Survey on legislation regarding wet cooling systems in European countries.
Wet cooling systems are often associated with large outbreaks of Legionnaires' disease. Several European countries have legislation for registering such systems. The authors aimed to obtain an overview of the situation in Europe. A questionnaire survey was sent to 35 of the countries that collaborate in the European Working Group for Legionella Infections. In two countries it was passed to a regional level (to three regions in both Belgium and the United Kingdom), so that 39 countries or regions were sent the survey; 37 responded. Nine countries stated having legislation for the registration of wet cooling systems. Separate legislation exists at a regional level for two regions in Belgium and all three regions in the UK, giving a total of twelve countries/regions with legislation. In nine of these countries/regions, the legislation has been introduced since 2001. All of these countries/regions require periodic microbiological monitoring between twice a year and weekly; in nine, the legislation requires periodic inspection of the systems. Regulations for the registration of wet cooling systems should be required by public health authorities. During an outbreak of legionellosis, a register of wet cooling systems can speed up the investigation process considerably. The authors believe that the European Centre for Disease Prevention and Control (ECDC) should take the initiative to propose European Community (EC) regulations for all Member States.


Herpes zoster (shingles) and postherpetic neuralgia.
Herpes zoster (HZ), commonly called shingles, is a distinctive syndrome caused by reactivation of varicella zoster virus (VZV). This reactivation occurs when immunity to VZV declines because of aging or immunosuppression. Herpes zoster can occur at any age but most commonly affects the elderly population. Postherpetic neuralgia (PHN), defined as pain persisting more than 3 months after the rash has healed, is a debilitating and difficult to manage consequence of HZ. The diagnosis of HZ is usually made clinically on the basis of the characteristic appearance of the rash. Early recognition and treatment can reduce acute symptoms and may also reduce PHN. A live, attenuated vaccine aimed at boosting immunity to VZV and reducing the risk of HZ is now available and is recommended for adults older than 60 years. The vaccine has been shown to reduce significantly the incidence of both HZ and PHN. The vaccine is well tolerated, with minor local injection site reactions being the most common adverse event. This review focuses on the clinical manifestations and treatment of HZ and PHN, as well as the appropriate use of the HZ vaccine.


Evaluation of the gastrointestinal tract in dogs using computed tomography.
Abdominal computed tomography (CT) studies of 19 dogs with no history or clinical signs of gastrointestinal disease, and two dogs with a histological diagnosis of gastrointestinal neoplasia were examined retrospectively. Gastrointestinal segments were evaluated subjectively for conspicuity, contrast enhancement, and wall layering after contrast medium administration. In dogs without gastrointestinal disease, there were 62.8% of gastrointestinal segments (serosa to serosa) and 77.7% of gastrointestinal walls (serosa to mucosa) visualized. Wall layering on postcontrast images was seen in 21.8% of gastrointestinal segments. There was significant association between gastrointestinal diameter and wall thickness. There was significant association between weight and gastrointestinal wall thickness in the following regions: gastric fundus, gastric body, gastric pylorus, gastric pyloric antrum, duodenal cranial flexure, jejunum and ascending colon, and between patient weight and gastrointestinal diameter in cranial duodenal flexure, descending duodenum, transverse duodenum, ascending duodenum, and jejunum. Measurements acquired from CT studies correlated well with previously published normal reference ranges for radiographic and ultrasonographic studies. Gastrointestinal neoplasia, diagnosed in two dogs, had a gastrointestinal wall thickness greater than the range of the dogs without gastrointestinal disease. Computed tomography offers identification of the gastrointestinal tract segments in dogs, allows for evaluation of gastrointestinal diameter and aids in investigation of gastrointestinal wall thickness.


SU-E-T-536: Is BJR Supplement #25 Recommendation for Megavoltage Energy Independent Scatter Factor Still Valid for Flattening Filter Free Photon Beams?
In the process of measuring and validating fundamental dosimetry data prior to the clinical use of a treatment unit, it is prudent to compare measurements with previously published equivalent data. During the commissioning of an accelerator with flattening filter free (FFF) photon beams (Varian True Beam 6 MV FFF and 10 MV FFF) we compared measured Phantom Scatter Factors (Sp) with the Normalized Peak Scatter Factors (NPSFs) from the British Journal of Radiology Supplement 25 (BJR #25). The purpose of this work was to determine whether the energy independent NPSFs BJR#25 are valid for comparison with FFF photon beams. All measurements were performed using a Varian TrueBeam linear accelerator with photon energies of 6-MV, 6-MV FFF and 10-MV FFF modes. For all measurements, a Scanditronix CC04 ionization chamber was used. Both water and in-air measurements were made to obtain NPSFs normalized to the 10 × 10 cm2 field size. For measurements in water, the chamber was positioned at 100 cm source-to-axis distance at the depth of dose maximum. For in-air measurements, the chamber was positioned at 100 cm source-to-axis distance with appropriate build-up cap. From BJR #25, NPSFs were obtained for comparison with the measurements. The NPSF agreement between the 6-MV and 6-MV FFF with the BJR#25 were all within ±0.5%. The agreement ranged from 0.996 to 1.004 and 0.995 to 1.002 for 6-MV and 6-MV FFF, respectively. We also found that 10-MV FFF showed very similar trend. The scatter factors reported in BJR #25 are valid for comparison for 6-MV, 6-MV FFF, and 10-MV. Additional investigation is needed to further understand the dosimetric characteristics of FFF mode.


Guar and its effects on metabolic control in type II diabetic subjects.
The effect of guar mini-tablets (5 g t.i.d.) on carbohydrate and lipid metabolism of outpatients with overt diabetes mellitus with glycosuria (is greater than 5 g/24 h) was determined in an open-controlled, randomized, multicenter, crossover study. A 4-wk pretreatment period was followed by a 6-wk treatment period. The treatment period consisted of a 2-wk guar period (treatment period II), which was followed by the wash-out period. The other half of the patients received treatment in the reverse order. Out of 93 patient records, 79 (41 sulfonylurea [SU] and 38 insulin-treated) were suitable for statistical analysis. No relevant weight-reducing effect of guar could be found in both 2-wk treatment periods. At the end of treatment period II, the lowering of the 1-h postprandial values of blood glucose (SU 12%, insulin 10%), cholesterol (SU and insulin 25%) was significant after 2-wk of guar treatment compared with the wash-out period. No clinically relevant changes in the safety laboratory parameters were observed during guar treatment. Side effects were observed in 40 of the 93 patients included in the trial. Treatment had to be discontinued in 11% of the patients due to gastrointestinal side effects. On the basis of our results,guar treatment in combination with sulfonylurea and insulin can be recommended for the improvement of carbohydrate and lipid metabolism.


Characteristics and Outcomes of Liver Transplantation for Primary Biliary Cholangitis in Young Patients: Analysis of the United Network for Organ Sharing Database.
Primary biliary cholangitis (PBC) in younger patients has been suggested to require liver transplantation (LT) in early adulthood, but data is limited on its outcomes. We aimed to evaluate the characteristics and outcome of LT in young patients with PBC in comparison with older adults. The United Network for Organ Sharing database was analyzed for all patients with PBC who underwent LT between 2000 and 2012. Based on age at the time of LT, subjects were divided into 2 groups: young patients (≤40 y) and older adults (≥41 y). Baseline demographics, clinical parameters, and outcomes of LT were then compared between the 2 groups. Univariable and multivariable analyses were performed to assess the factors associated with outcomes of LT. A total of 2084 patients with PBC were included in the analysis with 158 young patients. Compared with older adults, younger patients were more likely to be male (27.2% versus 15.4%) and nonwhite (43.7% versus 21.5%), but they were less likely to have obesity, diabetes, or hypertension (P < 0.05) and had a lower mortality (8.2% versus 15.1%) but higher retransplantation rate (14.6% versus 4.7%) (P < 0.001). On multivariable analysis, older age, dialysis or ventilator use, and lower albumin were associated with high post-LT mortality. Compared with older adults, early-onset PBC in younger patients requiring LT had higher percentage of males and nonwhites and had a lower prevalence of metabolic comorbidities but higher retransplantation rates. Further studies are warranted to confirm these findings.


Job Demands as Risk Factors of Exposure to Bullying at Work: The Moderating Role of Team-Level Conflict Management Climate.
Conflict management climate is an important organizational resource that is theorized to prevent interpersonal frustration from escalating into harsh interpersonal conflicts and even workplace bullying. The present study investigates whether team-level perceptions of conflict management climate moderate the relationship between previously investigated psychosocial predictors of workplace bullying (i.e., role conflicts, workload, cognitive demands) and perceived exposure to bullying behaviors in the workplace. We collected data from crews on ferries operating on the Norwegian coastline consisting of 462 employees across 147 teams. As hypothesized, multilevel analyses showed positive main effects of role conflict and cognitive demands (but not workload) on exposure to bullying behaviors. Also, the hypothesized moderation effect of team-level conflict management climate on the relationship between individual-level job demands and exposure to bullying behaviors was significant for role conflict and cognitive demands, but not for workload. Specifically, the positive relationships between the two job demands and exposure to bullying behaviors were stronger for employees working in teams with a weak (vs. a strong) conflict management climate. These findings contribute to the bullying research field by showing that conflict management climate may buffer the impact of stressors on bullying behaviors, most likely by preventing interpersonal frustration from escalating into bullying situations.


