Orphan toxin OrtT (YdcX) of Escherichia coli reduces growth during the stringent response.
Toxin/antitoxin (TA) systems are nearly universal in prokaryotes; toxins are paired with antitoxins which inactivate them until the toxins are utilized. Here we explore whether toxins may function alone; i.e., whether a toxin which lacks a corresponding antitoxin (orphan toxin) is physiologically relevant. By focusing on a homologous protein of the membrane-damaging toxin GhoT of the Escherichia coli GhoT/GhoS type V TA system, we found that YdcX (renamed OrtT for orphan toxin related to tetrahydrofolate) is toxic but is not part of TA pair. OrtT is not inactivated by neighboring YdcY (which is demonstrated to be a protein), nor is it inactivated by antitoxin GhoS. Also, OrtT is not inactivated by small RNA upstream or downstream of ortT. Moreover, screening a genomic library did not identify an antitoxin partner for OrtT. OrtT is a protein and its toxicity stems from membrane damage as evidenced by transmission electron microscopy and cell lysis. Furthermore, OrtT reduces cell growth and metabolism in the presence of both antimicrobials trimethoprim and sulfamethoxazole; these antimicrobials induce the stringent response by inhibiting tetrahydrofolate synthesis. Therefore, we demonstrate that OrtT acts as an independent toxin to reduce growth during stress related to amino acid and DNA synthesis.


Multiple sclerosis in Pakistan: Current status and future perspective.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) which commonly leads to disability. We reviewed articles on MS from Pakistan using PubMed, Google Scholar and Pak Medinet to present different aspects of the disease and the status of disease modifying treatments in Pakistan and South Asia. MS is not as uncommon in Pakistan as it has been previously thought to be. Estimated prevalence of MS in Pakistan may be 10 per 100,000 population. Data suggests that most features of MS found in Pakistan are similar to those found in the West. These features include a female preponderance, mean age of onset in the third decade of life and similar risk factors including viral infections, smoking, and vitamin D deficiency, as well as genetic risk factors. Relapsing-remitting multiple sclerosis (RRMS) is the most common disease pattern seen in Pakistan which is also consistent with data from other regions. Treatment modalities in Pakistan include immunomodulatory and immunosuppressive drugs. In order to improve care for MS patients in Pakistan, it is extremely important to obtain a population-based prevalence of MS in the country and a national MS registry, along with implementing programs for patients' awareness and the training of doctors, especially internists. There are many disease modifying therapies (DMT) available in Pakistan but no data is available on the utilization and impact of these DMTs.


Assessing spatiotemporal variation in abundance: A flexible framework accounting for sampling bias with an application to common pochard (Aythya ferina).
Assessing trends in the relative abundance of populations is a key yet complex issue for management and conservation. This is a major aim of many large-scale censusing schemes such as the International Waterbird Count (IWC). However, owing to the lack of sampling strategy and standardization, such schemes likely suffer from biases due to spatial heterogeneity in sampling effort. Despite huge improvements of the statistical tools that allow tackling these statistical issues (e.g., GLMM, Bayesian inference), many conservationists still prefer to rely on stand-alone turn-key statistical tools, often violating the prerequisites put forward by the developers of these tools. Here, we propose a straightforward and flexible approach to tackle the typical statistical issues one can encounter when analyzing count data of monitoring schemes such as the IWC. We rely on IWC counts of the declining common pochard populations of the Northwest European flyway as a case study (period 2002-2012). To standardize the size of sampling units and mitigate spatial autocorrelation, we grouped sampling sites using a 75 × 75 km grid cells overlaid over the flyway of interest. Then, we used a hierarchical modeling approach, assessing population trends with random effects at two spatial scales (grid cells, and sites within grid cells) in order to derive spatialized values and to compute the average population trend at the whole flyway scale. Our approach allowed to tackle many statistical issues inherent to this type of analysis but often neglected, including spatial autocorrelation. Concerning the case study, our main findings are that: (1) the northwestern population of common pochards experienced a steep decline (4.9% per year over the 2002-2012 period); (2) the decline was more pronounced at high than low latitude (11.6% and 0.5% per year at 60° and 46° of latitude, respectively); and, (3) the decline was independent of the initial number of individuals in a given site (random across sites). Beyond the case study of the common pochard, our study provides a conceptual statistical framework for estimating and assessing potential drivers of population trends at various spatial scales.


