Percutaneous dilatational tracheostomy. A safe, cost-effective bedside procedure.
To evaluate the safety and cost-effectiveness of percutaneous dilatational tracheostomy performed in the intensive care unit. Retrospective review of 65 patients with cost-effectiveness analysis. University-affiliated tertiary care teaching hospital with a 34-bed combined medical-surgical intensive care unit. All patients who underwent percutaneous dilatational tracheostomy under the supervision of a single general surgeon during a 19-month period. Cost analysis was based on comparison with standard operative tracheostomies performed during the same period. Percutaneous dilatational tracheostomy was completed in all patients in whom it was attempted, regardless of airway anatomy, body habitus, and ventilator settings. The mean duration of the procedure performed in the intensive care unit was 13.6 minutes (95% confidence interval, 11.7 to 15.5 minutes). Intraoperative complications occurred in 14 patients (22%), most of which were minor technical difficulties, and none resulted in serious morbidity. Postoperative complications occurred in six patients (9%), including one death secondary to premature decannulation, three bleeding complications, one episode of subcutaneous emphysema, and one air leak. Two long-term airway complications after percutaneous dilatational tracheostomy were documented during a mean 7.5-month follow-up of 28 patients. Mean patient charges for the procedure performed in the intensive care unit by a surgeon, nurse, and respiratory therapist were $997 (95% confidence interval, $975 to $1018) compared with $2642 (95% confidence interval, $2513 to $2772) for standard tracheostomy (P<.001). This represented a savings of $1645 (95% confidence interval, $1492 to $1798) per tracheostomy. Percutaneous dilatational tracheostomy is a safe, rapid, cost-effective alternative to standard open tracheostomy. It can be performed at the bedside, obviating the need to transport critically ill patients from their optimal intensive care unit environment.


Inverse Relationship Between Organ-Specific Autoantibodies and Systemic Immune Mediators in Type 1 Diabetes and Type 2 Diabetes: Action LADA 11.
We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). Type 1 diabetes patients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetes patients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.


When metacognition fails: impaired awareness of deficit in Alzheimer's disease.
Two new measures were developed to assess quantitatively the degree to which patients with Alzheimer's disease (AD) are aware of their memory deficit, and to evaluate the relation between dementia severity and awareness of deficit. Results of a questionnaire measure indicated that AD patients rated their own difficulties with cognitive activities of daily life significantly lower than relatives rated patients' problems, and this discrepancy was related to patients' dementia severity. On another measure involving task performance predictions, AD patients were inaccurate in predicting their performance on most cognitive tasks when compared to both their actual performance and relatives' predictions, despite generally accurate prediction of their relatives' performance on the same tasks. These results are discussed in terms of a breakdown in metacognitive processes.


Asymmetric cryorolling for fabrication of nanostructural aluminum sheets.
Nanostructural Al 1050 sheets were produced using a novel method of asymmetric cryorolling under ratios of upper and down rolling velocities (RUDV) of 1.1, 1.2, 1.3, and 1.4. Sheets were rolled to about 0.17 mm from 1.5 mm. Both the strength and ductility of Al 1050 sheets increase with RUDVs. Tensile strength of Al sheets with the RUDV 1.4 is larger 22.3% of that for RUDV 1.1, which is 196 MPa. The TEM observations show the grain size is 360 nm when the RUDV is 1.1, and 211 nm for RUDV 1.4.


Structure of apo-CAP reveals that large conformational changes are necessary for DNA binding.
The binding of cAMP to the Escherichia coli catabolite gene activator protein (CAP) produces a conformational change that enables it to bind specific DNA sequences and regulate transcription, which it cannot do in the absence of the nucleotide. The crystal structures of the unliganded CAP containing a D138L mutation and the unliganded WT CAP were determined at 2.3 and 3.6 A resolution, respectively, and reveal that the two DNA binding domains have dimerized into one rigid body and their two DNA recognition helices become buried. The WT structure shows multiple orientations of this rigid body relative to the nucleotide binding domain supporting earlier biochemical data suggesting that the inactive form exists in an equilibrium among different conformations. Comparison of the structures of the liganded and unliganded CAP suggests that cAMP stabilizes the active DNA binding conformation of CAP through the interactions that the N(6) of the adenosine makes with the C-helices. These interactions are associated with the reorientation and elongation of the C-helices that precludes the formation of the inactive structure.


Associations between dry dietary factors and canine calcium oxalate uroliths.
To identify factors in dry diets associated with the occurrence of calcium oxalate (CaOx) uroliths in dogs. 600 dogs with CaOx uroliths and 898 dogs without urinary tract diseases. Univariate and multivariate logistic regression were performed. Compared with diets with the highest concentrations of sodium, dry diets with the lowest concentrations of sodium, phosphorus, calcium, chloride, protein, magnesium, or potassium were linearly associated with increased risk of CaOx urolith formation. Significant nonlinear associations between increased occurrence of CaOx uroliths and urine acidifying potential and low moisture content were observed. Significant nonlinear associations between decreased occurrence of CaOx uroliths and carbohydrate and fiber contents were observed. A significant association between the occurrence of CaOx uroliths and dietary fat was not observed. Results suggest that dry diets formulated to contain high concentrations of protein, calcium, phosphorus, magnesium, sodium, potassium, and chloride may minimize formation of CaOx uroliths. In addition, comparison of risk and protective factors of various diet ingredients fed to dogs with CaOx uroliths suggests that although similar findings were observed in canned and dry formulations, in general, greater risk is associated with dry formulations. However, before these hypotheses about dietary modifications are adopted by food manufacturers, they must be investigated by use of appropriately designed clinical studies of dogs with CaOx urolithiasis.


Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.
IM862 is a naturally occurring dipeptide (L-glu-L-trp) with immunomodulatory and antiangiogenic properties. A significant anticancer activity has been reported recently in AIDS-related Kaposi's sarcoma, a tumour of endothelial cell origin. The high vascularity and responsiveness to immunotherapy of renal cell carcinoma (RCC) makes such a tumour a potential target for IM862. In all, 25 patients were accrued in a prospective phase II trial using a standard two-step design. The main inclusion criteria were WHO performance status </=2, age over 18 years, expected survival >3 months, normal marrow, kidney and liver functions. IM862 was given intranasally at a dose of 20 mg three times daily. Each cycle consisted of 8 consecutive weeks of treatment. All 25 patients were fully evaluable for response and 24 for toxicities. Median age was 62 years (range 42-76), median WHO PS was 1 (0-2). No grade 2 or 3 toxicities related to the study drug have been recorded. Eight patients had stable disease (SD) and 17 progressed while on treatment. Median survival was 7.9 months (range 2.7-20). Median time to progression was 1.9 months (range 1.2-12.6). Median duration of SD was 6 months (range 5.2-12.6+). Analysis of blood angiogenic markers showed a significant decrease of plasma vascular endothelial growth factor (VEGF) levels after 4 and 8 weeks of therapy. Treatment with IM862 has no toxicity, but does not lead to any significant objective responses in metastatic RCC. IM862 should not be further evaluated as a single agent at these doses and schedule for this population of patients. The decrease in VEGF levels warrants further investigation of IM862 as an antiangiogenic therapy.


Advances in radionuclide therapeutics in orthopaedics.
Radiopharmaceuticals not only are used for diagnostic purposes but also increasingly in the treatment of many orthopaedic-related disorders. With the development of specific bone-seeking radiopharmaceuticals, the side effects of treatment are minimized, therapeutic effects are sustained, and concomitant use with other modalities may have synergistic effects. These new radiopharmaceuticals, such as strontium 89 and samarium 153-ethylene diamine tetramethylene phosphate, have been used as palliative treatment for patients with bone pain from osseous metastases. Excellent clinical responses with acceptable hematologic toxicity have been observed, and clinical results rival those of external beam radiation therapy. Radiosynovectomy has become a procedure of choice at many institutions to treat recurrent hemarthrosis and chronic synovitis in patients whose hemophilia is poorly controlled with medical management. Radiosynovectomy also remains a viable option to treat chronic synovitis secondary to inflammatory arthropathies, particularly rheumatoid arthritis.


The appropriateness and persistence of testosterone replacement therapy in Ontario.
To examine the concordance between testosterone replacement therapy (TRT) use and established reimbursement criteria, as well as compare the persistence of use among available formulations (injectable, oral, topical gel, transdermal patch) among elderly men in Ontario, Canada. We conducted a retrospective cohort study of men aged 66 years or older in Ontario newly treated with testosterone between 1 January 2009 and 31 December 2012 using linked health administrative data. Continuous use was defined on the basis of prescription refills issued within 180 days of the preceding prescription. We studied men who received at least two consecutive TRT prescriptions. We estimated the prevalence of hypogonadism, human immunodeficiency virus, specialist visits and lab tests for serum testosterone prior to initiation of TRT to investigate concordance with prescribing criteria. We also performed a Kaplan-Meier analysis to test for differences in the median time to discontinuation among formulations. Among the 4797 men who received at least two TRT prescriptions, only 38.7% met the reimbursement criteria for use prior to initiating therapy. The median time to discontinuation differed significantly among formulations and was longest among recipients of oral TRT products (383 days), and lower for recipients of topical gels (319 days), injectable (283 days) and transdermal patches (160 days; Log-rank test p < 0.001). A large proportion of older men in Ontario do not appear to meet reimbursement criteria prior to commencing therapy, and many discontinue TRT within a year of initiation. Copyright © 2016 John Wiley & Sons, Ltd.