Long term efficacy of extracorporeal shock wave therapy [ESWT] for treatment of refractory chronic abacterial prostatitis.
To evaluate the effect and safety of extracorporeal shockwave therapy (ESWT) on chronic pelvic pain syndrome (CPPS)/chronic abacterial prostatitis after failure of most other modalities of treatment, the maintenance of the treatment effect for up to one year post treatment and whether the patients are in need for further sessions. In a follow-up survey of 41 patients, the study inclusion criteria were CPPS patients who failed at least previously 3 modalities of treatment other than ESWT, who were treated by ESWT once a week for one month with a protocol of 2500 pulses at 1 bar over 13 min, Nonaddiction to drugs and narcotics. The exclusion criteria included being under treatment by another method another diagnosis such as prostate cancer, therapy plan alteration, and noninclination to continue this treatment. Then the patients were followed up at 2 weeks, 6 months and 12 months after finishing the course of ESWT. The study was designed as an open-label uncontrolled therapeutic clinical trial which was conducted in Jordan university hospital through the period 2015-2016. Data were compared using paired samples t-test. Of our total 55 patients 8 of them did not complete the study protocol, 6 of them had missed follow up over the whole follow up period and 41 patients were evaluated. The patient's age group ranged between 18 and 78 years with a mean age of 42 and a median age of 43. The mean of National Institutes of Health -Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Score (IPSS), American Urological Association Quality of Life Due to Urinary Symptoms (AUA QOL_US) and International Index of Erectile Function (IIEF) were evaluated pre and post ESWT at 2 weeks, 6 months and 12 months and it showed statistically significant improvement in all parameters with maintenance of the effect without any significant side-effect of the treatment over the 12 months. The evidence in this study would support the safety and efficacy of ESWT in refractory cases of CPPS at least for one year post treatment.


Overexpressing TNF-alpha in pancreatic ductal adenocarcinoma cells and fibroblasts modifies cell survival and reduces fatty acid synthesis via downregulation of sterol regulatory element binding protein-1 and activation of acetyl CoA carboxylase.
The effect of tumor necrosis factor-alpha (TNF-α) gene delivery has been suggested as a potentially useful therapeutic approach to improve the chemotherapeutic treatment of patients with pancreatic ductal adenocarcinoma (PDA), but the exact mechanism of its action is not clearly understood. In this study, we analyzed the expression profile of TNF-α in PDA tissue and explored its potential role in fatty acid synthase (FAS) regulation in PDA cells and in fibroblasts. Quantitative real-time polymerase chain reaction was used to examine the expression of TNF-α in PDA, matching adjacent tissues, and benign lesions. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan-Meier survival curves were generated. In vitro, we overexpressed the TNF-α gene in PDA cells and fibroblasts and analyzed its effect on cell survival, migration, and on members of the FAS signaling pathway. We also evaluated TNF-α effects on a panel of inflammation-, angiogenesis-, and metastasis-related markers. In the tumor tissue of PDA patients, compared with their matched adjacent tissue, expression levels of TNF-α were not statistically different and did not correlate with survival or any other examined clinicopathological features. Overexpression of TNF-α significantly (p < 0.05) reduced PDA and fibroblast cell migration. In PDA cells that highly overexpress TNF-α, this was associated with a significant reduction of FAS mRNA and protein expression levels and significant (p < 0.05) reduction of SREBP-1 and ACC mRNA. Reduction of FAS by TNF-α was inhibited when either SREBP-1 or ACC was knocked down by siRNA. PDA cells and fibroblasts that overexpress TNF-α displayed differential regulation of several inflammation-related markers and reduced levels of metastasis-related genes. Our data demonstrate a previously unknown multi-targeted involvement of TNF-α in PDA lipogenesis and inflammation and metastasis and suggest that intratumoral introduction of TNF-α may have the potential as a novel therapeutic approach in human PDA.


Efficacy of topical 5-aminosalicylates in preventing relapse of quiescent ulcerative colitis: a meta-analysis.
Topical 5-aminosalicylates (5-ASAs) such as mesalamine are effective in inducing remission in patients with mild to moderately active ulcerative colitis (UC). However, there has been no meta-analysis of their efficacy in preventing relapse of quiescent UC. We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials through July 2011 for randomized controlled trials comparing the effects of topical 5-ASAs with placebo in adults with quiescent UC. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity. The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Adverse events data were summarized. The search identified 3061 citations; we analyzed data from seven (555 patients). All trials used mesalamine, but only one included patients with extensive disease. The duration of therapy ranged from 6-24 months. The RR of relapse of disease activity in patients with quiescent UC who were given topical mesalamine, compared with placebo, was 0.60 (95% confidence interval, 0.49-0.73; NNT = 3); there was no significant heterogeneity between studies (I(2) = 21%, P = .27). No significant differences in rates of adverse events rates were detected (RR = 1.01; 95% confidence interval, 0.59-1.72). On the basis of a meta-analysis of 7 randomized controlled trials, topical mesalamine is effective in preventing relapse of quiescent UC, with no greater number of adverse events than placebo. However, because most studies included only patients with left-sided disease or proctitis, the efficacy of topical mesalamine in preventing relapse in patients with more extensive quiescent UC is not known.


6,6'-Dihydroxy terpyridine: a proton-responsive bifunctional ligand and its application in catalytic transfer hydrogenation of ketones.
The ligand 6,6'-dihydroxy terpyridine (dhtp) is presented as a bifunctional ligand capable of directing proton transfer events with metal-coordinated substrates. Solid-state analysis of a Ru(II)-dhtp complex reveals directed hydrogen-bonding interactions of the hydroxyl groups of dhtp with a Ru-bound chloride ligand. The utility of dhtp was demonstrated by chemoselective transfer hydrogenation of ketones.


Sub-cutaneous fat thickness measured by magnetic resonance imaging, ultrasound, and calipers.
Sub-cutaneous fat thickness was measured at 12 sites on the body surface of 24 males and 26 females using magnetic resonance imaging (MRI), skinfold calipers, and A-mode ultrasound. The mean of the 12 fat thickness measurements and individual site thicknesses were compared between individuals using analysis of variance. In males, the mean thicknesses for ultrasound and calipers were similar (P greater than 0.05) but both were less than the MRI (P less than 0.001). MRI and ultrasound were similar in females but less than calipers (P less than 0.001). A good between-subject correlation was found between all three methods in the males but only the calipers and MRI were well correlated in females. Within-subject correlations are poor for all measures and in both sexes. Factor loadings for a varimax rotation of two principal components indicate that the fat is distributed in 1 of 2 patterns: either principally on the trunk or on the limbs. The principal component analysis and the result of canonical correlations obtained from the factor loadings confirm the findings of the analysis of variance, in that a general level of fatness is measurable by all three methods over a range of subjects. However, the pattern of fat thicknesses measured over a number of specific sites by one method of measurement is unlikely to be duplicated by either of the other two methods on the same individual.


Serum α-tocopherol and γ-tocopherol concentrations and prostate cancer risk in the PLCO Screening Trial: a nested case-control study.
Vitamin E compounds exhibit prostate cancer preventive properties experimentally, but serologic investigations of tocopherols, and randomized controlled trials of supplementation in particular, have been inconsistent. Many studies suggest protective effects among smokers and for aggressive prostate cancer, however. We conducted a nested case-control study of serum α-tocopherol and γ-tocopherol and prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, with 680 prostate cancer cases and 824 frequency-matched controls. Multivariate-adjusted, conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tocopherol quintiles. Serum α-tocopherol and γ-tocopherol were inversely correlated (r = -0.24, p<0.0001). Higher serum α-tocopherol was associated with significantly lower prostate cancer risk (OR for the highest vs. lowest quintile = 0.63, 95% CI 0.44-0.92, p-trend 0.05). By contrast, risk was non-significantly elevated among men with higher γ-tocopherol concentrations (OR for the highest vs. lowest quintile = 1.35, 95% CI 0.92-1.97, p-trend 0.41). The inverse association between prostate cancer and α-tocopherol was restricted to current and recently former smokers, but was only slightly stronger for aggressive disease. By contrast, the increased risk for higher γ-tocopherol was more pronounced for less aggressive cancers. Our findings indicate higher α-tocopherol status is associated with decreased risk of developing prostate cancer, particularly among smokers. Although two recent controlled trials did not substantiate an earlier finding of lower prostate cancer incidence and mortality in response to supplementation with a relatively low dose of α-tocopherol, higher α-tocopherol status may be beneficial with respect to prostate cancer risk among smokers. Determining what stage of prostate cancer development is impacted by vitamin E, the underlying mechanisms, and how smoking modifies the association, is needed for a more complete understanding of the vitamin E-prostate cancer relation.