Smoking cessation interventions in South Asian countries: protocol for scoping review.
Unfortunately, like many other health risks, smoking rate has been on the rise in developing countries. Half of current smokers in the world reside in only three countries of Asia that include India. Many smoking cessation interventions that were developed and successfully implemented in the context of developed countries have not been equally successful in South Asia. Hence, there is a dire need of culturally relevant smoking cessation interventions. We propose a scoping review with objectives to explore the extent and nature of interventions for smoking cessation and its associated factors in South Asian Region by systematically reviewing the available published and unpublished literature. The review has been registered in Joanna Briggs Institute (JBI) systematic reviews register and details are given in the Methodology section. The updated framework of JBI for scoping review methodology will be used as guide for conduct of this scoping review. Electronic databases (PubMed, CINAHL plus, Proquest Theses and Dissertations, EBSCO Dentistry and Oral Sciences, and Wiley Cochrane Library), reference lists of selected studies and grey literature will be considered for inclusion in this review. The literature search is anticipated to be carried out in December-January 2020. Initially, two reviewers in consultation with a librarian will develop search syntax followed by search from the selected sources. Consequently, the reviewers will screen all the titles, abstracts and full articles to establish relevance of each study for inclusion. Factors associated with smoking cessation will be coded and categorised applying qualitative content analysis, while interventions extracted from the literature will be described with the stated level of effectiveness.


A systematic review of income generation interventions, including microfinance and vocational skills training, for HIV prevention.
Income generation interventions, such as microfinance or vocational skills training, address structural factors associated with HIV risk. However, the effectiveness of these interventions on HIV-related outcomes in low- and middle-income countries has not been synthesized. The authors conducted a systematic review by searching electronic databases from 1990 to 2012, examining secondary references, and hand-searching key journals. Peer-reviewed studies were included in the analysis if they evaluated income generation interventions in low- or middle-income countries and provided pre-post or multi-arm measures on behavioral, psychological, social, care, or biological outcomes related to HIV prevention. Standardized forms were used to abstract study data in duplicate and study rigor was assessed. Of the 5218 unique citations identified, 12 studies met criteria for inclusion. Studies were geographically diverse, with six conducted in sub-Saharan Africa, three in South or Southeast Asia, and three in Latin America and the Caribbean. Target populations included adult women (N = 6), female sex workers/bar workers (N = 3), and youth/orphans (N = 3). All studies targeted females except two among youth/orphans. Study rigor was moderate, with two group-randomized trials and two individual-randomized trials. All interventions except three included some form of microfinance. Only a minority of studies found significant intervention effects on condom use, number of sexual partners, or other HIV-related behavioral outcomes; most studies showed no significant change, although some may have had inadequate statistical power. One trial showed a 55% reduction in intimate partner violence (adjusted risk ratio 0.45, 95% confidence interval 0.23-0.91). No studies measured incidence/prevalence of HIV or sexually transmitted infections among intervention recipients. The evidence that income generation interventions influence HIV-related behaviors and outcomes is inconclusive. However, these interventions may have important effects on outcomes beyond HIV prevention. Further studies examining not only HIV-related outcomes but also causal pathways and intermediate variables, are needed. Additional studies among men are also needed.


Estrogen-related receptor alpha interacts cooperatively with peroxisome proliferator-activated receptor-gamma coactivator-1alpha to regulate osteocalcin gene expression.
Osteocalcin is one of the most abundant non-collagenous proteins in bone that is commonly used as a preliminary biomarker in bone formation. Osteocalcin also regulates energy metabolism as a hormone. Estrogen-related receptor alpha (ERRα) is primarily thought to regulate energy homeostasis through interacting with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Intriguingly, ERRα may play a functional role in bone formation. We have found there are 3 ERRα response elements (ERR response element, ERRE) in the osteocalcin promoter, and ERRα interacted cooperatively with PGC-1α could improve the osteocalcin promoter activity, whereas ERRα specific antagonist, XCT-790, inhibits this enhancement. XCT-790 inhibits osteocalcin and ERRα target gene PDKs expression in osteoblast cells. Thus ERRs might have physiological roles in bone formation and energy metabolism through modulating osteocalcin gene expression.