Selective gas capture via kinetic trapping.
Conventional approaches to the capture of CO2 by metal-organic frameworks focus on equilibrium conditions, and frameworks that contain little CO2 in equilibrium are often rejected as carbon-capture materials. Here we use a statistical mechanical model, parameterized by quantum mechanical data, to suggest that metal-organic frameworks can be used to separate CO2 from a typical flue gas mixture when used under nonequilibrium conditions. The origin of this selectivity is an emergent gas-separation mechanism that results from the acquisition by different gas types of different mobilities within a crowded framework. The resulting distribution of gas types within the framework is in general spatially and dynamically heterogeneous. Our results suggest that relaxing the requirement of equilibrium can substantially increase the parameter space of conditions and materials for which selective gas capture can be effected.


An internet-based survey of synesthesia in multiple sclerosis: Incidence, characteristics and implications.
Objective Prior work raises the interesting possibility that both multiple sclerosis and synesthesia share a common etiology, that being immune system dysfunction, as well as neuroanatomical and neurochemical abnormalities, including those involving white matter and serotonergic pathways, respectively. Given these links between these two syndromes, we examined the possibility that prevalence of synesthesia would be elevated in a population of individuals with MS, relative to what is thought to be the prevalence in the neurotypical population. It was not known whether synesthesia might be a marker for subsequent development of MS, or if synesthesia might reflect neurological damage resulting from MS disease progression. Method Individuals with self- reported clinically definite MS were recruited online via the internet and social media using sites specifically relevant to the MS community. Data from 147 individuals who completed several questionnaires related to synesthesia were analyzed. Results Depending on criteria, between approximately 7 and 16% of individuals with MS reported synesthesia here. This is an estimated 1.57 to 3.55 times increased incidence of synesthesia here relative to previous findings in neurotypical samples. Limitations of the study include that this was an internet survey, and that synesthesia was not directly assessed in this sample. Conclusions Results suggest a link between the syndromes, primarily indicating that synesthesia may be a marker for subsequent MS development, and the implications and directions for future study are discussed.


Evaluating Blood Loss and the Effect of Antiplatelet Treatment in Foot and Ankle Amputations.
The interrelationship between diabetes mellitus and cardiovascular disease is well-documented, and, secondary to the latter, is the use of antiplatelet therapy. Although diabetes and the associated vascular manifestations are driving forces behind lower extremity amputations, few data are available on the risks of perioperative antiplatelet therapy with foot and ankle amputations. The goal of the present study was to address the surgical effect of continuing or discontinuing antiplatelet therapy before foot and/or ankle amputation. The following data were retrospectively collected: blood loss, pre- and postoperative hematocrit and hemoglobin, operative time, amputation type, age, diabetic status, antiplatelet treatment, and number of transfusions during the perioperative period. Perioperative antiplatelet therapy was defined as exposure to aspirin or clopidogrel within 3 days before surgery. To compare the outcomes between groups, the following factors were analyzed using bivariate analyses and then multivariate regression models: (1) the need for transfusions, (2) high blood loss (>20 mL), (3) volume of blood loss, and (4) operative time. The noninferiority of continued antiplatelet use was assessed in terms of operative time and blood loss, using a noninferiority margin of 10 minutes or 10 mL, respectively. Antiplatelet therapy was not a statistically significant risk factor for any of the studied outcomes on multivariate analysis. Equivalence testing revealed that continuing antiplatelet therapy is not inferior to discontinuing perioperative therapy in terms of blood loss and operative time. Multivariate analysis of the data suggested that antiplatelet therapy has no statistically significant impact on blood loss, transfusion rate, or operative time.


Measuring treatment coverage for neglected tropical disease control programs: analysis of a survey design.
Monitoring of treatment coverage following mass drug administration is essential to ensure program success. Coverage results reported by drug administrators are often validated by using population surveys. This study evaluates the design of a multistage cluster sample survey conducted in 2007-2008 and implemented at the district level to assess drug coverage in the 4 African countries of Burkina Faso, Ghana, Niger, and Uganda. Estimates of precision of coverage were calculated, and factors contributing to the observed variance were analyzed. Precision of ±5 percentage points was obtained in 39% (n = 12) of cases, and precision of ±10 percentage points was obtained in 77% (n = 24) of cases. The factor having the largest impact on the actual precision obtained in these surveys was the high level of clustering, the impact of which is incorporated in the design effect. Key recommendations are made for the design and analysis of future surveys; guidelines are presented for thinking through the number of clusters that should be selected and how a cluster should be designed.


Availability of vaccines against major animal diseases in the European Union.
This paper presents the results of a survey in which countries within the European Union and the European Economic Area were requested to provide information on the availability of vaccines against 47 major diseases of animals as part of the DISCONTOOLS project within the European Technology Platform for Global Animal Health. The objective of the survey was to help identify those diseases to which priority should be given by both the public and private sectors in terms of developing new tools to assist in their control. The survey also provides information on the availability of vaccines authorised at national level against the diseases concerned which may be useful in the event of a disease emergency or to enhance preparedness.


Echoes of old HIV paradigms: reassessing the problem of engaging men in HIV testing and treatment through women's perspectives.
With the introduction of 2016 World Health Organization guidelines recommending universal antiretroviral therapy (ART), there has been increased recognition of the lack of men engaging in HIV testing and treatment. Studies in sub-Saharan Africa indicate there have been challenges engaging men in HIV testing and HIV-positive men into treatment. This qualitative study explored women's perspective of their male partner's attitudes towards HIV and ART and how it shapes woman's experience with ART. Data were collected through in-depth interviews and focus group discussions with HIV-positive pregnant and postpartum women on Option B+ and health care workers in Malawi and Zimbabwe. In Malawi, 19 in-depth interviews and 12 focus group discussions were conducted from September-December 2013. In Zimbabwe, 15 in-depth interviews and 21 focus-group discussions were conducted from July 2014-March 2014. The findings highlighted that many men discourage their partners from initiating or adhering to ART. One of the main findings indicated that despite the many advancements in HIV care and ART regimens, there are still many lingering negative beliefs about HIV and ART from the earlier days of the epidemic. In addition to existing theories explaining men's resistance to/absence in HIV testing and treatment as a threat to their masculinity or because of female-focused health facilities, this paper argues that men's aversion to HIV may be a result of old beliefs about HIV and ART which have not been addressed. Due to lack of accurate and up to date information about HIV and ART, many men discourage their female partners from initiating and adhering to ART. The effect of lingering and outdated beliefs about HIV and ART needs to be addressed through strengthened communication about developments in HIV care and treatment. Universal ART offers a unique opportunity to curb the epidemic, but successful implementation of these new guidelines is dependent on ART initiation and adherence by both women and men. Strengthening men's understanding about HIV and ART will greatly enhance women's ability to initiate and adhere to ART and improve men's health.


Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in Staphylococcus epidermidis.
Expression of the gene cluster icaADBC is necessary for biofilm production in Staphylococcus epidermidis. The ica operon is negatively controlled by the repressor IcaR. Here, the crystal structure of IcaR was determined and the refined structure revealed a homodimer comprising entirely alpha-helices, typical of the tetracycline repressor protein family for gene regulations. The N-terminal domain contains a conserved helix-turn-helix DNA-binding motif with some conformational variations, indicating flexibility in this region. The C-terminal domain shows a complementary surface charge distribution about the dyad axis, ideal for efficient and specific dimer formation. The results of the electrophoretic mobility shift assay and isothermal titration calorimetry suggested that a 28 bp core segment of the ica operator is implicated in the cooperative binding of two IcaR dimers on opposite sides of the duplex DNA. Computer modeling based on the known DNA-complex structure of QacR and site-specific mutagenesis experiments showed that direct protein-DNA interactions are mostly conserved, but with slight variations for recognizing the different sequences. By interfering with the binding of IcaR to DNA, aminoglycoside gentamicin and other antibiotics may activate the icaADBC genes and elicit biofilm production in S. epidermidis, and likely S. aureus, as a defense mechanism.