Long-Term Cardiac Function After Peripartum Cardiomyopathy and Preeclampsia: A Danish Nationwide, Clinical Follow-Up Study Using Maximal Exercise Testing and Cardiac Magnetic Resonance Imaging.
Background Long-term clinical studies of peripartum cardiomyopathy ( PPCM ) are few. We aimed to measure the long-term effect of PPCM on cardiac function in comparison with the long-term effects of severe preeclampsia and uncomplicated pregnancy. Methods and Results A nationwide Danish cohort of women diagnosed with PPCM from 2005 to 2014 ( PPCM group) were invited to participate in a clinical follow-up study including maximal cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Matched women with previous severe preeclampsia (preeclampsia group) and previous uncomplicated pregnancies (uncomplicated pregnancies group) served as comparison groups. A total of 84 women with 28 in each group participated. Median time to follow-up after PPCM was 91 months. Most women (85%) in the PPCM group reported no symptoms of heart failure. Mean left ventricular ejection fraction in the PPCM group was normal at 62%, but significantly lower than in the preeclampsia group and the uncomplicated pregnancies group where mean left ventricular ejection fraction was 69% and 67%, respectively ( P<0.0001). Women in the PPCM group also had impaired diastolic function with reduced left ventricular peak filling rate, left atrial passive emptying volume, and left atrial passive emptying fraction. Maximal exercise capacity (peak VO 2) was also reduced in the PPCM group compared with the preeclampsia group and the uncomplicated pregnancies group, and PPCM , high body mass index, and low left ventricular ejection fraction independently predicted reduced peak VO 2. Only 1 woman with PPCM had late gadolinium enhancement. Conclusions Women generally recovered left ventricular ejection fraction and were asymptomatic 7 years after PPCM , but had subtle diastolic dysfunction on cardiac magnetic resonance imaging and reduced peak VO 2. Focal myocardial fibrosis assessed with late gadolinium enhancement was, however, uncommon.


Approach to amoebic colitis: Epidemiological, clinical and diagnostic considerations in a non-endemic context (Barcelona, 2007-2017).
Amoebic colitis is the most frequent clinical manifestation of invasive intestinal infection due to Entamoeba histolytica and a common cause of diarrhoea worldwide. Since higher transmission rates are usually related to poor health and exposure to unhygienic conditions, cases reported in Europe usually involve immigrants and international travellers. The goal of this study was to characterise both the clinical and the epidemiological features of a European population diagnosed with amoebic colitis and then to evaluate the diagnostic tools and therapeutic options applied. This was a retrospective observational study in which data from all patients diagnosed with amoebic colitis attending at the International Health Units of two tertiary referral hospitals, Germans Trias i Pujol University Hospital (Badalona, North Barcelona Metropolitan Area) and Vall d'Hebron University Hospital (Barcelona city) between 2007 and 2017 were analysed. During the study period 50 patients were diagnosed with amoebic colitis. Thirty-six (72%) were men, and immigrants accounted for 46% of all cases. Antecedents of any international travel were reported for 28 (56%), the most frequent destinations having been the Indian subcontinent, South and Central America and sub-Saharan Africa. Preexisting pathological conditions or any kind of immunosuppression were identified in 29 (58%) patients; of these, 13 (26%) had HIV infection-all of them men who have sex with men-and 5 (10%) had inflammatory bowel disease. Diarrhoea, abdominal pain and dysentery were the most frequently recorded symptoms of invasive amoebae. Diagnosis was made through microbiological study in 45 (90%) and/or histological identification of amoebae in colon biopsies in 10 (20%). After treatment with metronidazole (82%) or tinidazole (8%), all patients had good outcomes. Post-acute intraluminal treatment was indicated in 28 (56%). Amoebic colitis should be suspected in patients with diarrhoea and compatible epidemiological risk factors (immigration, travelling abroad or men who have sex with men), especially if some degree of immunosuppression concurs. These risk factors must be taken into account in any diagnostic approach to inflammatory bowel disease (IBD), and active searches for stool parasites should be performed in such cases to rule out misdiagnosis or simultaneous amoebic infection. Treatment should include intraluminal anti-amoebic treatment in order to avoid relapse and prevent further spread of the disease.


Trastuzumab monotherapy versus combination therapy for treating recurrent breast cancer: time to progression and survival.
HER2 expression is an important prognostic and predictive factor of treatment efficacy in breast cancer. Trastuzumab, in particular, is a key drug in the treatment of HER2-positive recurrent breast cancer. However, the difference in treatment efficacy between trastuzumab monotherapy and combination therapy with chemotherapy is unclear. In order to elucidate this point, both treatments were compared in terms of efficacy by metastatic site, time to progression (TTP), and survival. The subjects were 1,471 breast cancer patients who had been evaluated for HER2 expression between 1998 and March 2006; 74 of these had recurrent breast cancer that had been treated with trastuzumab. Of these 74 patients, 39 received trastuzumab alone and 45 trastuzumab in combination with chemotherapy. The items of investigation were clinical effect, TTP, survival, biological markers such as ER/PgR, proliferation (Ki67) or p53 overexpression, nuclear grade, performance status (PS), lymph node metastasis, and tumor size. The HER2-positive rate was 23.3%, and the degree of malignancy in these HER2-positive patients was high; postoperative disease-free survival (DFS) was low. However, this tendency was clear in patients with hormone-responsive breast cancer. In patients with hormone-non-responsive breast cancer, HER2 negativity had a significantly higher Ki67 value, and there was no difference in DFS between patients with HER2-positive and -negative tumors. Among the 74 patients with recurrent breast cancer, the response rate to trastuzumab was 64.9%; however, among patients who received the combination treatment, the response rate was 86%. In patients with liver metastasis, the effect of trastuzumab alone was low, but that of the combination treatment was significantly high. TTP was 5.7 months and 15.9 months with trastuzumab alone and the combination therapy, respectively. Furthermore, a significant difference was seen in post-treatment survival; however, there was no significant difference in survival after a recurrence. In the multivariate analysis on factors for TTP, PS, clinical effect, and combination treatment were significant. However, good PS and early treatment were the significant factors in post-treatment survival. The effect of trastuzumab in patients with recurrent breast cancer who received the combination treatment was significantly high and TTP was long. However, this was not a significant factor in terms of overall survival. In particular, a good PS and early treatment were important in post-treatment survival.


Paget's disease of bone: an endocrine society clinical practice guideline.
The aim of this guideline was to formulate practice guidelines for the diagnosis and treatment of Paget's disease of the bone. The guideline was developed by an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. We recommend that plain radiographs be obtained of the pertinent regions of the skeleton in patients with suspected Paget's disease. If the diagnosis is confirmed, we suggest that a radionucleotide bone scan be done to determine the extent of the disease. After diagnosis of Paget's disease, we recommend measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients. We suggest treatment with a bisphosphonate for most patients with active Paget's disease who are at risk for future complications. We suggest a single 5-mg dose of iv zoledronate as the treatment of choice in patients who have no contraindication. In patients with monostotic disease who have a normal serum total alkaline phosphatase, we suggest that a specific marker of bone formation and bone resorption be measured, although these may still be normal. Serial radionuclide bone scans may determine the response to treatment if the markers are normal. We suggest that bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget's disease and may reverse paraplegia associated with spinal Paget's disease. We suggest treatment with a bisphosphonate before surgery on pagetic bone.


Skin morphology and humoral non-specific defence parameters of mucus and plasma in rainbow trout, coho and Atlantic salmon.
Susceptibility to different diseases among related species, such as coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhyncus mykiss) and Atlantic salmon (Salmo salar), is variable. The prominence of these species in aquaculture warrants investigation into sources of this variability to assist future disease management. To develop a better understanding of the basis for species variability, several important non-specific humoral parameters were examined in juvenile fish of these three economically important species. Mucous protease, alkaline phosphatase and lysozyme, as well as plasma lysozyme activities and histological parameters (epidermal thickness and mucous cell density, and size) were characterized and compared for three salmonids: rainbow trout, Atlantic salmon and coho salmon. Rainbow trout had a thicker epidermis and significantly more mucous cells per cross-sectional area than the other two species. Rainbow trout also had significantly higher mucous protease activity than Atlantic salmon and significantly higher lysozyme (plasma and mucus) activities than coho and Atlantic salmon, in seawater. Atlantic salmon, on the other hand, had the lowest activities of mucous lysozyme and proteases, the thinnest epidermal layer and the sparsest distribution of mucous cells, compared with the two other salmonids in seawater. Only coho salmon had sacciform cells. Atlantic and coho salmon had higher mucous lysozyme activities in freshwater as compared to seawater. There was no significant difference between mucous lysozyme activities in any of the three species reared in freshwater; however, rainbow trout still had a significantly higher plasma lysozyme activity compared with the other two species. All three species exhibited significantly lower mucous alkaline phosphatase and protease activities in freshwater than in seawater. Our results demonstrate that there are significant histological and biochemical differences between the skin and mucus of these three salmonid species, which may change as a result of differing environments. Variation in these innate immune factors is likely to have differing influences on each species response to disease processes.


