especially during a crisis, if the medial wall of the orbit is thin or if the skull base has been broken, exposing the dura. USG can also provide early warning of an impending complication. USG also has several practical advantages over navigation systems: the cost of USG is much lower, preparation for surgery is unnecessary, visual information can be obtained in real time, and measurement accuracy (estimated to be about 2 mm for navigation systems) is not a consideration. Thus, USG can be easily used to avoid complications in most surgeries for chronic sinusitis. Flowing water also allows the nasal eavity to be completely washed and sterilized at the end of the surgery. This not only prevents post-operative infection, but enables sinus function to be more quickly recovered. In addition, the pressure from the balloon also prevents post-operative nasal hemorrhaging. This allows patients to be safely discharged from the hospital at an earlier time. The balloon can also be used for non-surgical purposes. For example, emergent epistaxis can be easily stopped by the insertion of this balloon, even if the doctor is not an otorhinolaryngologist. In addition, the balloon's soft pressure allows it to be left in the nose for long periods without any complications. We conclude that this simple balloon, which we have named the "Noda Balloon", is extremely useful for nasal treatments.

Pharmacological modulation of electromechanical coupling in the proximal and distal regions of the guinea-pig renal pelvis. 1. The effect of drugs affecting calcium and potassium channels and intracellular calcium handling/release on electromechanical coupling in the smooth muscle of the guinea-pig proximal vs. distal renal pelvis were investigated by using the single sucrose gap method. 2. Spontaneous action potentials discharged from the proximal renal pelvis were bell-shaped, did not show a pronounced plateau and had a small after-hyperpolarization. Spontaneous action potentials from the distal renal pelvis were characterized by a fast depolarization, a pronounced plateau and after-hyperpolarization. 3. Nifedipine (1 microM) suppressed action potentials in both regions of the renal pelvis. A submaximally effective concentration of nifedipine (50 nM) shortened action potential duration and reduced contractility in both regions of the renal pelvis. On the other hand Bay K 8644 (1 microM) markedly prolonged the duration of the action potential and increased contractility in both regions of the renal pelvis. 4. Tetraethylammonium (0.5 mM) markedly prolonged the action potential duration and contraction in the distal renal pelvis without affecting action potentials in the proximal renal pelvis. Similar effects were produced by a slightly higher concentration of tetraethylammonium (2 mM) in the proximal renal pelvis. 5. Charybdotoxin (30 nM) markedly prolonged the duration of action potential and increased and prolonged the contraction in both the proximal and distal renal pelvis. 6. 4-aminopyridine (1 mM) selectively increased the frequency of action potentials in the distal renal pelvis without affecting other parameters of the action potential nor contractility. 4-aminopyridine had no effect in the proximal renal pelvis. 7. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (10 microM) transiently increased the frequency of action potentials in both regions of the renal pelvis; CPA markedly delayed the repolarizing phase of the action potential in both the proximal and distal renal pelvis and, in parallel, increased contractility. 8. We conclude that action potentials generated from the proximal and distal regions of the guinea-pig renal pelvis are evenly dependent upon the availability of L-type Ca channels; that Ca-dependent maxi K channels provide a major contribution to the repolarization of action potentials in both regions of the renal pelvis, thus regulating duration/intensity of Ca influx and contraction; that release of Ca from the internal store is not important in providing activator Ca for contraction but regulates duration of the action potential and may be involved in setting the frequency of discharge of pacemaker cells.

Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 Years. Bisphosphonates (BPs) delay the onset or reduce the incidence of skeletal complications in patients with bone metastases. However, there are few data on the renal safety and activity of i.v. BPs beyond 2 years of administration. We retrospectively analyzed serum creatinine (SCr) levels and skeletal-related events (SREs) in cancer patients receiving i.v. BPs for >or= 24 months. All patients received 90 mg pamidronate every 3-4 weeks. Pre- and post-treatment SCr levels and the peak levels attained were recorded. A notable SCr increase was defined as: an increase >0.5 mg/dl for patients with baseline SCr <1.4 mg/dl; an increase >1 mg/dl for patients with baseline SCr >1.4 mg/dl; or doubling over baseline. The following parameters were also analyzed: the proportion of patients with at least one SRE, the distribution of each type of SRE, the time to first SRE, and the skeletal morbidity rate (SMR). Fifty-seven patients with bone metastases resulting from breast cancer (BC) (n = 48), multiple myeloma (n = 7), renal cell carcinoma (n = 1), and prostate cancer (n = 1) were evaluated. The median age at the start of treatment was 57 years (range, 27-81); 25% of the patients were >70 years old. Forty-three patients received pamidronate then switched to zoledronic acid. The median overall duration of BP administration was 34 months (range, 24+ to 131+), with a median duration of zoledronic acid therapy of 25 months (range, 2-40). Twenty-seven of 48 BC patients received different chemotherapy regimens (median number of lines, 2; range, 1-6). The median SCr levels were: baseline, 0.82 mg/dl (range, 0.4-1.4); time of analysis, 0.89 mg/dl (0.4-2); highest level, 1.0 mg/dl (0.5-2). A notable SCr increase was observed in seven patients (12.2%; all grade 1). Twenty-six patients (45.6%) experienced SREs after starting BP treatment. The median time to first SRE was 911 days (95% confidence interval, 731; 1,023). The SMR was 0.20 events per year. Ten patients ceased treatment because of: an SCr level of 2 mg/dl (n = 1) physician decision (n = 6) and jaw osteonecrosis (n = 3). Ten patients died of progressive disease. i.v. BPs are safe and active during prolonged treatment administration, and renal function is maintained in patients receiving multiple cytotoxic therapies. Jaw osteonecrosis occurred in 5% of the study population, and its causal relationship with BP treatment requires further observation and study.

Studies in gastric carcinogenesis. V. The effects of ascorbic acid on N-nitroso compound formation in human gastric juice in vivo and in vitro. The concentrations of nitrite, thermo- and acetic acid-labile TEA-responsive compounds (TACs) and N-nitroso compounds (NOCs) as a group were measured in human gastric juice collected just before and 1, 2 and 4 h after oral ingestion of 1 g ascorbic acid (AA) or 200 mg sodium nitrate, separately or in combination. Individual responses of gastric [nitrite] following ingestion of AA alone varied widely, with both decreases and increases being observed, and showed no correlation with gastric pH. While a mixed response was also noted for [NOC] and [TAC], substantial decreases were observed in 5/6 individuals with initial [NOC] greater than 0.2 microM and 3/3 individuals with initial [TAC] greater than 0.2 microM, implying that (i) AA effectively inhibited gastric nitrosation and (ii) a basal amount of NOCs and TACs was present in gastric juice which could not be lowered by AA ingestion. Statistical analysis indicated that global mean values of gastric [NOC] were significantly reduced (P less than 0.02) 1-4 h after ingestion of AA. Ingestion of 200 mg sodium nitrate alone resulted in increases in gastric [NOC], which in some cases were very substantial. While nitrosation appeared lower following ingestion of the same dose of nitrate in combination with 1 g AA, the difference from the effects of nitrate alone was not statistically significant. In aqueous buffer, pH 2.5, and in the presence of 1 mM AA, 50 microM nitrite was consumed with a t1/2 of 50 min only if molecular oxygen had first been removed from the system. In the presence of oxygen, no consumption of nitrite could be detected in 50 min, reflecting nitrite recycling (oxidation of nitric oxide to higher oxides of nitrogen and hydrolysis back to nitrite). It is likely that nitrite recycling occurring after collection of gastric juice accounted for the inconsistent responses of gastric nitrite following ingestion of AA. Incubation of human gastric juice, pH 2.5, in vitro in the presence of 50 microM sodium nitrite for 60 min resulted in an increase of [NOC] and [TAC] from 0.10 to 0.70 and 1.10 microM respectively. Nitrosation was efficiently inhibited by AA, 2.27 mM AA resulting in 87 and 100% inhibition respectively. Removal of oxygen from the reaction mixture did not have any significant effect on the extent of nitrosation in the presence or absence of AA.

Ovarian expression of insulin-like growth factor-I (IGF-I), IGF binding proteins, and growth hormone (GH) receptor in heifers actively immunized against GH-releasing factors. Active immunization against GRF at 6 months of age delays puberty in beef heifers. The objectives of the present study were to determine whether active immunization against GRF at an earlier age would affect normal onset of puberty and follicular growth and to determine whether these changes were related to alterations in ovarian insulin-like growth factor I (IGF-I) or IGF binding protein (IG-FBP) messenger RNA (mRNA) levels. Heifers were immunized against human serum albumin (HSAi; n = 15) or against GRF conjugated to HSA (GRFi; n = 18) at 3 months of age. A third group of heifers was not immunized (CON; n = 16). Immunization against GRF delayed puberty beyond 13 months of age in 75% of treated heifers. Unilateral ovariectomy at 191 days of age revealed that the delay in puberty was associated with a reduction in the number of large ( > or = 7 mm in diameter) follicles. Large follicles were present in only 22% of GRFi heifers compared to 77% of HSAi heifers. The number of small ( < or = 3 mm in diameter) and medium (4 to 6 mm in diameter) follicles was not affected by GRFi. The percentage of 1- to 3-mm follicles that were atretic was not different between HSAi (65%) and GRFi (62%) heifers. Unilateral ovariectomy had no effect on age at puberty. Immunization against GRF decreased (P < 0.01) concentrations of IGF-I in serum (23 +/- 2 ng/ml) compared to HSAi heifers (109 +/- 11 ng/ml). IGF-I levels in follicular fluid (FFL) of medium and small follicles were also decreased by GRFi from 82 +/- 3 ng/ml in HSAi heifers to 48 +/- 6 ng/ml (P < 0.01). Levels of IGFBP-3 (determined by ligand blot analysis) in serum and FFL of small follicles were decreased by GRFi (P < 0.01). In contrast, IGFBP-2 serum levels were increased from 422 +/- 32 ng/ml in HSAi heifers to 657 +/- 6 ng/ml in GRFi heifers (P < 0.05). Likewise, IGFBP-2 levels in FFL from small and medium follicles were increased from 785 +/- 44 ng/ml to 926 +/- 44 ng/ml (P < 0.05). Ligand blot analysis indicated that IGFBP levels were lower in FFL from large vs. small follicles. The band intensities of IGFBP-4 and -5 were drastically reduced ( > 80%) while the decreases in IGFBP-2 and -3 were less marked ( < 50%). The decreased levels of IGFBP-5 in FFL from large follicles was not associated with an increase in proteolytic fragments detectable by immunoblot analysis. While mRNA transcripts for IGF-I, GH receptor, and IGFBP-2, -3, -4, and -5 were readily detectable in ovarian tissue, GRFi had no effect on ovarian levels of mRNA for each of these proteins. This suggests that the decrease in follicular development associated with GRFi may be related to changes in circulating IGF-I and/or IGFBPs.

Sonographic diagnosis of IUGR-macrosomia. Many sonographic methods have been suggested for identification of the fetus with a growth abnormality. Clearly, optimal management depends on early diagnosis. In recent years, advances in sonography have improved the ability to identify abnormal growth patterns and evaluate fetal well-being. When abnormal fetal growth is suspected, a thorough sonographic evaluation should be performed. This evaluation includes measurements of the abdominal circumference, femur length,) BPD, HC, AC, FL, and amniotic fluid volume. If these measurements confirm the suspicion of abnormal fetal growth, careful search for anomalies is mandatory. If there is no evidence of fetal compromise that would warrant delivery, measurements should be repeated in 2-3 weeks to evaluate interval growth. The following conclusions could be drawn from this literature review: 1. Intrauterine growth retardation and macrosomia are multifactorial diseases with varying degrees of severity. It is unlikely that a single sonographic parameter will allow an accurate diagnosis of all cases. 2. The type and degree of growth retardation and macrosomia depend on the intensity and duration of the underlying disease. Thus, an ultrasound assessment performed long before delivery may be of limited value. 3. Most of the sonographic parameters reviewed in this chapter are gestational age dependent. Unfortunately, gestational age is often unknown. Gestational age independent indices such as the amniotic fluid volume, FL/AC ratio, and the rate of fetal growth should be helpful in this situation. 4. The constitutionally small infant whose only problem is low birth weight should not be expected to present with any abnormal indices other than a low EFW. On the other hand, newborns who appear to be malnourished but whose birth weight is at or slightly above the tenth percentile for gestational age, may present with abnormal indirect indices indicating growth retardation (ie, HC/AC, FL/AC, Doppler velocimetry or oligohydramnios) despite a normal estimate of fetal weight. In addition, if the diagnosis of IUGR is made only with the use of birthweight for gestational age criteria, these infants are likely to be misclassified and labelled AGA. However, an abnormal ponderal index would indicate that these neonates are growth retarded. It can be concluded from this review that the use of sonographic measurements for diagnosing IUGR or macrosomia is associated with a high specificity and a somewhat lower sensitivity. Therefore, it would seem that the current ultrasound methods are more useful for excluding the possibility of abnormal fetal growth rather than for confirming it.

Prediction of metabolic function from limited data: Lumped hybrid cybernetic modeling (L-HCM). Motivated by the need for a quick quantitative assessment of metabolic function without extensive data, we present an adaptation of the cybernetic framework, denoted as the lumped hybrid cybernetic model (L-HCM), which combines the attributes of the classical lumped cybernetic model (LCM) and the recently developed HCM. The basic tenet of L-HCM and HCM is the same, that is, they both view the uptake flux as being split among diverse pathways in an optimal way as a result of cellular regulation such that some chosen metabolic objective is realized. The L-HCM, however, portrays this flux distribution to occur in a hierarchical way, that is, first among lumped pathways, and next among individual elementary modes (EM) in each lumped pathway. Both splits are described by the cybernetic control laws using operational and structural return-on-investments, respectively. That is, the distribution of uptake flux at the first split is dynamically regulated according to environmental conditions, while the subsequent split is based purely on the stoichiometry of EMs. The resulting model is conveniently represented in terms of lumped pathways which are fully identified with respect to yield coefficients of all products unlike classical LCMs based on instinctive lumping. These characteristics enable the model to account for the complete set of EMs for arbitrarily large metabolic networks despite containing only a small number of parameters which can be identified using minimal data. However, the inherent conflict of questing for quantification of larger networks with smaller number of parameters cannot be resolved without a mechanism for parameter tuning of an empirical nature. In this work, this is accomplished by manipulating the relative importance of EMs by tuning the cybernetic control of mode-averaged enzyme activity with an empirical parameter. In a case study involving aerobic batch growth of Saccharomyces cerevisiae, L-HCM is compared with LCM. The former provides a much more satisfactory prediction than the latter when parameters are identified from a few primary metabolites. On the other hand, the classical model is more accurate than L-HCM when sufficient datasets are involved in parameter identification. In applying the two models to a chemostat scenario, L-HCM shows a reasonable prediction on metabolic shift from respiration to fermentation due to the Crabtree effect, which LCM predicts unsatisfactorily. While L-HCM appears amenable to expeditious estimates of metabolic function with minimal data, the more detailed dynamic models [such as HCM or those of Young et al. (Young et al., Biotechnol Bioeng, 2008; 100: 542-559)] are best suited for accurate treatment of metabolism when the potential of modern omic technology is fully realized. However, in view of the monumental effort surrounding the development of detailed models from extensive omic measurements, the preliminary insight into the behavior of a genotype and metabolic engineering directives that can come from L-HCM is indeed valuable.

Diagnostic problems and advances in inflammatory bowel disease. This review summarizes current diagnostic problems and advances with regard to patterns of inflammation and dysplasia in ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease have a variety of characteristic but non-specific pathologic features. In approximately 5% of inflammatory bowel disease cases, a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established, in which case the term "indeterminate" colitis is used. Most cases of indeterminate colitis are related to fulminant colitis, a condition in which the classic features of ulcerative colitis or Crohn's disease may be obscured by severe ulceration with early superficial fissuring ulceration, transmural lymphoid aggregates, and relative rectal sparing. Approximately 20% of patients with indeterminate colitis develop severe pouch complications, which is intermediate in frequency between ulcerative colitis (8-10%) and Crohn's disease (30-40%). In order to establish a diagnosis of ulcerative colitis or Crohn's disease, it is important to evaluate pathologic material in conjunction with clinical, laboratory, radiologic, and endoscopic features and to recognize the variety of changes that may be seen in fulminant ulcerative colitis. There are a number of exceptions to the classic principles of inflammatory bowel disease pathology that may lead to diagnostic confusion. For instance, apparent skip lesions on biopsy analysis may occur in patients with ulcerative colitis in the following settings; long term oral or topical therapy, focal ascending colon, cecum and/or appendiceal involvement in patients with left sided ulcerative colitis, upper gastrointestinal involvement in patients with ulcerative colitis, and at initial presentation of ulcerative colitis in pediatric patients. In all of these circumstances, the finding of patchy disease and/or rectal sparing should not be misinterpreted as either evidence against a diagnosis of ulcerative colitis, or as representing skip areas characteristic of Crohn's disease. Patients with ulcerative colitis and Crohn's disease are at increased risk for the development of dysplasia and carcinoma. Recent studies suggest that given a similar duration and extent of disease, patients with Crohn's disease have a similar risk of dysplasia and cancer as patients with ulcerative colitis. Dysplasia in ulcerative colitis may be classified as flat or elevated (dysplasia associated lesion or mass [DALM]). Patients with flat high grade dysplasia are generally treated with colectomy. However, there is recent evidence to suggest that patients with flat low grade dysplasia, particularly if detected at the time of initial endoscopic exam, or if its multifocal or synchronous, should also be treated with colectomy. Elevated lesions in ulcerative colitis (DALM) are subdivided into "adenoma-like" and "non-adenoma-like" lesions based on their endoscopic appearance. Recent data suggests that adenoma-like lesions, regardless of the grade of dysplasia, or the location of the lesion (i.e., inside or outside areas of established colitis) may be treated adequately by polypectomy if there are no other areas of flat dysplasia in the patient. Although there are some histologic and molecular features that can help differentiate sporadic adenomas from adenoma-like polypoid dysplastic lesions related to ulcerative colitis, none of these adjunctive techniques can help distinguish these lesions definitively in any single patient. Patients with a non-adenoma-like DALM, (irregular, broad based, or strictured lesion) should be treated with colectomy because of the high probability of adenocarcinoma. The surveillance and treatment options for patients with flat and elevated dysplasia in ulcerative colitis are reviewed in detail.

Bayesian approach to incorporating different types of biomedical knowledge bases into information retrieval systems for clinical decision support in precision medicine. By providing clinicians with information regarding treatment options for molecular sub-types of complex diseases with genetic origin, such as cancer, information retrieval (IR) systems play an important role in precision medicine. In this paper, we propose Bayesian Precision Medicine (BPM), a novel probabilistic framework for query expansion in information retrieval systems for Clinical Decision Support (CDS) in Precision Medicine (PM). Such systems can assist clinicians with selecting personalized treatment of complex diseases based on the patients' genomic data, such as gene mutations. In particular, we focus on a clinical decision support scenario in which clinicians provide two types of information in their queries: (1) short description of a patient's case, which may contain information regarding the type of cancer that a patient has as well as symptoms and demographics, and (2) gene mutations, which may contain gene names, mutation code and type of mutation. The goal of an IR system in this scenario is to rank biomedical articles from a large collection, such as the MEDLINE, based on their relevance to the provided query. One of the main challenges faced by IR systems in this scenario is semantic matching of heterogeneous information (gene names, medical terminology and other query keywords) in queries and relevant biomedical articles. To address this challenge, we propose a probabilistic framework that enables mapping gene mutations provided in a given query onto the biomedical concepts that are related to the entire query and can be effectively utilized for query expansion. The BPM obtains candidate query expansion concepts from biomedical knowledge bases, the Unified Medical Language System (UMLS) and the Drug-Gene Interaction Database (DGIdb), as well as the top-ranked MEDLINE articles retrieved for the original query. The BPM then utilizes information from the Catalog of Somatic Mutations in Cancer (COSMIC) and co-occurrence statistics in MEDLINE to assess the relatedness of candidate query expansion concepts to gene mutations and other information provided in a query. Experimental evaluation of the BPM was conducted on a large subset of MEDLINE articles as well as abstracts from the American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO) proceedings. Experimental results on a publicly available benchmark provided by the 2017 TREC precision medicine track indicate that the proposed probabilistic framework is effective at utilizing both genomic and textual information in queries to improve the accuracy of IR systems for CDS in PM through query expansion.

Ocular lesions associated with attachment of the copepod Ommatokoita elongata (Lernaeopodidae: Siphonostomatoida) to corneas of Pacific sleeper sharks Somniosus pacificus captured off Alaska in Prince William Sound. Twenty eyes from 10 Pacific sleeper sharks Somniosus pacificus, infected with the copepod Ommatokoita elongata, were collected in Prince William Sound, Alaska, and the eyes of an additional 18 S. pacificus captured in the same area were inspected for copepods. Prevalence of infection by adult female O. elongata was 97% (n = 28); mean intensity of infection was 1.89 (+/-1SD = 0.32) adult female copepods per infected shark and 1.0 (+/- 1SD = 0.0) adult female copepods per infected eye. Five of the 20 collected eyes were infected by O. elongata chalimi, and 9 of 20 eyes had 1 to several remnants of bullae embedded in the cornea. Bullae were each associated with a corneal opacity, and anchoring plugs of chalimi were associated with pinpoint lesions in the cornea or conjunctiva. All eyes exhibited marked edema and erosion of the bulbar conjunctiva, and this torus-shaped lesion corresponded to each O. elongata adult female's presumed feeding and abrasion radius. Histological examinations revealed lesions in the anterior segment of eyes to be generally similar, but graded, in severity, and in all eyes they involved the conjunctiva, cornea, filtration angle, and iris. Epithelial lesions were characterized by corneal ulceration, dysplasia, hyperplasia, and heterophilic keratitis, and by ulcerative conjunctivitis accompanied by epithelial hyperplasia with rete peg formation. Disorganization of fibers, necrosis, mineralization, minimal heterophilic influx, and perilimbic neovascularization were associated with bullae in the corneal stroma. Within the limbus there was diffuse histiocytic and lymphocytic inflammation and marked lymphofollicular hyperplasia. Heterophilic and mononuclear anterior uveitis affecting the filtration angle and anterior surface of the iris was also observed in most eyes. One eye had a partial transcorneal prolapse of a ruptured lens, with degenerative changes in the ruptured lens and severe keratitis associated with the anchoring devices of an adult copepod and several chalimi. Fourteen eyes exhibited 1 to several, randomly distributed, small, round to irregular, corneal opacities or pits that were not associated with copepods, and it is likely that these opacities represented lesions associated with adult female or larval anchoring devices from past infections. The avascular cornea represents a niche that is somewhat shielded from host immune reactions, and this, and the fact that the general body surface of sleeper sharks is covered by tall and sharp placoid scales, may partially explain the corneal attachment of O. elongata adult females. It was concluded that O. elongata infections can lead to severe vision impairment in Pacific sleeper sharks but that these infections do not significantly debilitate hosts because they probably do not need to rely on acute vision for their survival.