Nutrition and metabolism in hepatocellular carcinoma.
Hepatocellular carcinoma is the fifth most common human cancer worldwide, with an overall 5-year survival in the range of 10%. In addition to the very substantial role of chronic viral hepatitis in causing hepatocellular carcinoma, nutritional status and specific nutritional factors appear to influence disease risk. This is apparent in the increased risk associated with non-alcoholic hepatic cirrhosis occurring in the context of obesity, the metabolic syndrome, and type 2 diabetes. Specific nutrients and ingested toxins, including ethanol, aflatoxin, microcystins, iron, and possibly components of red meat, also are associated with increased hepatocellular carcinoma risk. Other dietary components, including omega-3 fatty acids and branched chain amino acids, may have protective effects. Recent data further suggest that several metabolic regulatory drugs, including metformin, pioglitazone, and statins, may have the potential to decrease the risk of hepatocellular carcinoma. The available data on these nutritional and metabolic factors in causing hepatocellular carcinoma are reviewed with the goal of identifying the strength of current knowledge and directions for future investigation.


Health risk behaviors among young adults with spina bifida.
Persons with spina bifida who adopt unhealthy lifestyles could be at increased risk of adverse health outcomes because the presence of spina bifida may magnify this risk. We estimated overall and age-specific prevalence of selected health risk behaviors (HRBs) in young people with spina bifida and examined the association between HRBs and depression. We performed analyses on data obtained from individuals with spina bifida (n=130; mean age 23y SD 4y 5mo; 64 males, 66 females; 64% lumbosacral lesion; 77% with shunt) who participated in a population-based survey conducted by the Arkansas Spinal Cord Commission in 2005. Compared with national estimates, young people with spina bifida tend to eat less healthy diets, do less exercise, and engage in more sedentary activities. Respondents were less likely to use substances (alcohol, tobacco, illegal drugs), which peaked among 25 to 31 year olds. About 90% saw a doctor in the previous year. Nearly one half reported mild or major depressive symptoms. In the logistic regression analysis after controlling for potential confounders (age, sex, ethnic group, education, employment, marital status, living arrangement, level of lesion, presence of shunt, mobility, self-rated health and healthcare utilization), major depressive symptoms were associated with current alcohol drinking (adjusted odds ratio: 4.74; 95% CI 1.18-19.04). Young adults with spina bifida exhibit unhealthy behaviors that continue into their late 20s. The findings highlight the need to increase awareness of their health risk profiles in the spina bifida community and show opportunities for mental health and health risk screening and counseling by healthcare providers.


Laparoscopic anti-reflux procedures with hepatic shoulder technique in the surgical management of large hiatal hernias and paraesophageal hernias: a follow-up study.
Numerous techniques have been historically proposed in the management of gastroesophageal reflux and paraesophageal hernias (PEH). A follow-up study (Quilici et al. in Surg Endosc 23(11):2620-2623, 2009) to a novel laparoscopic approach introduced in 2009 and performed in 49 patients is presented. All procedures were performed via laparoscopy. Thirty-two patients underwent a Nissen Fundoplication, eleven a reduction of the PEH with a Nissen fundoplication, two without a fundoplication, and four with a Collis-Nissen fundoplication. In all patients, the left hepatic lobe was freed, repositioned, and anchored under and inferior to the gastroesophageal junction, propping the gastroesophageal junction anteriorly. This maneuver entirely covers and closes the diaphragmatic defect. At the time of laparoscopy, several patients were found not to be suitable candidates for this procedure (morphology of the left hepatic lobe). Forty-nine procedures were completed. One patient was re-explored on POD 2 for a tight hiatus post-Collis fundoplication. Post-operatively, all other patients did well without notable, unusual complaints. The average length of stay was 2.2 days. Although not statistically significant, 43 patients had no recurrence of symptoms with the longest follow-up at 10 years, two patients were lost to follow-up, one patient had a recurrence of the PEH and three patients stated they were experiencing some form of gastroesophageal reflux requiring medical management. In selected patients, patients with an "at-risk" crural closure during a laparoscopic anti-reflux procedure or PEH can safely be managed via a laparoscopic anti-reflux procedure with the hepatic shoulder technique. This technique has shown good early post-operative results and could be used as an alternative to a laparoscopic mesh-reinforced fundoplication in difficult crural closures or in the management of large paraesophageal hernias.


One pot microwave synthesis of highly stable AuPd@Pd supported core-shell nanoparticles.
A series of 1 wt% supported Au, Pd and AuPd nanoalloy catalysts were prepared via microwave assisted reduction of PdCl2 and HAuCl4 in a facile, one pot process. The resulting materials showed excellent activity for the direct synthesis of hydrogen peroxide from hydrogen and oxygen, with a synergistic effect observed on the addition of Au into a Pd catalyst. Detailed electron microscopy showed that the bimetallic particles exhibited a core-shell morphology, with an Au core surrounded by an Au-Pd shell, with a size between 10-20 nm. The presence of Au in the shell was confirmed by EDX studies, with corroborating data from XPS measurements showing a significant contribution of both Au and Pd in the spectra, with the Au signal increasing as the total Au content of the catalyst increased. No PdO was observed, suggesting a complete reduction of the metal chloride nanoparticles. Unlike similar catalysts prepared by sol-immobilisation methodology, the core-shell structures showed excellent stability during the hydrogen peroxide synthesis reaction, and no catalyst deactivation was observed over 4 reuse cycles. This is the first time the preparation of stable core-shell particles have been reported using microwave assisted reduction. The observation that these particles are core-shell, without the need of a complicated synthesis or high thermal treatment and form in just 15 minutes presents an exciting opportunity for this experimental technique.


Short- and long-term mortality after an acute illness for elderly whites and blacks.
To estimate racial differences in mortality at 30 days and up to 2 years following a hospital admission for the elderly with common medical conditions. The Medicare Provider Analysis and Review File and the VA Patient Treatment File from 1998 to 2002 were used to extract patients 65 or older admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia. A retrospective analysis of risk-adjusted mortality after hospital admission for blacks and whites by medical condition and in different hospital settings. Black Medicare patients had consistently lower adjusted 30-day mortality than white Medicare patients, but the initial survival advantage observed among blacks dissipated beyond 30 days and reversed by 2 years. For VA hospitalizations similar patterns were observed, but the initial survival advantage for blacks dissipated at a slower rate. Racial disparities in health are more likely to be generated in the posthospital phase of the process of care delivery rather than during the hospital stay. The slower rate of increase in relative mortality among black VA patients suggests an integrated health care delivery system like the VA may attenuate racial disparities in health.


High female survival promotes evolution of protogyny and sexual conflict.
Existing models explaining the evolution of sexual dimorphism in the timing of emergence (SDT) in Lepidoptera assume equal mortality rates for males and females. The limiting assumption of equal mortality rates has the consequence that these models are only able to explain the evolution of emergence of males before females, i.e. protandry-the more common temporal sequence of emergence in Lepidoptera. The models fail, however, in providing adaptive explanations for the evolution of protogyny, where females emerge before males, but protogyny is not rare in insects. The assumption of equal mortality rates seems too restrictive for many insects, such as butterflies. To investigate the influence of unequal mortality rates on the evolution of SDT, we present a generalised version of a previously published model where we relax this assumption. We find that longer life-expectancy of females compared to males can indeed favour the evolution of protogyny as a fitness enhancing strategy. Moreover, the encounter rate between females and males and the sex-ratio are two important factors that also influence the evolution of optimal SDT. If considered independently for females and males the predicted strategies can be shown to be evolutionarily stable (ESS). Under the assumption of equal mortality rates the difference between the females' and males' ESS remains typically very small. However, female and male ESS may be quite dissimilar if mortality rates are different. This creates the potential for an 'evolutionary conflict' between females and males. Bagworm moths (Lepidoptera: Psychidae) provide an exemplary case where life-history attributes are such that protogyny should indeed be the optimal emergence strategy from the males' and females' perspectives: (i) Female longevity is considerably larger than that of males, (ii) encounter rates between females and males are presumably low, and (iii) females mate only once. Protogyny is indeed the general mating strategy found in the bagworm family.


Police Violence among Adults Diagnosed with Mental Disorders.
Police violence is reportedly common among those diagnosed with mental disorders characterized by the presence of psychotic symptoms or pronounced emotional lability. Despite the perception that people with mental illness are disproportionately mistreated by the police, there is relatively little empirical research on this topic. A cross-sectional general population survey was administered online in 2017 to 1,000 adults in two eastern U.S. cities to examine the relationship between police violence exposure, mental disorders, and crime involvement. Results from hierarchical logistic regression and mediation analyses revealed that a range of mental health conditions are broadly associated with elevated risk for police violence exposure. Individuals with severe mental illness are more likely than the general population to be physically victimized by police, regardless of their involvement in criminal activities. Most of the excess risk of police violence exposure related to common psychiatric diagnoses was explained by confounding factors including crime involvement. However, crime involvement may necessitate more police contact, but does not necessarily justify victimization or excessive force (particularly sexual and psychological violence). Findings support the need for adequate training for police officers on how to safely interact with people with mental health conditions, particularly severe mental illness.