Changes in activities of several enzymes involved in carbohydrate metabolism during the cell cycle of Saccharomyces cerevisiae.
Activity changes of a number of enzymes involved in carbohydrate metabolism were determined in cell extracts of fractionated exponential-phase populations of Saccharomyces cerevisiae grown under excess glucose. Cell-size fractionation was achieved by an improved centrifugal elutriation procedure. Evidence that the yeast populations had been fractionated according to age in the cell cycle was obtained by examining the various cell fractions for their volume distribution and their microscopic appearance and by flow cytometric analysis of the distribution patterns of cellular DNA and protein contents. Trehalase, hexokinase, pyruvate kinase, phosphofructokinase 1, and fructose-1,6-diphosphatase showed changes in specific activities throughout the cell cycle, whereas the specific activities of alcohol dehydrogenase and glucose-6-phosphate dehydrogenase remained constant. The basal trehalase activity increased substantially (about 20-fold) with bud emergence and decreased again in binucleated cells. However, when the enzyme was activated by pretreatment of the cell extracts with cyclic AMP-dependent protein kinase, no significant fluctuations in activity were seen. These observations strongly favor posttranslational modification through phosphorylation-dephosphorylation as the mechanism underlying the periodic changes in trehalase activity during the cell cycle. As observed for trehalase, the specific activities of hexokinase and phosphofructokinase 1 rose from the beginning of bud formation onward, finally leading to more than eightfold higher values at the end of the S phase. Subsequently, the enzyme activities dropped markedly at later stages of the cycle. Pyruvate kinase activity was relatively low during the G1 phase and the S phase, but increased dramatically (more than 50-fold) during G2. In contrast to the three glycolytic enzymes investigated, the highest specific activity of the gluconeogenic enzyme fructose-1, 6-diphosphatase 1 was found in fractions enriched in either unbudded cells with a single nucleus or binucleated cells. The observed changes in enzyme activities most likely underlie pronounced alterations in carbohydrate metabolism during the cell cycle.


Expansion of T-cell receptor zeta dim effector T cells in acute coronary syndromes.
The T-cell receptor zeta (TCR zeta)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR zeta-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR zeta(dim) T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR zeta(dim) T cells in coronary artery disease. We examined the expression of TCR zeta-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4(+) TCR zeta(dim) T cells were found in patients with acute coronary syndromes (ACS, n=66; median 5.3%, interquartile 2.6 to 9.1% of total CD4(+) T cells; P<0.0001) compared to chronic stable angina (CSA, n=32; 1.6%; 1.0 to 4.1%) and controls (n=42; 1.5%; 0.5 to 2.9%). Such increase was significantly greater in ACS patients with elevated levels of C-reactive protein, and it persisted after the acute event. Moreover, TCR zeta(dim) cells were also more represented within CD8(+) T cell, NK, and CD4(+)CD28(null) T cell subsets in ACS compared to CSA and controls. Finally, CD4(+) and CD8(+) TCR zeta(dim) T cells isolated from ACS displayed an enhanced transendothelial migratory capacity. TCR zeta(dim) T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.


High-resolution inkjet printing of all-polymer transistor circuits.
Direct printing of functional electronic materials may provide a new route to low-cost fabrication of integrated circuits. However, to be useful it must allow continuous manufacturing of all circuit components by successive solution deposition and printing steps in the same environment. We demonstrate direct inkjet printing of complete transistor circuits, including via-hole interconnections based on solution-processed polymer conductors, insulators, and self-organizing semiconductors. We show that the use of substrate surface energy patterning to direct the flow of water-based conducting polymer inkjet droplets enables high-resolution definition of practical channel lengths of 5 micrometers. High mobilities of 0.02 square centimeters per volt second and on-off current switching ratios of 10(5) were achieved.


The effects of hyperbaric oxygen treatment on vigility of spermatozoids: preliminary report.
The aim of this study was to evaluate the effect of hyperbaric oxygen treatment (HBO) to the vigilance of spermatozoids. The sperm samples were obtained from the patients (n=10) with diagnosed oligospermia. The motility of spermatozoids in tested samples was not lower than 30% but it did not exceed the critical proportion of 50%. Three groups of samples were formed, with respectively 10 samples in each group. All of them were exposed to HBO conditions of 2.5 ATA for 90 minutes. Group I was exposed to HBO conditions without any addition of medium. Group II was added 5 ml of EBSS solution. Tyrode's solution in volume of 5 ml was added to group III. The evaluation of functional characteristics of sperm was carried out 30 minutes after completion of HBO treatment. Statistically significant increased in motor activity was registered in three all groups (p<0.05). The biggest increased in vigilance of spermatozoids was found in the samples of the group III (p<0.01), exceeding the critical proportion of 50% in all of the samples. The obtained results suggest that the acute exposure of the sperm samples to HBO has favorable impact to functional capacity of spermatozoids in view of their better motility.


The Montana Radon Study: social marketing via digital signage technology for reaching families in the waiting room.
I tested a social marketing intervention delivered in health department waiting rooms via digital signage technology for increasing radon program participation among priority groups. I conducted a tri-county, community-based study over a 3-year period (2010-2013) in a high-radon state by using a quasi-experimental design. We collected survey data for eligible participants at the time of radon test kit purchase. Radon program participation increased at the intervention site (t38 = 3.74; P = .001; 95% confidence interval [CI] = 4.8, 16.0) with an increase in renters (χ(2)1,228 = 4.3; P = .039), Special Supplementary Nutrition Program for Women, Infants, and Children families (χ(2)1,166 = 3.13; P = .077) and first-time testers (χ(2)1,228 = 10.93; P = .001). Approximately one third (30.3%; n = 30) attributed participation in the radon program to viewing the intervention message. The intervention crossover was also successful with increased monthly kit sales (t37 = 2.69; P = .01; 95% CI = 1.20, 8.47) and increased households participating (t23 = 4.76; P < .001; 95% CI = 3.10, 7.88). A social marketing message was an effective population-based intervention for increasing radon program participation. The results prompted policy changes for Montana radon programming and adoption of digital signage technology by 2 health departments.


Evidence-based management of resident-performed cataract surgery: an investigation of compliance with a preferred practice pattern.
To evaluate compliance with the American Academy of Ophthalmology (AAO) Cataract in the Adult Eye Preferred Practice Pattern (PPP) in a resident ophthalmology clinic. Retrospective chart review. All patients undergoing first-eye cataract surgery by ophthalmology residents with attending supervision at a Veterans Affairs Medical Center between January 1, 2006, and July 31, 2007. Electronic medical records (EMRs) were reviewed for compliance with the AAO Cataract in the Adult Eye PPP. Frequency of resident compliance with all 39 elements of the AAO Cataract in the Adult Eye PPP. A total of 129 patients met the inclusion criteria. The mean compliance with the PPP was 81%, with 62% of the elements having 90% or greater compliance. Compliance was below the mean for those PPP elements requiring patient input or assessment, including 0% for considering patient preference in the determination of anesthesia management, 73% for patient assessment of preoperative functional status, and 66% for patient assessment of postoperative vision. Compliance with the AAO Cataract in the Adult Eye PPP in this resident ophthalmology clinic can be improved by increasing the documentation of patient input about their visual function both preoperatively and postoperatively. Further study of compliance with evidence-based guidelines is needed in ophthalmology, particularly in teaching hospitals where new providers are developing their approach to care.


Client and therapist agreement about the client's problems-Associations with treatment alliance and outcome.
A shared understanding of the patient's symptoms and problems is seen by most theories as a crucial aspect of the collaboration in therapy, presumably influencing alliance and outcome. The empirical ground for this argument is not solid, however. Several studies have found weak associations between a common view of the patient's problems and outcome. The purpose of the present study was to analyze whether agreement in the understanding of the patient's depression and anxiety problems was important for alliance and outcome. The study used data from a practice-based study using the CORE system with 846 patients who received psychological treatment in primary care. The analyses indicated that although patients who were assessed by their therapists as having depression and anxiety problems scored higher on these subscales than other patients, about half of the patients reported such problems when the therapists did not, and vice versa. Agreement was not associated with better alliance or outcome. Productive collaboration in psychotherapy may be based on other factors than agreement about symptoms.


Effects of leather industry on health and recommendations for improving the situation in Pakistan.
The leather industry and its associated sectors contribute significantly to the Pakistani economy. There are around 600 tanneries in Pakistan that are concentrated in 3 major cities (Kasur, Karachi, Sialkot). Waste discharge from tanneries pollutes the air, soil, and water, causing serious health problems. Exposure to such contaminated environmental milieu has been seen to culminate in a multiple array of disease processes such as asthma, dermatitis, hepatic and neurological disorders, and various malignancies. An overall dearth of research on the occupational hazards of employment in the leather industry as well as its effects on pediatric population was observed during literature review with particular reference to Pakistan. It is recommended that research should be conducted about the health hazards in the leather industry in Pakistan as well as globally to gather data that can be translated into effective prevention programs for both adults as well as pediatric populations.


Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for β-Arrestin-Biased D2R Agonists.
By means of a formal structural hybridization of the antipsychotic drug aripiprazole and the heterocyclic catecholamine surrogates present in the β2-adrenoceptor agonists procaterol and BI-167107 (4), we designed and synthesized a collection of novel hydroxy-substituted heteroarylpiperazines and heteroarylhomopiperazines with high dopamine D2 receptor (D2R) affinity. In contrast to the weak agonistic behavior of aripiprazole, these ligands are capable of effectively mimicking those interactions of dopamine and the D2R that are crucial for an active state, leading to the recruitment of β-arrestin-2. Interestingly, some ligands show considerably lower intrinsic activity in guanine nucleotide exchange experiments at D2R and consequently represent biased agonists favoring β-arrestin-2 recruitment over canonical G protein activation. The ligands' agonistic properties are substantially driven by the presence of an endocyclic H-bond donor.