Genome-wide association study to identify genomic regions influencing spontaneous fertility in maize haploids.
Efficient production and use of doubled haploid lines can greatly accelerate genetic gains in maize breeding programs. One of the critical steps in standard doubled haploid line production is doubling the haploid genome using toxic and costly mitosis-inhibiting chemicals to achieve fertility in haploids. Alternatively, fertility may be spontaneously restored by natural chromosomal doubling, although generally at a rate too low for practical applications in most germplasm. This is the first large-scale genome-wise association study to analyze spontaneous chromosome doubling in haploids derived from tropical maize inbred lines. Induction crosses between tropicalized haploid inducers and 400 inbred lines were made, and the resulting haploid plants were assessed for haploid male fertility which refers to pollen production and haploid fertility which refers to seed production upon self-fertilization. A small number of genotypes were highly fertile and these fertility traits were highly heritable. Agronomic traits like plant height, ear height and tassel branch number were positively correlated with fertility traits. In contrast, haploid induction rate of the source germplasm and plant aspect were not correlated to fertility traits. Several genomic regions and candidate genes were identified that may control spontaneous fertility restoration. Overall, the study revealed the presence of large variation for both haploid male fertility and haploid fertility which can be potentially exploited for improving the efficiency of doubled haploid derivation in tropical maize germplasm.


The synthesis of heteroleptic phosphines.
Heteroleptic phosphines (R2PR(1)) are a class of essential ligands for inorganic and organometallic chemistry. However, the syntheses of these phosphines are often fraught with laborious synthetic hurdles. Consequently, a renewed interest in innovative synthetic methods to access heteroleptic phosphines is emerging. This Perspective presents an overview of modern synthetic approaches to heteroleptic phosphines as well as a discussion of the strengths and limitations of these synthetic methods. A major emphasis is placed on simple and direct routes to phosphines and significant synthetic innovations for P-C bond-forming reactions.


Comparison of oxidative stress biomarkers in renal tissues of D-galactose induced, naturally aged and young rats.
Ageing of kidneys is a clinical health issue of the society. Age-related renal insufficiency has important implications due to impaired redox homeostasis. We examined protein, DNA and lipid oxidation biomarkers as well as protein-bound sialic acid (SA) in the kidney tissues of D-galactose induced ageing rats, naturally aged rats and their corresponding young control group. Intraperitoneal injection of D-galactose (60 mg/kg/day) for 6 weeks to young male Sprague-Dawley rats (20-week-old) was used to establish mimetic ageing model. In this study, we investigated the levels of protein carbonyl groups (PCO), various thiol fractions such as total thiol groups (T-SH), protein (P-SH) and non-protein thiol groups (NP-SH), lipid oxidation parameters such as lipid hydroperoxides (LHP) and malondialdehyde (MDA), SA and 8-hydroxy-2'deoxyguanosine (8-OHdG) parameters for comparison of naturally aged, induced aged and young rats. In D-galactose induced aged group, PCO, LHP, MDA, and 8-OHdG concentrations were significantly higher than young control group, whereas T-SH, P-SH levels were significantly lower than the young rats. In addition, NP-SH and SA concentrations were similar between the mimetic ageing and young control groups. In naturally ageing rats, PCO and MDA levels were significantly higher, whereas T-SH, P-SH, NP-SH concentrations were low compared to young controls. On the other hand, SA and 8-OHdG levels were not different between the naturally ageing group and the young control group. Our results demonstrated that the rats in the mimetic ageing group, have significant similarities with the naturally aged rats in terms of impaired redox homeostasis and can be used as a reliable animal model for renal ageing.


Caffeine Improved Time to Exhaustion But Did Not Change Alternative Maximal Accumulated Oxygen Deficit Estimated During a Single Supramaximal Running Bout.
The aim of the current study was to investigate the effects of acute caffeine supplementation on anaerobic capacity determined by the alternative maximal accumulated oxygen deficit (MAODALT) in running effort. Eighteen recreational male runners [29 ± 7years; total body mass 72.1 ± 5.8 kg; height 176.0 ± 5.4cm; maximal oxygen uptake (VO2max) 55.8 ± 4.2 ml·kg-1 ·min-1] underwent a graded exercise test. Caffeine (6 mg·kg-1) or a placebo were administered 1 hr before the supramaximal effort at 115% of the intensity associated with VO2max in a double-blind, randomized cross-over study, for MAODALT assessment. The time to exhaustion under caffeine condition (130.2 ± 24.5s) was 11.3% higher (p = .01) than placebo condition (118.8 ± 24.9 s) and the qualitative inference for substantial changes showed a very likely positive effect (93%). The net participation of the oxidative phosphorylation pathway was significantly higher in the caffeine condition (p = .02) and showed a likely positive effect (90%) of 15.3% with caffeine supplementation. The time constant of abrupt decay of excess postexercise oxygen consumption (τ1) was significantly different between caffeine and placebo conditions (p = .03) and showed a likely negative effect (90%), decreasing -8.0% with caffeine supplementation. The oxygen equivalents estimated from the glycolytic and phosphagen metabolic pathways showed a possibly positive effect (68%) and possibly negative effect (78%) in the qualitative inference with caffeine ingestion, respectively. However, the MAODALT did not differ under the caffeine or placebo conditions (p = .68). Therefore, we can conclude that acute caffeine ingestion does not modify the MAODALT, reinforcing the robustness of this method. However, caffeine ingestion can alter the glycolytic and phosphagen metabolic pathway contributions to MAODALT.