Differential evolution of blood pressure and renal lesions after RAS blockade in Lyon hypertensive rats.
The present work aimed to assess, in Lyon hypertensive (LH) rats, whether an early and prolonged inhibition of the renin-angiotensin system (RAS) could result in a blood pressure (BP) lowering and nephroprotection that persist after its withdrawal. Male LH rats received orally from 3 to 12 wk of age either an angiotensin-converting enzyme inhibitor perindopril at the doses of 0.4 and 3 mg x kg(-1) x day(-1) or an AT(1) receptor antagonist losartan at the dose of 10 mg x kg(-1) x day(-1). BP, histological changes in the kidney, and urinary protein excretion were examined during and 10 wk after cessation of the treatments. Both perindopril and losartan decreased BP, prevented renal lesions, and limited urinary protein excretion. After cessation of the treatment, BP returned to the level of never-treated LH rats in rats having received 3 mg x kg(-1) x day(-1) of perindopril while it remained slightly lower in those treated with 0.4 mg x kg(-1) x day(-1) of perindopril or with losartan. This lack of marked persistent antihypertensive effect contrasted with a durable decrease in urinary protein excretion and improvement of the renal histological lesions. In conclusion, it is possible to separate the BP-lowering effects of RAS blockade from those on glomerulosclerosis and urinary protein excretion.


Ossifying pituitary adenoma co-existing with astrocytoma and pituitary adenoma associated with gangliocytoma: two unusual conditions.
Bone formation in pituitary adenoma is an extremely rare finding. Only five previous cases have been published. This is the sixth case report of an ossifying pituitary adenoma and the first case report of a pituitary adenoma with bone formation coexisting with WHO grade II astrocytoma. MRI imaging revealed an unusual eggshell cap-like calcified structure surrounding the tumor. Histologically, the adenoma contained irregularly anastomosing trabeculae with well-formed lacunae and osteoblasts along the margins. Our second case concerns a 25-year-old male patient who presented with complains of off and on headache for 12 months. MRI (head) revealed a 4x3cm well defined rounded lesion in the sella and suprasellar extension that was isointense in T1, hyperintense on T2 with cystic areas and homogenous contrast enhancement. On morphological examination, a cellular tumor admixed with foci of large ganglion cells embedded in a neuropil stroma was noted. On immunohistochemistry, tumor cells were focally positive for pancytokeratin, growth hormone and synaptophysin; and ganglion cells were positive for neurofilament and synaptophysin. No GFAP positive cells were seen. The Ki67 index was < 1%. Based on these findings, a diagnosis of gangliocytoma associated with pituitary adenoma was considered.


NMR analysis of the structure, dynamics, and unique oligomerization properties of the chemokine CCL27.
Chemokines have two essential interactions in vivo, with G protein-coupled receptors, which activate intracellular signaling pathways, and with glycosaminoglycans (GAGs), which are involved in cell surface localization and transport. Although it has been shown that chemokines bind and activate their respective G protein-coupled receptors as monomers, many chemokines oligomerize upon GAG binding, and the ability to oligomerize and bind GAGs is required for in vivo function. In this study, we investigated the structure, dynamics, and oligomerization behavior of cutaneous T-cell-attracting chemokine (CTACK, also known as CCL27) by NMR. (15)N relaxation and translational self-diffusion rates indicate that CCL27 oligomerizes, but in contrast to many other chemokines that form relatively discrete oligomers, CCL27 transitions between monomer, dimer, and tetramer species over a relatively narrow concentration range. A three-dimensional structure determination was pursued under conditions where CCL27 is primarily dimeric, revealing the standard motif for a chemokine monomer. Analysis of chemical shift perturbations of (1)H-(15)N HSQC spectra, relaxation-dispersion experiments, and filtered nuclear Overhauser effects suggest that CCL27 does not adopt a discrete CXC or CC dimer motif. Instead, CCL27 has uncommon oligomerization behavior, where several equilibria involving relatively low affinity interactions between different interfaces seem to be simultaneously at work. However, interaction with heparin avidly promotes oligomerization under conditions where CCL27 is monomeric by itself. We hypothesize that the plasticity in the oligomerization state may enable CCL27 to adopt different oligomeric structures, depending on the nature of the GAG binding partner, thereby providing a mechanism for increased diversity and specificity in GAG-binding and GAG-related functions.


A population-based assessment of specialty physician involvement in cancer clinical trials.
Clinical trials are critical for evaluating new cancer therapies, but few adult patients participate in them. Physicians have an important role in facilitating patient participation in clinical trials. We examined the characteristics of specialty physicians who participate in clinical trials by enrolling or referring patients, the types of trials in which they participate, and factors associated with physicians who report greater involvement in clinical trials. We analyzed data from the Cancer Care Outcomes Research and Surveillance Consortium. The study included 1533 specialty physicians who cared for colorectal and lung cancer patients (496 medical oncologists, 228 radiation oncologists, and 809 surgeons) and completed a survey conducted during 2005-2006 (response rate = 61.0%). Descriptive statistics were used to characterize physicians' personal and practice characteristics, and regression models were used to examine associations between these characteristics and physician participation in clinical trials. All statistical tests were two-sided. A total of 87.8% of medical oncologists, 66.1% of radiation oncologists, and 35.0% of surgeons reported referring or enrolling one or more patients in clinical trials during the previous 12 months. The mean number of patients referred or enrolled by these physicians was 17.2 (95% confidence interval [CI] = 15.5 to 18.9) for medical oncologists, 9.5 (95% CI = 7.7 to 11.3) for radiation oncologists, and 12.2 (95% CI = 9.8 to 14.6) for surgeons (P < .001). Specialty type, involvement in teaching, and affiliation with a Community Clinical Oncology Program (CCOP) and/or a National Cancer Institute-designated cancer center were associated with physician trial participation and enrolling more patients (all Ps < .05). Two-thirds of physicians with a CCOP or National Cancer Institute-designated cancer center affiliation reported participating in trials. Features of specialty physicians' practice environments are associated with their trial participation, but many physicians at CCOPs and cancer centers do not participate.


Pharmacognostical evaluation of Barringtonia acutangula leaf.
Barringtonia acutangula (L.) Gaertn. (Family: Lecythidaceae) is an evergreen tree with simple, alternate leaves, long pendulous racemes, dark scarlet flowers, and ellipsoid to ovoid berries containing one ovoid black seed. The present study deals with a detailed pharmacognostical study on the leaf of the crude drug, B. acutangula. Morphoanatomy of the leaf was studied using light and confocal microscopy and World Health Organization (WHO) guidelines on quality control methods for medicinal plant materials. Literature reveals that the phytoconstituents like tanginol, barrinic acid, and barringenic acid are present in the wood and fruits of this plant. Our preliminary phytochemical studies of the powdered leaves revealed the presence of terpenes, flavanoids, carbohydrates, tannins, steroids, and glycosides. The physico-chemical, morphological, histological parameters, and High Performance-Thin Layer Chromatographic (HPTLC) profile presented in this paper may be proposed as parameters to establish the authenticity of B. acutangula and can possibly help to differentiate the drug from its other species and the pharmacognostic profile of the leaves presented here will assist in standardization viz., quality, purity, and sample identification.


Concordance between self-reported and actual hepatitis C virus infection status in a cohort of people who inject drugs.
Accurate knowledge of individual hepatitis C virus (HCV) status is an important component of comprehensive health services for people who inject drugs (PWID). In this paper we compare the perceived HCV status of PWID in a longitudinal cohort study with their actual status, as verified by HCV-RNA testing. Participants who consented to blood testing at first follow up (352/688) were included. Self-reported HCV status (positive/negative/don't know), was compared with serology test results for participants. In comparing self-report with HCV-RNA results, 274 of 352 participants had valid serology and self-report results; of these, 220 (80%) accurately reported their HCV status. The findings of this study suggest that large proportions of PWID know their true HCV infection status, but the discordant participants represent potential HCV infection risks. Despite the majority of participants displaying concordance, this study reinforces the need for regular blood testing and the giving of accurate, practical and comprehensive HCV result information.