Incidence and Epidemiology of Perioperative Transfusion-Related Pulmonary Complications in Pediatric Noncardiac Surgical Patients: A Single-Center, 5-Year Experience.
Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related fatalities. While these transfusion-related pulmonary complications (TRPCs) have been well detailed in adults, their burden in pediatric subsets remains poorly defined. We sought to delineate the incidence and epidemiology of pediatric TRPCs after intraoperative blood product transfusion. In this retrospective cohort study, we evaluated all consecutive pediatric patients receiving intraoperative blood product transfusions during noncardiac surgeries between January 2010 and December 2014. Exclusion criteria were cyanotic heart disease, preoperative respiratory insufficiency, extracorporeal membrane oxygenation, and American Society of Anesthesiologists physical status VI. Medical records were electronically screened to identify those with evidence of hypoxemia, and in whom a chest x-ray was obtained within 24 hours of surgery. Records were then manually reviewed by 2 physicians to determine whether they met diagnostic criteria for TACO or TRALI. Disagreements were adjudicated by a third senior physician. Of 19,288 unique pediatric surgical patients, 411 were eligible for inclusion. The incidence of TRPCs was 3.6% (95% confidence interval [CI], 2.2-5.9). TACO occurred in 3.4% (95% CI, 2.0-5.6) of patients, TRALI was identified in 1.2% (95% CI, 0.5-2.8), and 1.0% (95% CI, 0.4-2.5) had evidence for both TRALI and TACO. Incidence was not different between males (3.4%) and females (3.8%; P = .815). Although a trend toward an increased incidence of TRPCs was observed in younger patients, this did not reach statistical significance (P = .109). Incidence was comparable across subsets of transfusion volume (P = .184) and surgical specialties (P = .088). Among the 15 patients experiencing TRPCs, red blood cells were administered to 13 subjects, plasma to 3, platelets to 3, cryoprecipitate to 2, and autologous blood to 3. Three patients with TRCPs were transfused mixed blood components. TRPCs occurred in 3.6% of transfused pediatric surgical patients, with the majority of cases attributable to TACO, congruent with adult literature. The frequency of TRPCs was comparable between genders and across surgical procedures and transfusion volumes. The observed trend toward increased TRPCs in younger children warrants further consideration in future investigations. Red blood cell administration was the associated component for the majority of TRPCs, although platelets demonstrated the highest risk per component transfused. Mitigation of perioperative risk associated with TRPCs in pediatric patients is reliant on further multiinstitutional studies powered to examine patterns and predictors of this highly morbid entity.


Position-Specific Enrichment Ratio Matrix scores predict antibody variant properties from deep sequencing data.
Deep sequencing of antibody and related protein libraries after phage or yeast-surface display sorting is widely used to identify variants with increased affinity, specificity, and/or improvements in key biophysical properties. Conventional approaches for identifying optimal variants typically use the frequencies of observation in enriched libraries or the corresponding enrichment ratios. However, these approaches disregard the vast majority of deep sequencing data and often fail to identify the best variants in the libraries. Here, we present a method, Position-Specific Enrichment Ratio Matrix (PSERM) scoring, that uses entire deep sequencing datasets from pre- and post-selections to score each observed protein variant. The PSERM scores are the sum of the site-specific enrichment ratios observed at each mutated position. We find that PSERM scores are much more reproducible and correlate more strongly with experimentally measured properties than frequencies or enrichment ratios, including for multiple antibody properties (affinity and non-specific binding) for a clinical-stage antibody (emibetuzumab). We expect that this method will be broadly applicable to diverse protein engineering campaigns. All deep sequencing datasets and code to perform the analyses presented within are available via https://github.com/Tessier-Lab-UMich/PSERM_paper.


"Referendum on Sunday, working group on Monday": A success story of implementing abortion services after legalization in Portugal.
A 2007 referendum legalized abortion in Portugal. Physicians played an important role advocating for legal reform and providing services thereafter. Implementers relied on a strong public health system with many gynecologists who required minimal training, and took decisions that allowed for rapid implementation. First, they emphasized medical abortion and integrated abortion into existing hospital obstetrics and gynecologic services, where eventual complications could be managed. They also offered immediate postabortion contraception, helping prevent criticism from abortion opponents who feared women would obtain multiple repeat abortions. Finally, they established referral networks guaranteeing access despite conscientious objection. Media campaigns were not needed as Portuguese women had good access to information. Portugal's success is largely due to key facilitators within a working group established by the Ministry of Health to implement the new law. Remaining challenges are the lack of choice between medical and surgical abortion, and some regions with relatively difficult geographic access to services.


Phloem transport, solute flux and the kinetics of sap exudation in Ricinus communis L.
The osmotic characteristics of phloem-sap exudation were examined in soil-grown and watercultured plants of Ricinus communis L. Prolonged exudation occurred from bark incisions in water-cultured plants. Fresh incisions caused large alterations in solute flux, but phloem-sap solute potential Ψs changed by less than ±8% over a period of 7 h. This was associated with a constancy in the levels of sucrose and K(+), the principal solutes in the sap. Studies with foliar-applied tracers and leaf-excision experiments suggested that exudation was maintained by solute loading from mature leaves. A wide range of mass transfer values through the phloem was found, these being a function of exudation rate. We consider that the exudation process possesses essentially similar characteristics to phloem transport in the intact plant. The way in which bark incisions bring about large changes in solute flux is discussed in terms of the physical properties of the sieve-tube system.


Comparison of chemistry analytes between 2 portable, commercially available analyzers and a conventional laboratory analyzer in reptiles.
Advantages of handheld and small bench-top biochemical analyzers include requirements for smaller sample volume and practicality for use in the field or in practices, but little has been published on the performance of these instruments compared with standard reference methods in analysis of reptilian blood. The aim of this study was to compare reptilian blood biochemical values obtained using the Abaxis VetScan Classic bench-top analyzer and a Heska i-STAT handheld analyzer with values obtained using a Roche Hitachi 911 chemical analyzer. Reptiles, including 14 bearded dragons (Pogona vitticeps), 4 blue-tongued skinks (Tiliqua gigas), 8 Burmese star tortoises (Geochelone platynota), 10 Indian star tortoises (Geochelone elegans), 5 red-tailed boas (Boa constrictor), and 5 Northern pine snakes (Pituophis melanoleucus melanoleucus), were manually restrained, and a single blood sample was obtained and divided for analysis. Results for concentrations of albumin, bile acids, calcium, glucose, phosphates, potassium, sodium, total protein, and uric acid and activities of aspartate aminotransferase and creatine kinase obtained from the VetScan Classic and Hitachi 911 were compared. Results for concentrations of chloride, glucose, potassium, and sodium obtained from the i-STAT and Hitachi 911 were compared. Compared with results from the Hitachi 911, those from the VetScan Classic and i-STAT had variable correlations, and constant or proportional bias was found for many analytes. Bile acid data could not be evaluated because results for 44 of 45 samples fell below the lower linearity limit of the VetScan Classic. Although the 2 portable instruments might provide measurements with clinical utility, there were significant differences compared with the reference analyzer, and development of analyzer-specific reference intervals is recommended.


Prism adaptation during walking generalizes to reaching and requires the cerebellum.
Adaptation of arm movements to laterally displacing prism glasses is usually highly specific to body part and movement type and is known to require the cerebellum. Here, we show that prism adaptation of walking trajectory generalizes to reaching (a different behavior involving a different body part) and that this adaptation requires the cerebellum. In experiment 1, healthy control subjects adapted to prisms during either reaching or walking and were tested for generalization to the other movement type. We recorded lateral deviations in finger endpoint position and walking direction to measure negative aftereffects and generalization. Results showed that generalization of prism adaptation is asymmetric: walking generalizes extensively to reaching, but reaching does not generalize to walking. In experiment 2, we compared the performance of cerebellar subjects versus healthy controls during the prism walking adaptation. We measured rates of adaptation, aftereffects, and generalization. Cerebellar subjects had reduced adaptation magnitudes, slowed adaptation rates, decreased negative aftereffects, and poor generalization. Based on these experiments, we propose that prism adaptation during whole body movements through space invokes a more general system for visuomotor remapping, involving recalibration of higher-order, effector-independent brain regions. In contrast, prism adaptation during isolated movements of the limbs is probably recalibrated by effector-specific mechanisms. The cerebellum is an essential component in the network for both types of prism adaptation.


Mob1p interacts with the Sid2p kinase and is required for cytokinesis in fission yeast.
A great deal is now known about how cells regulate entry into mitosis, but only recently have the mechanisms controlling exit from mitosis and cytokinesis begun to be revealed. In the budding yeast Saccharomyces cerevisiae, Mob1p interacts with the Dbf2p kinase and cells containing mutations in these genes arrest in late anaphase [1] [2]. Proteins related to Mob1p are present in both plants and animals, but information about Mob1p function has been obtained only from budding yeast. Here, we describe the identification and characterization of Mob1p from Schizosaccharomyces pombe. Mob1p associates with the Sid2p kinase and like Sid2p, Mob1p is required for the initiation of cytokinesis, but not for mitotic exit. Mob1p localizes to the spindle pole body (SPB) and to the cell-division site during cell division, suggesting that it might be involved in transducing the signal to initiate cell division from the SPB to the division site. Mob1p is required for Sid2p localization, and Mob1p localization requires the function of the cdc7, cdc11, cdc14, spg1, sid1, sid2, and sid4 genes, suggesting that together with Sid2p, Mob1p functions at the end of the signaling cascade required to regulate the onset of cytokinesis at the end of mitosis.