'Collagenous colitis' with watery diarrhoea--a new entity?
A case of chronic watery diarrhoea showed in rectal biopsy a thick subepithelial collagenous deposit in the colorectal mucosa. This deposit was of the same type as that described in the jejunal mucosa in collagenous sprue, and seems to have been the cause of the diarrhoea.


Does a history of non-vertebral fracture identify women without osteoporosis for treatment?
Postmenopausal women with a prior fracture have an increased risk for future fracture. Whether a history of non-vertebral fracture defines a group of women with low bone mass but without osteoporosis for whom alendronate would prevent new non-vertebral fracture is not known. Secondary analysis of data from the Fracture Intervention Trial (FIT). Of 2,785 postmenopausal women with a T-score at the femoral neck between -1 and -2.5 and without prevalent radiographic vertebral deformity, 880 (31.6%) reported experiencing a fracture after 45 years of age. Women were randomized to placebo or alendronate (5 mg/day years for the first 2 years and 10 mg/day thereafter) and were followed for an average of 4.2 +/- 0.5 years. Incident non-vertebral fractures were confirmed by x-rays and radiology reports. In the placebo arm, a self-report of prior fracture identified women with a 1.5-fold (hazard ratio [RH] 1.46, 95% C.I. 1.04-2.04) increased risk for incident non-vertebral fracture. However, there was no evidence that the effect of alendronate differed across subgroups of women with (RH 1.26 for alendronate vs placebo, 95% C.I. 0.89-1.79) and without prior fracture (RH 1.02 for alendronate vs placebo, 95% C.I. 0.76-1.38; P = 0.37 for interaction). Assessing a clinical risk factor, prior non-vertebral fracture, did not identify women with low bone mass for whom alendronate reduced future non-vertebral fracture risk.


Development of Child and Family-Centered Engagement Guidelines for Clinical Administration of the Challenge to Measure Advanced Gross Motor Skills: A Qualitative Study.
This article describes a qualitative study aimed at producing child-centered guidelines for the administration of a measure of children's advanced gross motor skills, the Challenge. The purpose of the guidelines is to promote collaborative interpretation and application of results. The study was conducted in three Canadian cities and included 31 children with cerebral palsy (GMFCS Level I or II) ages 8 to 18 and one parent/caregiver per child (N = 62 participants). Following Challenge administration, each child and one of their caregivers took part in separate qualitative interviews. Analyses were oriented to exploring understandings of the purposes of testing, impressions of the child's performance, and perceptions of how results might inform activity choices and interventions. Three themes were generated: investments in doing well; I know my child/myself; and caregivers' interpretations of child's performance. Themes were then integrated with principles of child and family-centered care to develop The Challenge Engagement Guidelines directed at reducing test anxiety and enhancing shared decision making. The Guidelines are the first of their kind to integrate child and family-centered principles into the administration protocol of a motor measure. Although developed for the Challenge, the principles have applicability to other rehabilitation measures.