Immunoreactivity of MIC2 (CD99) and terminal deoxynucleotidyl transferase in bone marrow clot and core specimens of acute myeloid leukemias and myelodysplastic syndromes. MIC2 ("thymus leukemia") antigen has been shown to be expressed by T cells and monocytes, as well as B cells and granulocyte-lineage cells. It is most intensely expressed by the most immature thymus T-lineage cells and is more intensely expressed by CD34-positive/CD33-positive myeloid cells (compared to more mature myeloid cells) and the earliest CD34-positive/CD10-positive B-cell precursor cells (compared to cells of later B-cell precursor stages). CD99 (MIC2) is characteristically expressed in precursor B- and T-cell lymphoblastic lymphomas/leukemias, as well as in Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET). It has also been shown to be expressed in a few terminal deoxynucleotidyl transferase (TdT)-positive myeloid processes, but has been uniformly negative in TdT-negative myeloid processes. A more recent study showed that 43% of acute myeloid leukemias (AMLs) and 55% of chloromas express CD99, concluding that CD99 is commonly expressed in AML and rarely seen in myeloproliferative disorders, myelodysplastic syndromes, or normal bone marrow. Although this study speculated that MIC2 expression was probably not limited to TdT-positive AML, there was no comparison with TdT reactivity in this study. Since AML and high-grade myelodysplastic syndrome may occasionally be difficult to distinguish morphologically from acute lymphoblastic leukemia and ES/ PNET, we undertook a study to analyze MIC2 expression in conjunction with TdT reactivity in distinguishing AML or high-grade myelodysplastic syndrome from acute lymphoblastic leukemia and ES/PNET. We studied bone marrow core and clot paraffin specimens from AML (classified according to criteria of the World Health Organization; n = 49), myelodysplastic syndromes (n = 4), precursor B-cell acute lymphoblastic leukemia (n = 4), ES/PNET (n = 1), and normal bone marrow (n = 3) with MIC2 (CD99) and TdT immunohistochemistry. Overall, CD99 was expressed in 24 (49%) of 49 AML cases, including all (11/11) TdT-positive cases. CD99 was expressed in all subtypes of AML except M5. Myelodysplastic syndromes and normal bone marrow specimens were uniformly CD99 negative. Expression of TdT was limited to a subset of AML-M0, -M1, -M2, and -M4, and AML with multilineage dysplasia. In contrast to a previous study, CD99 expression was not restricted to TdT-positive hematologic proliferations. In particular, the CD99-positive M3 and M7 AMLs were TdT negative. An M5 AML may likely be excluded based on a uniform TdT-negative/CD99-negative immunophenotype. In addition, in our experience, CD99 should be routinely evaluated on bone marrow clots, owing to decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution-decalcified specimens.

Improving health professionals' management and the organisation of care for overweight and obese people. Obesity is increasing throughout the industrialised world. If left unchecked it will have major implications for both population health and costs to health services. Health professionals have a key role to play in tackling the obesity problem, but little is known about how they may be encouraged to work more effectively with overweight and obese people. The main objective was to determine whether health professionals' management or the organisation of care for overweight and obese people could be improved. We searched the specialised registers of the Cochrane Effective Practice and Organisation of Care Group (May 1997), the Cochrane Depression, Anxiety and Neurosis Group (August 1997), the Cochrane Diabetes Group (August 1997), the Cochrane Controlled Trials Register (September 1997), MEDLINE to January 1998, EMBASE to December 1997, Cinahl (1982 to November 1997), PsycLit (1974 to December 1997), Sigle (1980 to November 1997), Sociofile (1974 to October 1997), Dissertation Abstracts (1861 to January 1998), Conference Papers Index (1973 to January 1998), Resource Database in Continuing Medical Education. We also hand searched seven key journals and contacted experts in the field. Randomised trials, controlled before-and-after studies and interrupted time series analyses of providers' management of obesity or the organisation of care to improve provider practice or patient outcomes. We addressed three a priori comparisons and a fourth post hoc comparison. 1. Interventions aimed at improving health professionals' management or the delivery of health care for overweight/obese patients are more effective than usual care. 2. Interventions aimed at redressing negative attitudes and related practices towards overweight/obese patients are more effective than usual care. 3. Organisational interventions designed to change the structure of services for overweight/obese people are more effective than educational or behavioural interventions for health professionals. 4. Comparisons of different organisational interventions. Two reviewers independently extracted data and assessed study quality. Twelve studies were included involving more than 393 providers and 3392 patients. Four studies were identified for comparison 1. Three were professional-oriented interventions (the use of reminders and training) and the fourth was a study of professional and organisational interventions of shared care. No studies were identified for comparisons 2 or 3. Eight studies were identified for post hoc comparison 4. These compared either the deliverer of weight loss interventions or the setting of interventions. The included studies were heterogeneous and of generally poor quality. At present, decisions about improving provision of services must be based on the evidence of patient interventions and good clinical judgement. Further research is needed to identify cost effective strategies for improving the management of obesity.

Uterine responses and equine chorionic gonadotropin concentrations after two intrauterine infusions with kerosene post early fetal loss in mares. Pregnancy loss during the normal lifespan of endometrial cups (∼37-120-150 days of gestation) may affect a mare's ability to conceive again in the same breeding season, as equine chorionic gonadotropin (eCG) secretion by retained endometrial cups can lead to abnormal ovulations and follicular growth. While intrauterine kerosene infusion has anecdotally been proposed as a treatment for endometrial cup retention, there are no controlled studies evaluating kerosene's ability to enhance endometrial cup regression following abortion. The objectives of this study were to assess uterine response, systemic side effects, and efficacy of intrauterine kerosene infusions after abortion. We hypothesized that kerosene infusions would hasten regression of endometrial cups without detrimental effects on the endometrium and the mare's general health. Twelve light-breed mares were enrolled in the study after an experimentally induced abortion with cloprostenol (n = 12) by 60 ± 2 days of gestation. Mares were randomly allocated to receive an intrauterine infusion with 500 mL of kerosene (n = 6) or 500 mL saline (n = 6) on days 21 and 35 after pregnancy termination. Uterine biopsies were collected at days 7, 21, 35, and 49 post-abortion to evaluate the degree of endometrial fibrosis with Picrosirius Red Stain and to be graded according to the Kenney & Doig 1986 classification. Furthermore, histomorphometry analysis of the endometrium lining, glandular epithelium and glandular density was performed. Endometrial lymphocyte B CD20+, lymphocyte T CD3+, and macrophage IBA-1+ cell populations were characterized by immunohistochemistry. Physical examinations, blood cell counts, and serum biochemistry were performed before, and for 2 days after each uterine infusion. Serum samples were collected for assessment of eCG concentrations. Continuous data were analyzed with MIXED procedure with repeated measures in SAS, categorical data with LOGISTIC procedure of SAS. Significance was set at p < 0.05. Kerosene infusion did not affect complete blood cell counts, serum chemistry parameters, or physical examinations. Concentrations of eCG decreased over time (p < 0.001), but there were no differences between groups or time by group interactions (p = 0.72). Histological evaluation of the uterus showed no signs of increased fibrosis or degeneration in the treatment group. In conclusion, while kerosene infusions did not appear to have detrimental effects on mare health, our findings suggest that the use of kerosene in the uterus does not enhance the regression of endometrial cups by 49 days post-abortion.

[From the racemate to the eutomer: (S)-ketamine. Renaissance of a substance?]. The pharmacological profile of ketamine: Until recently, clinically available ketamine was a racemic mixture containing equal amounts of two enantiomers, (S)- and (R)-ketamine. The pharmacological profile of racemic ketamine is characterized by the so called dissociative anesthetic state and profound sympathomimetic properties. Among the different sites of action, N-methyl-D-aspartate (NMDA)-receptor antagonism is considered to be the most important neuropharmacological mechanism of ketamine. Effects on opiate receptors, monoaminergic and cholinergic transmitters, and local anesthetic effects are obvious as well. Following intravenous administration, a rapid onset of action is seen within 1 min, lasting for about 10 min. The anaesthetic state is terminated due to redistribution, followed by hepatic and renal elimination with a half-life period of 2-3 h. For alternative administration, the intramuscular and oral route is also appropriate. The most important adverse effects are hallucinations and excessive increases in blood pressure and heart rate. These reactions can be attenuated or avoided by combining of ketamine with sedative or hypnotic drugs like midazolam and/or propofol. During controlled ventilation, increases in intracranial pressure are unlikely to occur. The special pharmacological profile of (S)-ketamine: In general, the pharmacological properties of (S)-ketamine are comparable to the racemic compound. On the different sites of action, qualitatively comparable effects were found, but significant quantitative differences also became obvious. When compared with (R)-ketamine and the racmic mixture, the analgesic and anesthetic potency of (S)-ketamine is threefold or twofold higher. Thus, a 50% reduction of dosage is possible to achieve comparable clinical results. Because of the faster elimination of (S)-ketamine, better control of anesthesia will be provided. In summary, the pharmacokinetic improvements of (S)-ketamine are characterized by a reduced drug load, along with more rapid recovery. The clinical use of (S)-ketamine: The clinical use of (S)-ketamine depends on its analgesic and sympathomimetic properties, whereas the anaesthetic potency remains in the background. In clinical anesthesiology, (S)-ketamine, especially in combination with midazolam and/or propofol, can be used for short procedures with preserved spontaneous ventilation, for induction of anesthesia in patients with shock or asthmatic disorders, and for induction and maintenance of anesthesia in caesarean sections. Additional indications are repeated anesthesia, for example, in burn patients, analgesia during delivery and diagnostic procedures and intramuscular administration in uncooperative patients. The value of (S)-ketamine as an analgesic component for total intravenous anesthesia has not been defined yet. In comparison with opioides, the advantages are related to improved hemodynamic stability and reduced postoperative respiratory depression. When (S)-ketamine, especially in combination with midazolam, is used for analgosedation in intensive care medicine, a reduction of exogenous catecholamine demand can be expected. Moreover, the effects on intestinal motility are superior to opioids. In combination with midazolam and propofol, excellent control of analgosedation was found, making both combinations suitable for situations in which repeated neurological assessment of patients is necessary. In emergency and disaster medicine, (S)-ketamine is of outstanding importance because of its minimal logistic requirements, the chance for intramuscular administration and the broad range of use for analgesia, anaesthesia and analgosedation as well. Further perspectives of (S)-ketamine may be the treatment of chronic pain and the assumed neuroprotective action of the substance.

Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation of canine glomerular hemodynamics. A micropuncture study. Glomerular hemodynamics are controlled by a variety of physical, nervous and hormonal factors including the potent vasoconstrictors, angiotensin (ANG) II and endothelin-1 (ET-1), and the vasodilator prostanoids (prostaglandin = PG) and nitric oxide (NO). Since no micropuncture data on the canine kidney exist with respect to the relative roles of the endogenous vasoactive hormones/autacoids NO, PG and ANG II in modulating glomerular hemodynamics, in the present study using the micropuncture technique in anesthetized dogs on a normal salt intake, we investigated the relative effects of these hormones/autacoids by means of the L-arginine analog, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor indomethacin (INDO), and the AT(1) receptor blocker EXP 3174. An intrarenal arterial (i.r.a.) bolus (within 5 min) of 2.5 mg of L-NAME led to a significant decrease in total renal blood flow (RBF) and single nephron glomerular blood flow (SNGBF) from 4.46 +/- 0.51 to 3.52 +/- 0.41 ml/min/g kidney weight and from 0.393 +/- 0.041 to 0.341 +/- 0.037 microl/min (p < 0.01), respectively, without a change in glomerular filtration rate (GFR). The increase in arteriolar resistance was more pronounced at the efferent (+31%) than at the afferent (+13%) arteriole, and K(f) decreased from 4.5 +/- 0.5 to 3.7 +/- 0.4 nl/min/mm Hg (p < 0.01). INDO (5 mg/kg i.v. bolus followed by 0.17 mg/kg/min i.v.) had no effect on glomerular hemodynamics. EXP 3174 (30 microg/kg/min i.r.a.) increased RBF and SNGBF from 4.35 +/- 0.45 to 4.99 +/- 0.50 ml/min/g kidney weight and from 0.403 +/- 0.028 to 0.478 +/- 0.039 microl/min (p < 0.01), respectively, without an effect on GFR. It reduced the efferent arteriolar resistance by 25% as compared to 13% at the afferent arteriolar level. EXP 3174 increased K(f) from 5.1 +/- 0.4 to 8.1 +/- 0.6 mm Hg (p < 0.01) in the presence of a decrease in effective filtration pressure from 13.2 +/- 1.7 to 8.3 +/- 1.0 mm Hg (p < 0.01). The glomerular hemodynamic effects of L-NAME were unaltered by pretreatment with INDO or EXP 3174, whereas its tubular effects were restored in the presence of EXP 3174. Thus, from these first micropuncture data in the anesthetized dog on a normal sodium intake we conclude that (1) acute intrarenal inhibition of NOS by L-NAME decreases RBF and SNGBF due to vasoconstriction of the afferent and, more pronounced, efferent arterioles. Since L-NAME simultaneously decreases K(f), GFR remains unaltered. (2) These renal hemodynamic effects of NOS inhibition were not mediated by prostanoids or intrarenal ANG II. Thus, the tonic activity of intrarenal NOS plays an important role in maintaining glomerular hemodynamics in the canine kidney.

Metabolomic findings in sepsis as a damage of host-microbial metabolism integration. Metabolomics globally evaluates the totality of the endogenous metabolites in patient's body, at the same time reflecting gene function, enzyme activity and degree of organ dysfunction in sepsis. The authors performed the analysis of the main chemical classes of low molecular weight compounds (amino acids, polyols, fatty acids, hydroxy acids, amines, nucleotides and their derivatives) that quantitatively distinguish patients with sepsis from healthy ones. The following keywords were used to find papers published in the Scopus and Web of Science databases from 2008 to 2015: (marker OR biomarker) AND (sepsis OR critical ill OR pneumonia OR hypoxia). Key words for the search were the following: metabolomics, metabolic profiling, sepsis, metabolism, biomarkers, critically ill patients, multiple organ failure. Several metabolomic findings in sepsis are still waiting for an explanation. When assessing metabolomic analysis results in patients with sepsis we should take into account the intervention of microbial metabolism. Among the low molecular weight compounds detected in septic patient blood, a special attention should be paid to the molecules which could be attributed to "common metabolites" of man and bacteria. The genomic region overlap and the production of enzymes which are similar in function and final products could be a possible reason for this phenomenon. For example, microbial biodegradation products of aromatic compounds are increased many times in blood of patients with sepsis. On the one hand, it shows a high metabolic activity of the bacteria. On the other hand, these molecules are intermediates in the metabolism of aromatic amino acids such as tyrosine and phenylalanine in human body. It is important that there are many clinical studies, which confirmed the diagnostic and prognostic significance of series of aromatic metabolites, including those with intrinsic biological activity. We can't exclude the presence of signaling pathways, cell receptors, transmembrane transporters and others which are common for a human and bacteria and their direct participation in mechanisms of organ dysfunction and hypotension in sepsis. Thus, today, we should not limit ourselves studying eukaryotic cells while searching for new molecular mechanisms of sepsis-associated organ failure and septic shock. We should take into account and simulate in the experiments the changes of a human internal environment, which occur during the radical microbiome "restructuring" in critically ill patients. This approach opens up new prospects for an objective monitoring of diseases, carrying out an assessment of the integral metabolic profile in a given time on common metabolites (particularly aromatic), and in future will provide new targets for therapeutic effects.

The Development and Validation of the Sexual and Relationship Distress Scale. Sexual distress is an important factor in the etiology, maintenance, and treatment of sexual difficulties, and as such, there is a need for validated measures. A limitation in the research and treatment of distressing sexual difficulties has been the lack of validated measures, and in particular, existing measures are unable to measure the impacts at the relationship level and currently focus on intra-personal distress. This study sought to develop and psychometrically evaluate a new measure of distress associated with sexual difficulties. An initial pool of 73 items was created from the results of an earlier qualitative study and administered using an online survey to 1,381 participants (462 men, 904 women, and 14 who identified as "other"), along with measures for the purposes of psychometric evaluation including the Female Sexual Distress Scale-Revised, Couples Satisfaction Index 16-item version, Depression Anxiety and Stress Scale-Short Form, and questions relating to sexual function. Exploratory factor analysis and confirmatory factor analysis in separate split-half samples were conducted, followed by analysis of validity and reliability of the resulting measure. The Sexual and Relationship Distress Scale (SaRDS) was developed to meet the need for a patient-reported outcome measure of individual and relationship distress within the context of sexual dysfunction and resulted in a psychometrically sound 30-item, 14-factor measure of sexual and relationship distress. The final 30 items explained 77.5% of the total variance and the confirmatory factor analysis showed that this model has an adequate fit (comparative fit index = .97, normed fit index = .95, root mean square error of approximation = .05). The final measure demonstrated good psychometric properties, with strong internal reliability (Cronbach alpha = .95 for the total score with individual sub-scales ranging from .70-.96), and convergent and discriminant validity when compared to current measures (Female Sexual Distress Scale-Revised, r = .82, P < .001; Couples Satisfaction Index, r = -.69, P < .001; Depression Anxiety and Stress Scale-Short Form, r = .37, P < .001). The SaRDS may prove useful for researchers and clinicians interested in understanding and improving the distress experienced within the context of sexual difficulties. The new measure is brief (30 items), easy to administer and score, easily understood (Flesch-Kincaid reading level = grade 3.9), and demonstrates high internal consistency, convergent and discriminant validity. The SaRDS has advantages over existing measures as it is brief yet includes sub-scales. However, it must be noted that a community sample was used for this study and it would be beneficial to include a clinical sample in future validation studies. Unlike most measures in this field, the SaRDS is multi-dimensional and assesses 14 distinct yet related types of sexual and relationship distress experienced in the context of sexual dysfunctions. It can be administered across genders and both members of a couple. It therefore has multiple uses within both research and clinical settings. Frost R, Donovan C. The Development and Validation of the Sexual and Relationship Distress Scale. J Sex Med 2018;15:1167-1179.

In vivo and in vitro metabolism and pharmacokinetics of cholinesterase inhibitor deoxyvasicine from aerial parts of Peganum harmala Linn in rats via UPLC-ESI-QTOF-MS and UPLC-ESI-MS/MS. Aerial parts of Peganum harmala Linn are a Uighur traditional medicinal herb in China used to treat amnesia, bronchial asthma, and cough. Deoxyvasicine (DVAS), a potent cholinesterase inhibitor exhibiting anti-senile dementia activity, is one of the chief active ingredients in aerial parts of P. harmala and plays a key role in mediating the pharmacological effects of P. harmala. However, the metabolic profiling and in vivo pharmacokinetic characteristics of DVAS still remain unknown. The aim of this present study was to investigate the metabolism and pharmacokinetic properties of DVAS in rats by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS/MS) method. The metabolic profiling of DVAS was evaluated in vitro and in vivo by rat liver microsomes (RLMs) incubation and by rat bio-specimens, such as urine, feces, plasma, and bile, after the oral administration of 45 mg/kg DVAS. An efficient and sensitive UPLC-ESI-MS/MS method was developed and validated to simultaneously determine DVAS and its major four metabolites, namely, vasicine, deoxyvasicinone, vasicinone, and 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-β-D-glucuronide in rat plasma. For pharmacokinetic studies, 32 Sprague-Dawley rats were randomly divided into four groups, namely, intravenous dosage group (2 mg/kg DVAS) and three oral dosage groups (5, 15, and 45 mg/kg DVAS). In addition, the activity of the components in plasma after intravenous administration of DVAS was evaluated by in vitro anti-butyrylcholinesterase (BChE) assays. A total of 23 metabolites were found in RLMs, plasma, urine, feces, and bile by UPLC-ESI-QTOF-MS. The metabolic pathway of DVAS in vivo and in vitro mainly involved hydroxylation, dehydrogenation, acetylation, methylation, glucuronidation, and O-sulphate conjugation, and the C-3 and C-9 sites were the main metabolic soft spots. All 23 metabolites were detected in the urine sample, and 13, 8, 22, and 6 metabolites were identified from rat feces, plasma, bile, and RLMs, respectively. The standard curves of DVAS and four metabolites in rat plasma showed good linearity in the concentration range of 0.82-524.00 ng/mL with acceptable selectivity, precision, accuracy, recovery, and stability. DVAS exhibited linear dose-proportional pharmacokinetics at doses of 5, 15, and 45 mg/kg after oral administration, and the average oral absolute bioavailability of DVAS was 47.46%. The in vitro anti-BChE assays implied that the inhibitive activities were mainly due to the different concentrations of prototype DVAS. DVAS can be rapidly absorbed and excreted by blood, and it is also extensively metabolized in vivo, and the anti-BChE activity in blood is mainly attributed to DVAS. These findings can lay a foundation for new drug development for DVAS.

An American approach to health system reform. In terms of the major objectives one would have for health system reform, this plan makes the following choices: 1. It would cover everyone, through Medicare (the elderly), employer-based coverage (some workers and dependents) or a state-level public program that would replace Medicaid (the poor, unemployed, and other workers and dependents). 2. There would be a standard minimum package of required benefits for employer-based and public programs, with legislative requirements on maximum cost-sharing. Choice of provider might be restricted in some states. 3. Administration of the private programs would be the responsibility, as now, of the employers and/or insurance companies. Administration of the public program would be the responsibility of the states, with the objective of maximizing responsiveness to local needs and conditions. 4. It would control costs through giving the states a substantial financial stake in ensuring that the public program costs did not grow faster than nominal GNP. State control would also allow the testing of different mechanisms for cost control, with the ultimate objective of identifying the most effective cost-containment strategies. 5. The cost would be borne by employers, employees, and taxpayers. Employers would be protected from exorbitant costs by being allowed the option of paying into a public plan rather than providing health insurance themselves. The poor and unemployed would be protected by having their coverage under the public program subsidized on a sliding scale. 6. The political feasibility test would be met by retaining a major role for insurance companies and by retaining the role of employer-based coverage--thus reducing the tax increase needed to ensure universal coverage. By allowing flexibility in design of cost-containment strategy, some of the controversy over this issue would also be deflected. Our proposal is also not without problems. First, our approach would still have adverse effects on the profitability of small businesses and on the employment prospects for low-wage workers--although these effects would be less than under conventional mandates and less than under proposals with higher tax rates. Second, some states may not want the responsibility we envision or have the capacity to carry it out. But several Canadian provinces are relatively small and are able to perform the same administrative functions within the Canadian national health system. In addition, since the federal government would continue to administer the Medicare program, states would have the option of tying their policies for hospital and physician payment and utilization control to those of Medicare.(ABSTRACT TRUNCATED AT 400 WORDS)

Valdecoxib: a review. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and related agents are nonselective inhibitors of both cyclooxygenase-1 (COX-1) and COX-2, which catalyze prostaglandin synthesis. This inhibition accounts not only for the analgesic, anti-inflammatory, and antipyretic effects of these agents, but also for side effects such as gastric mucosal damage and renal toxicity. Substantial evidence suggests that sparing COX-1 is advantageous for gastric safety. This article reviews available information on the new COX-2-selective inhibitor valdecoxib, including its clinical pharmacology, pharmacokinetics, adverse effects, potential drug interactions, and contraindications and warnings. Results of clinical trials of efficacy and tolerability are summarized. Articles for inclusion in this review were identified through searches of PubMed and MEDLINE (1966-December 2002) and International Pharmaceutical Abstracts (1970-December 2002). Search terms included valdecoxib, Bextra, COX-2-selective inhibitors, coxibs, and selective cyclooxygenase inhibitors. The reference lists of identified articles were reviewed for additional publications. Product information was also obtained from the manufacturer of valdecoxib. Fourteen clinical studies involving > 4000 patients have been conducted. Valdecoxib was significantly more effective than placebo in the treatment of adult rheumatoid arthritis, osteoarthritis, pain associated with primary dysmenorrhea, and postoperative pain. Valdecoxib was comparable to naproxen for the treatment of rheumatoid arthritis in 1 study and equivalent to naproxen for the treatment of osteoarthritis in other studies. Three studies found valdecoxib comparable to naproxen sodium for the relief of moderate to severe pain due to primary dysmenorrhea, and others found valdecoxib comparable to oxycodone plus acetaminophen and significantly more effective than rofecoxib for the relief of pain associated with dental surgery (P < 0.05). Four safety studies and 2 reviews of clinical trials documented lower rates of endoscopic gastroduodenal ulcer formation with valdecoxib compared with ibuprofen, naproxen, and diclofenac (P < 0.001 to P < 0.05). Valdecoxib did not inhibit platelet function (bleeding time and platelet aggregation) in healthy adults or in the elderly. Due to the risk of potentially serious skin and allergic reactions, patients who are allergic to sulfa-containing drugs should not take valdecoxib. The drug should be discontinued immediately if rash develops. In clinical trials, valdecoxib was effective for the treatment of osteoarthritis, rheumatoid arthritis, and moderate to severe pain associated with primary dysmenorrhea. As with the other COX-2-selective inhibitors (celecoxib and rofecoxib), valdecoxib appears to produce less gastrointestinal toxicity than conventional nonselective NSAIDs, although some of the relevant clinical studies have been published only as abstracts. Use of valdecoxib should be reserved for patients at risk for NSAID-induced gastrointestinal problems.