Evidence for a new fumarate hydratase gene mutation in a unilateral type 2 segmental leiomyomatosis.
Multiple cutaneous and uterine leiomyomata syndrome (MCUL; MIM 150800) is a rare condition that sometimes predisposes to renal cancer. It is caused by deleterious mutations in the fumarate hydratase (FH) gene. In many patients, skin leiomyomas have been reported to develop according to a segmental type 1 or type 2 distribution. We report a patient showing multiple leiomyomas distributed according to a segmental type 2 distribution and covering several areas exclusively on the left side of his body. To search for a specific mutation in the FH gene associated with this phenotype. Genomic DNA from peripheral blood leucocytes of the proband was sequenced and screened for mutation of the FH gene. Heterozygosity for an as yet undescribed mutation c.695delG, leading to a truncated protein p.Gly232AspfsX24, was found. We report a new mutation in the FH gene and discuss the unusual pattern of purely unilateral distribution in the present case.


Antidepressant treatment and adherence to antiretroviral medications among privately insured persons with HIV/AIDS.
In order to examine relationships between depression treatments (antidepressant and/or psychotherapy utilization) and adherence to antiretroviral therapy (ART), we conducted a retrospective analysis of medical and pharmacy insurance claims for privately insured persons living with HIV/AIDS (PLWHA) diagnosed with depression (n = 1,150). Participants were enrolled in 80 insurance plans from all 50 states. Adherence was suboptimal. Depression treatment initiators were significantly more likely to be adherent to ART than the untreated. We did not observe an association between psychotherapy utilization and ART adherence, yet given the limitations of the data (e.g., there is no information on types of psychological treatment and its targets), the lack of association should not be interpreted as lack of efficacy.


Quantification of active ROM after arthroscopic Bankart repair with rotator interval closure.
Several series report patients homogeneously treated using arthroscopic Bankart repair exclusively, or in some cases arthroscopic Bankart repair with rotator interval closure. Current international literature has few reports on arthroscopic Bankart repair with rotator interval closure procedures undertaken on a homogeneous series of patients. The purpose of this study was to evaluate the residual active range of motion (ROM) and clinical outcome in this patient population. Fourteen patients affected by recurrent anterior instability were consecutively treated. Rowe, Walch-Duplay, and UCLA scores, as well as differences in active ROM of both shoulders (treated and contralateral), were recorded. A significant reduction in active external rotation was noted along the side of the arm (P<.001) and at 90 degrees of abduction (P=.007). The average reduction was 12.14 degrees and 7.21 degrees, respectively, which represents 17.8% and 8% of the arc of motion of the opposite side in external rotation. No significant differences were found for flexion, abduction, and internal rotation. According to Walch-Duplay and Rowe scores, 71.4% and 85.7% of patients had excellent or good results. Arthroscopic Bankart repair with rotator interval closure results in a reduction of external rotation and provides satisfactory stability results.


Alcoholism in a coronary care unit population.
To estimate prospectively the concordance between diagnoses of alcoholism by a physician and by use of a questionnaire-type screening test in patients in a coronary care unit, we studied 608 patients admitted to a coronary care unit in a 5 1/2-month period. The results from the Self-Administered Alcoholism Screening Test (SAAST) were compared with the diagnoses by physicians recorded in the medical records for the same patients. A strong association (P < 0.001) existed between the clinicians' identification of an alcohol problem and the SAAST scores indicative of such a problem. However, 23 (4.2%) patients were identified as alcoholics by the SAAST but not by clinicians, and 16 (2.9%) patients were identified as alcoholics by clinicians but not by the SAAST. The SAAST was well accepted in this coronary care unit and can complement and extend the clinicians' impression, although each approach may identify some patients that the other will miss. Routine use of the SAAST in the coronary care unit or other hospital settings is feasible and, with appropriate clinician assessment and physician involvement, should yield more complete evaluation and case finding for alcoholism.


Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association.
The guidelines presented in this consensus statement are intended to serve researchers, clinicians, reviewers, and regulators in the selection of the most appropriate primary outcome for a clinical trial of cardiac arrest therapies. The American Heart Association guidelines for the treatment of cardiac arrest depend on high-quality clinical trials, which depend on the selection of a meaningful primary outcome. Because this selection process has been the subject of much controversy, a consensus conference was convened with national and international experts, the National Institutes of Health, and the US Food and Drug Administration. The Research Working Group of the American Heart Association Emergency Cardiovascular Care Committee nominated subject leaders, conference attendees, and writing group members on the basis of their expertise in clinical trials and a diverse perspective of cardiovascular and neurological outcomes (see the online-only Data Supplement). Approval was obtained from the Emergency Cardiovascular Care Committee and the American Heart Association Manuscript Oversight Committee. Preconference position papers were circulated for review; the conference was held; and postconference consensus documents were circulated for review and comments were invited from experts, conference attendees, and writing group members. Discussions focused on (1) when after cardiac arrest the measurement time point should occur; (2) what cardiovascular, neurological, and other physiology should be assessed; and (3) the costs associated with various end points. The final document underwent extensive revision and peer review by the Emergency Cardiovascular Care Committee, the American Heart Association Science Advisory and Coordinating Committee, and oversight committees. There was consensus that no single primary outcome is appropriate for all studies of cardiac arrest. The best outcome measure is the pairing of a time point and physiological condition that will best answer the question under study. Conference participants were asked to assign an outcome to each of 4 hypothetical cases; however, there was not complete agreement on an ideal outcome measure even after extensive discussion and debate. There was general consensus that it is appropriate for earlier studies to enroll fewer patients and to use earlier time points such as return of spontaneous circulation, simple "alive versus dead," hospital mortality, or a hemodynamic parameter. For larger studies, a longer time point after arrest should be considered because neurological assessments fluctuate for at least 90 days after arrest. For large trials designed to have a major impact on public health policy, longer-term end points such as 90 days coupled with neurocognitive and quality-of-life assessments should be considered, as should the additional costs of this approach. For studies that will require regulatory oversight, early discussions with regulatory agencies are strongly advised. For neurological assessment of post-cardiac arrest patients, researchers may wish to use the Cerebral Performance Categories or modified Rankin Scale for global outcomes. Although there is no single recommended outcome measure for trials of cardiac arrest care, the simple Cerebral Performance Categories or modified Rankin Scale after 90 days provides a reasonable outcome parameter for many trials. The lack of an easy-to-administer neurological functional outcome measure that is well validated in post-cardiac arrest patients is a major limitation to the field and should be a high priority for future development.


Mucocele-like lesions of the breast: a long-term follow-up study.
Mucocele-like lesions (MLL) of the breast were originally described as benign lesions composed of multiple cysts lined by uniform flat to cuboidal epithelium with extravasated mucin, but subsequent reports described the coexistence of columnar cell lesions (CCL), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Several reports have investigated whether core biopsy can diagnose MLL reliably; however, there is only one report with a long-term follow-up after excision of MLL. We report here 15 surgically excised MLL with a long-term follow-up. Fifteen lesions diagnosed as MLL from 13 patients who had undergone excisional biopsy between January 2001 and December 2006 were retrieved and followed-up for 24-99 months (median 63.8). Two lesions were accompanied with CCL, 5 with ADH and 3 with low grade DCIS. Four lesions (2 ADH, 2 DCIS) were additionally resected and their histology revealed 2 ADH, one DCIS and one MLL with CCL. Of 4 lesions (3 ADH, one DCIS) without additional resection, one lesion (ADH) relapsed accompanied with DCIS at 37 months after excision. MLL were frequently accompanied with CCL, ADH or low grade DCIS. Complete resection may be recommended in case of MLL with ADH or DCIS because of intralesional heterogeneity and the probabilities of relapse.


Hormonal contraception and thrombotic risk: a multidisciplinary approach.
Heightened publicity about hormonal contraception and thrombosis risk and the publication of new guidelines by the World Health Organization in 2009 and the Centers for Disease Control and Prevention in 2010 addressing this complex issue have led to multidisciplinary discussions on the special issues of adolescents cared for at our pediatric hospital. In this review of the literature and new guidelines, we have outlined our approach to the complex patients referred to our center. The relative risk of thrombosis on combined oral contraception is three- to fivefold, whereas the absolute risk for a healthy adolescent on this therapy is only 0.05% per year. This thrombotic risk is affected by estrogen dose, type of progestin, mechanism of delivery, and length of therapy. Oral progestin-only contraceptives and transdermal estradiol used for hormone replacement carry minimal or no thrombotic risk. Transdermal, vaginal, or intrauterine contraceptives and injectable progestins need further study. A personal history of thrombosis, persistent or inherited thrombophilia, and numerous lifestyle choices also influence thrombotic risk. In this summary of one hospital's approach to hormone therapies and thrombosis risk, we review relative-risk data and discuss the application of absolute risk to individual patient counseling. We outline our approach to challenging patients with a history of thrombosis, known thrombophilia, current anticoagulation, or family history of thrombosis or thrombophilia. Our multidisciplinary group has found that knowledge of the guidelines and individualized management plans have been particularly useful for informing discussions about hormonal and nonhormonal options across varied indications.