Individual asymmetry as a predictor of fitness in the bat Carollia perspicillata.
The measurement of fitness in wild populations is a challenging task, and a number of proxies have been proposed with different degrees of success. Developmental instability/stability (DI) is an organismal property associated with variance in bilateral asymmetry (fluctuating asymmetry-FA) and a correlated effect on fitness. This study provides evidence to corroborate the hypothesis that asymmetry partly reflects DI and is correlated with a reduction in fitness measured by survival and reproduction in bats. We studied two colonies of the bat Carollia perspicillata in southeastern Brazil over 5 years, marking and recapturing individuals. Gaussian mixture models for signed Forearm Asymmetry (ForA) distribution indicated that ~20% of asymmetry variation was due to DI heterogeneity among individuals. ForA, body condition (Scaled Mass Index-SMI) and Forearm Length (ForL) were used as predictors of survival probability in Cormack-Jolly-Seber models. Asymmetry was negatively associated with survival, whereas SMI and ForL were positively associated. The male C. perspicillata defend sites within the roost that are favoured by female harems, but there are mating opportunities for bachelor males, leading to both territorial disputes and sperm competition. As predicted by sexual selection, ForA was negatively associated with relative Testicle Length, a measure of reproductive potential. In females, ForA was negatively associated with the probability of two pregnancies (as opposed to one) in a given breeding season. The effect magnitudes and directions of associations suggest that asymmetry, even though not perfectly reflecting DI variation, is a useful predictor for fitness components in C. perspicillata.


Diet and inflammatory bowel disease: a case-control study.
We conducted a population-based case-control study of inflammatory bowel disease and dietary habits in Stockholm during 1984-1987. We obtained retrospective information about food intake 5 years previously by a postal questionnaire for 152 cases with Crohn's disease, 145 cases with ulcerative colitis, and 305 controls. The relative risk of Crohn's disease was increased for subjects who had a high (55 gm or more per day) intake of sucrose (relative risk = 2.6, 95% confidence interval = 1.4-5.0) and was decreased for subjects who had a high (15 gm or more per day) intake of fiber (relative risk = 0.5, 95% confidence interval = 0.3-0.9). The most striking finding was an increased relative risk of both Crohn's disease and ulcerative colitis associated with consumption of fast foods: the relative risk associated with consumption of fast foods at least two times a week was estimated at 3.4 (95% confidence interval = 1.3-9.3) for Crohn's disease and 3.9 (95% confidence interval = 1.4-10.6) for ulcerative colitis. Although coffee seemed to provide a protective effect for both diseases, there are reasons to consider this finding an artifact.


Prospective new biologic therapies for psoriasis and psoriatic arthritis.
Psoriasis and psoriatic arthritis are immune-mediated, chronic, inflammatory diseases that place a heavy burden on the lifestyle of patients affected. Current understanding of the pathophysiology of these conditions has produced very encouraging new medical developments, largely a consequence of research that has targeted precise elements of the immune cascade, expanding the repertoire of therapeutic options available to dermatologists. Promising new treatments, such as antibodies to interleukin-12 and -23, show superior efficacy and safety in treating psoriasis; the more sophisticated tumor necrosis factor antagonists significantly improve symptoms of rheumatic and psoriatic arthritis and may also be effective in the treatment of plaque psoriasis. In this article, innovative, new treatments for psoriasis and psoriatic arthritis are critically reviewed.


Electrocardiographic safety evaluation of dihydroartemisinin piperaquine in the treatment of uncomplicated falciparum malaria.
Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram.


Assessment of antidepressant-like effects of dextromethorphan on differential reinforcement of low-rate 72-s performance in rats.
The effectiveness of ketamine for treatment-resistant depression along with several other clinical advantages, such as rapid onset and reduced adverse effects associated with serotonin transporter inhibition, has garnered interest in other similar acting psychedelics as novel antidepressant drugs. The antitussive dextromethorphan exhibits glutamate N-methyl-d-aspartate receptor antagonism, sigma-1 receptor agonism, and serotonin reuptake inhibition, which has exhibited antidepressant effects in limited human studies and animal models. The present study sought to further examine dextromethorphan using a differential reinforcement of low-rate 72-s schedule, which can be used to screen antidepressant drugs, in male and female rats. The tricyclic antidepressant drug imipramine and the psychostimulant d-amphetamine also were examined. Sex differences were not shown for baseline performance or for the drugs tested. Further, performance did not differ between the estrus and diestrus stages. Dextromethorphan alone and with quinidine produced an antidepressant-like effect by reducing the number of responses emitted, increasing the number of reinforcers earned, and shifting inter-response times to the right, although significant response suppression occurred at these doses. An antidepressant-like effect was shown with imipramine, but d-amphetamine increased the number of responses emitted and did not affect the number of reinforcers earned. The present findings provide additional support for antidepressant effects produced by dextromethorphan.