Microbiological Survey of Packaged Ready-to-Eat Red Meats at Retail in New Zealand.
A microbiological survey was undertaken on packaged ready-to-eat red meats available at retail in New Zealand. A total of 1,485 samples (297 lots of five samples each) were collected according to a sampling plan based on market share and regulatory regimes (Animal Products Act 1999 and Food Act 1981) and were tested against the microbiological limits specified in Food Standards Code (FSC) 1.6.1 applicable at the time of sampling. Each lot was tested as a composite for the presence or absence of Salmonella spp., coagulase-producing staphylococci, Listeria monocytogenes, and other Listeria spp. at the end of the manufacturer's stated shelf life. Individual samples within a positive lot were subsequently enumerated for L. monocytogenes. None of the samples contained Salmonella spp. or had coagulase-producing staphylococci counts above the acceptable level specified in FSC 1.6.1 (>100 CFU/g). Data showed that 93.6% (278 of 297 lots) of ready-to-eat red meat complied with the FSC 1.6.1 criteria applicable at the time of the survey. The failure of 19 lots (6.4%) was due to the presence of L. monocytogenes from product obtained from 8 of 33 producers tested. Thirteen samples of 95 positive samples were found to contain between 50 and 500 CFU/g L. monocytogenes, but all of these samples were manufactured by the same operator. Pulsed-field gel electrophoresis typing of all of the L. monocytogenes isolates obtained from the survey identified 12 different pulsotypes. Different pulsotypes were often identified in samples from the same operator sampled on separate occasions. A total of 46 lots (15.5%) contained Listeria spp. (including L. monocytogenes). The detection of Listeria in samples may highlight the existence of problems in operator processing and/or packaging processes and suggests that improvements in good hygienic practice and implementation of more effective risk mitigation strategies are needed.


Effect of solvent and rewetting time on dentin adhesion.
The purpose of this in vitro study was to determine the influence of solvent and rewetting time on microtensile dentin bond strengths of four dentin adhesives. Sixty human molar specimens were divided into four dentin adhesive treatment groups: (1) a water-based total-etch dentin adhesive, EBS Multi; (2) an ethanol-based total-etch adhesive, Excite; (3) an acetone-based total-etch adhesive, Prime & Bond NT; and (4) an ethanol- and water-based total-etch adhesive, Single Bond. For each dentin adhesive, three specimens were assigned to five dentin moisture conditions. Specimens were tested in the tensile mode. When adhesives were applied to moist dentin, bond strengths varied from 26.2 MPa for Prime & Bond NT to 29.5 MPa for Single Bond without any statistical differences. When applied to dentin that had been dried for 15 seconds, Prime & Bond NT and Excite resulted in the lowest mean bond strengths, but they were statistically similar to each other (7.9 and 8.3 MPa, respectively). Single Bond resulted in a mean bond strength of 12.7 MPa, which was significantly lower than that of EBS Multi (24.1 MPa). For the latter, all mean bond strengths were statistically similar when some amount of moisture was present on the surface. For the other three adhesives, mean bond strengths returned to the range obtained on moist dentin only when dentin was rewet for 30 seconds. Bond strengths upon rewetting depend on the type of solvent in the bonding system, and rewetting time.


Sustainable biobanks: a case study for a green global bioethics.
This paper argues that as we move to redefine global bioethics, there is a need to be attentive to the ethical issues associated with the environmental sustainability of data and digital infrastructures in global health systems. We show that these infrastructures have thus far featured little in environmental impact discussions in the context of health, and we use a case study approach of biobanking to illustrate this. We argue that this missing discussion is problematic because biobanks have environmental impacts associated with data and digital infrastructures. We consider several ethical questions to consider these impacts: what ethical work does the concept of environmental sustainability add to the debate; how should this concept be prioritised in decision-making; and who should be responsible for doing so? We call on global bioethics to play a role in advancing this dialogue and addressing these questions.


Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle.
Neurally mediated relaxation of canine colonic smooth muscle is associated with an increase in the resting membrane potential and is blocked by inhibition of nitric oxide synthesis. N omega-nitro-L-arginine completely prevented nerve-mediated relaxation, an effect that was reversed by L-arginine but not D-arginine. Vasoactive intestinal peptide (VIP) also relaxed canine colonic smooth muscle. Part of this relaxation was due to activation of inhibitory nerves and this effect was mediated by nitric oxide. In addition to the neurally mediated effect, VIP affected smooth muscle directly. This relaxation was associated with a reduction of the plateau phase of the slow-wave type action potential, without an effect on the resting membrane potential. This action of VIP was similar to that of forskolin which suggests that VIP increases intracellular cyclic AMP. In summary, nitric oxide mediates inhibitory innervation to smooth muscle as well as activation of inhibitory nerves by VIP. The electrophysiological mechanism by which VIP directly affects smooth muscle is described, an effect not mediated by nitric oxide.


Magnetoresistance in Co/2D MoS2/Co and Ni/2D MoS2/Ni junctions.
Semiconducting single-layer (SL) and few-layer MoS2 have a flat surface, free of dangling bonds. Using density functional theory coupled with non-equilibrium Green's function method, we investigate the spin-polarized transport properties of Co/2D MoS2/Co and Ni/2D MoS2/Ni junctions with MoS2 layer numbers of N = 1, 3, and 5. Well-defined interfaces are formed between MoS2 and metal electrodes. The junctions with a SL MoS2 spacer are almost metallic owing to the strong coupling between MoS2 and the ferromagnets, while those are tunneling with a few layer MoS2 spacer. Both large magnetoresistance and tunneling magnetoresistance are found when fcc or hcp Co is used as an electrode. Therefore, flat single- and few-layer MoS2 can serve as an effective nonmagnetic spacer in a magnetoresistance or tunneling magnetoresistance device with a well-defined interface.


Coexistence of distinct intramolecular electron transfer pathways in polyoxometalate based molecular triads.
Polyoxometalate (POM)-associated charge-separated states, formed by the photoinduced oxidation of a covalently attached photosensitizer and reduction of the POM, have attracted much attention due to the remarkable catalytic properties of the reduced POMs. However, short lifetimes of the POM-associated charge-separated state, which in some cases lead to the backward electron transfer being more rapid than the formation of the charge-separated state itself, are generally observed. Recently, we reported on the first example of a relative long-lived (τ = 470 ns) charge-separated state in a Ru(ii) bis(terpyridine)-POM molecular dyad. In this manuscript, further studies on extended molecular structures - two molecular triads - which contain an additional electron donor, phenothiazine (PTZ) or π-extended tetrathiafulvalene (exTTF), are discussed. We show that the excitation of the photosensitizer leads to the population of two distinct MLCT states, which differ in the distribution of excess electron density on the two distinct tpy ligands. These two MLCT states decay separately and, thus, constitute the starting points for distinct intramolecular electron-transfer pathways leading to the simultaneous population of two partially charge-separated states, i.e. PTZ˙+-Ru(tpy)2˙--POM and PTZ-RuIII(tpy)2-POM˙-. These independent decay pathways are unaffected by the choice of the electron donor. Thus, the initial charge distribution within the coordination environment of the photocenter determines the nature of the subsequent (partially) charge separated state that is formed in the triads. These results might open new avenues to design molecular interfaces, in which the directionality of electron transfer can be tuned by the choice of initial excitation.


What do medical students in Alexandria know about female genital mutilation?
We explored the knowledge, beliefs and attitudes of 330 5th year medical students in Alexandria University towards female genital mutilation (FGM). The students' basic knowledge about the practice of FGM was unsatisfactory. Students were unaware of the prevalence of FGM in Egypt and the practices and procedures of FGM. They were also poorly informed about the complications of FGM, and the ethical and legal aspects of FGM in the country. As a result, 52.0% of the students supported the continuation of the practice and 73.2% were in favour of its "medicalization" as a strategy for reducing the risks of FGM. Most students (86.9%) thought that the issue of FGM should be incorporated into the undergraduate medical curriculum.


Brain-derived neurotrophic factor and neurotrophin-3 support the survival and neuritogenesis response of developing cochleovestibular ganglion neurons.
The effects of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the differentiation of avian cochleovestibular ganglion and their possible association with the hydrolysis of glycosyl-phosphatidylinositol (GPI) were studied. BDNF and NT-3 (2 ng/ml) promoted neurite outgrowth in explants of both cochlear and vestibular ganglia. This effect on neuritogenesis was stage-dependent, reaching a maximum at E7 for NT-3 and at E9 for BDNF. The magnitude of the response of the vestibular ganglion to BDNF was always smaller than that of the cochlear ganglion of an equivalent stage. BDNF and NT-3 stimulation of neuronal survival and neurite extension was also demonstrated in dissociated neuronal cell cultures. The effect was concentration-dependent with saturation of the response occurring at 4 ng/ml for BDNF and at 2 ng/ml for NT-3, the half-maximal effect occurring at 2 and 1 ng/ml, respectively, for the most sensitive stages of the chick cochlear ganglion. Inositol phosphoglycan (IPG) did not mimic the effects of BDNF or NT-3 on neuronal survival and neurite outgrowth, nor was it able to potentiate their responses. Antibodies raised against IPG did not block the effects of these neurotrophins. The results suggest that BDNF and NT-3 may act in cooperation to establish the innervation pattern of the inner ear. Unlike their early proliferative effects, neurotrophic effects are uncoupled from the GPI/IPG signal transduction system.


Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.
To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 18.104.22.168), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.


Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method.
Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair(®) pediatric 5 mg chewable tablets among Mediterranean volunteers. An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. The relationship between concentration and peak area ratio was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient (R (2)) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0→last, AUC0→inf, and C max, respectively. The 90% confidence intervals were within the predefined limits of 80.00%-125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. Broncast(®) pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair(®) pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice.


Stem cells and reprogramming: breaking the epigenetic barrier?
Increasing evidence suggests that epigenetic regulation is key to the maintenance of the stem cell state. Chromatin is the physiological form of eukaryotic genomes and the substrate for epigenetic marking, including DNA methylation, post-translational modifications of histones and the exchange of core histones with histone variants. The chromatin template undergoes significant reorganization during embryonic stem cell (ESC) differentiation and somatic cell reprogramming (SCR). Intriguingly, remodeling of the epigenome appears to be a crucial barrier that must be surmounted for efficient SCR. This area of research has gained significant attention due to the importance of ESCs in modeling and treating human disease. Here we review the epigenetic mechanisms that are key for maintenance of the ESC state, ESC differentiation and SCR. We focus on murine and human ESCs and induced pluripotent stem cells, and highlight the pharmacological approaches used to study or manipulate cell fate where relevant.


Missense mutations define a restricted segment in the C-terminal domain of phytochrome A critical to its regulatory activity.
The phytochrome family of photoreceptors has dual molecular functions: photosensory, involving light signal perception, and regulatory, involving signal transfer to downstream transduction components. To define residues necessary specifically for the regulatory activity of phytochrome A (phyA), we undertook a genetic screen to identify Arabidopsis mutants producing wild-type levels of biologically defective but photochemically active and dimeric phyA molecules. Of eight such mutants identified, six contain missense mutations (including three in the same residue, glycine 727) clustered within a restricted segment in the C-terminal domain of the polypeptide. Quantitative photobiological analysis revealed retention of varying degrees of partial activity among the different alleles--a result consistent with the extent of conservation at the position mutated. Together with additional data, these results indicate that the photoreceptor subdomain identified here is critical to the regulatory activity of both phyA and phyB.


Electron Transport through Metal/MoS2 Interfaces: Edge- or Area-Dependent Process?
In ultrathin two-dimensional (2-D) materials, the formation of ohmic contacts with top metallic layers is a challenging task that involves different processes than in bulk-like structures. Besides the Schottky barrier height, the transfer length of electrons between metals and 2-D monolayers is a highly relevant parameter. For MoS2, both short (≤30 nm) and long (≥0.5 μm) values have been reported, corresponding to either an abrupt carrier injection at the contact edge or a more gradual transfer of electrons over a large contact area. Here we use ab initio quantum transport simulations to demonstrate that the presence of an oxide layer between a metallic contact and a MoS2 monolayer, for example, TiO2 in the case of titanium electrodes, favors an area-dependent process with a long transfer length, while a perfectly clean metal-semiconductor interface would lead to an edge process. These findings reconcile several theories that have been postulated about the physics of metal/MoS2 interfaces and provide a framework to design future devices with lower contact resistances.


A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).
This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment.


Nodular regenerative hyperplasia rarely leads to liver transplantation: A 20-year cohort study in all Dutch liver transplant units.
Nodular regenerative hyperplasia is an uncommon liver condition associated with several autoimmune disorders and drugs. The clinical symptoms of nodular regenerative hyperplasia vary from asymptomatic to severe complications of portal hypertension (nodular regenerative hyperplasia-syndrome). The purpose of this study was to identify the prognosis and optimal management, as well as the role of liver transplantation, in nodular regenerative hyperplasia. The pathology databases of all three Dutch liver transplant units were retrospectively scrutinised for explanted livers diagnosed with nodular regenerative hyperplasia or without clear diagnosis. Pre- and post-transplantation clinical, biochemical, radiological and histological information was obtained from electronic and paper records. In total, 1886 patients received a liver transplant. In 255 patients, nodular regenerative hyperplasia could not be excluded. After detailed chart review, the native livers of 11 patients (0.6%) (82% male, median age: 44 years) displayed nodular regenerative hyperplasia. Seven patients (64%) had underlying disorders or drug exposure which possibly caused nodular regenerative hyperplasia. Laboratory and imaging abnormalities were present in all patients but did not contribute to the diagnosis of nodular regenerative hyperplasia. Five-year survival was 73% (median follow-up: four years, range: 2-248 months). Nodular regenerative hyperplasia is a rare finding in patients, predominantly young males, transplanted for end-stage liver disease with unknown aetiology. Nonetheless, liver transplantation may have an important role in end-stage nodular regenerative hyperplasia-syndrome.


Contrasting patterns of genome-level diversity across distinct co-occurring bacterial populations.
To understand the forces driving differentiation and diversification in wild bacterial populations, we must be able to delineate and track ecologically relevant units through space and time. Mapping metagenomic sequences to reference genomes derived from the same environment can reveal genetic heterogeneity within populations, and in some cases, be used to identify boundaries between genetically similar, but ecologically distinct, populations. Here we examine population-level heterogeneity within abundant and ubiquitous freshwater bacterial groups such as the acI Actinobacteria and LD12 Alphaproteobacteria (the freshwater sister clade to the marine SAR11) using 33 single-cell genomes and a 5-year metagenomic time series. The single-cell genomes grouped into 15 monophyletic clusters (termed "tribes") that share at least 97.9% 16S rRNA identity. Distinct populations were identified within most tribes based on the patterns of metagenomic read recruitments to single-cell genomes representing these tribes. Genetically distinct populations within tribes of the acI Actinobacterial lineage living in the same lake had different seasonal abundance patterns, suggesting these populations were also ecologically distinct. In contrast, sympatric LD12 populations were less genetically differentiated. This suggests that within one lake, some freshwater lineages harbor genetically discrete (but still closely related) and ecologically distinct populations, while other lineages are composed of less differentiated populations with overlapping niches. Our results point at an interplay of evolutionary and ecological forces acting on these communities that can be observed in real time.


Impact of Ischemic Lesion Location on the mRS Score in Patients with Ischemic Stroke: A Voxel-Based Approach.
Previous studies indicated that ischemic lesion volume might be a useful surrogate marker for functional outcome in ischemic stroke but should be considered in the context of lesion location. In contrast to previous studies using the ROI approach, which has several drawbacks, the present study aimed to measure the impact of ischemic lesion location on functional outcome using a more precise voxelwise approach. Datasets of patients with acute ischemic strokes from the Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) were used. Primary outcome was functional outcome as assessed by the modified Rankin Scale 3 months after stroke. Ischemic lesion volume was determined on CT scans 3-9 days after stroke. Voxel-based lesion-symptom mapping techniques, including covariates that are known to be associated with functional outcome, were used to determine the impact of ischemic lesion location for outcome. Of the 500 patients in the MR CLEAN trial, 216 were included for analysis. The mean age was 63 years. Lesion-symptom mapping with inclusion of covariates revealed that especially left-hemispheric lesions in the deep periventricular white matter and adjacent internal capsule showed a great influence on functional outcome. Our study confirms that infarct location has an important impact on functional outcome of patients with stroke and should be considered in prediction models. After we adjusted for covariates, the left-hemispheric corticosubcortical fiber tracts seemed to be of higher functional importance compared with cortical lesions.


Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials.
Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48 h up to 18 years old, who remained comatose after resuscitation, were randomized within 6 h of return of circulation to hypothermia or normothermia (target 33.0 °C or 36.8 °C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean = 100, SD = 15), was evaluated among patients with pre-arrest scores ≥70. 624 patients were randomized. Among 517 with pre-arrest VABS-II scores ≥70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p = 0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p = 0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p = 0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.


Genetic analysis of activity, brain and behavioral associations in extended families with heavy genetic loading for bipolar disorder.
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated. Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences. More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified. Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.


Inactivation of Pure Bacterial Biofilms by Impaction of Aerosolized Consumer Products Containing Nanoparticulate Metals.
The ability of nanotechnology-enabled consumer sprays to inactivate bacteria has direct health implications. This research investigated the ability of six nanosilver-based consumer sprays to inactivate bacteria. We determined the minimal inhibitory concentrations (MICs) of the products by an agar dilution method, collected particles released from sprays onto bacterial films using impactors, and determined metal concentrations in the products using ICPMS. Also, the size of silver nanoparticles in the products' suspensions was determined using single particle (sp)ICPMS. Two of the six nanoproducts inhibited growth of Escherichia coli and Bacillus atrophaeus bacteria (MICs of 40,000 and 160,000 ppm). Collection of particles aerosolized from these two products onto films of the same bacteria inhibited bacterial growth; however, the mass concentration deposited onto bacterial films was lower than the MICs. Furthermore, these two nanoproducts had the lowest silver concentrations compared to the other four nanosilver products. Yet, they had the smallest nanosilver particles: mean size of ~20 to 30 nm vs. ~45 nm for the other products. Their suspensions were more acidic (pH ~3-5) and had higher concentrations of zinc and magnesium compared to other products. This research illustrates that some consumer nanoproducts have antibacterial potential and may affect our microbiota. Yet, the inactivation potential cannot solely be presumed based on the nanosilver presence and concentration in the product; the final nanoproduct's form, including its matrix, must be considered. As nanomaterials are increasingly incorporated into consumer goods, this research highlights the need to investigate final-form consumer nanoproducts and their potential to affect our microbial environment.