Tricyclic and related drugs for nocturnal enuresis in children. Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s. To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis. We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles. We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting. Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author. Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response. There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.

Strategies to improve the nutritive value of rice bran in poultry diets. III. The addition of inorganic phosphorus and a phytase to duck diets. 1. In the first of 2 experiments ducklings grown from 2 to 19 d were given diets with 0, 200 or 400 g rice bran, with or without a phytase and with 1 or 3 g inorganic phosphorus (Pi) per kg for rice bran-based diets only. In the 2nd experiment rice bran concentrations were 0, 300 or 600 g rice bran per kg with or without a phytase and 1 g Pi/kg. Ducks were grown from 19 to 40 d of age. 2. In experiment 1, a response to phytase was observed for weight gain and food intake on most diets except those with 200 g rice bran (3 g Pi) and 4.00 g rice bran (1 g P)i/kg. Main effects showed that 400 g rice bran depressed growth rate and food conversion ratio (FCR); increasing Pi depressed food intake, while food phytase increased food intake and growth rate over 2 to 19 d. There were several interactions. Dry matter and P retention were reduced but N digestibility improved when rice bran was increased from 200 g to 400 g/kg at 2 to 10 d of age; apparent metabolisable energy (AME) and calcium retentions were improved, similar results being seen at 10 to 19 d of age. Calcium and P retentions increased with the addition of food phytase and, at 10 to 19 d of age, phytase increased dry matter digestibility. Increasing Pi improved calcium and P retention, but only at 2 to 10 d of age. 3. Tibia ash (g or g/kg) content of bone was lowest on the diet without rice bran and without phytase; Pi concentration had no effect but phytase increased tibia ash on diets with 0 and 200 g rice bran and 1 g Pi/kg. Retention of several minerals in tibia ash declined at the highest rice bran inclusion rate; Pi level and phytase both increased Mg retention. 4. In experiment 2, food intake and growth rate of ducks, but not FCR, declined as rice bran inclusion increased from 0 to 600 g/kg. Phytase improved growth rate but not food intake and FCR on all 3 diets. Dry matter digestibility declined with increasing rice bran inclusion, but AME increased; retention of P and Mg declined but those of Ca and Fe increased. Phytase improved dry matter digestibility and retention of N and P. AME also increased but this was only on diets with 0 and 600 g rice bran/kg. There were reductions of 8% and 10% in P excreted in experiments 1 and 2 respectively when food phytase was added. 5. Tibia ash declined with increasing dietary inclusion of rice bran. Zn and Mn in ash tended to decline and Mg to increase; Ca and P showed no change in concentration in tibia ash. Again, phytase increased tibia ash content in bone. 6. It was concluded that there were a number of unexpected benefits from adding a food phytase to these diets, which resulted in improved nutrient yield and bird performance, although several of the diets appeared to be adequate in available P.

Relationship of coronary artery plaque composition to coronary artery stenosis severity: results from the prospective multicenter ACCURACY trial. The purpose of this study was to determine the relationship of coronary artery plaque composition as detected by coronary computed tomographic angiography (CCTA) to luminal diameter stenosis severity quantified by quantitative coronary angiography (QCA) in individuals without known coronary artery disease (CAD) presenting with stable chest pain syndrome. While CCTA has been previously evaluated for its ability to detect and exclude coronary artery stenosis, CCTA also permits assessment of other important plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and plaque severity by invasive angiography may provide valuable insight into the pathophysiology of coronary artery plaque. Patients enrolled in the ACCURACY trial, a 16-site multicenter study of patients with stable chest pain syndrome but without known CAD undergoing both CCTA and invasive coronary angiography (ICA), comprised the study population. CCTAs were scored on a per-segment basis for plaque composition and graded as non-calcified (>70% non-calcified), calcified (>70% calcified) or "mixed" (30-70% non-calcified or calcified) by concordance of ≥ 2 of 3 readers. CCTAs were also scored on a per-patient basis, and individuals were categorized as possessing primarily non-calcified plaques, primarily calcified plaques or primarily mixed plaques. Quantitative coronary angiography (QCA) was performed in all patients, used as the reference standard for stenosis severity, and interpreted blinded to patient characteristics and CCTA results. 230 subjects comprised the study population (59.1% male, 57 ± 10 years). QCA was performed in all subjects following CCTA (mean inter-test interval 5.9 ± 4.3 days), and demonstrated obstructive CAD in 24.8% and 13.9% at the 50% and 70% stenosis severity threshold, respectively. On a per-segment based analysis, obstruction by QCA at both the 50% and 70% stenoses thresholds was more often for mixed composition plaques by CCTA (69.1% and 67.9%, respectively), as compared to non-calcified plaques (24.7% and 28.6%, respectively) and calcified plaques (6.1% and 3.6%, respectively) [p < 0.01 for comparisons]. On a per-patient basis, patients with mixed plaque or mixtures of plaque types more often exhibited obstructive coronary stenosis by QCA at the 50% level (39/96; 40.6%) compared to those with primarily non-calcified (12/43; 27.9%) or primarily calcified (4/29; 13.8%) plaques [p = 0.02]. In this multicenter trial of chest pain patients without known CAD, QCA-confirmed obstructive coronary stenosis was associated with mixed plaque composition by CCTA at both the per-segment and the per-patient levels. Coronary artery segments exhibiting calcified plaque were rarely associated with obstructive coronary stenosis.

[A field epidemiological study on the risk factors of injury caused by typhoon]. To determine the risk factors involved in the typhoon episodes and to put forward and evaluate the intervention measures. We defined a confirmed injury case as: 'a person with fall,scalpel and stab, collision, drowning, injuries and trauma due to flying debris and building collapse, asphyxiation due to entrapment in collapsed buildings by typhoon from 0 am,August 12 to 6 pm, August 14 2004' and a death case as: 'a person with fall, scalpel and stab, collision, drowning, injuries and trauma due to flying debris and building collapse, asphyxiation due to entrapment in collapsed buildings by typhoon from 0 am, August 12 to 12 am, August 18 2004'. We investigated all hospitalized injured cases in ten hospitals and telephoned to those who were not hospitalized and the cases of death. We did case-control study with 1 pair versus 2 cases. 74 cases were selected in ten hospitals. The controls were neighbors of the controls matched by occupation, sex, village, and within 5 years of age without injury in this typhoon. We asked the cases and the controls on their alertness regarding typhoon and what actions taken when typhoon arrived. There were 392 injury cases in all ten hospitals and 50 death cases. The attack rate of injury was 27.3 per 100 000. The fatal rate was 11.3% with the death rate 3.1 per 100 000. We investigated 209 injury cases and 31 death cases. The number of cases who were injured from 1 to 6 hours before typhoon landing accounted for 64.6% (155) of all cases. The peak of epidemic curve was 4 hours before the landing of typhoon. Data on the analysis of 74 cases and 148 controls revealed that 42% (31) of the cases were outside their homes before and during typhoon compared to 15% (22) of the controls (OR = 3.9, 95% CI: 1.9-7.7). Compared with 20% (30) control persons (OR = 17,95% CI: 4.2-68). 28% (21) cases did not receive the alert of typhoon before it arrived compared with 18% (27) control persons (OR = 3.3, 95% CI:1.3-8.6). 53% (39) of the cases did not pay attention to the alert of typhoon before typhoon arrived. Staying outdoor, not receiving or did not take seriously about the alert of typhoon seemed to be the risk factors of injury by the typhoon episode, suggesting that the government should increase the emergency preparedness and to raise the awareness on risks associated with typhoon.

A comparison of several serologic tests to detect antibodies to Toxoplasma gondii in naturally exposed bottlenose dolphins (Tursiops truncatus). Toxoplasma gondii infection in marine mammals is intriguing and indicative of contamination of the ocean environment and coastal waters with oocysts. In a previous study, 138 of 141 (97.8%) bottlenose dolphins (Tursiops truncatus) from the coasts of Florida and California had antibodies to T. gondii by the modified agglutination test (MAT). Although the MAT has been found to be highly sensitive and specific for T. gondii antibodies from several species of terrestrial animals, it has not yet been validated for T. gondii infections in marine mammals. Furthermore, T. gondii has yet not been isolated from dolphins. In the present study, sera from 146 (60 from the 2004 samples and 86 from the 2003 samples) T. truncatus from the coastal areas of South Carolina and Florida were tested for antibodies to T. gondii. Sera from 2004 were tested by the MAT, the indirect fluorescent antibody test (IFAT), the Sabin-Feldman dye test (DT), an indirect hemagglutination test (IHAT), an enzyme-linked immunosorbent assay (ELISA), and Western blot. All 60 dolphins were seropositive, with MAT titers of 1:20 in 3, 1:40 in 19, 1:80 in 29, 1:160 in 2, 1:1,280 in 3, 1:2,560 in 2, and 1:5,120 or higher in 2, and these results were confirmed in another laboratory. The DT titers of these dolphins were <1:10 in 53, 1:800 in 3, 1:1,600 in 2, and 1:3,200 in 2. The IHAT titers were <1:64 in 52, 1:128 in 1, 1:512 in 2, and 1:2,048 in 5. The IFAT titers were <1:20 in 3, 1:20 in 11, 1:40 in 36, 1:80 in 2, 1:160 in 1, and 1:320 or higher in 7. All 7 DT-positive dolphins had high MAT titers, but 2 were negative by the IHAT. Western blot results closely followed MAT results; ELISA results matched MAT results, which were 1:40 or higher. In sera from the 2003 samples, MAT antibodies were found in 86 of 86 dolphins with titers of 1:25 in 29, 1:50 in 23, 1:100 in 27, 1:200 in 3, 1:1,600 in 1, and 1:3,200 in 3; these sera were not tested by other means. Overall, MAT antibodies were found in all 146 dolphin sera tested. Because marine mammals are considered sentinel animals indicative of contamination of the coastal and marine waters by T. gondii oocysts, serologically positive infections need to be validated by the detection of T. gondii organisms in the tissues of seropositive animals.

Toxicology and carcinogenesis studies of 2,3',4,4',5-pentachlorobiphenyl (PCB 118) (CAS No. 31508-00-6) in female harlan Sprague-Dawley rats (gavage studies). Dioxin Toxic Equivalency Factor Evaluation Overview- Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds"(DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. Polychlorinated biphenyls (PCBs) and their mixtures including 2,3',4,4',5-pentachlorobiphenyl (PCB 118) were produced commercially before 1977 for the electric industry as dielectric insulating fluids for transformers and capacitors. Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling. This PCB 118 study was conducted as part of the dioxin TEF evaluation that included multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. Female Harlan Sprague-Dawley rats were administered PCB 118 (at least 99% pure) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 80 female rats were administered 100, 220, 460, 1,000, or 4,600 g PCB 118/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 80 vehicle control female rats received the corn oil/acetone vehicle alone. Groups of 30 female rats received 10 or 30 g/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 4,600 g/kg PCB 118 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Survival of all dosed groups of rats was similar to that of the vehicle control group. Mean body weights of 1,000 g/kg rats were 7% less than those of the vehicle controls after week 36, and those of the 4,600 g/kg core study and stop-exposure groups were 7% less than those of the vehicle controls after week 7. Following cessation of treatment, the body weight gain in the stop-exposure group was similar to that of the vehicle control group. In general, exposure to PCB 118 lead to dose-dependent decreases in the concentrations of serum total thyroxine (T4) and free T4 in all dosed groups. There were no effects on triiodothyronine or thyroid stimulating hormone levels in any dosed groups evaluated at the 14-, 31-, and 53-week interim evaluations. There were increases in hepatic cell proliferation in the 4,600 g/kg group at 14, 31, and 53 weeks. Administration of PCB 118 led to dose-dependent increases in CYP1A1-associated 7-ethoxyresorufin-O-deethylase, CYP1A2-associated acetanilide4-hydroxylase, and CYP2B-associated pentoxyresorufin-O-deethylase activities at the 14-, 31-, and 53-week interim evaluations. Analysis of PCB 118 concentrations in dosed groups showed dose- and duration of dosing-dependent increases in fat, liver, lung, and blood. The highest concentrations were seen in fat at 2 years with lower concentrations observed in the liver, lung, and blood. At the 53-week interim evaluation, three 4,600 g/kg rats had liver cholangiocarcinoma and one had hepatocellular adenoma. At 2 years, there were significant treatment-related increases in the incidences of cholangiocarcinoma and hepatocellular adenoma. Four incidences of hepatocholangioma occurred in the 4,600 g/kg core study group. At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, inflammation, oval cell hyperplasia, pigmentation, multinucleated hepatocyte, eosinophilic and mixed cell foci, diffuse fatty change, toxic hepatopathy, nodular hyperplasia, necrosis, bile duct hyperplasia and cyst, and cholangiofibrosis. The incidences of these lesions were often decreased in the 4,600 g/kg stop-exposure group compared to the 4,600 g/kg core study group. In the lung at 2 years, a significantly increased incidence of cystic keratinizing epithelioma occurred in the 4,600 g/kg core study group compared to the vehicle control group incidence. Incidences of bronchiolar metaplasia of the alveolar epithelium were significantly increased in the groups administered 460 g/kg or greater, and the incidence of squamous metaplasia was significantly increased in the 4,600 g/kg core study group. The incidence of carcinoma of the uterus in the 4,600 g/kg stop-exposure group was significantly greater than those in the vehicle control and 4,600 g/kg core study groups at 2 years. A marginal increase in squamous cell carcinoma occurred in the 220 g/kg group. At 2 years, there were marginally increased incidences of exocrine pancreatic adenoma or carcinoma in the 460, 1,000, and 4,600 g/kg core study groups. Numerous nonneoplastic effects were seen in other organs including: adrenal cortical atrophy and cytoplasmic vacuolization, pancreatic acinar cell cytoplasmic vacuolization and arterial chronic active inflammation, follicular cell hypertrophy of the thyroid gland, inflammation and respiratory epithelial hyperplasia of the nose, and kidney pigmentation. Under the conditions of this 2-year gavage study, there was clear evidence of carcinogenic activity of PCB 118 in female Harlan Sprague-Dawley rats based on increased incidences of neoplasms of the liver (cholangiocarcinoma, hepatocholangioma, and hepatocellular adenoma) and cystic keratinizing epithelioma of the lung. Occurrences of carcinoma in the uterus were considered to be related to the administration of PCB 118. Occurrences of squamous cell carcinoma of the uterus and acinar neoplasms of the pancreas may have been related to administration of PCB 118. Administration of PCB 118 caused increased incidences of nonneoplastic lesions in the liver, lung, adrenal cortex, pancreas, thyroid gland, nose, and kidney. Synonyms: 1,1'-Biphenyl, 2,3',4,4',5-pentachloro-(9CI); 1,1'-biphenyl, 2,3',4,4',5-pentachloro-; 2,3',4,4',5-pentachloro-1,1'-biphenyl; 2,4,5,3',4'-pentachlorobiphenyl; 3,4,2',4',5'-pentachlorobiphenyl; biphenyl, 2,3',4,4',5-pentachloro-; CB 118.

Externalization of phosphatidylserine may not be an early signal of apoptosis in neuronal cells, but only the phosphatidylserine-displaying apoptotic cells are phagocytosed by microglia. Earlier reports on nonneural cells have shown that the normally inner plasma membrane lipid, phosphatidylserine (PS), flip-flops out during the early stages of apoptosis, whereas DNA laddering and plasma membrane permeabilization occur during the late stages. In this study, the applicability of these parameters to CNS-derived neuronal cells was tested using hippocampal HN2-5, cells that undergo apoptosis under anoxia. Because such insults on unsynchronized cells, e.g., undifferentiated HN2-5 cells, result in both early and late apoptotic cells, we mechanically separated these cells into three fractions containing (a) cells that had completely detached during anoxia, (b) cells that remained weakly attached to the tissue culture dish and, once detached by trituration in serum-containing medium, did not reattach, and (c) cells that reattached in 2-3 h. Fractions a and b contained cells that showed pronounced DNA laddering, whereas cells in fraction c did not show any DNA laddering. Double staining with fluorescein isothiocyanate-annexin V (which binds to PS) and propidium iodide (which stains the DNA in cells with a permeable cell membrane) revealed that all cells in fraction a had a permeable cell membrane (propidium iodide-positive) and PS molecules in the outer leaflet of the plasma membrane (fluorescein isothiocyanate-annexin V-positive). By contrast, fractions b and c contained cells with no externalized PS molecules. Cells in fractions a-c also showed, respectively, 50-, 21-, and 5.5-fold higher caspase-3 (CPP32) activity than that in healthy control cells. All these results show that fraction a contained late apoptotic cells, which also had the highest CPP32 activity; cells in fraction b were at an intermediate stage, when DNA laddering had already occurred; and fraction c contained very early apoptotic cells, in which no DNA laddering had yet occurred. Therefore, in the neuronal HN2-5 cells, externalization of PS occurs only during the final stages of apoptosis when the cells have completely lost their adhesion properties. Further experiments showed that ameboid microglial cells isolated from neonatal mouse brain phagocytosed only the cells in fraction a. These results show that in CNS-derived HN2-5 cells, (a) PS externalization is a late apoptotic event and is concomitant with a complete loss of surface adhesion of the apoptotic cells and (b) PS externalization is crucial for microglial recognition and phagocytosis of the apoptotic HN2-5 cells. Thus, PS externalization could be causally linked to the final detachment of apoptotic neuronal cells, which in turn prepares them for rapid phagocytosis by microglia.

[The status of carotid arteries and the main vascular risk factors in cerebral infarctions of "anterior circulation"]. The aim of the work was to examine the degree of carotid stenosis, the structure of atherosclerotic plaques, and the predominance of the main vascular risk factors in patients with multiple lacunar and comparatively large "non-lacunar" cerebral infarctions. A study WAS made of the data on 110 patients (mean age 62.5 years) with multiple cerebral infarctions revealed by MRT and with stenoses of the internal carotid artery (ICA) of varying degrees of severity. Minor lacunar infarctions (LI) were present in 62 cases whereas comparatively large "non-lacunar" infarctions (NLI) in 48 cases. All the patients underwent standard neurologic examination, laboratory analyses, MRT of the brain with angiography (MRA) of the extra-intrecrania1 vessels, transcranial Doppler (TCD), and examination of the heart for revealing the cardioembolic nature of cerebral infarctions. Among patients with both LI and NLI, arterial hypertension was the most frequently occurring risk factor in 53 (85%) and 35 (73%) patients respectively. In the study groups, there were no appreciable differences in the incidence of high hematocrit, hyperfibrinogenemia, tobacco-smoking, and diabetes mellitus. Patients with NLI demonstrated hypercholesterolemia, CAD and atherosclerosis of the peripheral vessels significantly more often (p<0.05). In the patient group with NLI, hemodynamically significant stenoses of the ICA were predominant: in 18 (37.5%) patients, they were moderate, in 12 (25%) critical, and 7 (14.6%) patients had occlusions whereas in LI, the portion of critical stenoses and ICA occlusions was cooperatively low - in 11 (17.7%) and in 5 (8.1%) patients respectively. Both groups showed the thickening of the complex of the medial CCA layer. Ultrasonopraphy of the vessels has revealed that in patients with NLI and LI, there predominated potentially embologenic plaques, namely in 69% and in 53% of cases, respectively. Our investigations allow to assume that arterial hypertension is the most frequently occurring risk factor of cerebral infarction (both minor lacunar and large "non-lacunar"). Factors such as CAD, hypercholesterolemia, DM, hemorheological disorders, end tobacco-smoking are likely to have an unfavorable impact on both general and cerebral hemodynamics as well as on the microcirculatory bed whereby being on the whole important risk factors of cerebral infarction. Hemodynamically significant stenoses, especially critical ones, occlusions, and embologenic plaques of the ICA are pathogenetically closely linked with the development of "non-lacunar" cerebral infarctions. At the same time they, under certain conditions, may become the cause of multiple lacunar cerebral infarctions.

Combating hyperthermia in acute stroke: a significant clinical concern. Moderate elevations of brain temperature, when present during or after ischemia or trauma, may markedly worsen the resulting injury. We review these provocative findings, which form the rationale for our recommendation that physicians treating acute cerebral ischemia or traumatic brain injury diligently monitor their patients for incipient fever and take prompt measures to maintain core-body temperature at normothermic levels. In standardized models of transient forebrain ischemia, intraischemic brain temperature elevations to 39 degrees C enhance and accelerate severe neuropathological alterations in vulnerable brain regions and induce damage to structures not ordinarily affected. Conversely, the blunting of even mild spontaneous postischemic hyperthermia confers neuroprotection. Mild hyperthermia is also deleterious in focal ischemia, particularly in reversible vascular occlusion. The action of otherwise neuroprotective drugs in ischemia may be nullified by mild hyperthermia. Even when delayed by 24 hours after an acute insult, moderate hyperthermia can still worsen the pathological and neurobehavioral outcome. Hyperthermia acts through several mechanisms to worsen cerebral ischemia. These include (1) enhanced release of neurotransmitters; (2) exaggerated oxygen radical production; (3) more extensive blood-brain barrier breakdown; (4) increased numbers of potentially damaging ischemic depolarizations in the focal ischemic penumbra; (5) impaired recovery of energy metabolism and enhanced inhibition of protein kinases; and (6) worsening of cytoskeletal proteolysis. Recent studies demonstrate the feasibility of direct brain temperature monitoring in patients with traumatic and ischemic injury. Moderate to severe brain temperature elevations, exceeding core-body temperature, may occur in the injured brain. Cerebral hyperthermia also occurs during rewarming after hypothermic cardiopulmonary bypass procedures. Several studies have now shown that elevated temperature is associated with poor outcome in patients with acute stroke. Finally, recent clinical trials in severe closed head injury have shown a beneficial effect of moderate therapeutic hypothermia. The acutely ischemic or traumatized brain is inordinately susceptible to the damaging influence of even modest brain temperature elevations. While controlled clinical investigations will be required to establish the therapeutic efficacy and safety of frank hypothermia in patients with acute stroke, the available evidence is sufficiently compelling to justify the recommendation, at this time, that fever be combatted assiduously in acute stroke and trauma patients, even if "minor" in degree and even when delayed in onset. We suggest that body temperature be maintained in a safe normothermic range (eg, 36.7 degrees C to 37.0 degrees C [98.0 degrees F to 98.6 degrees F]) for at least the first several days after acute stroke or head injury.