Congenital long-QT syndrome in type 1 diabetes: a unique association.
Kurnaz E, Savaş Erdeve Ş, Özgür S, Keskin M, Özbudak P, Çetinkaya S, Aycan Z. Congenital long-QT syndrome in type 1 diabetes: a unique association. Turk J Pediatr 2019; 61: 791-793. In contrast to acquired long QT syndrome (LQTS), congenital LQTS is a relatively rare channelopathy with an incidence of 1/2,500. We describe a patient found to have a prolonged QTc in the setting of newly diagnosed Type 1 DM. To the best of our knowledge, this unique association has not been previously reported. Currently, it is shown that glucose ingestion aggravated cardiac repolarization disturbances in LQT2 patients and prolonged the cardiac repolarization phase in healthy controls. Our case presented to the hospital with syncope after increased glucose level. Therefore, it seems that increased glucose level may have prolonged QTc interval and aggravated cardiac repolarization disturbances in the presented case. By this report, we want to emphasize the importance of hyperglycaemia in congenital LQTS.


Towards simulation-free MR-linac treatment: utilizing male pelvis PSMA-PET/CT and population-based electron density assignments.
Objective. This study aimed to investigate the dosimetric impact of using population-based relative electron density (RED) overrides in lieu of simulation computerized tomography (CT) in a magnetic resonance linear accelerator (MRL) workflow for male pelvis patients. Additionally, the feasibility of using prostate specific membrane antigen positron emission tomography/CT (PSMA-PET/CT) scans to assess patients' eligibility for this proposed workflow was examined.Approach. In this study, 74 male pelvis patients treated on an Elekta Unity 1.5 T MRL were retrospectively selected. The patients' individual RED values for 8 organs of interest were extracted from their simulation-CT images to establish population-based RED values. These values were used to generate individual (IndD) and population-based (PopD) RED dose plans, representing current and proposed MRL workflows, respectively. Lastly, this study compared RED values obtained from CT and PET-CT scanners in a phantom and a subset of patients.Results. Population-based RED values were mostly within two standard deviations of ICRU Report 46 values. PopD plans were comparable to IndD plans, with the average %difference magnitudes of 0.5%, 0.6%, and 0.6% for mean dose (all organs), D0.1cm3(non-target organs) and D95%/D98% (target organs), respectively. Both phantom and patient PET-CT derived RED values had high agreement with corresponding CT-derived values, with correlation coefficients ≥ 0.9.Significance. Population-based RED values were considered suitable in a simulation-free MRL treatment workflow. Utilizing these RED values resulted in similar dosimetric uncertainties as per the current workflow. Initial findings also suggested that PET-CT scans may be used to assess prospective patients' eligibility for the proposed workflow. Future investigations will evaluate the clinical feasibility of implementing this workflow for prospective patients in the clinical setting. This is aimed to reduce patient burden during radiotherapy and increase department efficiencies.


Outcomes of single-stage compared to two-stage basilic vein transposition fistulae.
Basilic vein transposition (BVT) fistulae are increasing in prevalence in the United States. We examined outcomes of BVT fistulae created in a single stage compared to those created in two stages. Prospective QA databases identified a consecutive cohort of 144 patients with BVT fistulae. Of these, 42% were created in one stage and 58% in two stages. Fistula maturation rates, mean time to fistula use and intensity of percutaneous interventions were compared; patency rates were compared from time of first intervention. Maturation rates (including assisted maturation) were 90% among 1-stage and 75% among 2-stage BVT (p = 0.02). Mean time to initiation of fistula use was 142 days (1-stage) and 146 days (2-stage) (p = 0.92). Intensity of percutaneous interventions was 1.84/patient-year of dialysis (PYD) (1-stage) and 2.15/PYD (2-stage) (p = 0.57). Secondary patency at 1, 2, 3, and 4 years for 1-stage BVT was 86%, 75%, 69%, and 57%; secondary patency at 1, 2, 3, and 4 years for 2-stage BVT was 76%, 71%, 49%, and 25%, respectively (p = 0.12). BVT creation in two stages confers only a modest reduction in maturation rates and secondary patency and therefore should be considered over a synthetic graft in patients with basilic veins deemed inadequate for 1-stage BVT.