Individual differences in high-level biological motion tasks correlate with autistic traits.
Human actions are rich in social cues and play an essential role in interacting with the social environment. Hence, the perception of biological motion (i.e., movement elicited by humans and other animals) is considered to be an important gauge of a person's social cognition capacities. It has been well-documented that Autism Spectrum Disorder (ASD) is associated with difficulties in social interactions. In the present study, we examined whether individual differences in biological motion perception relate to the degree of autistic traits among people in the typically-developing population. We employed three tasks that require different degrees of involvement of global action processing: action discrimination in noise, action inversion effect in binocular rivalry, and inter-personal interaction recognition. We found that individuals with higher numbers of autistic traits showed similar action discrimination performance as individuals with fewer autistic traits but exhibited a reduced inversion effect in binocular rivalry, and a decreased ability to recognize meaningful human interactions. These findings provide converging evidence that global processing of biological motion is affected in people with a high degree of autistic traits.


Sunscreen application and its importance for the sun protection factor.
To achieve a good sun protection, a layer thickness of 2 mg/sq cm is often recommended. Fifty individuals were asked to apply five different sunscreens ad libitum. Ten percent dihydroxyacetone was added to the sunscreens in order to make them fluoresce when irradiated with Wood's light. The layer thickness was calculated by dividing the amount applied by the area. The thicknesses of the sunscreen layers varied little between different parts of the body and different brands; in general it was close to 1 mg/sq cm. The corresponding protection factor was measured for two sunscreens on 20 persons. The results indicate that the sun protection factor under ad libitum conditions is only 50% of what would be achieved using a layer thickness of 2 mg/sq cm.


Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.
Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ. This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic. Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas. VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients.


Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions.
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed. To this end, it is necessary to better understand the mechanisms of APAP hepatotoxicity. Up to now, in addition to mitochondrial oxidative stress, many other cellular processes, including phase I/phase II metabolism, endoplasmic reticulum stress, autophagy, sterile inflammation, microcirculatory dysfunction, and liver regeneration, have been identified to be involved in the pathogenesis of AILI, providing new targets for developing more effective therapeutic interventions against APAP-induced liver injury. In this review, we summarize intracellular and extracellular events involved in APAP hepatotoxicity, along with emphatic discussions on the possible therapeutic approaches targeting these different cellular events.


Early temporal changes in ecto-nucleotidase activity after cortical stab injury in rat.
During a variety of insults to the brain adenine nucleotides are released in large quantities from damaged cells, triggering multiple cellular responses to injury. Here, we evaluated changes in extracellular ATP, ADP and AMP hydrolysis at different times (0-24 hours) after unilateral cortical stab injury (CSI) in adult rats. Results demonstrated that 24 hours following CSI, ATP and ADP hydrolyzing activities were not significantly altered in injured cortex. Based on calculated V (ATP)/V (ADP) ratio it was concluded that ATP/ADP hydrolysis was primarily catalyzed by NTPDase1 enzyme form. In contrast, AMP hydrolysis, catalyzed by 5'-nucleotidase, was significantly reduced at least 4 hours following CSI. Kinetic analysis and Lineweaver-Burk transformation of the enzyme velocities obtained over the range of AMP concentrations (0.05-1.50 mM) revealed that inhibition of 5'-nucleotidase activity after CSI was of the uncompetitive type. Taken together our data suggest that injured tissue has reduced potential for extracellular metabolism of adenine nucleotides in early stages after CSI.


Evaluation of activated charcoal as treatment for Yellow tulp (Moraea pallida) poisoning in cattle.
The efficacy of activated charcoal as a treatment for cattle (n = 57) poisoned by Yellow tulp (Moraea pallida) was investigated. Treatment with activated charcoal resulted in full recovery, irrespective of the degree of posterior paresis, provided that this clinical sign did not develop within the first 12 hours after initial exposure to Yellow tulp-infested grazing. For instance, despite treatment, 1 of 7 cattle succumbed after manifesting mild posterior paresis 6 to 8 h after initial exposure and 3 of 3 treated cattle died after developing severe posterior paresis within 6 to 12 h.


Added Value of Estrogen Receptor, Progesterone Receptor, and L1 Cell Adhesion Molecule Expression to Histology-Based Endometrial Carcinoma Recurrence Prediction Models: An ENITEC Collaboration Study.
Endometrial carcinoma mortality is mainly caused by recurrent disease, and various immunohistochemical markers to predict recurrences have been studied. Loss of the estrogen receptor (ER) and progesterone receptor (PR) and the presence of the L1 cell adhesion molecule (L1CAM) are promising markers, but their combined value has not been studied. Expression of ER, PR, and L1CAM was immunohistochemically determined in 293 endometrial carcinomas from 11 collaborating European Network for Individualized Treatment of Endometrial Cancer centers. Estrogen receptor, PR, or L1CAM staining was considered positive or negative when expressed by greater than or equal to 10% or less than 10% of the tumor cells, respectively. The association between these markers and clinicopathological markers, and their combined value in predicting survival were calculated, both in the entire cohort and in a selected groups of stage I endometrioid and low-risk stage I endometrioid carcinomas. Estrogen receptor and PR were negative in 19% and 28% of the cases, respectively, and L1CAM was positive in 18%. All 3 were associated with advanced stage, high-grade, nonendometrioid histology, lymphovascular space invasion (LVSI), and reduced disease-free survival. Only advanced stage, loss of PR, and LVSI were associated with reduced disease-free survival in multivariate analysis. A prognostic model including these 3 markers was superior to 1 including only the 3 immunohistochemical markers, which was superior to the traditional model. In both the stage I endometrioid and the low-risk stage I endometrioid groups, only loss of PR was associated with reduced disease-free survival. Loss of ER and PR, and the presence of L1CAM are associated with high risk characteristics, and loss of PR is the strongest predictor of recurrent disease. Although a combination of these 3 markers is slightly superior to the traditional histological markers, a prognostic model including stage, PR expression, and LVSI is the most promising model in the identification of high risk carcinomas. In the stage I endometrioid carcinomas, PR immunohistochemistry appears to be of additional value in predicting recurrences.


Quantifying skeletal muscle properties in cadaveric test specimens: effects of mechanical loading, postmortem time, and freezer storage.
Investigators currently lack the data necessary to define the state of skeletal muscle properties within cadaveric specimens. The purpose of this study is to define the temporal changes in the postmortem properties of skeletal muscle as a function of mechanical loading and freezer storage. The tibialis anterior of the New Zealand white rabbit was chosen for study. Modulus and no-load strain were found to vary significantly from live after eight hours postmortem. Following the changes that occur during rigor mortis, a stable region of postmortem, post-rigor properties occurred between 36 to 72 hours postmortem. A freeze-thaw process was not found to have a significant effect on the post-rigor response. The first loading cycle response of post-rigor muscle was unrepeatable but stiffer than live passive muscle. After preconditioning, the post-rigor muscle response was repeatable. The preconditioned post-rigor response was less stiff than the live passive response due to a significant increase in no-load strain. Failure properties of postmortem muscle were found to be significantly different from live passive muscle with a significant decrease in failure stress (61 percent) and energy (81 percent), while failure strain was unchanged. These results suggest that the post-rigor response of cadaveric muscle is unaffected by freezing but sensitive to even a few cycles of mechanical loading.