A wavelet-based multiresolution regularized least squares reconstruction approach for optical tomography.
In this paper, we present a wavelet-based multigrid approach to solve the perturbation equation encountered in optical tomography. With this scheme, the unknown image, the data, as well as the weight matrix are all represented by wavelet expansions, thus yielding a multiresolution representation of the original perturbation equation in the wavelet domain. This transformed equation is then solved using a multigrid scheme, by which an increasing portion of wavelet coefficients of the unknown image are solved in successive approximations. One can also quickly identify regions of interest (ROI's) from a coarse level reconstruction and restrict the reconstruction in the following fine resolutions to those regions. At each resolution level a regularized least squares solution is obtained using the conjugate gradient descent method. This approach has been applied to continuous wave data calculated based on the diffusion approximation of several two-dimensional (2-D) test media. Compared to a previously reported one grid algorithm, the multigrid method requires substantially shorter computation time under the same reconstruction quality criterion.


Pomegranate and its Many Functional Components as Related to Human Health: A Review.
Pomegranate (Punica granatum L.) is an ancient fruit that is widely consumed as fresh fruit and juice. The use of pomegranate fruit dates from ancient times and reports of its therapeutic qualities have echoed throughout the ages. Both in vitro and in vivo studies have demonstrated how this fruit acts as antioxidant, antidiabetic, and hypolipidemic and shows antibacterial, antiinflammatory, antiviral, and anticarcinogenic activities. The fruit also improves cardiovascular and oral health. These beneficial physiological effects may also have preventive applications in a variety of pathologies. The health benefits of pomegranate have been attributed to its wide range of phytochemicals, which are predominantly polyphenols, including primarily hydrolyzable ellagitannins, anthocyanins, and other polyphenols. The aim of this review was to present an overview of the functional, medical, and physiological properties of this fruit.


Effect of liquid droplet surface tension on impact dynamics over hierarchical nanostructure surfaces.
Analyzing impact dynamics is important for practical applications of superhydrophobic surfaces, because these nonwetting surfaces frequently encounter impacting liquid droplets in real environments. Thus, various studies have been conducted to investigate impact dynamics by examining the correlation between the behaviors of impacting liquid droplets and several determining parameters, such as impacting velocity, surface structure and surface energy. The impacting behaviors of pure water droplets were the main focus in most previous studies; the effect of surface tension, another critical parameter, on impact dynamics has rarely been investigated. In the current work, we have newly studied the effects of liquid surface tension on impact dynamics using an ethanol-water solution as a model liquid system. We systematically varied the liquid's surface tension between 72 and 32 mN m-1 by changing the ethanol concentration from 0 to 20 wt%. This range of composition drastically changed the surface tension while it did not significantly affect other physical properties, such as density and viscosity. For an impact dynamics study, two surfaces, namely ZnO nanowires (NWs) and ZnO/Si hierarchical (HIE) structures, were prepared. As the surface tension decreased, the static water contact angle (CA) decreased on both surfaces. Under dynamic conditions, our analysis using a high-speed camera and a quartz crystal microbalance (QCM) showed that lowering the surface tension causes the transition from the anti-wetting to wetting state. The transition We numbers were obtained on both surfaces for various surface tensions of liquids. Under the same dropping conditions of liquids, the ZnO/Si HIE surface shows higher transition We numbers than the ZnO NW surface, which is due to the higher fraction of air pockets in the hierarchical structure, originating from dual dimensional structures. To understand the mechanism of dynamic transition, we developed a model for ZnO/Si HIE structures based on three determining pressures: anti-wetting, wetting, and effective water hammer pressures. The modeling results explain the experimental observations. The results of our model system are highly useful for understanding the impact dynamic behaviors of various liquids on non-wetting surfaces.


Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues.
Lung carcinoma is the leading cause of cancer-related death in the United States, and non-small cell carcinoma accounts for 85% of all lung cancer cases. One major characteristic of non-small cell carcinoma is the appearance of desmoplasia and deposition of dense extracellular collagen around the tumor. The desmoplastic response provides a radiologic target but may impair sampling during traditional image-guided needle biopsy and is difficult to differentiate from normal tissues using single label free imaging modality; for translational purposes, label-free techniques provide a more promising route to clinics. We thus investigated the potential of using multimodal, label free optical microscopy that incorporates Coherent Anti-Stokes Raman Scattering (CARS), Two-Photon Excited AutoFluorescence (TPEAF), and Second Harmonic Generation (SHG) techniques for differentiating lung cancer from normal and desmoplastic tissues. Lung tissue samples from patients were imaged using CARS, TPEAF, and SHG for comparison and showed that the combination of the three non-linear optics techniques is essential for attaining reliable differentiation. These images also illustrated good pathological correlation with hematoxylin and eosin (H&E) stained sections from the same tissue samples. Automated image analysis algorithms were developed for quantitative segmentation and feature extraction to enable lung tissue differentiation. Our results indicate that coupled with automated morphology analysis, the proposed tri-modal nonlinear optical imaging technique potentially offers a powerful translational strategy to differentiate cancer lesions reliably from surrounding non-tumor and desmoplastic tissues.


Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11.
Little is known about the molecular mechanisms underlying the formation of the principal sensory nucleus (PrV) of the trigeminal nerve, a major relay station for somatotopic pattern formation in the trigeminal system. Here, we show that mice lacking Drg11, a homeodomain transcription factor, exhibit defects within the PrV, which include an aberrant distribution of Drg11-/- cells, altered expression of a molecular marker, unusual projections of primary afferents from trigeminal ganglion cells, and, subsequently, increased cell death. In addition, surviving PrV cells exhibit delayed and more spatially restricted ascending projections to the ventral posterior medial nucleus of the thalamus (VPm). These early embryonic abnormalities in the PrV lead to the failure to develop whisker-related patterns in the PrV, VPm, and somatosensory cortex. By contrast, somatotopic patterns exist in the spinal trigeminal subnuclei interpolaris (SpVi) and subnuclei caudalis (SpVc) and the dorsal column nucleus-based lemniscal and cortical pathway. Thus, the deficits in the trigeminal system of Drg11-/- mice are specific to the PrV. Our results demonstrate that Drg11 is essential for proper cellular differentiation and, subsequently, for the formation of the whisker-related lemniscal and cortical structures.


Human proximal tubule cells form functional microtissues.
The epithelial cells lining the proximal tubules of the kidney mediate complex transport processes and are particularly vulnerable to drug toxicity. Drug toxicity studies are classically based on two-dimensional cultures of immortalized proximal tubular cells. Such immortalized cells are dedifferentiated, and lose transport properties (including saturable endocytic uptake) encountered in vivo. Generating differentiated, organotypic human microtissues would potentially alleviate these limitations and facilitate drug toxicity studies. Here, we describe the generation and characterization of kidney microtissues from immortalized (HK-2) and primary (HRPTEpiC) human renal proximal tubular epithelial cells under well-defined conditions. Microtissue cultures were done in hanging drop GravityPLUS™ culture plates and were characterized for morphology, proliferation and differentiation markers, and by monitoring the endocytic uptake of albumin. Kidney microtissues were successfully obtained by co-culturing HK-2 or HRPTEpiC cells with fibroblasts. The HK-2 microtissues formed highly proliferative, but dedifferentiated microtissues within 10 days of culture, while co-culture with fibroblasts yielded spherical structures already after 2 days. Low passage HRPTEpiC microtissues (mono- and co-culture) were less proliferative and expressed tissue-specific differentiation markers. Electron microscopy evidenced epithelial differentiation markers including microvilli, tight junctions, endosomes, and lysosomes in the co-cultured HRPTEpiC microtissues. The co-cultured HRPTEpiC microtissues showed specific uptake of albumin that could be inhibited by cadmium and gentamycin. In conclusion, we established a reliable hanging drop protocol to obtain functional kidney microtissues with proximal tubular epithelial cell lines. These microtissues could be used for high-throughput drug and toxicology screenings, with endocytosis as a functional readout.


Clinical utility of plasma glypican-3 and osteopontin as biomarkers of hepatocellular carcinoma.
α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC. We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis. The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors. The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.


Efficient deamination of 5-methylcytidine and 5-substituted cytidine residues in DNA by human APOBEC3A cytidine deaminase.
Deamination of 5-methylcytidine (5MeC) in DNA results in a G:T mismatch unlike cytidine (C) deamination which gives rise to a G:U pair. Deamination of C was generally considered to arise spontaneously. It is now clear that human APOBEC3A (A3A), a polynucleotide cytidine deaminase (PCD) with specificity for single stranded DNA, can extensively deaminate human nuclear DNA. It is shown here that A3A among all human PCDs can deaminate 5-methylcytidine in a variety of single stranded DNA substrates both in vitro and in transfected cells almost as efficiently as cytidine itself. This ability of A3A to accommodate 5-methyl moiety extends to other small and physiologically relevant substituted cytidine bases such as 5-hydroxy and 5-bromocytidine. As 5MeCpG deamination hotspots characterize many genes associated with cancer it is plausible that A3A is a major player in the onset of cancer.


Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer.
Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.