What can claims data tell the case manager? This article seeks to use claims data to evaluate provision of service in 4 diagnosis-related groups (DRGs) for a rural hospital in an effort to better understand an increasing length of stay (LOS) and a decreasing case mix index (CMI). The complexity of the patient drives the services delivered, but does it drive the DRG assignment? Reimbursement for inpatient medical services is driven by DRG assignment and has an associated expected LOS. LOS is a result of the combination of physician practice patterns, available services, and the medical complexity of the patient. Itemized hospital charges can provide sufficient information to examine service delivery in broad categories. When compared to the services delivered through a professional protocol, physician practice benchmarks can be created. Identifying those services that are consistent and inconsistent with the protocol can prove illuminating and point to under- and overutilization, inadequate documentation, as well as opportunities for physician education. Although this study was undertaken using hospital inpatient claims, the study can be recreated in almost any practice setting where there is a consistent mechanism to capture the provision of services. In the broader scheme, as case management practice transitions from functional models to outcome models, the relevance of these issues becomes more profound. The information gleaned from such a study can not only benefit case management administrators but inform and impact those involved in case management at any level. Indeed, the information can illuminate practice patterns for those beyond the case management sector and can include financial administrators, physician practice managers, and physicians. A combination of developmental and casual-comparative methodology was applied to this study. The results of this study will create baselines for current practice patterns from which improvement opportunities in both resource and quality management can be identified. Casual-comparative research identifies a consequence and attempts to trace it back to its origin. In this case, the discharge diagnosis, a function of documentation, is the consequence, and this study attempts to determine whether physician practice patterns are accurately reflected in that documentation. The sample consisted of the itemized claims data for all patients discharged from Putnam Community Medical Center (PCMC) between January 1 and June 30, 2006, with a discharge DRG of 127, 089, 088, or 143. Records that did not have sufficient charges to map provision of care were excluded. An analysis of the charges for the selected DRGs illustrates the actual care provided to the patient, rather than the resultant coding based on physician documentation. This finding leads to 1 of 3 conclusions: physician documentation is inadequate to allow accurate coding of services delivered; the physician may be ordering unnecessary services/interventions; or medical record coding may be suboptimal. The scope of today's acute care case management department often includes social work, utilization review, discharge planning, and resource management. Within that scope is the accountability for certain aspects of the hospital's financial performance, not the least of which is LOS. A clear understanding of the payer mix and the effect upon financial performance is necessary. Management of DRG reimbursement-based contracts requires investigation of practice patterns that may increase LOS, and documentation that can affect medical coding decisions. The results of these activities can guide clinical practice guideline adoption or development and identify opportunities to fine-tune documentation to better reflect services provided and support utilization decisions. Case Management Society of America (CMSA) Standards of Practice charge the profession with engaging strategies whenever possible to improve outcomes. Performance indicators include advocacy, resource management/stewardship, and research utilization. Addressing physician practice patterns and reducing nonessential services are examples of advocacy at the service-delivery level. These activities are also examples of resource management/stewardship as they seek to "promote the most effective and efficient use of healthcare services and financial resources" (CMSA, 2002, p. 19). The standards of practice call for research utilization and encourage research activities that are appropriate to case management practice and the subsequent sharing of those findings. In this way, the profession is enriched and promotes cost-effective, quality care and case management practice.

A study of user requests regarding the fully electronic health record system at Seoul National University Bundang Hospital: challenges for future electronic health record systems. Although the adoption rates for Electronic Health Records (EHRs) are growing, significant opportunities for further advances in EHR system design remain. The goal of this study was to identify issues that should be considered in the design process for the successful development of future systems by analyzing end users' service requests gathered during a recent three-year period after a comprehensive EHR system was implemented at Seoul National University's Bundang Hospital in South Korea. Data on 11,400 service requests from end users of the EHR system made from 2008 through 2010 were used in this study. The requests were categorized as program modification/development, data request, insurance-fee identification/generation, patient-record merging, or other. The authors further subcategorized the requests for program modification/development into the following nine areas of concern: (1) indicators and statistics, (2) patient safety and quality of care, (3) special task-oriented functionalities, (4) ease of use and user interface, (5) system speed, (6) interoperability and integration, (7) privacy and security, (8) customer service, and (9) miscellaneous. The system users were divided into four groups--direct care, care support, administrative/insurance, and general management--to identify each group's needs and concerns. The service requests for program modification/development, data request, insurance-fee identification/generation, patient-record merging, and other issues constituted approximately 49.2%, 33.9%, 11.4%, 4.0%, and 1.5% of the total data set, respectively. The number of data-request service requests grew over the three years studied. Different groups of users were found to have different concerns according to their activities and tasks. Within the program-modification/development category, end users were most frequently concerned with ease of use and user interface (38.1% of the total) and special task-oriented functionalities (29.3% of the total) in their use of the EHR system, with increasing numbers of requests in both categories over the three years. Users in the direct-care group differed from the other groups in that they most frequently submitted requests related to ease of use and user interface, followed by special functionalities, patient safety and quality care, and customer service, while users in other groups submitted requests concerning ease of use and user interface and special functionalities with a similarly high frequency. Users have continued to make suggestions about their needs and requirements, and the EHR system has evolved to optimize ease of use and special functionalities for particular groups of users and particular subspecialties. Based on our experiences and the lessons we have learned in the course of maintaining full-EHR systems, we suggest that the key goals to be considered for future EHR systems include innovative new user-interface technologies; special extended functions for each user group's specific task-oriented requirements; powerful, easy-to-use functions to support research; new flexible system architecture; and patient-directed functions.

Alternating chemotherapy and accelerated split-course irradiation in locally advanced nonsmall cell lung carcinoma. The prognosis of patients with locally advanced nonsmall cell lung carcinoma (NSCLC), which is usually unresectable, is very poor, and patient survival rarely reaches 1 year. However, prolonged survival correlated with objective responses has been observed among patients with intrathoracic disease treated with a combination of cytotoxic drugs and local irradiation despite the lack of consensus regarding the schedule of such combined therapy. From October 1989 to November 1993, a Phase II study was conducted to evaluate the tolerability and efficacy of alternating chemotherapy and accelerated split-course radiotherapy in the treatment of patients with locally advanced NSCLC. Sixty-three consecutive patients with unresectable Stage III NSCLC entered this study. The treatment was composed of 3 cycles of combined chemotherapy and radiotherapy at 4-week intervals. Chemotherapy with cisplatin (30 mg/m2/day) and etoposide (100 mg/m2/day) was delivered intravenously on Days 1, 2, and 3, followed by radiotherapy on Days 4-8. A course of radiotherapy consisted of 1.5 gray (Gy) per fraction twice a day (3 Gy per day) for 5 consecutive days, for a total dose of 15 Gy. Response was assessed after 3 courses, for a total irradiation dose of 45 Gy. In cases of objective antitumoral response with operable tumor, surgery was performed. A fourth course of chemotherapy and radiotherapy, for a total dose up to 60 Gy in 12 weeks, was administered to all patients. Two additional courses of chemotherapy were given, for a total of six. Of the 63 patients, 62 were evaluable for response. Six had a complete remission and 36 a partial response, resulting in an overall response rate of 67.7%. Nine patients underwent surgery (pneumonectomy for seven patients and lobectomy for two patients), and the complete disappearance of any residual tumor was documented histologically in four. Of the 290 chemotherapy courses delivered, there were 31 of Grade 3-4 toxicity, mainly leukopenia and vomiting. The median times of freedom from disease progression and overall survival were 8 months (confidence interval [CI], 7-9.5) and 14 months (CI, 10-22), respectively. The 1-, 2-, and 5-year survival rates of the 62 patients were 54%, 35%, and 21%, respectively. Patients who responded had a significantly longer median survival (16 months) than nonresponders (7 months) (P = 0.02). However, there was no difference in the survival of resected and nonresected patients. This treatment schedule resulted in a high response rate with prolonged survival. However, the toxicity of this approach was not negligible, even though it did not preclude this strategy. This combined modality must be compared with other combinations of alternating or sequential chemoradiotherapy.

Neutering increases the risk of obesity in male dogs but not in bitches - A cross-sectional study of dog- and owner-related risk factors for obesity in Danish companion dogs. Knowledge of risk factors for canine obesity is an important pre-requisite of effective preventative strategies. This study aimed to investigate risk factors for canine obesity in adult companion dogs across Zealand, Denmark. Client-owned dogs (>2 years of age and without chronic illness) were recruited and examined at eight companion animal veterinary practices in areas with varying socio-economic characteristics. The body condition score (BCS) of the dogs was examined by two investigators based on a 9-point scoring scheme. Dog owners answered a questionnaire that had prompts regarding: 1) dog characteristics, including neuter status, 2) owner characteristics, 3) feeding and exercise practices and 4) the owners' attachment to the dog. The effect of these factors on BCS and the risk of being heavy/obese (BCS scores 7-9) were analysed in two separate analyses. A total of 268 dogs were included in the analysis, of which 20.5% were found to be heavy/obese. The average BCS was 5.46. In terms of dog characteristics, neutering dramatically increased both BCS and the risk of being heavy/obese in male dogs but not in bitches. BCS and the risk of being heavy/obese increased in senior bitches and decreased in senior male dogs. The risk of being heavy/obese was higher in dogs with overweight and obese owners. Regarding feeding and exercise practices, providing only one meal per day increased BCS and risk of being heavy/obese. Treats during relaxation increased the risk of dogs being heavy/obese. It also increased the dogs' BCS, but only if the owners were overweight or obese. An increased duration of daily walking increased the risk of the dog being heavy/obese, but only if the owner was overweight or obese. Allowing the dog to run free in the garden/property decreased the risk of the dog being heavy/obese. The owners' attachment to the dog was not associated with the dogs' BCS or dogs' being heavy/obese. An important and novel finding was that neutering increased the risk of being overweight or obese for male dogs while bitches were at risk irrespective of neuter status. Furthermore, a complex interaction between owners' weight status, feeding practices and the risk of dogs being overweight or obese was found, which stresses the need to consider companion animal obesity from a One Health perspective in future prospective studies. Finally, this study was unable to confirm that canine obesity is a product of owners being too attached to their dogs.

[The surgery of the tip of the nose]. Surgery of the nasal tip has stimulated the creation of more surgical techniques than any other aspect of rhinoplastic surgery, to achieve an improved shape that seems natural while enhancing the balance and harmony of the face. The region described as tip of the nose is extremely varied from person to person, because of the different shape of its anatomical structures. For that reason to obtain a good result is necessary for the surgeon the perfect knowledge of the anatomy, the acquisition of surgical concepts and technical skill. The purpose of this paper is to describe the anatomy, the surgical technique and the principal method to correct the most common defects of the nasal tip; some of these proposed by many Authors are also discussed critically. Concerning the anatomy, the Authors describe the upper and the lower lateral cartilages, the lateral and medial crura of the alar cartilages, that form the "dome", the sesamoid complex: smaller cartilage that support the lateral crus, the septum cartilage, their ligaments and the maxillary spine. Are also exposed some concepts regarding the weak triangle of Converse and, in general, the soft tissues of the nasal tip. They also described some basilar incisions to approach the tip cartilage: marginal, intercartilaginous, intracartilaginous and transfixion. This surgical techniques allow to modified the cartilages that can be corrected in different manner. Some of these modifications concerning alar cartilages, septal cartilage, area of dome cartilage, and the most common techniques to operated on it, eversion and luxation, are also exposed. The last part of the paper concerning: a) the exposition of some anesthetical problems and their surgical approach; b) the description and discussion of some surgical techniques proposed in the literature by many Authors. Regarding the most common necessities to modified the nasal tip we include: a) to change the tip projection: in its two opposite directions, increasing and decreasing, where the first purpose is one of the most difficult objectives in tip surgery, using the medial cruras or in more difficult cases a colummellar strut; b) to reduce tip fullness, that normally requires a partial resection and/or a weakening of the lateral crura; c) to alter tip rotation: normally to obtain a upward, rarely for a down ward rotation to increase the length of the nose. In this case all these modifications are described following the theoretical concept of tripod, where the nasal tip is considered mechanically as a tripod with a lower leg represented by the medial crura and the two upper legs of the two lateral cruras.

Needlescopic, laparoscopic, and open appendectomy: a comparative study. The benefits of laparoscopic appendectomy appear to be controversial. Since 1994, several abdominal procedures have been completed by using the needlescopic technique, but there appear to be no prospective studies to demonstrate the perceived benefits of needlescopic appendectomy. The authors compared open, laparoscopic, and needlescopic appendectomy in a randomized fashion with regard to duration of surgery, length of hospitalization, analgesic dosage, and surgery-associated complications. From March to July 1998, 75 patients admitted at the emergency station of the authors' hospital with a final diagnosis of acute appendicitis without tumor formation were randomized to receive one of the three treatment categories: open (OA), laparoscopic (LA), and needlescopic (nLA) appendectomy. Laparoscopic and needlescopic appendectomy were performed by using a three-port technique, although the size of the trocar used varied. There were 26 patients in the OA group, 23 in the LA group, and 26 in the nLA group. The mean operation durations for the OA, LA, and nLA groups were 55.4 +/- 28.0 minutes, 69.1 +/- 48.8 minutes, and 62.3 +/- 26.3 minutes, respectively, and these were not significantly different from one another. The mean number of the analgesic doses (Pethidine 1 mg/kg) required was 1.3 +/- 1.2 mg/kg, 0.5 +/- 0.8 mg/kg, and 0.2 +/- 0.6 mg/kg, respectively. Significant differences were noted when comparing the OA with the LA or nLA groups (OA vs. LA, P = 0.02; OA vs. nLA, P = 0.0002; LA vs. nLA, P = 0.06). The mean oral intake durations were 32.2 +/- 16.9 hours, 21.0 +/- 14.6 hours, and 20.8 +/- 16.4 hours, respectively, after surgery for the OA, LA, and nLA groups, and the between-group differences were statistically significant for the OA versus LA group ( P = 0.004) and for the OA versus nLA group ( P = 0.003). The mean durations of hospitalization for the OA, LA, and nLA groups were 3.6 +/-1.8 days, 2.8 +/- 1.4 days, and 2.4 +/- 0.9 days, and difference was detected between the OA and the nLA groups ( P = 0.02). The OA group rendered a greater wound-complication rate and ileus than did the other two groups, but the differences were not detected between the three categories ( P = 0.065, 0.6935). The result of the current study confirmed that the nLA procedure is a feasible and safe one. The nLA procedure provided substantial advantages over the OA procedure in the contexts of diminished postoperative pain and shorter hospital stay without significant increases in postoperative complication rate or surgical time.

The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews. The aim of this review is to examine the clinical and cost-effectiveness of screening for lung cancer using computed tomography (CT) to assist policy making and to clarify research needs. Electronic databases and Internet resources. A systematic review was undertaken and selected studies were assessed using the checklists and methods described in NHS Centre for Reviews and Dissemination (CRD) Report 4. Separate narrative summaries were performed for clinical effectiveness and cost-effectiveness. Cost-effectiveness analysis resulting in a cost per quality-adjusted life-year was not feasible, therefore the main elements of such an appraisal were summarised and the key issues relating to the existing evidence base were discussed. Twelve studies of CT screening for lung cancer were identified, including two randomised controlled trials (RCTs) and ten studies of screening without comparator groups. The quality of reporting of these studies was variable, but the overall quality was adequate. The two RCTs were of short duration (1 year) and therefore there was currently no evidence that screening improves survival or reduces mortality. The proportion of people with abnormal CT findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number need to screen to detect one lung cancer = 31-249). Incidence rates of lung cancer were lower (0.1-1% per year). Detection of stage I and resectable tumours was high, 100% in some studies. Adverse events, as a result of investigation or surgery, or the screening process per se were poorly reported. Incidental findings of other abnormalities requiring medical follow-up were reported to be as high as 49%. Six full economic evaluations of population CT screening programmes for lung cancer were included in the review. The magnitude of cost-effectiveness ratios reported varied widely. None was set in the UK and generalisation was complicated by wide variation in the data used in different countries and a paucity of UK data for comparison. All six made the fundamental assumption that screening with CT for lung cancer reduced mortality. At the current time, there is no evidence to support that assumption. In the absence of evidence of health gains from screening for lung cancer, in terms of either quantity or quality of life, and faced with a range of uncertainties, from the frequency of abnormal screening findings within a population to the natural history of screening detected lung cancers, it is not feasible at the current time to develop accurately and meaningfully an economic argument for CT screening for lung cancer in the UK. For subgroups, in particular certain occupational groups, there is evidence of increased risk of lung cancer, but the role of screening has not been demonstrated by the current studies. The accepted National Screening Committee criteria are not currently met, with no RCTs, no evidence to support clinical effectiveness and no evidence of cost-effectiveness. RCTs are needed to examine the effect of CT screening on mortality, either with whole-population screening or for particular subgroups; to determine the rate of positive screening and detected lung cancers. Research is also needed to understand better the natural history and epidemiology of screening-detected lung cancers, particularly small, well-differentiated adenocarcinomas; as well as the impacts on quality of life. Increased collection is needed of UK health service data regarding resource use and safety data for lung cancer management and services. Research is also needed into the feasibility and logistics of tracing people who have in the past worked in industry where there was exposure to lung carcinogens.

Purification and characterization of an alpha 1 beta 2 isoform of CapZ from human erythrocytes: cytosolic location and inability to bind to Mg2+ ghosts suggest that erythrocyte actin filaments are capped by adducin. CapZ ("capping protein") is a heterodimeric actin capping protein that blocks actin filament assembly and disassembly at the fast growing (barbed) filament ends and is proposed to function in regulating actin filament dynamics as well as in stabilizing actin filament lengths in muscle and nonmuscle cells. We show here that erythrocytes contain a nonmuscle isoform of capZ (EcapZ) that is present exclusively in the cytosol and is not associated with the short actin filaments in the erythrocyte membrane skeleton. This is unlike other cell types where capZ is associated with cytoskeletal actin filaments and suggests that cytosolic EcapZ may be inactive, or alternatively, that the barbed ends are capped by adducin, a membrane skeleton protein that was shown recently to cap actin filament barbed ends in vitro [Kuhlman, P. A., Hughes, C. A., Bennett, V., & Fowler, V. M. (1996) J. Biol. Chem. 271, 7986]. To distinguish between these possibilities, we purified EcapZ from erythrocyte cytosol and characterized its biochemical and functional properties. Two-dimensional gel electrophoresis and western blotting reveals the EcapZ subunit composition to be alpha1beta2, as described for capZ from many other nonmuscle cells, with no evidence for posttranslational modifications. Purified EcapZ is fully functional in blocking actin elongation from barbed filament ends (Kcap approximately 1-5 nM) as well as in nucleating actin polymerization. Furthermore, cytosolic EcapZ binds to actin filament barbed ends, indicating that sequestering of EcapZ by a cytosolic inhibitory factor or insufficient amounts of EcapZ in cytosol also cannot account for its absence from the membrane skeleton. To test directly whether the barbed ends of the erythrocyte actin filaments were already capped, we measured binding of purified EcapZ to isolated membranes. Purified EcapZ does not cosediment with membranes prepared by hypotonic lysis in the presence of magnesium, suggesting that the barbed ends of the erythrocyte actin filaments are capped under these conditions but not by EcapZ. In contrast, purified EcapZ stoichiometrically reassociates with all the actin filament barbed ends in membranes prepared by hypotonic lysis in 5 mM sodium phosphate, pH 8.0 (5P8), conditions in which the barbed filament ends were previously reported to be uncapped. Comparison of the amounts of adducin associated with membranes prepared in the presence and absence of magnesium reveals that 60-80% of the adducin dissociates from the membrane during hemolysis and washing in 5P8 buffer, suggesting that the barbed ends become artifactually uncapped due to loss of adducin. The erythrocyte actin filaments may thus represent a specialized class of membrane-associated actin filaments that are capped by adducin instead of capZ.

A study of idiom comprehension in children with semantic-pragmatic difficulties. Part II: Between-groups results and discussion. Using a play-based methodology and a symptom checklist, this study investigated idiom comprehension in 26 children aged between 6-11 who were considered to have semantic-pragmatic difficulties. This group was compared with two groups of mainstream children and a group of children with (other) language disorders not primarily of a semantic or pragmatic nature. The results indicate that the children with semantic-pragmatic difficulties did, as a group, demonstrate significantly fewer appropriate idiomatic interpretations and significantly more inappropriate interpretations than did any of the other three groups. However, the higher level of inappropriate scores in the semantic-pragmatic difficulties group reflected a large number of 'fuzzy' actions rather than significantly higher rates of literality. This may indicate an awareness among these children that the literal meaning is inappropriate in the absence of adequate idiom vocabulary. It may also reflect difficulty in retrieving known idioms from memory and/or in selecting the most appropriate meaning from several possibilities in context. Despite relative weakness, the children with semantic-pragmatic difficulties displayed appropriate interpretations considerably more often than they evidenced inappropriate ones. Within-group analysis reveals that the children diagnosed with Asperger syndrome or high-functioning autism performed less well than did those diagnosed with 'semantic-pragmatic disorder'. Nevertheless, both of these subgroups encompassed a considerable range of comprehension ability with regard to the 12 common idioms tested. Analysis of the play task performance and symptom checklist suggests that this variation probably reflects differences in the critical semantic and pragmatic skills underpinning idiom comprehension. These include flexibility of thought, theory of mind, attention to context, prosody and overall coherence, as well as the ability to integrate world knowledge and current contextual information to guide inferencing. In combination with definition task data and broader knowledge of symptomatology, the play task may be used to identify the sites and sources of idiom comprehension breakdown in individual children. It is probable that idiom comprehension in this group of children with semantic-pragmatic difficulties was facilitated by the inclusion of only concrete idioms and by the visual support provided by the play set. Nevertheless, the moderate to age-appropriate ability displayed by this group in this context suggests that the characterization of children with semantic-pragmatic difficulties as predominantly literal needs to be revised. Rather than seeking a blanket characterization of an essentially heterogeneous group, it may be more useful to consider idiom comprehension a secondary manifestation of semantic and/or pragmatic difficulties. Since the children who exhibit these difficulties vary in symptomatology and, probably, in aetiology, it follows that they will also vary with respect to idiom comprehension and the reasons for its breakdown.

Relationships between 24h observations in intraocular pressure vs blood pressure, heart rate, nitric oxide and age in the medical chronobiology aging project. To evaluate associations between intraocular pressure (IOP) and blood pressure (BP), heart rate (HR), serum nitric oxide (NO), diurnal variations, diabetes and aging in data collected during 24h studies of men conducted over 34y. As part of the Medical Chronobiology Aging Project, male Army veterans, ages 22 to 81y, without a history of eye disease, were studied around-the-clock in May 1969 (n = 13), 1979 (n = 11), 1988 (n = 11), 1993 (n = 11), 1998 (n =12) and 2003 (n = 10). Measurements of IOP (R & L eyes, supine position), BP and HR (sitting position), and collection of blood were obtained every 3h (8 readings/24h) from 19:00h to 16:00h the next day. Individual time series were analyzed for circadian characteristics by the least-squares fit of a 24& 12h cosine. After normalizing all data to percent of mean to reduce inter-subject variability in levels, grouped data were analyzed for time-effect by ANOVA and for circadian rhythm by multiple component (24h&12h) cosine fitting. Individual 24h averages were analyzed by simple and multiple regression for relationships between IOP and systemic variables, diabetic status and age. Over the 34y study span, 22 men provided sixty-three 24h profiles for IOP & HR, 61 for BP, and 21 for NO. Using all normalized data, a significant circadian rhythm was found for each variable at p <0.001. Circadian peaks (orthophases) are located in the late morning for IOP-R (10:20h) and IOP-L (10:52h), and in the evening for HR (18:52h), NO (20:00h), SBP (20:40h) and DBP (21:44h). An out-of-phase relationship of about 10h is noted on a group basis between IOP vs BP, HR and NO. The locations of individual circadian peaks for IOP-R were found around the clock, but with a significant predominance between 10:00 and 16:00h (day type), and 04:00-10:00h (morning type). In contrast, BP, HR and NO showed a significant clustering of evening type or night type peaks. The overall mean IOP for the right eye was slightly, but not significantly, higher than the left eye (17.60+/-0.21 vs 17.34+/-0.18 mmHg; p = 0.385), with a strong positive correlation between both eyes (R = 0.952, p <0.0001). IOP showed a significant positive correlation with SBP (R = 0.49, p <0.001), diabetic status (R = 0.47, p <0.001), age (R = 0.32, p = 0.011), and HR (R = 0.28, p = 0.031). A multiple regression using SBP, DBP, HR, age and diabetic status (5 men became diabetic over the 34y study span) as independent variables resulted in SBP being the strongest predictor of IOP (p = 0.0001), followed by DBP (p = 0.0103). After adjustment for BP, independent effects of age (p = 0.187), HR (p = 0.789) and diabetic status (p = 0.153) were eliminated from the prediction equation. The results of these studies reveal significant circadian variations in IOP, BP, HR and NO, with peak levels, on average, near noon for IOP and in the evening for BP, HR and NO. An increase in SBP was associated with an increase in IOP. While SBP and DBP are significant predictors of IOP levels, single measurements during regular clinic hours may not reveal the full functional relationship between the variables measured in our studies. Therefore, circadian information on total 24h patterns may contribute to the reliability of diagnosis and guide proper individualized timing of optimal patient management (e.g., for glaucoma, hypertension, diabetes, among other conditions).