ZMM proteins during meiosis: crossover artists at work.
Faithful segregation of homologous chromosomes (homologs) during meiosis depends on chiasmata which correspond to crossovers between parental DNA strands. Crossover forming homologous recombination takes place in the context of the synaptonemal complex (SC), a proteinaceous structure that juxtaposes homologs. The coordination between molecular recombination events and assembly of the SC as a structure that provides global connectivity between homologs represents one of the remarkable features of meiosis. ZMM proteins (also known as the synapsis initiation complex = SIC) play crucial roles in both processes providing a link between recombination and SC assembly. The ZMM group includes at least seven functionally collaborating, yet structurally diverse proteins: The transverse filament protein Zip1 establishes stable homolog juxtaposition by polymerizing as an integral component of the SC. Zip2, Zip3, and Zip4 likely mediate protein-protein interactions, while Mer3, Msh4, and Msh5 directly promote steps in DNA recombination. This review focuses on recent insights into ZMM functions in yeast meiosis and draws comparisons to ZMM-related proteins in other model organisms.


c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination.
Hepatocyte growth factor/scatter factor (HGF) and its receptor tyrosine kinase Met are key regulators of epithelial motility and morphogenesis. Recent studies indicate that the HGF/Met pathway also plays a role in B cell differentiation, whereas uncontrolled Met signaling may lead to B cell neoplasia. These observations prompted us to explore HGF/Met signaling in B cells. In this study, we demonstrate that HGF induces strong tyrosine phosphorylation of the proto-oncogene product c-Cbl in B cells and increases Cbl association with the Src family tyrosine kinases Fyn and Lyn, as well as with phosphatidylinositol-3 kinase and CrkL. In addition, we demonstrate that c-Cbl mediates HGF-induced ubiquitination of Met. This requires the juxtamembrane tyrosine Y1001 (Y2) of Met, but not the multifunctional docking site (Y14/15) or any additional C-terminal tyrosine residues (Y13-16). In contrast to wild-type c-Cbl, the transforming mutants v-Cbl and 70Z/3 Cbl, which lack the ubiquitin ligase RING finger domain, suppress Met ubiquitination. Our findings identify c-Cbl as a negative regulator of HGF/Met signaling in B cells, mediating ubiquitination and, consequently, proteosomal degradation of Met, and suggest a role for Cbl in Met-mediated tumorigenesis.


Epidemiology of invasive Streptococcus pyogenes infections in France in 2007.
Invasive group A streptococcal (GAS) infections cause significant morbidity and mortality. A national survey was initiated to assess the burden of invasive GAS infections in France, describe their clinical characteristics, and assess the molecular characteristics of GAS strains responsible for these infections. The survey was conducted in 194 hospitals, accounting for 51% of acute care hospital admissions in France. Clinical data, predisposing factors, and demographic data were obtained, and all GAS isolates were emm sequence typed. We identified 664 cases of invasive GAS infections, with an annual incidence of 3.1 per 100,000 population. The case-fatality ratio was 14% and rose to 43% in the case of streptococcal toxic shock syndrome. Bacteremia without identified focus (22%) and skin/soft tissue infections (30%) were the most frequent clinical presentations. Necrotizing fasciitis was frequent in adults (18%) and uncommon in children (3%). The 3 predominant emm types were emm1, emm89, and emm28, accounting for 33%, 16%, and 10% of GAS isolates, respectively. The emm1 type was associated with fatal outcomes and was more frequent in children than in adults. Six clusters of cases were identified, with each cluster involving 2 invasive cases due to GAS strains which shared identical GAS emm sequence types. Four clusters of cases involved eight postpartum infections, one family cluster involved a mother and child, and one cluster involved two patients in a nursing home. Invasive GAS infection is one of the most severe bacterial diseases in France, particularly in persons aged ≥ 50 years or when associated with toxic shock syndrome.


Using a Computer Simulation to Improve Psychological Readiness for Job Interviewing in Unemployed Individuals of Pre-Retirement Age.
Unemployed individuals of pre-retirement age face significant challenges in finding a new job. This may be partly due to their lack of psychological readiness to go through a job interview. We view psychological readiness as one of the psychological attitude components. It is an active conscious readiness to interact with a certain aspect of reality, based on previously acquired experience. It includes a persons' special competence to manage their activities and cope with anxiety. We created Job Interview Simulation Training (JIST) - a computer-based simulator, which allowed unemployed job seekers to practice interviewing repeatedly in a stress-free environment. We hypothesized that completion of JIST would be related to increase in pre-retirement job seekers' psychological readiness for job interviewing in real life. Participants were randomized into control (n = 18) and experimental (n = 21) conditions. Both groups completed pre- and post-intervention job interview role-plays and self-reporting forms of psychological readiness for job interviewing. JIST consisted of 5 sessions of a simulated job interview, and the experimental group found it easy to use and navigate as well as helpful to prepare for interviewing. After finishing JIST-sessions the experimental group had significant decrease in heart rate during the post-intervention role-play and demonstrated significant increase in their self-rated psychological readiness, whereas the control group did not have changes in these variables. Future research may help clarify whether JIST is related to an increase in re-employment of pre-retirement job seekers.


Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4.
Developing anti-viral therapies targeting HIV-1 transcription has been hampered by the limited structural knowledge of the proteins involved. HIV-1 hijacks the cellular machinery that controls RNA polymerase II elongation through an interaction of HIV-1 Tat with the positive transcription elongation factor P-TEFb, which interacts with an AF4 family member (AFF1/2/3/4) in the super elongation complex (SEC). Because inclusion of Tat•P-TEFb into the SEC is critical for HIV transcription, we have determined the crystal structure of the Tat•AFF4•P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (1-266), human Cdk9 (7-332), and human AFF4 (27-69). Tat binding to AFF4•P-TEFb causes concerted structural changes in AFF4 via a shift of helix H5' of Cyclin T1 and the α-3 10 helix of AFF4. The interaction between Tat and AFF4 provides structural constraints that explain tolerated Tat mutations. Analysis of the Tat-binding surface of AFF4 coupled with modeling of all other AF4 family members suggests that AFF1 and AFF4 would be preferred over AFF2 or AFF3 for interaction with Tat•P-TEFb. The structure establishes that the Tat-TAR recognition motif (TRM) in Cyclin T1 interacts with both Tat and AFF4, leading to the exposure of arginine side chains for binding to TAR RNA. Furthermore, modeling of Tat Lys28 acetylation suggests that the acetyl group would be in a favorable position for H-bond formation with Asn257 of TRM, thereby stabilizing the TRM in Cyclin T1, and provides a structural basis for the modulation of TAR RNA binding by acetylation of Tat Lys28.


What interventions are effective on reducing inequalities in maternal and child health in low- and middle-income settings? A systematic review.
The deadline for achieving Millennium Development Goals 4 and 5 is approaching, but inequalities between disadvantaged and other populations is a significant barrier for progress towards achieving these goals. This systematic review aims to collect evidence about the differential effects of interventions on different sociodemographic groups in order to identify interventions that were effective in reducing maternal or child health inequalities. We searched the PubMed, EMBASE and other relevant databases. The reference lists of included reviews were also screened to find more eligible studies. We included experimental or observational studies that assessed the effects of interventions on maternal and child health, but only studies that report quantitative inequality outcomes were finally included for analysis. 22 articles about the effectiveness of interventions on equity in maternal and child health were finally included. These studies covered five kinds of interventions: immunization campaigns, nutrition supplement programs, health care provision improvement interventions, demand side interventions, and mixed interventions. The outcome indicators covered all MDG 4 and three MDG 5 outcomes. None of the included studies looked at equity in maternal mortality, adolescent birth rate and unmet need for family planning. The included studies reported inequalities based on gender, income, education level or comprehensive socioeconomic status. Stronger or moderate evidence showed that all kinds of the included interventions may be more effective in improving maternal or child health for those from disadvantaged groups. Studies about the effectiveness of interventions on equity in maternal or child health are limited. The limited evidence showed that the interventions that were effective in reducing inequity included the improvement of health care delivery by outreach methods, using human resources in local areas or provided at the community level nearest to residents and the provision of financial or knowledge support to demand side.


Experimental study of Brillouin scattering in fluorine-doped single-mode optical fibers.
We experimentally investigate Brillouin scattering properties in fluorine-doped single-mode optical fibers. The effective acoustic velocities determined from the measured dependences of acoustic resonance frequencies on optical wavelength are approximately equal to the individual acoustic velocities in the core and/or cladding regions. Brillouin gain coefficients are experimentally characterized and compared with that in a standard GeO(2)-doped single-mode fiber. The result indicates that the acousto-optic coupling efficiencies in all fibers are almost 100%, which means that Brillouin threshold value can not be simply increased by fluorine doping. Moreover, it is found that the dependences of acoustic resonance frequencies on applied strain or temperature change are quantitatively enhanced by fluorine dopants, which is in opposite trend when compared with germanium ones.


[Alcohol and drug use disorders in patients with traumatic brain injury: neurobehavioral consequences and caregiver burden].
To describe the prevalence of alcohol and drugs use in patients with traumatic brain injury (TBI), and to assess their relationship with neuropsychiatric disorders, functioning and caregiver burden. 156 patients with a history of moderate and severe TBI were evaluated. The use of alcohol and drugs was determined. The Neuropsychiatric Inventory (NPI) and the Zarit questionnaire were applied to caregivers. The patients functioning were assessed with the Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE). 36 patients (23%) were regular users of alcohol and other drugs before the TBI. Neuropsychiatric disorders were more frequent and severe in this group, especially irritability and agitation-aggressiveness. Their caregivers perceived a higher burden. After TBI, 16 patients (44.4%) relapsed in alcohol-drugs consumption. Having a higher age and living with a partner were associated with higher rates of abstinence. The history of alcohol and drugs abuse is common in patients with TBI and it is a risk factor for development of behavioral disorders. More active interventions are needed aimed to detect these cases and work for prevention of relapse after trauma.