Local knowledge, use pattern and geographical distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria.
All parts of Moringa oleifera are medicinally valuable with overlapping uses in treating myriads of ailments and diseases including body pains and weakness, fever, asthma, cough, blood pressure, arthritis, diabetes, epilepsy, wound, and skin infection. Moringa also has robust ability to challenge terminal diseases such as HIV/AIDs infections, chronic anemia, cancer, malaria and hemorrhage. The present study was to obtain ethnobotanical information on the use and local knowledge variation, geographical distribution, and to collect different landraces of Moringa oleifera from the different agro-ecological regions in Nigeria, for further studies. Ethnobotanical data were collected through face to face interviews, semi structured questionnaires and discussions with selected people who had knowledge about the plant. The fidelity level (FL %) and use value for different use categories of Moringa oleifera and its parts were estimated. The variation in ethnobotanical knowledge was evaluated by comparing the mean use value among ethnic, gender and age groups using sample T test. Garmi GPS was used to determine the locations (latitude and longitude) and height in different areas to assess the geographical spread of the species. Seven (7) categories of use (Food, medicine, fodder, fencing, firewood, gum and coagulant) were recorded for Moringa oleifera. Food and medicinal uses showed highest fidelity level while the leaves and the seeds were the plant parts most utilized for the same purposes. There were significant differences among the ethnic, gender and age groups regarding the ethno-botanical use value. The geographical distribution pattern shows that the Moringa oleifera is well distributed in all ecological zones of Nigeria, well adapted to the varied climatic conditions and gaining unprecedented awareness among the people. Though considered an introduced species, Moringa oleifera has found wide acceptance, recognition and usefulness among the various ethnicities in the studied areas. The sources of introduction, domestication and ethnic differentiation influenced the distribution pattern across the geographical areas.


Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: A double-blinded randomized clinical trial.
In some children with ADHD, sub-optimal levels of various nutrients including PUFA especially omega-3 has been observed, and contradictory reports exist on the results of studies conducted on the positive therapeutic effects of PUFA in patients with ADHD. The aim of this study was to investigate the effectiveness of methylphenidate and PUFA on treatment of patients with ADHD in Zahedan, Iran. In this clinical trial, 40 children between 6 and 12 years of age with ADHD were investigated in Zahedan in 2014. Patients were randomly divided into two groups of methylphenidate plus PUFA and methylphenidate plus placebo. ADHD rating scale was filled before and after the study for patients of both groups. Finally, data were analyzed using SPSS18, paired-samples t-test and chi-square. Mean age of patients was 2.9±1.8 years. Thirty-three children (82.5%) were boys and seven children (17.5%) were girls. Mean severity of signs in the group under methylphenidate plus PUFA treatment was 39.9±4.9 before treatment and 20.1±6.0 after 8 weeks of treatment (p<0.001). Mean severity of signs in the group under methylphenidate plus placebo treatment was 41.2±2.7 before treatment and 26.1±9.0 after 8 weeks of treatment (p<0.001). Mean reduction in the severity of symptoms in the group under methylphenidate therapy was 19.7±5.9 and in PUFA and placebo group it was 15.1±9.3 (p<0.067). Response to treatment (a reduction of at least 25% in the signs) in the group taking methylphenidate plus PUFA was 90% (18 patients) and in methylphenidate plus placebo group, it was 60% (12 patients) (p=0.028). This study shows that PUFA is an efficient nutrient to treat ADHD and it can be used to treat patients. However, definitive conclusion requires repeating the study with a larger sample and longer study period. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015092724209N2. The authors received no financial support for the research, authorship, and/or publication of this article.


Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.
Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.


When evaluating DNA evidence within a likelihood ratio framework, should the propositions be exhaustive?
We seek to develop a rational approach to forming propositions when little information is available from the outset, as this often happens in casework. If propositions used when evaluating evidence are not exhaustive (in the context of the case), then there is a theoretical risk that an LR greater than one may be associated with a proposition in the numerator that - if all meaningful propositions had been considered - would in fact have a lower posterior probability after consideration of the evidence. Ideally, all propositions should be considered. However, with multiple propositions, some terms will be larger than others and for simplification very small terms can be neglected without changing the order of magnitude of the value of the evidence (i.e. LR). Our analysis shows that mathematically a contributor's DNA can be assumed to be present under both prosecution and alternative propositions (Hp and Ha) if there is a reasonable prior probability of their DNA being present and their inclusion is supported by the profile. This is because the terms associated to these sub-propositions will dominate our LR. For example, in the absence of specific information, when considering two persons of interest (POI) as potential contributors to a mixed DNA profile we suggest the assumption of one when examining the presence of the other, after checking that both collectively explain the profile well. This represents more meaningful propositions and allows better discrimination. Slooten and Caliebe have shown that the overall LR is the weighted average of LRs with the same number of contributors (NoC) under both propositions. The weights involve both an assessment of the probability of the crime scene DNA profile and the probability of this NoC given the background information.


Breaking immunological tolerance through OX40 (CD134).
Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process.


SOphrology Intervention to Improve WELL-Being in Hospital Staff (SO-WELL): Protocol for a Randomized Controlled Trial Study.
Stress at work and psychosocial risks are a major public health problem. Sophrology and neurolinguistic programming (NLP) have demonstrated benefits in terms of mental, physical and social health, both in the general population and in patients, and both in and out of hospital settings. However, these approaches have never been provided at the hospital for the benefit of health professionals at risk of suffering at work. In general, we aim to demonstrate the effectiveness of a hospital sophrology/NLP intervention for health care professionals at risk of stress-related disorders. The secondary objectives are to study (i) within-group, and (ii) between-group): (1) effects on mental, physical, and social health; (2) persistence of effect; (3) relationships between job perception and mental, physical, and social health; (4) intervention success factors (personality and job perception, attendance and practice, other); (5) effects on other stress biomarkers (other measures of autonomic nervous system activity, DHEAS, cortisol, etc.). Our study will be a randomized controlled prospective study (research involving the human person of type 2). The study will be proposed to any health-care workers (HCW) or any non-HCW (NHCW) from a healthcare institution (such as CHU of Clermont-Ferrand, other hospitals, clinics, retirement homes). Participants will benefit from NLP and sophrology interventions at the hospital. For both groups: (i) heart rate variability, skin conductance and saliva biomarkers will be assessed once a week during the intervention period (6 to 8 sophrology sessions) and once by month for the rest of the time; (ii) the short questionnaire will be collected once a week during the whole protocol (1-2 min); (iii) the long questionnaire will be assessed only 5 times: at baseline (M0), month 1 (M1), month 3 (M3), month 5 (M5) and end of the protocol (M7). The protocol, information and consent form had received the favorable opinion from the Ethics Committee. Notification of the approval of the Ethics Committee was sent to the study sponsor and the competent authority (ANSM). The study is registered in ClinicalTrials.gov under the identification number NCT05425511 after the French Ethics Committee's approval. The results will be reported according to the CONSORT guidelines. The psychological questionnaires in this study are self-assessed. It is also possible that responses suffer from variation. For the study, participants need to attend 6 to 8 sophrology sessions and one visit per month for 7 months, which might seem demanding. Therefore, to make sure that participants will complete the protocol, two persons will be fully in charge of the participants' follow-up.


Formulation of essential oil-loaded chitosan-alginate nanocapsules.
Naturally occurring polymers such as alginate (AL) and chitosan (CS) are widely used in biomedical and pharmaceutical fields in various forms such as nanoparticles, capsules, and emulsions. These polymers have attractive applications in drug delivery because of their biodegradability, biocompatibility, and nontoxic nature. The pharmaceutical applications of essential oils such as turmeric oil and lemongrass oil are well-known, and their active components, ar-turmerone and citral, respectively, are known for their antibacterial, antifungal, antioxidant, antimutagenic, and anticarcinogenic properties. However, these essential oils are unstable, volatile, and insoluble in water, which limits their use for new formulations. Therefore, this study focuses on developing a CS-AL nanocarrier for the encapsulation of essential oils. The effects of process parameters such as the effect of heat and the concentrations of AL and CS were investigated. Various physicochemical characterization techniques such as scanning electron microscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy were performed. Results of characterization studies showed that 0.3 mg/mL AL and 0.6 mg/mL CS produced minimum-sized particles (<300 nm) with good stability. It was also confirmed that the oil-loaded nanocapsules were hemocompatible, suggesting their use for future biomedical and pharmaceutical applications. Furthermore, the antiproliferative activity of turmeric oil- and lemongrass oil-loaded nanocapsules was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in A549 cell lines and it was found that both the nanoformulations had significant antiproliferative properties than the bare oil.


Hyperglucagonemia during insulin deficiency accelerates protein catabolism.
Hyperglucagonemia coexists with insulin deficiency or insulin resistance in many conditions where urinary nitrogen excretion is increased, but the precise role of glucagon in these conditions is controversial. The purpose of this study was to evaluate the effect of hyperglucagonemia on protein metabolism in insulin-deficient subjects. We used the stable isotope of an essential amino acid (L-[1-13C]leucine) as a tracer of in vivo protein metabolism. A combined deficiency of insulin and glucagon was induced by intravenous infusion of somatostatin. Hyperglucagonemia and hypoinsulinemia were induced by infusions of somatostatin and glucagon. When somatostatin alone was infused leucine flux increased, indicating a 6-17% increase in proteolysis. When somatostatin and glucagon were infused, leucine flux increased, indicating a 12-32% increase in proteolysis. The increase in leucine flux during the infusion of somatostatin and glucagon was higher than the increase during infusion of somatostatin alone. Somatostatin alone did not change leucine oxidation, whereas the somatostatin plus glucagon increased leucine oxidation 100%. We conclude that hyperglucagonemia accelerates proteolysis and leucine oxidation in insulin-deficient humans.