Cerebral blood flow and metabolism in relation to electrocortical activity with severe umbilical cord occlusion in the near-term ovine fetus. The purpose of this study was to determine the change in cerebral blood flow and substrate metabolism in relation to electrocortical activity in the near-term ovine fetus with repeated umbilical cord occlusion of a severe degree. Eight near-term fetal sheep were studied through a 2-hour control period, a 6-hour experimental period with repeated cord occlusion of 4 minutes' duration every 90 minutes, and a 16-hour recovery period. Regional cerebral blood flow was measured with the microsphere technique before, during, and after the first cord occlusion; blood flow in the superior sagittal sinus, the cerebral perfusion pressure, and the electrocortical activity were monitored continuously. Brachiocephalic arterial and sagittal venous blood were sampled at selected time points for blood gas and pH, oxygen content, and glucose and lactate levels. Severe umbilical cord occlusion as studied resulted in profound hypoxemia with modest hypercapnia and acidemia, to a similar degree with each insult, but with a return to preocclusion values after occluder release. Glucose values also fell acutely with each cord occlusion by approximately 30% but showed an overall increase through the experimental period, from 0.80 to 1.44 mmol/L; lactate values showed an increase, from 1.21 to 6.10 mmol/L (both P 1 <.01). Fetal electrocortical activity was disrupted markedly, with an abrupt flattening of the electrocortical amplitude by 1.5 minutes of each cord occlusion on average and with an overall increase in indeterminate state activity during the experimental and through the recovery periods. Cerebral blood flow increased approximately 2.5- and 2.8-fold, as measured at 2 and 3.5 minutes during the first cord occlusion (both P <.01) and with the regional flow increase greater in the subcortex and brainstem. Cerebral extraction of oxygen fell toward zero, as measured at 2 minutes during the second and fourth occlusions (P <.05) with oxygen uptake no longer measurable; glucose extraction was now increased approximately 2-fold (P <.05), which indicates that anaerobic metabolism of glucose must be the predominant source of energy at this time. Superior sagittal sinus blood flow also increased in all animals, approximately 1.4- and 1.6-fold at 2 and 3.5 minutes of the first cord occlusion, but much less than the corresponding increase in arterial inflow; the increase was in response to subsequent occlusions was further reduced. Severe umbilical cord occlusion in the near-term ovine fetus results in a rapid decrease in the availability of oxygen to the brain. The low PO (2) gradient from blood to tissue rate limits for oxygen consumption by 2 minutes of insult (despite the marked increase in blood flow) and signals the shift to anaerobic metabolism, the suppression in electrocortical activity, and the probable shutdown of other energy-using processes.

[Effects of cyclin dependent protein kinase inhibitor olomoucine on the microenvironment of axonal regeneration after spinal cord injury: an experiment with rats]. To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the microenvironment of axonal regeneration after spinal cord injury (SCI). Forty-five SD rats were randomly divided into 3 equal groups: SCI group undergoing SCI by hemisection technique and peritoneal injection of dimethyl sulfoxide (DMSO) solution 30 min after the SCI, SCI + olomoucine (SCI + Olo) group undergoing SCI by hemisection technique and peritoneal injection of olomoucine solution 30 min after the SCI, and sham operation group undergoing sham operation and peritoneal injection of DMSO solution 30 min after the operation. Three days after the operation the injured spinal cord segments of 5 rats from each group were taken out. Western blotting was used to detect the expression of the cell cycle related proteins, cyclin A, cyclin B, cyclin E, and proliferating cell nuclear antigen (PCNA). Immunofluorescence (IF) staining was used to detect the expression of glial fibrillary acidic protein (GFAP), growth associated protein-43 (GAP-43) and chondroitin sulphate proteoglycan (CSPG). Four weeks after the operation specimens of the injured spinal cord segment 15 mm in length were taken out from 5 rats in each group to undergo histological examination. The locomotion function of the hindlimbs was determined by modified Gale combined behavioral scoring (SBS) 1 day and 1, 2, 4, 6, and 8 weeks after the operation. Western blotting 3 days after the operation showed that the expressions of cyclin A, cyclin B, cyclin E, and PCNA were very weak in the sham operation group, were significantly increased in the SCI group, and were significantly down-regulated in the SCI + Olo group compared with those of the SCI group. IF staining showed that the number of astrocytes was small and the expressions of GFAP, CSPG, and GAP-43 were weak in the sham operation group; in the SCI group the astrocytic proliferation and glial scar was obvious, and the expressions of GFAP, CSPG, and GAP-43 were significantly increased compared with those of the sham operation group (all P < 0.05); and the astrocytic proliferation was significantly weaker and no obvious glial scar could be seen, and the expressions of GFAP and CSPG were weaker in the SCI + Olo group in comparison with the SCI group, however, the GAP-43 expression of the sham operation group was significantly increased compared with that of the sham operation group (P < 0.05). The hindlimbs of the SCI + Olo group and sham operation group were paralyzed without significant difference in the CBS values between these 2 groups, however, two weeks after the operation, the locomotion function scores at different time points of the SCI + Olo group were all significantly improved in comparison with that of the SCI group (all P < 0.05). Olomoucine promotes the recovery of the locomotion function of the paralyzed hindlimbs, probably through microenvironmental improvement of axonal regeneration by inhibiting the glial scar formation and CSPG secretion as well as upregulating the GAP-43 expression.

An incremental evaluation of the diagnostic value of thallium single-photon emission computed tomographic imaging and lung/heart ratio concerning both the presence and extent of coronary artery disease. The goal was to assess the incremental diagnostic value of thallium single-photon emission computed tomographic (SPECT) imaging and lung/heart ratio (LHR) over other clinical and exercise electrocardiographic (ECG) variables concerning the presence and extent (three vessel/left main) of coronary artery disease. Multivariable logistic regression analysis that used an incremental study design was applied to clinical, exercise test, SPECT, LHR, and catheterization data from 323 patients with suspected coronary disease. The following variables were evaluated as predictors of presence and extent of disease: clinical (age, sex, symptoms, diabetes, and smoking), exercise ECG (millimeters of ST segment depression, slope of ST segment depression, peak heart rate, change in systolic blood pressure, and metabolic equivalents of the task), and thallium (defect reversibility and intensity of hypoperfusion and LHR). Discrimination and incremental value were assessed by receiver operating characteristic (ROC) curve analysis. SPECT imaging (segment hypoperfusion score) was an independent predictor of both presence and extent of disease (p < 0.0001) irrespective of the percent stenosis criterion used. However, it added significant incremental diagnostic information over clinical and exercise ECG data only concerning presence (e.g., ROC curve areas: presence of disease-clinical plus exercise ECG = 83 +/- 2 vs clinical, exercise ECG, plus SPECT = 87 +/- 2, p < 0.001; extent of disease-clinical plus exercise ECG = 83 + 4 vs clinical, exercise ECG, plus SPECT = 85 +/- 3, p = 0.11). Thallium LHR was an independent predictor of both presence and extent of disease (p < 0.05), but the incremental information added to SPECT data did not reach statistical significance (e.g., ROC curve areas: presence of disease--SPECT = 87 +/- 2 vs SPECT plus LHR = 88 +/- 2, p = 0.24; disease extent--SPECT = 85 +/- 2 vs SPECT plus LHR = 86 +/- 2, p = 0.24). However, when combined, LHR and SPECT data had significant incremental value over clinical and exercise ECG data alone concerning extent of disease (e.g., ROC curve areas: clinical plus exercise ECG = 83 +/- 4 vs clinical, exercise ECG, SPECT and LHR = 86 +/- 3, p = 0.04). SPECT thallium imaging variables are independent predictors of both presence and extent of coronary disease. However, they have significant incremental value over clinical and exercise ECG data concerning only presence of disease. Thallium LHR is an independent predictor of both presence and extent of disease but adds only a small insignificant amount of incremental diagnostic information over SPECT data. However, there was significant incremental value to the addition of LHR to SPECT data concerning extent of disease.

Effect of quality of gynaecological ultrasonography on management of patients with suspected ovarian cancer: a randomised controlled trial. The diagnostic accuracy of ultrasonography for differentiating between benign and malignant adnexal masses is proportional to the expertise of the operator. However, we do not know whether improved diagnostic accuracy will affect the management of these tumours. We assessed the effect of the quality of gynaecological ultrasonography on the management of patients with suspected ovarian cancer in a randomised controlled trial. 165 patients who were referred to the regional gynaecological cancer centre at Guy's and St Thomas' NHS Foundation Trust (London, UK), between June 7, 2004, and April 23, 2006, with suspected adnexal tumours met the inclusion criteria. Of these, 150 patients were randomly assigned to either level II (routine) ultrasonography (n=73) or to level III (expert) ultrasonography (n=77). The primary endpoint was the number of major surgical staging procedures (including a laparotomy and at least an oophorectomy and omental biopsy) in each group of the study. Secondary endpoints were: total number of surgical procedures; number of minimally invasive procedures (eg, operative laparoscopy or ultrasonography-guided cyst aspiration); number of additional diagnostic tests (eg, CT or laparoscopy); number of follow-up scans; diagnostic accuracy of level II and level III ultrasonography; and duration of hospital stay. All analyses were by intention to treat. This study is registered on the Current Controlled Trials website http://www.controlled-trials.com/mrct/trial/230201/ISRCTN02631195. More major surgical staging procedures for suspected ovarian cancer were done in the level II group than in the level III group of the study (27 of 73 [37%] vs 17 of 77 [22%], respectively; difference between groups 15% [95% CI 0-29]; RR 1.68 [1.00-2.81]; p=0.049). The total number of surgical procedures was similar between the two groups: 35 of 73 (48%) in the level II group and 33 of 77 (43%) in the level III group (RR 1.12 [0.79-1.59]; p=0.53). The median duration of hospital stay for patients who were operated on was 6 days (range 3-13) in the level II group and 5 days (range 1-9) in the level III group (p=0.01). A likely histological diagnosis was provided to clinicians after ultrasonography for 76 of 77 (99%) patients in the level III group compared with only 38 of 73 (52%) patients in the level II group. 18 of 150 (12%) patients recruited were eventually diagnosed with ovarian malignancy. The sensitivity and specificity of ultrasonography was 2 of 5 (40%; [95% CI 6.5-84.6]) and 10 of 10 (100%; [34-100]), respectively, in the level II group and 7 of 8 (88%; [47-98]) and 27 of 28 (96%; [82-99]), respectively, in the level III group. Improved quality of ultrasonography has a measurable effect on the management of patients with suspected ovarian cancer in a tertiary gynaecology cancer centre, and results in a significant decrease in the number of major staging procedures and a shorter inpatient hospital stay.

Sex differences in body composition early in life. Early development of the percentage of fat and muscle is rarely considered, but is important because excessive fat is related to the development of diabetes and other morbidities later in life. In pediatric medicine, there are few to no data comparing sex differences in body composition in the first months of life despite the fact that males are typically longer and weigh more than girls at birth. The purpose of this study was to determine whether observed sex differences in body composition at birth persist through the first 6 months of life. Participants were healthy, full-term, male and female newborns. Children throughout the Oklahoma City, Oklahoma, metropolitan area were enrolled. The inclusion criteria were: mothers aged 18 to 45 years at the time of delivery; a term pregnancy lasting >or=37 weeks of gestation (determined by mother's physician); weight adequate for gestational age; and a hospital stay for the infant of <3 days following delivery. The exclusion criteria were: maternal tobacco use or alcohol consumption (>1 drink per week) during pregnancy; gestational diabetes; preeclampsia; and infants with presumed or known congenital birth defects. Baseline assessment at birth included length and weight. Newborns had their body composition (percent fat [%fat], total fat, and fat-free mass) determined at approximately 1 month of age using whole body plethysmography. Mothers were invited to have their children take part in a 5-month extension that conducted additional body composition measurements at 3 and 6 months of age. Sixty-four girls (mean [SD] age at time of testing, 20.9 [7.9] days; birth weight, 3500 [388] g; birth length, 49.9 [2.4] cm; white race, 73.4%) and 53 boys (mean age at time of testing, 20.2 [7.3] days; birth weight, 3353 [413] g; birth length, 51.0 [2.4] cm; white race, 69.8%) were assessed and included in the study. At birth, girls were significantly shorter and weighed more than boys (both, P < 0.05). At ~1 month of age, body composition revealed that girls had significantly greater %fat (15.1% vs 12.7%; P < 0.05) and less fat-free mass (3182 [303] vs 3454 [361] g; P < 0.001) than did boys. At 3 months of age, girls continued to have significantly less fat-free mass (4379 [347] vs 4787 [310] g; P < 0.01) than did boys; however, by 6 months of age, no significant sex difference was observed in any body composition variable studied. In this small sample of healthy, full-term newborns, at ~1 month of age, statistically significant differences in %fat and fat-free mass existed between girls and boys; however, by 6 months of age, these differences no longer existed.

Building essential biodiversity variables (EBVs) of species distribution and abundance at a global scale. Much biodiversity data is collected worldwide, but it remains challenging to assemble the scattered knowledge for assessing biodiversity status and trends. The concept of Essential Biodiversity Variables (EBVs) was introduced to structure biodiversity monitoring globally, and to harmonize and standardize biodiversity data from disparate sources to capture a minimum set of critical variables required to study, report and manage biodiversity change. Here, we assess the challenges of a 'Big Data' approach to building global EBV data products across taxa and spatiotemporal scales, focusing on species distribution and abundance. The majority of currently available data on species distributions derives from incidentally reported observations or from surveys where presence-only or presence-absence data are sampled repeatedly with standardized protocols. Most abundance data come from opportunistic population counts or from population time series using standardized protocols (e.g. repeated surveys of the same population from single or multiple sites). Enormous complexity exists in integrating these heterogeneous, multi-source data sets across space, time, taxa and different sampling methods. Integration of such data into global EBV data products requires correcting biases introduced by imperfect detection and varying sampling effort, dealing with different spatial resolution and extents, harmonizing measurement units from different data sources or sampling methods, applying statistical tools and models for spatial inter- or extrapolation, and quantifying sources of uncertainty and errors in data and models. To support the development of EBVs by the Group on Earth Observations Biodiversity Observation Network (GEO BON), we identify 11 key workflow steps that will operationalize the process of building EBV data products within and across research infrastructures worldwide. These workflow steps take multiple sequential activities into account, including identification and aggregation of various raw data sources, data quality control, taxonomic name matching and statistical modelling of integrated data. We illustrate these steps with concrete examples from existing citizen science and professional monitoring projects, including eBird, the Tropical Ecology Assessment and Monitoring network, the Living Planet Index and the Baltic Sea zooplankton monitoring. The identified workflow steps are applicable to both terrestrial and aquatic systems and a broad range of spatial, temporal and taxonomic scales. They depend on clear, findable and accessible metadata, and we provide an overview of current data and metadata standards. Several challenges remain to be solved for building global EBV data products: (i) developing tools and models for combining heterogeneous, multi-source data sets and filling data gaps in geographic, temporal and taxonomic coverage, (ii) integrating emerging methods and technologies for data collection such as citizen science, sensor networks, DNA-based techniques and satellite remote sensing, (iii) solving major technical issues related to data product structure, data storage, execution of workflows and the production process/cycle as well as approaching technical interoperability among research infrastructures, (iv) allowing semantic interoperability by developing and adopting standards and tools for capturing consistent data and metadata, and (v) ensuring legal interoperability by endorsing open data or data that are free from restrictions on use, modification and sharing. Addressing these challenges is critical for biodiversity research and for assessing progress towards conservation policy targets and sustainable development goals.

Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene. Interleukin-1beta (IL-1beta) is a potent stimulator of bone resorption, and has been implicated in the pathogenesis of high bone turnover and osteoporosis. IL-1 receptor antagonist (IL-1ra) is a competitive inhibitor of IL-1beta effects and the biological effects of IL-1beta are therefore proportional to the ratio IL-1beta/IL-1ra. The coding regions of IL-1beta were examined for sequence variations by SSCP and sequencing after polymerase chain reaction (PCR) of genomic DNA. Three previously described polymorphisms (C(-511)-T, G(3877)-A and C(3954)-T) in the IL-1beta gene were determined by restriction fragment length polymorphism (RFLP) using Ava I, Aci I, and Taq I after PCR. The 86-base pair repeat polymorphism in IL-1ra was examined by PCR and electrophoresis and the T11100-C polymorphism in the IL-1ra gene was examined by RFLP using MspA1I after PCR. All polymorphisms were related to bone mass, biochemical markers of bone turnover, and presence of fracture in a study including 389 osteoporotic patients with vertebral fractures and normal controls. Two normal women were heterozygous for a shift from cytosine to thymine (C3263-T) in exon 4 of the IL-1beta gene. This substitution did not affect the amino acid sequence. We did not find other sequence variations in the IL-1beta gene apart from the already known polymorphisms. The distribution of C(-511)-T, G(3877)-A, and C(3954)-T genotypes was similar in the osteoporotic and the normal controls. No significant differences could be shown in bone mass or bone turnover. In the IL-1ra gene almost complete linkage was confirmed between the already known polymorphisms: G(1731)-A, G(1821)-A, A(1868)-G, G(1887)-C, T(8006)-C, C(8061)-T, 86 base pair variable number tandem repeat (VNTR), A(9589)-T, and a new polymorphism: T(1934)-C. The A1A1/A3 genotypes of the IL-1ra VNTR polymorphism were significantly more frequent in osteoporotic patients (56.2%) compared with age-matched normal controls (43.3%) (chi2 = 4.09; p = 0.043). The relative risk of osteoporotic fractures was increased to 1.68 (95% CI, 1.01-2.77) in individuals with A1A1/A3 genotypes. Bone mineral density (BMD) of the lumbar spine was reduced in individuals with A1A1/A3 genotypes (p = 0.014, analysis of variance [ANOVA]). The difference in bone mass between A1A1/A3 and A2A1/A2 tended to increase with increasing age. T1100-C genotypes were distributed similarly in osteoporotic patients and normal controls and the polymorphism was without effect on bone mass and biochemical markers of bone turnover. In conclusion, an 86-base pair repeat polymorphism in the IL-lra gene is associated with increased risk of osteoporotic fractures. Other polymorphisms in the IL-1ra and the IL-1beta genes are not associated with osteoporotic fractures or alterations in bone mass or bone turnover.

Suppression of hepatocyte apoptosis and induction of DNA synthesis by the rat and mouse hepatocarcinogen diethylhexylphlathate (DEHP) and the mouse hepatocarcinogen 1,4-dichlorobenzene (DCB). Nongenotoxic rodent hepatocarcinogens do not damage DNA but cause liver tumours in the rat and mouse, associated with the induction of hepatic DNA synthesis. Previously, we have demonstrated that nongenotoxic hepatocarcinogens such as phenobarbitone and the peroxisome proliferator (PP), nafenopin, also suppress rat hepatocyte apoptosis. The nongenotoxic chemicals 1,4-dichlorobenzene (DCB) and the PP, diethylhexyl phthalate (DEHP), both induce high levels of DNA synthesis in rat liver in vivo, but only DEHP is hepatocarcinogenic in this species. Here, we investigate whether the difference in rat carcinogenicity of these two hepatic mitogens may be due to differences in their ability to suppress hepatocyte apoptosis. In rat hepatocytes in vitro, MEHP (the active metabolite of DEHP) induced DNA synthesis 2.5-fold (P = 0.001) and suppressed 10- and 4-fold, respectively both spontaneous (P = 0.0008) and transforming growth factor beta1 (TGFbeta1)-induced (P = 0.0001) apoptosis. DCB gave a small (1.7-fold) increase in DNA synthesis (P = 0.03) and a small (1.7- to 2-fold) suppression of both spontaneous (P = 0.022) and TGFbeta1-induced (P = 0.015) apoptosis. We next analysed the induction of DNA synthesis and the suppression of apoptosis in rat liver in vivo. Both DEHP and DCB were able to induce DNA synthesis although, as seen in vitro, the induction by DCB (4.2-fold; P = 0.023) was less marked than that with DEHP (13.4-fold; P = 0.007). Similarly, DEHP and DCB were both able to suppress rat hepatocyte apoptosis in vivo but the magnitude of the suppression was comparable; apoptosis was reduced to undetectable levels in four out of five animals with DCB and three out of five with DEHP. Since both chemicals suppressed apoptosis and induced DNA synthesis in rat liver but, overall, DCB was less potent, the disparate hepatocarcinogenic potential of these two chemicals could arise from differences in the magnitude of growth perturbation. To test this hypothesis, we repeated the studies in mouse, a species where both DCB and DEHP are hepatocarcinogenic. Both in vitro and in vivo, DCB and DEHP/MEHP were able to suppress apoptosis and induce hepatocyte DNA synthesis in the mouse with comparable potencies. The data support the hypothesis that the carcinogenicity of nongenotoxic hepatocarcinogens is associated strongly with the ability to perturb hepatocyte growth regulation. However, the ability to effect such changes is not unique to nongenotoxic carcinogens and is common to some noncarcinogenic chemicals, such as DCB, suggesting that the growth perturbation may need to exceed a threshold for carcinogenesis.

[Opening-wedge osteotomy of the proximal tibia]. The aim of this study was to evaluate the accuracy of correction and short-term outcomes of treatment by opening-wedge tibial osteotomy with the use of allograft and a modified Puddu plate fixation. Between February 2001 and March 2003, 33 operations on 30 patients, at an average age of 54 years, with gonarthrosis and varus deformity were evaluated. Grade III arthritis was diagnosed in 24 knees (73 %) and grade II in nine knees (27 %). The preoperative planning as well as intraoperative correction were based on the limb mechanical axis, as shown on an X-ray image of the whole lower extemity. Tibial osteotomy was performed from the medial approach and the position was fixed, in contrast to the original method, with an allograft and a T-plate. The corrrection was planned so that the mechanical limb axis should intersect the articular space at 62 % of its length laterally. The limb was postoperatively immobilized for 4 weeks in a knee brace allowing walking. Limited weight bearing was recommended from the third week. The outcome of treatment was evaluated at 11 months of follow-up by the Lysholm scoring system. Correction of the limb mechanical axis involved the axis intersecting the plane of the joint space on average at 60.2 % of its length, as against the planned 62 %; the average deviation from the planned correction was 2.1 degrees. Lysholm scores improved on average by 23 points. Improvement by 20 points was regarded as a good outcome and was achieved in 31 joints (94 %). Two joints (6 %) showed poor outcomes due to associated complications. The complications included a fissure of the lateral tibial plateau in one knee, failed stabilization with subsequent loss of correction and pseudoarthrosis development in one joint, prolonged healing with a partial loss of correction (5 degrees) in one patient, and superficial infection in one patient. In patients with knee arthritis and varus deformity, the achievement of optimal correction of the mechanical limb axis is the prerequisite for a long-term good outcome. Optimal correction, as characterized by Puddu, is attained when the mechanical axis intersects the joint space at 62 % of its length laterally. Hernigou et al. define the hip-knee-ankle angle in the range of 183 degrees -186 degrees as an optimal postoperation correction. In our experience, osteotomy combined with our modification of fixation is an exact method for correcting the axis; in addition, it is simple and is associated with a low occurrence of postoperative complications. In view of a possible total knee arthroplasty, there is less disturbance in the tibial plateau-diaphysis alignment and the tibial tuberosity level is preserved. Opening-wedge tibial osteotomy with the use of a Puddu plate and allograft in our modification is an effective, exact and simple method of correcting the lower extremity axis, and is associated with few complications. We do not recommend this method for interventions planned to achive corrections of more than 16 degrees, because these have a higher occurrence of complications. The use of allograft seems to have good prospects; another option for achieving large correction includes application of an LCP plate.

Increased low density lipoprotein degradation in aorta of irradiated mice is inhibited by preenrichment of low density lipoprotein with alpha-tocopherol. We previously reported that upper thoracic exposure to ionizing radiation (IR) accelerates fatty streak formation in C57BL/6 mice and that such effects are inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase (SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in circulating lipid or lipoprotein levels. We thus proposed that IR promotes changes in the artery wall that enhance the deposition of lipoprotein lipids. To address this hypothesis, we examined the effects of IR on aortic accumulation and degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or were sham irradiated (controls) and were then placed on the high fat diet. Five days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL) (which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose ((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable counts in retroorbital blood samples, > or =95% of donor LDL was cleared within 24 h and there were no differences in time-averaged plasma concentrations of the two forms of LDL among irradiated and control mice. Aortic values increased markedly within the first hour and thereafter exhibited a slow increase up to 24 h. There were no differences between irradiated and control mice at 1 h, when values primarily reflected LDL entry, but a divergence was observed thereafter. At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P = 0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated with LDL degradation products. Consistent with the proposed involvement of oxidative or redox-regulated events, IR-induced LDL degradation was lower in SOD-transgenic than wild-type mice (P<0.05). The importance of LDL oxidation was suggested by observations that IR-induced LDL degradation was significantly reduced by preenriching LDL with alpha-tocopherol. On the basis of these results, we propose that IR elicits SOD-inhibitable changes in the artery wall that enhance LDL oxidation and degradation leading to the deposition of LDL-borne lipids. These studies provide additional support for the role of oxidation in lipoprotein lipid deposition and atherogenesis and suggest that IR promotes an arterial environment that stimulates this process in vivo.

Effect of controlled atmosphere storage, modified atmosphere packaging and gaseous ozone treatment on the survival of Salmonella Enteritidis on cherry tomatoes. In recent years, outbreaks of infections associated with raw and minimally processed fruits and vegetables have been reported. The objective of this study was to analyse the growth/survival of Salmonella Enteritidis at spot-inoculated or stem-injected cherry tomatoes during passive modified atmosphere packaging (MAP), controlled atmosphere (CA) and to compare the results with those of air storage at 7 and 22 degrees C. During MAP, the gas composition equilibrated to 6% O2/4% CO2. CO2 level was maintained as 5% through the term of CA storage at 7 and 22 degrees C. The results demonstrate that S. Enteritidis can survive and/or grow during the storage of tomatoes depending on the location site of the pathogen on fruit, suspension cell density and storage temperature. During MAP, CA and air storage, S. Enteritidis with initial population of 7.0 log10 cfu/tomato survived on tomato surfaces with an approximate decrease of 4.0-5.0 log10 cfu/tomato in population within the storage period; however, in the case of initial population of 3.0 log10 cfu/tomato, cells died completely on day 4 during MAP storage and on day 6 during both CA and air storage. The death rate of S. Enteritidis on the surfaces of tomatoes that were stored in MAP was faster than that of stored in air and in CA. Storage temperature was effective on the survival of S. Enteritidis for the samples stored at ambient atmosphere; cells died completely on day 6 at 7 degrees C and on day 8 at 22 degrees C. Stem scars provided protective environments for Salmonella; an approximate increase of 1.0 log10 cfu/tomato in stem-scar population was observed during MAP, CA and air storage at 22 degrees C within the period of 20 days. Cells survived with no significant change in number at 7 degrees C. During the research, the effect of ozone treatment (5-30 mg/l ozone gas for 0-20 min) was also considered for surface sanitation before storage. Gaseous ozone treatment has bactericidal effect on S. Enteritidis, inoculated on the surface of the tomatoes and can be used for surface sanitation of S. Enteritidis on tomatoes before storage at different conditions. Ten mg/l ozone gas treatment with different time intervals of 5 and 15 min was found to be effective respectively on low and high dose inoculum levels of S. Enteritidis attached for 1 h. Another variable considered during ozone treatment was the 4 h attachment time.

[Mid-Term to Long-Term Results of Revision Total Hip Arthroplasty Using the Oval-Shaped Acetabular Cup - TC Type]. INTRODUCTION The purpose of our paper is to evaluate the mid-term to long-term results and to confirm the basic criteria of a high-quality revision implant: safe bridging of bone defects, achievement of reliable primary fixation of revision acetabular cup, achievement of good secondary stability with documentable osteointegration of cup and demonstration of remodelling of transplanted bone tissue in the area of defects and in spaces between the implant ribs. MATERIAL AND METHODS Altogether 36 patients (38 cups) were evaluated who had undergone revision hip arthroplasty in the period from 2004 to 2010. The mean follow-up was 8.2 years (5.1-11.6 years after the reimplantation, more than 10 years in 16 patients who underwent surgery). The position and osseointegration of the implant were assessed by digital radiography, the remodelling of transplanted bone tissues in the area of defects and between the implant ribs by computed tomography with reducing artefacts around the metal implant (Aquilion 64 - Toshiba Medical Systems), and for the clinical outcomes the Harris Hip Score was used. RESULTS Preoperatively, the condition of the hip joint based on the Harris Hip Score was in 30 cases evaluated as poor, in 8 patients as satisfactory. At the time of final evaluation, 8 patients achieved excellent results, in 19 patients the condition of the joint was very good (in 2 patients bilaterally), in 6 patients it was considered satisfactory and in 3 patients poor. The mean value for HHS increased from 39.5 to 84.5. Based on the radiography evaluation, in 27 patients (in 2 patients bilaterally) the osseointegration of the revision cup was good, in 8 cases with a radiolucent line of 2-4 mm in width in DeLee zone III, in one case proximal migration of the cup occurred caused by deep infection. The informed consent form for pelvic CT was signed by 25 patients of our cohort. Remodelling of bone tissue in the space between the ribs of the implant was always detected, the presence of bone cysts was not reported, the bone defects following the application of autologous spongioplasty in the monitored patients were healed. In 6 patients, an ingrowth of fibrous tissue of 2-4 mm in width in the convexity of the cup was detected. The mean survival of the revision oval-shaped cup - TC type with a follow-up of 8.2 years after the reimplantation based on Kaplan-Meier analysis was 91.4 %. DISCUSSION The number of revision total hip arthroplasties due to a younger age of patients who undergo alloplasty keeps growing. The choice of a revision implant should always match the intraoperative finding and the bone tissue quality. The standard uncemented implants with osteoactive surface can be opted for when anterior and posterior column of the acetabulum are intact (IIA and IIB according to Paprosky). Starting from type IIC, also the proximal part of acetabulum shall be considered. At our department, preference is given to the revision cup - TC type. The oval shape facilitates a lower degree of bone resection and easier restoration of the anatomical centre of rotation. Careful debridement of granulating and necrotic tissue, thorough treatment of bone defects and osteoactive surface of implants in case of adequate primary fixation of the cup substantially contribute to the quality of its osseointegration. Greater rigidity of fixation verified by pull-out tests enables to insert angular stable screws into the gaps in the proximal part of the cup. There is still room for improvement in treating the bone defect. The application of allogenic bone grafts into the defects and spaces between the ribs of the TC cup is more challenging than the use of augmentation in the systems with trabecular titanium. Based on the evaluation of CT scans, remodelling of the transplanted bone occurs, therefore the defect zone is reduced. CONCLUSIONS The oval-shaped uncemented cup - type TC meets the requirements placed on a state-of the art revision implant, moreover its specific construction helps improve the conditions where another re-operation of acetabulum is necessary. By evaluating mid-term to long-term results of non-homogenous group of 36 patients (38 cups) we have obtained data on joint function comparable to similar groups with revision uncemented implants presented in our and foreign literature. Key words: revision oval-shaped cup, bone remodelling, pull-out tests, angular stable screws, computed tomography.

Measurements and Monte Carlo Simulations of 241Am Activities in Three Skull Phantoms: EURADOS-USTUR Collaboration. An international intercomparison was organized by Working Group 7, Internal Dosimetry, of the European Radiation Dosimetry Group in collaboration with Working Group 6, Computational Dosimetry, for measurement and Monte Carlo simulation of Am in three skull phantoms. The main objectives of this combined exercise were (1) comparison of the results of counting efficiency in fixed positions over each head phantom using different germanium detector systems, (2) calculation of the activity of Am in the skulls, (3) comparison of Monte Carlo simulations with measurements (spectrum and counting efficiency), and (4) comparison of phantom performance. This initiative collected knowledge on equipment, detector arrangements, calibration procedures, and phantoms used around the world for in vivo monitoring of Am in exposed persons, as well as on the Monte Carlo skills and tools of participants. Three skull phantoms (BfS, USTUR, and CSR phantoms) were transported from Europe (10 laboratories) to North America (United States and Canada). The BfS skull was fabricated with real human bone artificially labeled with Am. The USTUR skull phantom was made from the US Transuranium and Uranium Registries whole-body donor (case 0102) who was contaminated due to an occupational intake of Am; one-half of the skull corresponds to real contaminated bone, the other half is real human bone from a noncontaminated person. Finally, the CSR phantom was fabricated as a simple hemisphere of equivalent bone and tissue material. The three phantoms differ in weight, size, and shape, which made them suitable for an efficiency study. Based on their own skull calibration, the participants calculated the activity in the three European Radiation Dosimetry Group head phantoms. The Monte Carlo intercomparison was organized in parallel with the measurement exercise using the voxel representations of the three physical phantoms; there were 16 participants. Three tasks were identified with increasing difficulty: (1) Monte Carlo simulation of the simple CSR hemisphere and the Helmholz Zentrum München high-purity germanium detector for calculating the counting efficiency for the 59.54 keV photons of Am, in established measurement geometry; (2) Monte Carlo simulation of particular measurement geometries using the BfS and USTUR voxel phantoms and the Helmholz Zentrum München high-purity germanium detector detector; and (3) application of Monte Carlo methodology to calculate the calibration factor of each participant for the detector system and counting geometry (single or multidetector arrangement) to be used for monitoring a person in each in vivo facility, using complex skull phantoms. The results of both exercises resulted in the conclusion that none of the three available head phantoms is appropriate as a reference phantom for the calibration of germanium detection systems for measuring Am in exposed adult persons. The main reasons for this are: (1) lack of homogeneous activity distribution in the bone material, or (2) inadequate shape/size for simulating an adult skull. Good agreement was found between Monte Carlo results and measurements, which supports Monte Carlo calibration of body counters as an alternative method when appropriate physical phantoms are not available and the detector and source are well known.

[Effect of nitric oxide synthase inhibitor L-NAME on the induction of brain ischemic tolerance in rats]. To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.

First Detection of Puccinia ballotiflora on Salvia greggii. Salvia greggii, autumn sage, is grown for its bright red to white flowers that bloom in late summer and fall. In February of 2008, a rust sample was sent to the CDFA plant pathology diagnostics laboratory in Sacramento from a nursery in Santa Barbara County, CA. Pustules were abundant on older leaves causing moderate defoliation of containerized stock. Only the varieties with entirely red or pink flowers were affected. S. greggii 'Hotlips,' a popular white/red bicolor, was unaffected. Amphigenous uredinia were cinnamon brown, round, powdery, and sometimes surrounded by yellow halos. Pustules were found primarily on the leaves, although a few were on the stems. Urediniospores were broadly obovoid, subglobose to broadly ellipsoid, echinulate, and 22 to 27 × 24 to 32 μm (24.9 × 26.9 μm average) with one apical pore and 2 to 3 equatorial pores. Urediniospore walls were cinnamon brown in color and measured 1.0 to 2.0 μm (1.5 μm average). No telia were observed. After the initial detection, this rust was found in additional nursery sites in Santa Cruz, Santa Clara, Santa Barbara, and Ventura counties in 2008 and 2009. In November of 2011, a sample from a landscape planting in Santa Barbara County of a similar rust with telia and teliospores was submitted. Urediniospores and teliospores were present in the same lesions. Lesions with teliospores were located primarily on the stems. Mature teliospores were two-celled, verrucose, chocolate brown, and 25 to 31 × 32 to 40 μm (28.6 × 35.3 μm average) with a pedicel ranging from 8 to 12 × 38 to 104 μm, sometimes attached obliquely. The rust matched the morphological characteristics of Puccinia ballotiflora (Syn = P. ballotaeflora Long) (2). To confirm pathogenicity, three 20-cm-tall plants of S. greggii 'Navajo Red' in 3.8-liter pots were spray inoculated with 10 ml of a 2.5 × 103 urediniospores per ml suspension and incubated in a dew chamber at 23°C for 2 days in the dark. Plants were transferred to a growth chamber maintained at 22°C with a 12-h photoperiod. Three plants were sprayed with sterile distilled water as controls. Uredinial pustules (1 to 2 mm) appeared on the abaxial surface of the leaves after 3 weeks. The pathogenicity test was repeated with similar results. The internal transcribed spacer region of rDNA and a portion of the 28S rDNA were amplified with primer pairs ITS5 (5'-GGAAGTAAAAGTCGTAACAAGG-3'), Rust1 (5'-GCTTACTGCCTTCCTCAATC-3'), and Rust2inv (5'-GATGAAGAACACAGTGAAA-3'), LR6 (5'-CGCAGTTCTGCTTACC-3') as described by Aime (1) and sequenced using the amplification primers, Rust2 (5'-TTTCACTGTGTTCTTCATC-3') and Rust3 (5'-GAATCTTTGAACGCACCTTG-3'). BLAST query of the assembled sequence, GenBank KF381491, was 91% identical to P. acroptili, JN204194, its closest match of similar length. P. ballotiflora has been found in Colombia on S. cataractarum, S. petiolaris, and S. mayori (3), and in Texas and Mexico on S. ballotiflora (4). To the best of our knowledge, this is the first detection of P. ballotiflora on S. greggii worldwide. P. ballotiflora is already widespread in the nursery trade in California and frequent fungicide applications are necessary to keep plants marketable. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) J. W. Baxter and G. B. Cummins. Lloydia 14:201, 1951. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Botany and Mycology Laboratory, Online publication http://nt.ars-grin.gov/fungaldatabases ARS, USDA, 2014 (4) F. D. Kern et al. Mycologia 25:448, 1933.

Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation. Antithrombotic therapies are known to prevent stroke for patients with atrial fibrillation (AF) but are often underused in community practice. To examine the prevalence of patients with acute ischemic stroke with known history of AF who were not receiving guideline-recommended antithrombotic treatment before stroke and to determine the association of preceding antithrombotic therapy with stroke severity and in-hospital outcomes. Retrospective observational study of 94 474 patients with acute ischemic stroke and known history of AF admitted from October 2012 through March 2015 to 1622 hospitals participating in the Get With the Guidelines-Stroke program. Antithrombotic therapy before stroke. Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS; range of 0-42, with a higher score indicating greater stroke severity and a score ≥16 indicating moderate or severe stroke), and in-hospital mortality. Of 94 474 patients (mean [SD] age, 79.9 [11.0] years; 57.0% women), 7176 (7.6%) were receiving therapeutic warfarin (international normalized ratio [INR] ≥2) and 8290 (8.8%) were receiving non-vitamin K antagonist oral anticoagulants (NOACs) preceding the stroke. A total of 79 008 patients (83.6%) were not receiving therapeutic anticoagulation; 12 751 (13.5%) had subtherapeutic warfarin anticoagulation (INR <2) at the time of stroke, 37 674 (39.9%) were receiving antiplatelet therapy only, and 28 583 (30.3%) were not receiving any antithrombotic treatment. Among 91 155 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 76 071 (83.5%) were not receiving therapeutic warfarin or NOACs before stroke. The unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8% [95% CI, 14.8%-16.7%]) and NOACs (17.5% [95% CI, 16.6%-18.4%]) than among those receiving no antithrombotic therapy (27.1% [95% CI, 26.6%-27.7%]), antiplatelet therapy only (24.8% [95% CI, 24.3%-25.3%]), or subtherapeutic warfarin (25.8% [95% CI, 25.0%-26.6%]); unadjusted rates of in-hospital mortality also were lower for those receiving therapeutic warfarin (6.4% [95% CI, 5.8%-7.0%]) and NOACs (6.3% [95% CI, 5.7%-6.8%]) compared with those receiving no antithrombotic therapy (9.3% [95% CI, 8.9%-9.6%]), antiplatelet therapy only (8.1% [95% CI, 7.8%-8.3%]), or subtherapeutic warfarin (8.8% [95% CI, 8.3%-9.3%]). After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.56 [0.51-0.60], 0.65 [0.61-0.71], and 0.88 [0.84-0.92], respectively) and in-hospital mortality (adjusted odds ratio [95% CI], 0.75 [0.67-0.85], 0.79 [0.72-0.88], and 0.83 [0.78-0.88], respectively). Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.

Influence of overall treatment time and radiobiological parameters on biologically effective doses in cervical cancer patients treated with radiation therapy alone. The aim of the study was to examine the influence of overall treatment time (OTT) on the value of calculated biological effective doses (BEDs) for different biological variables. These variables were: tumour proliferation rate, different cell radiosensitivity (alpha=0.2, 0.3, and 0.4 /Gy), and different start time for repopulation (Tk=21, 28, and 35 days). Also the influence of age (</= 50 years >), Hb level (</= 116 g/l>), tumor proliferation rate (bromodeoxyuridine labelling index; BrdUrdLI), and DNA ploidy on survival after shorter (</= 60 days) or longer (>60 days) OTT was investigated. The study included 229 patients with cervix carcinoma treated entirely by standard radiotherapy (RT) (external beam RT plus low-medium dose-rate (LDR/MDR) brachytherapy (BT) at the Center of Oncology in Krakow. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill. BEDs 10 (for tumours) were calculated with consideration of OTT for each patient and tumour proliferation rate (standardized potential doubling time; standardized Tpot) based on BrdUrdLI assessed on biopsy material before RT. Median OTT was 90 days (range 30-210). The mean calculated total BED for point A for tumour and 'early reactions' was equal to 103.0 Gy10. The longest median survival time--52 months--was seen for patients treated with OTT </= 60 days. If OTT exceeded 90 days to more than 120 days, loss in BED10 for relatively radiosensitive tumours (alpha=0.3-0.4/Gy and Tk=28 days) was equal to 0.37-0.26 Gy/day. However, for radioresistant tumours (alpha=0.2/Gy) it was 0.6 Gy/day. For fast proliferating tumours (BrdUrdLI >8.8%) BED loss was 1.4 Gy/day and for slowly proliferating tumours (BrdUrdLI </= 8.8%) it was 0.2 Gy/day. Assuming shorter (21 days) or longer (35 days) periods for Tk and relatively radiosensitive tumours similar BED loss of 0.38 Gy/day was observed. Kaplan-Meier analysis revealed that OTT </= 60 days was a significant prognostic factor for overall survival (OS) (p=0.019), disease-free survival (DFS) (p=0.0173), and local control (LC) (p=0.011). BED10 had significant influence on survival (p=0.047). Cox multivariate analysis revealed that for OTT shorter than 60 days the only favourable significant parameters were: age >50 years (p=0.003) and high Hb level (>116 g/l) (p=0.041). For longer treatments (OTT >60 days) the unfavourable parameters were: age </= 50 years (p=0.037), BrdUrdLI </= 8.8% (p=0.003), tumour aneuploidy (p=0.043), and BED10 </= 103 Gy (p=0.017). The examined tumour biological parameters should be taken into account for RT and provide a basis for adjuvant RT.

Controlling Supramolecular Chirality in Multicomponent Self-Assembled Systems. Chirality exists as a ubiquitous phenomenon in nature, from molecular level l-amino acids, d-sugar, secondary structures of proteins, DNA, RNA, and nanoscale helices to macroscopic conch and even galaxy. The aggregation of molecular building blocks with or without chiral centers might bring about asymmetric spatial stacking, which further results in the appearance of nonsymmetry in extended scales like helical nanofibers. This phenomenon, known as supramolecular chirality, is an important branch of supramolecular and self-assembly chemistry, which relates intimately with biomimetics, asymmetric catalysis, and designing chiroptic advanced materials. One of the important research focuses among supramolecular chirality is about rational manipulation of chirality amplification and handedness, presenting a profound influence on the performance of resulting soft materials such as circularly polarized luminescence and cell adhesion on hydrogels. The control over supramolecular chirality normally relies on two factors, i.e., thermodynamic and kinetic variables dependent on molecular structural parameters and environmental contributions, respectively. Supramolecular chirality in two or more component-based systems places an emphasis on thermodynamic control as it occurs from either integrated coassembly or separated self-sorting, which is more sophisticated than that of single component systems. Thus, the study on supramolecular chirality in multicomponent systems could mimic complicated biosystems, allowing for better understanding about the origin of natural chirality and extended applications as biomimetics. To date, the exploration of supramolecular chirality in multicomponent systems is restricted on both fundamental and application aspects when compared to more matured single component systems. Over the past few years, we have carried out systematic studies on several systems expressing supramolecular chirality from chiral amplification or symmetry breaking. We emphasized more the thermodynamic control by introducing a second component to form noncovalent bonding like hydrogen bonding or coordination interactions. In this Account, we would specifically discuss rational manipulation of the occurrence, transfer, and inversion of supramolecular chirality by taking several of the latest representative examples. In the multicomponent systems, in addition to the building blocks with chiral centers, the second or third components could be structural analogues and achiral small molecules such as bipyridines, melamine, metal ions, inorganic nanomaterials, and even solvents. These second or third components are able to incorporate during the aggregation to form coassembly via noncovalent bonds, influencing spatial arrangements of building blocks within various dimensions from vesicles and nanofibers to organic/inorganic hybrids. Other than chirality, morphology, stimulus responsiveness, and properties could also be well tailored by controlling interactions between different components.

[Effects of Guizhi Fuling Decoction on YKL-40 and hs-CRP of patients with non-ST segment elevation acute coronary syndrome]. To investigate the changes of serum levels of chitinase-3-like-1 protein (YKL-40) and high-sensitivity C-reactive protein (hs-CRP) in patients with non-ST segment elevation acute coronary syndrome (ACS), to explore its correlation with its severity, and to observe the effects of Guizhi Fuling Decoction (GFD) on levels of blood lipids, YKL-40, and hs-CRP. Recruited were 72 patients with unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI) at Department of Integrative Medicine, First Affiliated Hospital of Xinxiang Medical College from August 2010 to June 2011. They were randomly assigned to the treatment group (36 cases) and the control group (36 cases). All patients were treated by routine treatment, but patients in the treatment group took GFD additionally. The course of treatment was four weeks. According to the severity degree, all patients were graded to four ranks: low-risk group of UA, medium-risk group of UA, high-risk group of UA, and NSTEMI. The levels of YKL-40 and hs-CRP, and the correlation of severity degree were analyzed. Before and after treatment levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were measured. Before treatment, at two weeks, and after treatment the serum levels of YKL-40 and hs-CRP were detected. The relationship of YKL-40, hs-CRP and the severity of the disease were analyzed. Levels of YKL-40 and hs-CRP were positively correlated with the severity of the disease respectively (r = 0.729, P < 0.05; r = 0.655, P < 0.05). The positive correlation also existed between YKL-40 and hs-CRP (r = 0.848, P < 0.05). There was no statistical difference in the levels of blood lipids, YKL-40, or hs-CRP between the two groups before treatment (P > 0.05). Compared with before treatment, the levels of YKL-40 and hs-CRP significantly decreased in both groups after two weeks of treatment (P < 0.05). The levels of TG, TC, LDL-C, YKL-40, and hs-CRP significantly decreased, while the HDL-C level increased in both groups after treatment (P < 0.05). The level of HDL-C in the treatment group was higher, while levels of YKL-40 and hs-CRP were lower after treatment, when compared with the control group (all P < 0.05). On the basis of anti-inflammation and adjusting blood lipids by Western medicine, GFD could further reduce the serum levels of YKL-40 and hs-CRP of ACS patients, elevate the HDL-C level, and play anti-atherosclerosis effects.

Treating anterior vaginal wall prolapse with polypropylene mesh via the transoburator route minimizing the complications with the use of preventing measures. A prospective study with 2-year follow-up. Our objectives were to evaluate the efficacy of the Perigee™ transoburator (TOT) mesh kit (American Medical Systems [AMS]-Minnetonka, MN, USA) in the treatment of ≥ stage 2 symptomatic AVP following a 2-year follow-up and to discuss the role of the pre-, peri- and postoperative measures taken to prevent complications A total of 50 patients were eligible and were subjected to AVP surgical treatment with the use of the Perigee™ system. All patients were followed-up at 4 weeks, 2, 6, 12 and 24 months. Our primary objective was treatment success and efficacy after anatomical examination of the patient at the 24-month follow-up. Efficacy was defined as ≤ stage I AVP. All patients completed the 24-month follow-up. Our secondary objective was to examine the complication rates in relation to the use of preventative measures. The proportion of patients with II to III stage significantly decreased postoperatively (P<0.001). A significantly improvement was found in all POP-Q measures (P<0.05) while mean vaginal length was similar to the preoperative values. At 24-month follow-up, 45 women were defined as ≤ stage I, indicating a 90% objective success rate (95% CI: 81.4-98.6%). Two patients had vaginal mesh extrusion (4.0%) both treated with conservative measures. No erosions occurred at any point postoperatively. De novo dyspareunia was reported in two of the 17 cases (11.8%) who reported being sexually active at follow-up. One of the two had also mesh extrusion and with appliance of the vaginal estrogen and the office excision of the exposed mesh the symptoms were resolved, while the other was treated with vaginal estrogen. Two cases (4.0%) reported de novo incontinence and both were treated with a TOT sling (monarc AMS) procedure three months after the cystocele repair. Three cases (6.0%) reported pain vaginal pain postoperatively and again our treatment of choice was vaginal estrogen cream for 4 weeks with the addition of antinflammatories for 10 days and their symptoms resolved. The treatment of AVP with the use of Perigee™ TOT system can be both effective and safe. The goal is the improvement of the quality of life of the patients and is important to avoid or to keep as minimum as possible the complications. Main complications that the surgeon should bear in mind are the vaginal erosion, vaginal mesh extrusion, de novo dyspareunia, de novo incontinence and vaginal pain. Proper patient selection, the appliance vaginal estrogen cream pre- and postoperatively and following strict surgical principles are the mainstay of the success of the TOT operation. It is crucial for POP procedures to be performed by high-volume surgeons in this field, with extensive knowledge of the pelvic floor anatomy and the mesh's characteristics. Of course this is a small study and further clinical studies with larger number of patients are needed in order to further scientific evaluate the TOT operation.

Hospitalisation and bed rest for multiple pregnancy. Bed rest used to be widely advised for women with a multiple pregnancy. The objective was to assess the effect of bed rest in hospital for women with a multiple pregnancy for prevention of preterm birth and other fetal, neonatal and maternal outcomes. The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and reference lists of relevant articles were searched. Date of last search: January 1999. Randomised trials which compare outcomes in women with a multiple pregnancy and their babies who were offered bed rest in hospital with women only admitted to hospital if complications occurred. Assessment for inclusion and methodological quality of the trials was done by the reviewer. Data were extracted by the reviewer and double entered. All eligible trials were included in the initial analysis. Prespecified sensitivity analyses have been carried out to evaluate the effect of trial quality, the effects of hospitalisation for bed rest in women with an uncomplicated twin pregnancy, in women with a triplet pregnancy and in women with a twin pregnancy complicated by cervical effacement and dilatation prior to labour. Six trials were included which involved over 600 women and 1400 babies. (1) Analyses of all trials. Routine bed rest in hospital for multiple pregnancy did not reduce the risk of preterm birth, or perinatal mortality. There was a trend to a decreased number of low birth weight infants born to women in the routinely hospitalised group, which became significant when the trial using alternate allocation was excluded (odds ratio (OR) 0.79; 95% confidence interval (CI) 0.63-0.99). No differences were seen in the number of very low birth weight infants. No support for the policy was found in other neonatal outcomes. No information is available on developmental outcomes for infants in any of the trials. Women's views about the care they received were reported rarely. (2) Analyses of hospitalisation for bed rest in women with an uncomplicated twin pregnancy. The risk of preterm birth was not reduced. Indeed significantly more women delivered very preterm (<34 weeks gestation) (OR 1.84; 95% CI 1.01-3.34). No differences were seen in perinatal mortality, or in other neonatal outcomes. Women receiving hospitalisation for bed rest had a decreased risk of developing hypertension (OR 0.55; 95% CI 0.32-0.97), although this effect was no longer apparent when the trial using alternate allocation was excluded. (3) Analyses of hospitalisation for bed rest in women with a triplet pregnancy. Most of the comparisons made between the hospitalised and control groups suggest beneficial treatment effects from routine hospitalisation for bed rest. However all the differences observed between the experimental and control groups were compatible with chance variation. (4) Analyses of hospitalisation for bed rest in women with a twin pregnancy complicated by cervical effacement and dilatation prior to labour. No differences were seen in the risk of preterm birth, perinatal mortality, fetal growth or in other neonatal outcomes. There is currently not enough evidence to support a policy of routine hospitalisation for bed rest in multiple pregnancy. No reduction in the risk of preterm birth or perinatal death is evident, although there is a suggestion that fetal growth is improved. For women with an uncomplicated twin pregnancy the results of this review suggest that it may be harmful in that the risk of very preterm birth is increased. Until further evidence is available to the contrary, the policy cannot be recommended for routine clinical practice.

The diagnostic value of 3D power Doppler ultrasound combined with VOCAL in the vascular distribution of breast masses. This study uses a three-dimensional energy Doppler technique combined with the Virtual Organ Computer-aided Analysis (VOCAL) method in order to determine the diagnostic threshold of blood flow index in breast tumors to provide a reference for evaluation and treatment options. We collected 322 solid lesions which had been operated. Each lesion met the definite pathological diagnosis; collected lesions included 262 cases of benign lesions and 60 cases of malignant lesions. All examinations were performed by using GE LOGIQ E9 with VOCAL software. Volume and four distinct vascular indices of gray mean (MG), power mean, ratio (R), and vascular flow index (VFI) were calculated by using the VOCAL software. Sampling and calculation were repeated three times and the mean value was calculated. The average age and power of the malignant group were greater than those of the benign group, ie p < .01 which had significant differences. The gray mean of the malignant group was lower than that of the benign group, ie p > .05 which had no significant differences between benign and malignant groups. The ratio, vascular flow index and volume had significant differences, i.e. p < .01. The area under the receiver operating characteristic curve (AUC) were 0.864, 0.830, 0.800, 0.758, and 0.764 for age, power, ratio, vascular flow index, and volume, respectively. The research indicators were higher than 50% of the curve showing their diagnostic value. The cut-off points of age, power, ratio, vascular flow index, and volume were 37.5, 26.56, 0.031, 0.846, and 1.75, respectively. Their corresponding sensitivity were 93.3%, 75%, 81.7%, 68.3%, 63.3%, and the specificity were 68.7%, 81%, 70.2%, 75.6%, and 81.7%, respectively. Comparison of vascular indices combined with the Breast imaging reporting and data System (BI-RADS) score and simple BI-RADS method, the AUC of power + BI-RADS, ratio + BI-RADS, VFI + BI-RADS, and BI-RADS alone are 0.928, 0.903, 0.895, and 0.796, respectively, which were higher than 50% of the curve. Sensitivity was 81.7%, 80%, 88.3%, 86.7%, and specificity was 88.5%, 85.5%, 77.1%, 69.5%, respectively. The power + BI-RADS method has the highest AUC among these three methods. Quantitative measurement of blood flow and blood vessel distribution in breast tumors by three-dimensional power Doppler ultrasound combined with the VOCAL method is more accurate and sensitive than the traditional two-dimensional ultrasound. And this method has potential promising applications in many current active research areas, such as the studies of random distribution of intratumoral blood vessels or the normalization of tumor blood vessels. Three-dimensional power Doppler ultrasound combined with the VOCAL method provides a new approach to achieving accurate judgments and the method evaluates the curative effect in breast cancer patients.

The prevalence of a false-positive myocardial perfusion stress SPET test in a skinny patient, induced by projection truncation. During the last decade, technical developments in myocardial perfusion single photon emission tomography (SPET) imaging systems have significantly improved the accuracy of diagnosing coronary artery disease. Nevertheless, the patient's position and/or the acquisition protocol can affect the studies' quality, possibly leading to misdiagnoses. In HJNM and in other journals the importance of proper positioning of the heart of the patient to be examined by myocardial perfusion SPET stress/rest testing, has been emphasized. According to our knowledge, only three cases of truncation artifact during SPET myocardial perfusion imaging acquired with original SPET cameras, related to improper positioning in very thin patients, have been reported. In all cases, patients were examined according to a single day stress/rest technetium-99m-sestamibi protocol, using a dual 90 degree detector system, equipped with high resolution, parallel-hole collimators. However, several published manuscripts have underlined the significance of appropriate patients' positioning in myocardial perfusion scintigraphy using dedicated, cadmium-zinc-telluride (CZT) or small field-of-view cardiac SPET systems. A typical case is that of a 47 years old man (height 187cm, weight 67kg), heavy smoker, with atypical chest pain. He exercised very well according to the Bruce protocol, achieving 95% of maximal age-predicted heart-rate and a technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion imaging with 370MBq of (99m)Tc-TF followed with a dual head camera (Infinia GE, USA), equipped with low-energy, high-resolution, parallel-hole collimators at 90° (L-mode configuration). Projection images were obtained from 45° RAO to 45° LPO position, in step and shoot mode (60 projections, 30sec per projection; matrix 64×64 and zoom 1.3). Auto body contour was not used. Unprocessed raw data, showed neither patient motion nor significant extracardiac activity that could result in false positive defects on myocardial perfusion stress images. However, truncation at the apex of the heart was observed. In detail, truncation of activity of apical portion of the heart from frame 45-60 (detector 1) and frames 1-5 (detector 2) was noticed. Processed stress images demonstrated a severe defect in the apex and the apical part of the anteroseptal wall. Moreover, less intense defects were observed in the inferior and septal walls. All acquisition parameters were double checked and a possible error regarding the "zoom" was ruled out. Hence, it became evident that the aforementioned artifact has originated from an eccentric patient's position and thus some heart projections were missed. A second stress acquisition was performed after repositioning the patient with emphasis on positioning the heart at the center of the field of view. As a result, improvement of the above mentioned defects, mainly in the apex and the apical anteroseptal wall. In the literature, a number of recent studies have mentioned the effect of the truncation artifact even with newly equipped gamma cameras, emphasizing the importance of the heart being in the field of view throughout the acquisition procedure. Few of them used parallel-hole collimation. In conclusion, it is suggested that in cases of very thin patients it is often necessary to avoid truncation artefacts by correctly positioning the patient's heart.

[The application of the system of «reminder stickers» for the rehabilitation programs with the use of behavioural therapy for the patients presenting with anxiety disorders]. This article was designed to report the results of research on the effectiveness of the new original «reminder stickers» technique proposed by the authors for the management of the patients undergoing rehabilitation based on behavioral therapy. The essence of this technique consists of providing the patients with systematic reminders of the need to implement skills aimed at coping with maladaptive sensations that accompany anxiety disorders. The objective of the present study was to evaluate the effectiveness of using the «reminder stickers» technique for the formation of stable responses to the correction of the target clinical symptoms. The study involved 118 patients suffering from anxiety disorders allocated to two groups for comparison. Group 1 was comprised of the patients (n=76) given the reminders while group 2 contained those (n=42) not included in the system of «reminder stickers». The difference between the parameters of interest in the two groups was estimated with the use of Mann-Whitney and Kolmogorov-Smirnov tests. The analysis of diary records of the patients was used to evaluate the frequency of occurrence of maladaptive sensations that required the application of the appropriate behavioural skills and the frequency of the missed or delayed responses as well as the level of subjective satisfaction of the patients with the stability of the acquired skills. It was shown that the patients given «reminder stickers» significantly more frequently reported situations that required the application of the appropriate skills within the first week after the initiation of monitoring than the patients of group 2 (р<0,0001). The frequency of the missed or delayed responses in these patients was significantly lower than in group 2 (р<0,0001) whereas the degree of subjective satisfaction with the stability of the acquired skills was much higher (р<0,0001). These differences persisted during week 2 after the onset of monitoring when the frequency of maladaptive sensations that required the application of the previously formed behavioural skills of therapeutic significance in the patients given «reminder stickers» remained lower than in the patients to whom no such «remainders» were provided (р=0,001). The frequency of the missed or delayed responses in these patients decreased significantly in comparison with that in group 2 (р<0,0001),) while the degree of subjective satisfaction of the patients with the stability of the acquired skills further increased (р<0,0001). The results of the study indicate that inclusion of «reminder stickers» in the structure of cognitive-behavioral therapy at the stages of formation of the skills needed to cope with maladaptive sensations enhances the ability of the patients presenting with anxiety disorders to much more often timely identify situations that require the use of the appropriate behavioural skills and to apply them. It is concluded that the application of the original «reminder stickers» technique ensures an adequate response of the patients to maladaptive sensations that accompany anxiety disorders.

Induction of cortical granule exocytosis of pig oocytes by spermatozoa during meiotic maturation. Pig oocytes were examined to test their ability to undergo cortical granule exocytosis upon penetration by spermatozoa during meiotic maturation. Immature or maturing oocytes (cultured in vitro for 0 h, 26 h and 46 h) were inseminated with ejaculated boar spermatozoa in vitro. Before and after insemination, oocytes were stained with peanut agglutinin labelled with fluorescein isothiocyanate and the cortical granule distributions were examined under the fluorescent microscope and the laser confocal microscope. Before insemination, all the oocytes at the germinal vesicle stage showed a uniform distribution of cortical granules throughout the cortical cytoplasm. The granules migrated centrifugally during maturation and were distributed just beneath the oolemma in the oocytes after germinal vesicle breakdown, forming a monolayer in metaphase I or metaphase II. Cortical granules were still present in all penetrated oocytes at the germinal vesicle stage 18 h after insemination; in contrast, 26% and 84% of the oocytes inseminated at the stages of germinal vesicle breakdown or at metaphase I and II, respectively, completely released their cortical granules. Nuclear activation rates of penetrated oocytes were 0%, 38% and 96% in oocytes cultured for 0 h, 26 h and 46 h, respectively. Of the nuclear-activated oocytes, 67% (oocytes cultured for 26 h) and 88% (oocytes cultured for 46 h) released cortical granules completely. Complete cortical granule exocytosis was not observed in nuclear-inactivated oocytes. Of the nuclear-activated oocytes, 67% (oocytes cultured for 26 h) and 80% (oocytes cultured for 46 h) of monospermic oocytes and 67% (oocytes cultured for 26 h) and 91% (oocytes cultured for 46 h) of polyspermic oocytes released cortical granules, and no statistical difference was observed between oocytes cultured for 26 h or 46 h, or between monospermic and polyspermic oocytes. The proportion of oocytes with cortical granule exocytosis increased as insemination time increased and was greatest 18 h after insemination in oocytes cultured for 26 h and 46 h; no obvious changes were observed when the insemination time was prolonged to 24 h. These results indicate that pig oocytes develop the ability to release cortical granules after penetration by spermatozoa following germinal vesicle breakdown, and that this ability is not fully developed until metaphase II. Cortical granule exocytosis is accompanied by nuclear activation, suggesting that both nuclear and cytoplasmic maturation are responsible for the cortical reaction. Polyspermy may be a result of a complete failure of cortical granule exocytosis in immature oocytes and delayed CG exocytosis in matured oocytes.

Open retropubic colposuspension for urinary incontinence in women. Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure. To assess the effects of open retropubic colposuspension for the treatment of urinary incontinence. We searched the Cochrane Incontinence Group Specialised Register (searched 13 March 2012), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and CINAHL, and handsearching of journals and conference proceedings, and the reference lists of relevant articles. We contacted investigators to locate extra studies. Randomised or quasi-randomised controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary incontinence that included open retropubic colposuspension surgery in at least one trial group. Studies were evaluated for methodological quality or susceptibility to bias and appropriateness for inclusion and data extracted by two of the review authors. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. This review included 53 trials involving a total of 5244 women.Overall cure rates were 68.9% to 88.0% for open retropubic colposuspension. Two small studies suggested lower incontinence rates after open retropubic colposuspension compared with conservative treatment. Similarly, one trial suggested lower incontinence rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower incontinence rate after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (risk ratio (RR) for incontinence 0.51; 95% CI 0.34 to 0.76 before the first year, RR 0.43; 95% CI 0.32 to 0.57 at one to five years, RR 0.49; 95% CI 0.32 to 0.75 in periods beyond five years).Evidence from 20 trials in comparison with suburethral slings (trans-vaginal tape or transobturator tape) found no significant difference in incontinence rates in all time periods assessed.In comparison with needle suspension, there was a lower incontinence rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42 to 1.03), after the first year (RR 0.48; 95% CI 0.33 to 0.71), and beyond five years (RR 0.32; 95% CI 15 to 0.71).Patient-reported incontinence rates at short, medium and long-term follow-up showed no significant differences between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials incontinence was less common after the Burch (RR 0.38; 95% CI 0.18 to 0.76) than after the Marshall Marchetti Krantz procedure at one to five year follow-up. There were few data at any other follow-up times.In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. Open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85% to 90%. After five years, approximately 70% of patients can expect to be dry. Newer minimal access procedures such as tension-free vaginal tape look promising in comparison with open colposuspension but their long-term performance is not known and closer monitoring of their adverse event profile must be carried out. Laparoscopic colposuspension should allow speedier recovery but its relative safety and long-term effectiveness is not known yet.

Regional, demographic and national influences on attitudes and beliefs with regard to physical activity, body weight and health in a nationally representative sample in the European Union. Although the benefits of physical activity regarding body-weight gain and health in general are now widely accepted, physical activity levels remain low among citizens in the western world. This could be attributed to certain attitudes and beliefs about physical activity. Identifying and understanding these parameters would be the first step in an attempt to increase the levels of physical activity in populations generally characterized as having a sedentary lifestyle. The aim of the present study was to identify the attitudes and beliefs regarding physical activity, body weight and health in a nationally representative sample in the EU and in particular to explore the demographic and national (cultural) influences on attitudes towards physical activity. In each member state of the EU, approximately 1000 adults aged 15 years and over, were selected to complete an interviewer-assisted face-to-face questionnaire. Overall, a sample of 15,239 individuals in the EU participated in the study. Subject selection was quota-controlled to ensure samples in each country were nationally representative. On a European level wide variations were observed regarding the levels, beliefs and attitudes towards physical activity. More positive beliefs were observed among Finns, while less positive beliefs were observed among southern Europeans. A similar pattern was observed for attitudes, with the Portuguese having the highest percentage feeling that they do not need to be more physically active than they already are. However, most southern Europeans felt that a campaign would encourage them to become more active than they already are. On a demographic level, the youngest, more educated and most physically active subjects had more positive attitudes and beliefs towards physical activity and the health benefits derived from it; while for the overweight, beliefs and attitudes toward physical activity were related primarily to the benefits related to weight control. Lower levels of physical activity, an unwillingness to become active among non-participants and confusion regarding the weight gain benefits and general health benefits of exercise were reported more frequently among southern Europeans and older and less educated subjects. The Finns scored highest in all these parameters, possibly due to the programmes implemented and the beliefs and behaviour changes observed in this country during the last few years. The actions taken in Finland and their benefits could be employed appropriately in the other European states.

Delta component variations in human sleep electroencephalogram. All night sleep was recorded polygraphically on 14 healthy adults, once for each person, and EEG was analyzed with bandpass filters. The integrated values during successive 10 second epochs were recorded consecutively at 1 mm intervals, separately for each frequency band. The variations of integrated values for long time span were clearly observed. The findings on 1-2 Hz component are reported exclusively in this report. (1) Four variation patterns were classified on the variations of integrated values of 1-2 Hz band component; long undulation, short undulation, irregular undulation and slight fluctuation. Short undulation was superimposed on long undulation. Long undulation had a gradually increasing slope, a plateau and steeply decreasing slope. Irregular undulation showed generally irregular fluctuations, without any definite variation patterns. During slight fluctuation the variations were small. Long undulation and irregular undulation corresponded to slow-wave sleep and slight fluctuation corresponded to REM sleep. The mean duration of each long undulation and irregular undulation was 31.2 and 11.9 minutes, respectively. In long undulations, 62.8% of the time was occupied by Stage 2 and the lesser ratio by Stages 3 and 4. In irregular undulation 89.1% of the time corresponded to Stage 2. (2) One sleep cycle was composed of the three sleep states which were accompanied with variation patterns, long undulation, irregular undulation and slight fluctuation. The sequence of the appearance of the former two patterns in one sleep cycle was classified into four types. About half of the sleep cycles in all records exhibited Type 1; the pattern started with long undulation, after one or several long undulations followed by irregular undulation and proceeded to slight fluctuation. The average number of long indulation in one sleep cycle was 1.58. (3) On all records, the highest long undulations appeared in the first cycle of all night sleep, in both frontal and central areas. In the occipital area, some of the highest crests appeared in the second cycle. When the highest of long undulations appeared, the height tended to decrease prior to wakening. The crest line of long undulation in frontal and central areas crossed in the latter period of all night sleep, in five controls. The mean voltage of long undulation in frontal, central and occipital areas was 52.4, 42.5 and 23.5 microvolts, respectively. The underlying physiological mechanism of delta waves in human sleep EEG and possible brain structures essential for long undulation and irregular undulation were discussed from both the clinical and experimental aspects.

First Report of Dry and Soft Rot of Cereus marginatus var. cristata Caused by Fusarium oxysporum in Italy. During the winter of 2013, 50% of 20,000 plants of Cereus marginatus var. cristata, Cactaceae family, grown in a commercial farm located in Liguria (northern Italy) showed symptoms of a dry or soft rot. In the case of dry rot, affected plants showed on the stem superficial necrosis and dry rot, irregularly shaped, 1 to 10 mm, while epidermal and cortical tissues were wounded. Affected plants survived but they lost ornamental value. In the case of soft rot, associated with conditions of higher relative humidity, rots on the stem extended as far as 4 cm in width. The internal part of bark, cambium, and xylem tissues as far as about 3 cm in depth was rotted. Vascular tissues were not discolored. Plants died in about 20 days. A Fusarium sp. was consistently isolated from symptomatic tissue on Komada selective medium (2) from plants showing soft rot. The isolates were purified and subcultured on potato dextrose agar (PDA). On PDA, the cultures produced a thick and soft growth of white to light pink mycelium and pale pink pigments in the agar. On Spezieller Nährstoffarmer agar (SNA), cultures produced short monophialides with unicellular, ovoid-elliptical microconidia measuring 3.7 to 8.2 × 1.7 to 3.5 (average 5.4 × 2.5) μm. On carnation leaf-piece agar (CLA), chlamydospores were abundant, terminal or intercalary, single or paired, but frequently also aggregated. On the same medium, at temperatures ranging from 20 to 24°C (14 h daylight, 10 h dark), cultures produced light orange sporodochia with macroconidia. These were 3 to 4 (sometimes 5) septate, nearly straight with a foot-shaped basal cell and a short apical cell, and measured 28.5 to 41.4 × 3.3 to 4.9 (average 35.0 × 4.0) μm. Such characteristics are typical of Fusarium oxysporum Schlechtendahl emend. Snyder & Hansen (3). Amplification of the internal transcribed spacer (ITS) of the rDNA using primers ITS1/ITS4 yielded a 504-bp amplicon (GenBank Accession No. KJ909935). Sequencing and BLASTn analysis of this amplicon showed a 100% homology with the sequence of F. oxysporum KC304802. To confirm pathogenicity, two Fusarium isolates were tested. For each isolate, three 2-year-old healthy plants of C. marginatus were inoculated by introducing into lesions (4 lesions/plant) artificially produced on the stem sterile needles contaminated with the pathogen (4). Inoculum was obtained from pure cultures grown on PDA. Control plants were punctured with sterile needles without inoculum. All the plants were placed in a greenhouse, at temperatures ranging between 16 and 24°C. For both tested strains, the first necrosis of stem tissues developed around the needles 7 days after the artificial inoculation, while non-inoculated plants remained healthy. Then, necrosis extended causing soft rot on plants maintained at relative humidity ranging from 55 to 65%. F. oxysporum identified by morphological characteristics was consistently isolated from symptomatic plants. The pathogenicity test was conducted twice. F. oxysporum has been reported on Cereus sp. in the United States and on C. peruvianus monstruosus in Italy (1). Currently, this disease is present in a few commercial nurseries in Liguria, although it could spread further and cause important economic losses. References: (1) A. Garibaldi et al. Plant Dis. 95:877, 2011. (2) H. Komada. Rev. Plant Prot. Res. 8:114, 1975. (3) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell, Ames, IA, 2006. (4) V. Talgø and A. Stensvand. OEPP/EPPO Bulletin 43:276, 2013.

Early surgical results with intent to treat by radical retropubic prostatectomy for clinically localized prostate cancer. To evaluate the early cancer control rates, morbidity and mortality in men undergoing radical retropubic prostatectomy (RRP) for clinically localized adenocarcinoma prostate. Patient's characteristics, operative data, progressive-free survival rates, morbidity and mortality were analyzed for 23 men with clinical T1-2 prostate cancer who underwent surgery with an intent to treat by RRP between December 1997 to July 2001. Patient's mean age was 63 +/- 6.2 years (range 51 to 76 years) with American Society of Anesthesiology (ASA) status I in 4%, II in 65% and III in 31%. Two third of the patients had lower urinary tract obstructive symptoms, followed by hematuria (9%) and back pain (4%). Clinical stages were T1b in 4%, T1c in 9%, T2a in 17%, T2b in 22% and T2c in 48% of the patients. Mean pre-operative serum prostate specific antigen (PSA) was 25 +/- 29 ng/ml (1.1 to 99.3). Bilateral pelvic lymphnode disection(PLND) and RRP was performed in 20 cases (nerve-sparing RRP 5 cases). In 3 cases with gross lymph node metastasis at frozen section, only bilateral orchidectomy was done. The mean operative time was 270 +/- 65 minutes and mean blood loss was 1097 +/- 654 mls. Packed cell transfusions were nil in 26%, 1-2 units in 44%, 3-4 units in 26% and 5 units in 4% of the patients who underwent RRP. The mean length of hospital stay was 10.2 +/- 1 days. Out of 20 patients who underwent RRP, 65% of tumors were confined to the specimen, 20% had seminal vesicle invasion and 15% had nodal metastasis. There was no peri-operative mortality while 2 patients developed epididymo-orchitis and 1 had myocardial ischemia (without infarction). Overall 87% of the patients were fully continent and 13% had mild to moderate stress urinary incontinence. The mean time of return of continence was 11.5 +/- 11.6 weeks. Two of the 3 patients (66%) with follow up information and having undergone nerve-sparing RRP are potent. At a mean follow up of 19.4 +/- 13 months (range 3-45 months), 20 of 23 total patients (87%) and 17 of 20 RRP patients (85%) remained free of disease recurrence with PSA < or = 0.4 ng/ml. Our early results confirm the excellent potential for cancer control and low morbidity of radical prostatectomy for men with localized prostate cancer. These results are in conformity with the vast Western experience. Long-term results will be provided.

Extended in vitro culture of human embryos demonstrates the complex nature of diagnosing chromosomal mosaicism from a single trophectoderm biopsy. What is the accuracy of preimplantation genetic testing for aneuploidies (PGT-A) when considering human peri-implantation outcomes in vitro? The probability of accurately diagnosing an embryo as abnormal was 100%, while the proportion of euploid embryos classified as clinically suitable was 61.9%, yet if structural and mosaic abnormalities were not considered accuracy increased to 100%, with a 0% false positive and false negative rate. Embryo aneuploidy is associated with implantation failure and early pregnancy loss. However, a proportion of blastocysts are mosaic, containing chromosomally distinct cell populations. Diagnosing chromosomal mosaicism remains a significant challenge for PGT-A. Although mosaic embryos may lead to healthy live births, they are also associated with poorer clinical outcomes. Moreover, the direct effects of mosaicism on early pregnancy remain unknown. Recently, developed in vitro systems allow extended embryo culture for up to 14 days providing a unique opportunity for modelling chromosomal instability during human peri-implantation development. A total of 80 embryos were cultured to either 8 (n = 7) or 12 days post-fertilisation (dpf; n = 73). Of these, 54 were PGT-A blastocysts, donated to research following an abnormal (n = 37) or mosaic (n = 17) diagnosis. The remaining 26 were supernumerary blastocysts, obtained from standard assisted reproductive technology (ART) cycles. These embryos underwent trophectoderm (TE) biopsy prior to extended culture. We applied established culture protocols to generate embryo outgrowths. Outgrowth viability was assessed based on careful morphological evaluation. Nine outgrowths were further separated into two or more portions corresponding to inner cell mass (ICM) and TE-derived lineages. A total of 45 embryos were selected for next generation sequencing (NGS) at 8 or 12 dpf. We correlated TE biopsy profiles to both culture outcomes and the chromosomal status of the embryos during later development. Of the 73 embryos cultured to 12 dpf, 51% remained viable, while 49% detached between 8 and 12 dpf. Viable, Day 12 outgrowths were predominately generated from euploid blastocysts and those diagnosed with trisomies, duplications or mosaic aberrations. Conversely, monosomies, deletions and more complex chromosomal constitutions significantly impaired in vitro development to 12 dpf (10% vs. 77%, P < 0.0001). When compared to the original biopsy, we determined 100% concordance for uniform numerical aneuploidies, both in whole outgrowths and in the ICM and TE-derived outgrowth portions. However, uniform structural variants were not always confirmed later in development. Moreover, a high proportion of embryos originally diagnosed as mosaic remained viable at 12 dpf (58%). Of these, 71% were euploid, with normal profiles observed in both ICM and TE-derived lineages. Based on our validation data, we determine a 0% false negative and 18.5% false positive error rate when diagnosing mosaicism. Overall, our findings demonstrate a diagnostic accuracy of 80% in the context of PGT-A. Nevertheless, if structural and mosaic abnormalities are not considered, accuracy increases to 100%, with a 0% false positive and false negative rate. The inherent limitations of extended in vitro culture, particularly when modelling critical developmental milestones, warrant careful interpretation. Our findings echo current prenatal testing data and support the high clinical predictive value of PGT-A for diagnosing uniform numerical aneuploidies, as well as euploid chromosomal constitutions. However, distinguishing technical bias from biological variability will remain a challenge, inherently limiting the accuracy of a single TE biopsy for diagnosing mosaicism. This research is funded by the Ghent University Special Research Fund (BOF01D08114) awarded to M.P., the Research Foundation-Flanders (FWO.KAN.0005.01) research grant awarded to B.H. and De Snoo-van't Hoogerhuijs Stichting awarded to S.M.C.d.S.L. We thank Ferring Pharmaceuticals (Aalst, Belgium) for their unrestricted educational grant. The authors declare no competing interests. N/A.

Complex diversity in a mainly tropical group of ant parasitoids: Revision of the Orasema stramineipes species group (Hymenoptera: Chalcidoidea: Eucharitidae). Twenty-nine species are recognized in the Orasema stramineipes species group, including 22 new species in what is now the most diverse species group of the New World ant-parasitoid genus Orasema Cameron. Orasema aenea Gahan syn. n. is synonymized with O. freychei (Gemignani), the holotype of which has been rediscovered. Orasema smithi Howard syn. n. is synonymized with Orasema minutissima Howard. Orasema violacea Gemignani syn. n. and its replacement name Orasema gemignanii De Santis syn. n. are synonymized with O. worcesteri (Girault). Twenty-two species are described as new: O. arimbome Dominguez, Heraty Burks n. sp., O. carchi Heraty, Burks Dominguez n. sp., and the following 20 species by Burks, Heraty Dominguez: O. chunpi n. sp., O. cozamalotl n. sp., O. evansi n. sp., O. hyarimai n. sp., O. kaspi n. sp., O. kulli n. sp., O. llanthu n. sp., O. llika n. sp., O. mati n. sp., O. nyamo n. sp., O. pirca n. sp., O. pisi n. sp., O. qillu n. sp., O. qincha n. sp., O. rikra n. sp., O. taku n. sp., O. tapi n. sp., O. torrensi n. sp., O. woolleyi n. sp., and O. yaax n. sp. The stramineipes-group has much greater diversity in tropical America than outside the tropics, and is much more diverse than its sister-group, the susanae-group, which is mainly present in temperate regions of Argentina. A hypothesis of phylogenetic relationships is proposed based on an analysis of 28S-D2 rDNA and cytochrome oxidase I (COI) for 14 stramineipes-group species. Species concepts were established using both morphological and molecular data. Most species in the stramineipes-group have a tropical distribution, with only a few species in temperate regions. Ant hosts for the group include Pheidole Westwood, Wasmannia Forel, and possibly Solenopsis Westwood (Formicidae: Myrmicinae). Orasema minutissima is a common parasitoid of Wasmannia auropunctata Roger in the Caribbean and has the potential to be a biological control agent in other areas of the world. Two distinct size morphs are recognized for O. minutissima, which are correlated with attacking either Wasmannia (small morph) or different castes of Pheidole (medium to large size morphs). Some species of Orasema have been regarded as pests due to scarring or secondary infections of leaves or fruit of banana, yerba mate or blueberry, but outbreaks are rare and the threat is usually temporary.

Fracture resistance of cingulum rest seats in CAD-CAM tooth-colored crowns for removable partial denture abutments. The prevalent use of computer-aided design and computer-aided manufacturing (CAD-CAM) for tooth-colored ceramic materials has led to several case reports and retrospective clinical studies of surveyed crowns used to support removable partial dentures. How the specific contour of a cingulum rest seat affects the fracture resistance of these CAD-CAM tooth-colored materials is unknown. The purpose of this in vitro study was to compare the fracture resistance of monolithic CAD-CAM tooth-colored mandibular canine-surveyed ceramic crowns with cingulum rest seats of different designs. Five groups (n=24/group) of CAD-CAM tooth-colored crowns were milled from the same standard tessellation language (STL) file: group EM, lithium disilicate-based material (IPS e.max CAD CEREC blocks); group SM, zirconia-based material (NexxZr T); group LP, zirconia-based material (Lava Plus High Translucency); group ZC, zirconia-based material (ZirCAD LT); and group MZ, composite resin (MZ100 CEREC blocks), used as a control. Crowns from each group were divided into 2 subgroups representing 2 shapes of cingulum rest seat design: round design subgroup (n=12) with 0.5-mm radius of curvature and sharp design subgroup (n=12) with 0.25-mm radius of curvature for the rest seat preparation. The crowns were cemented with resin cement to a composite resin die on a steel nut. After 24 hours of storage in water at 37°C, the specimens were statically loaded to fracture with a custom metal retainer on top of the cingulum rest seat by using a universal testing machine at a crosshead speed of 1.5 mm/min. Two-way ANOVA and the Tukey honestly significant difference tests were used to control the familywise error rate (α=.05). Representative specimens were examined using an optical stereomicroscope at ×10 magnification and a scanning electron microscope to determine the failure patterns and fracture mechanism. The results of the ANOVA test indicated statistically significant differences by materials and rest seat designs (P<.001). The mean ±standard deviation maximal load capacity was 773.5 ±255.0 N for group MZ, 1124.9 ±283.9 N for group EM, 2784.1 ±400.5 N for group SM, 2526.9 ±547.1 N for group LP, and 3200.8 ±416.8 N for group ZC. The round design subgroups had an approximately 30% higher mean failure load than the sharp design subgroups for all surveyed crowns. The present in vitro study demonstrated that zirconia-based groups fractured at twice the load as the lithium disilicate group. Of the 3 zirconia-based groups, group ZirCAD had a statistically greater fracture resistance than the other groups. Designing the cingulum rest seat to have a broad round shape provides a statistically significant higher fracture resistance than a sharp-shape design (P<.05).

Median arcuate ligament syndrome: vascular surgical therapy and follow-up of 18 patients. The median arcuate ligament syndrome (MALS) or celiac artery compression syndrome is a rare vascular disorder caused by an extrinsic compression of the celiac artery from the median arcuate ligament, prominent fibrous bands, and ganglionic periaortic tissue. Clinical symptoms are postprandial abdominal pain, nausea, vomiting, unintentional weight loss, and sometimes, abdominal pain during body exercise caused by an intermittent visceral ischemia. The aim of this study was to evaluate the operative management of patients with MALS in our institution, especially in consideration of various vascular reconstructive techniques. Between June 2000 and January 2009, a total of 341 patients were treated in our department for vascular pathologies of the visceral arteries (225 chronic visceral ischaemia, 84 acute visceral ischaemia, and 14 visceral artery aneurysms). In a retrospective study of 18 patients with MALS, the records, clinical symptoms, diagnostic evaluation, and surgical procedures were compiled. This was completed by a reassessment for a follow-up. A MALS was diagnosed in 15 female (83.3%) and three male (16.7%) patients. The mean patient age was 46.2 years (range 20-68 years). The diagnosis of MALS was based on a radiological analysis in all patients by a digitally subtracted angiogram, but duplex ultrasound was used lately more frequently to study the influence of respiration on the stenotic degree of the celiac trunk. All 18 patients were treated with open surgery in an elective situation. Due to the local and specific pathology of the celiac trunk with a fixed stricture or stenosis, out of 18 cases beside decompression, 11 (primary, seven; secondary, four patients) further procedures were performed on the celiac artery (aorto-celiac vein interposition n = 6, aorto-hepatic vein interposition n = 1, resection of the celiac artery and end-to-end anastomosis n = 2, patchplasty of the celiac artery with vein n = 1, and transaortic removal of a stent of the celiac artery n = 1) Follow-up was obtained in 15 patients (83.33%) with a mean duration after surgery of about three and a half years (40.68 months, range from 2 to 102 months). Eleven of the 15 patients (73.33%) were completely free of abdominal symptoms, and nine of them had gained between 3 and 10 kg in weight after surgery. The weight of two patients remained stable. Of the 11 patients with a successful outcome in the follow-up, six of them had undergone decompression solely. In the other five patients, vascular co-procedures on the celiac trunk had been performed. The MALS is a rare vascular disorder caused by an extrinsic compression of the celiac artery and induces upper abdominal, mostly, postprandial pain. A definite diagnosis of MALS can be achieved by lateral aortography of the visceral aorta and its branches during inspiration and expiration. Open surgical therapy is a safe and reliable procedure with no mortality and low morbidity. As to the local and specific pathology of the celiac trunk after decompression with fixed stricture or stenosis, further vascular procedures are necessary. The long-time follow-up seemed adequate. The laparoscopic approach reduces the procedure of decompression only, something which seemed inadequate for most cases. Endovascular treatment with percutaneous transluminal angioplasty and insertion of a stent does not solve the underlying problem of extrinsic compression of the celiac trunk and often requires open procedures during the long-term course. Due to the low incidence of MALS, no guidelines will do justice to all the patients sufficiently, and the choice of treatment must depend on the specific clinical situation for each patient.

Adverse sedation events in pediatrics: a critical incident analysis of contributing factors. Factors that contribute to adverse sedation events in children undergoing procedures were examined using the technique of critical incident analysis. We developed a database that consists of descriptions of adverse sedation events derived from the Food and Drug Administration's adverse drug event reporting system, from the US Pharmacopeia, and from a survey of pediatric specialists. One hundred eighteen reports were reviewed for factors that may have contributed to the adverse sedation event. The outcome, ranging in severity from death to no harm, was noted. Individual reports were first examined separately by 4 physicians trained in pediatric anesthesiology, pediatric critical care medicine, or pediatric emergency medicine. Only reports for which all 4 reviewers agreed on the contributing factors and outcome were included in the final analysis. Of the 95 incidents with consensus agreement on the contributing factors, 51 resulted in death, 9 in permanent neurologic injury, 21 in prolonged hospitalization without injury, and in 14 there was no harm. Patients receiving sedation in nonhospital-based settings compared with hospital-based settings were older and healthier. The venue of sedation was not associated with the incidence of presenting respiratory events (eg, desaturation, apnea, laryngospasm, approximately 80% in each venue) but more cardiac arrests occurred as the second (53.6% vs 14%) and third events (25% vs 7%) in nonhospital-based facilities. Inadequate resuscitation was rated as being a determinant of adverse outcome more frequently in nonhospital-based events (57.1% vs 2.3%). Death and permanent neurologic injury occurred more frequently in nonhospital-based facilities (92.8% vs 37.2%). Successful outcome (prolonged hospitalization without injury or no harm) was associated with the use of pulse oximetry compared with a lack of any documented monitoring that was associated with unsuccessful outcome (death or permanent neurologic injury). In addition, pulse oximetry monitoring of patients sedated in hospitals was uniformly associated with successful outcomes whereas in the nonhospital-based venue, 4 out of 5 suffered adverse outcomes. Adverse outcomes despite the benefit of an early warning regarding oxygenation likely reflect lack of skill in assessment and in the use of appropriate interventions, ie, a failure to rescue the patient. This study-a critical incident analysis-identifies several features associated with adverse sedation events and poor outcome. There were differences in outcomes for venue: adverse outcomes (permanent neurologic injury or death) occurred more frequently in a nonhospital-based facility, whereas successful outcomes (prolonged hospitalization or no harm) occurred more frequently in a hospital-based setting. Inadequate resuscitation was more often associated with a nonhospital-based setting. Inadequate and inconsistent physiologic monitoring (particularly failure to use or respond appropriately to pulse oximetry) was another major factor contributing to poor outcome in all venues. Other issues rated by the reviewers were: inadequate presedation medical evaluation, lack of an independent observer, medication errors, and inadequate recovery procedures. Uniform, specialty-independent guidelines for monitoring children during and after sedation are essential. Age and size-appropriate equipment and medications for resuscitation should be immediately available regardless of the location where the child is sedated. All health care providers who sedate children, regardless of practice venue, should have advanced airway assessment and management training and be skilled in the resuscitation of infants and children so that they can successfully rescue their patient should an adverse sedation event occur.

[Smartphone addiction: French validation of the Internet Addiction Test-Smartphone version (IAT-smartphone) and associated psychopathological features]. Since their first appearance in 1992 smartphones have improved constantly, and their use, combined with the rapid spread of the Internet, has increased dramatically. The recent emergence of this technology raises new issues, at both individual and societal levels. Several studies have investigated the physical and psychological harm that may be caused by smartphones. The issue of excessive smartphone use as an addictive disorder is frequently raised and debated, although it is not acknowledged in international classifications. In France, there is no validated assessment tool for smartphone addiction. Therefore, the aims of this research were: to validate a French translation of the Internet Addiction Test-smartphone version (IAT-smartphone); to study the links between smartphone addiction, Internet addiction, depression, anxiety and impulsivity. Two hundred and sixteen participants from the general population were included in the study (January to February 2016), which was available online using Sphinx software. We assessed smartphone addiction (French version of the Internet Addiction Scale - smartphone version, IAT-smartphone), specificity of smartphone use (time spent, types of activity), Internet addiction (Internet Addiction Test, IAT), impulsivity (UPPS Impulsiveness Behavior Scale), and anxiety and depression (Hospital Anxiety and Depression scale, HAD). We tested the construct validity of the IAT-smartphone (exploratory factor analysis, internal consistency, non-parametric correlation tests for convergent validity). We also carried out multiple linear regressions to determine the factors associated with IAT-smartphone. Mean age was 32.4±12.2 years; 75.5% of the participants were women. The IAT-smartphone had a one-factor structure (explaining 42 % of the variance), excellent internal consistency (α=0.93) and satisfactory convergent validity. Smartphone addiction was associated with Internet addiction (ρ=0.85), depression (ρ=0.31), anxiety (ρ=0.14), and some impulsivity subscales, including "negative urgency" (ρ=0.20; P<0.01), "positive urgency" (ρ=0.20; P<0.01), and "lack of perseverance" (ρ=0.16; P<0.05). Age was negatively associated with the IAT-S total score (ρ=-0.25; P<0.001), and there was a non-significant difference between the IAT-S total scores of men and women (29.3±10.2 vs. 32.7±12.4; P=0.06). Multiple linear regression showed that age, anxiety, depression, average time spent on the smartphone, impulsivity and Internet addiction explained 71.4 % of the variance of IAT-smartphone scores. However, this score dropped to 13.2 % when Internet addiction was removed from the model. This variable alone explained 70.8 % of the IAT-smartphone scores. The French version of the IAT-smartphone is a reliable and valid questionnaire to assess smartphone addiction. This addiction appears to be strongly linked to anxiety, depression and impulsivity. The strong association between smartphone addiction and Internet addiction suggests that smartphone addiction is one of the many forms of Internet addiction. In fact, smartphones may not be the object of the addiction but rather a medium facilitating Internet access as it makes it possible to connect anywhere anytime. This raises the issue of the potential role of smartphones in speeding up and facilitating the development of Internet addiction.

Risk of Venous Thromboembolism After Laparoscopic Surgery for Gynecologic Malignancy. To determine the incidence of venous thromboembolism (VTE) after laparoscopic surgery for gynecologic cancer. Retrospective analysis of the ACS-NSQIP database (Canadian Task Force Classification II.1). Academic and community healthcare institutions across the United States. Women who underwent at least 1 major laparoscopic surgery for uterine, ovarian, and cervical cancers. Data were collected on surgical procedures, patient demographic variables, type of malignancy and VTE, and mortality outcomes within 30 days of surgery. VTE was defined as deep venous thrombosis requiring therapy and pulmonary embolism confirmed by imaging or autopsy within 30 days of surgery. Of the 2219 patients included in the final analysis, 15 patients (.7%) were diagnosed with VTE within 30 days after surgery. Six patients (.3%) were diagnosed before discharge, and 9 patients (.4%) were diagnosed after discharge. The median time from surgery to diagnosis was 6 days (range, 0-28 days). Although most patients included in the study had uterine cancer (86%, n = 1913), no difference was noted based on the site of cancer (.5% for cervical cancer, .7% for endometrial cancer, and .8% for ovarian cancer; p = .95). There was no difference in rate of VTE when stratified by age (p = .10), body mass index (p = .68), diabetes (p = .22), smoking (p = .60), respiratory morbidities (p = .55), cardiac disease (p = .22), hypertension (p = .13), preoperative blood transfusion (p = .90), or American Society of Anesthesiologists class (p = .10). There was a trend toward higher risk of VTE among patients with disseminated cancer compared with those with early cancers (3.6% vs .6%, p = .05). No difference was found in the risk of VTE based on operative time (.7% for <2 hours, .6% for 2-3 hours, and .7% for >3 hours; p = .96). No difference was noted in the risk of VTE among those who underwent lymphadenectomy compared with those who did not (.9% vs .5%, p = .35). In multivariable logistic regression analysis adjusting age (p = .12), body mass index (p = .90), operative time (p = .71), and lymphadenectomy (p = .30), none of these variables was significantly associated with risk of VTE. In multivariable analysis adjusting for other confounders, VTE within 30 days was a significant predictor of higher 30-day mortality (OR, 26.0; 95% CI, 2.2-306.9; p = .01). The rate of VTE is low after major laparoscopic surgery for gynecologic cancers but is associated with increased 30-day mortality. Universal or extended thromboprophylaxis does not appear to be indicated for all patients. Further studies are needed to identify patients at high risk for postoperative VTE who may benefit from pharmacologic prophylaxis.