Invited review: crossbreeding in dairy cattle from a German perspective of the past and today.
Several crossing experiments in dairy cattle are currently in progress. Most of them are based on Holstein-Friesian, superior in milk production, and Jersey, known for highly concentrated milk and early maturity. Crossbreeding can lead to combination of favorable characteristics from the breeds involved, based on breed additive genetic effects. Further, heterosis can be of additional economic benefit, but the magnitude of heterosis is not well established for many breed combinations, and traits and effects of heterosis are not heritable. These unknowns, and possible recombination losses in rotational crossbreeding systems, are the challenges to practical application of crossbreeding in dairy cattle. Crossbreeding, if widely implemented, impacts existing breeding schemes and should be pursued after careful economic evaluation. In the former East Germany, crossbreeding in dairy cattle led to a new synthetic breed, a milk-emphasized dual-purpose breed called Schwarzbuntes Milchrind der DDR (SMR). The SMR composite was based on a 3-breed cross, including native East German Black and White, Danish Jersey, and Canadian Holstein-Friesian. The SMR breed was used in commercial milk production in East Germany in the 1970s and 1980s. This paper describes the goals in creating and performance of SMR and summarizes related work during the SMR period. Current German crossing experiments and profitability for different amounts of heterosis will be introduced.


Effects of abiotic factors and species interactions on estimates of male plant function: a meta-analysis.
The majority of angiosperms are hermaphroditic with total fitness comprised of both male and female components of reproduction. However, most studies examining the effects of abiotic factors and species interactions on fitness have focussed on female reproduction, potentially biasing our understanding of the consequences of environmental factors on total fitness. Here, we use meta-analysis to test how environmental factors affect male function. We obtained 278 effect sizes from 96 studies that measured male function responses to manipulated environmental factors. We found significant effects of abiotic factors and species interactions on estimates of male function, with responses varying depending on environmental factor identity. Male and female responses were correlated for abiotic factor manipulations, but varied based on the type of species interaction (antagonistic or mutualistic). This suggests that measuring only female function may misrepresent whole-plant reproduction depending on context. Finally, we found differences amongst components of male function in response to environmental factors, suggesting that some male function estimates may fail to capture the effects of environmental factors on male fitness. Our results demonstrate the importance of incorporating male function into ecological and evolutionary studies to provide a more accurate understanding of the effects of environmental factors on total fitness.


Water oxidation catalysis by birnessite@iron oxide core-shell nanocomposites.
In this work, magnetic nanocomposite particles were prepared for water oxidation reactions. The studied catalysts consist of maghemite (γ-Fe2O3), magnetite (Fe3O4), and manganese ferrite (MnFe2O4) nanoparticles as cores coated in situ with birnessite-type manganese oxide shells and were characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, thermal, chemical, and surface analyses, and magnetic measurements. The particles were found to be of nearly spherical core-shell architectures with average diameter of 150 nm. Water oxidation catalysis was examined using Ce(4+) as the sacrificial oxidant. All core-shell particles were found to be active water oxidation catalysts. However, the activity was found to depend on a variety of factors like the type of iron oxide core, the structure and composition of the shell, the coating characteristics, and the surface properties. Catalysts containing magnetite and manganese ferrite as core materials displayed higher catalytic activities per manganese ion (2650 or 3150 mmolO2 molMn(-1) h(-1)) or per mass than nanoiron oxides (no activity) or birnessite alone (1850 mmolO2 molMn(-1) h(-1)). This indicates synergistic effects between the MnOx shell and the FeOx core of the composites and proves the potential of the presented core-shell approach for further catalyst optimization. Additionally, the FeOx cores of the particles allow magnetic recovery of the catalyst and might also be beneficial for applications in water-oxidizing anodes because the incorporation of iron might enhance the overall conductivity of the material.


Considerations in the assessment and management of ADHD within the TGDNB population.
In this article we consider current literature around Attention Deficit Hyperactivity Disorder (ADHD) in the transgender, gender diverse and non-binary (TGDNB) population. Literature review. N/A conclusions: We outline specific considerations pertaining to the assessment and treatment of ADHD in this group and highlight evidential gaps and avenues for future research. We conclude that TGDNB individuals should be considered a "special population" with regards to ADHD and encourage mental health practitioners to consider specific TGDNB mental health needs beyond capacity assessments and gender-affirming care.


Absconding: A review of the literature 1996-2008.
Absconding is a significant problem with potential for harm to patients or the general public. The consequences of absconding include physical harm, prolonged treatment time, and substantial economic costs. The aim of this systematic literature review is to synthesize quality literature about absconding from psychiatric facilities, identify gaps in knowledge, and make recommendations for practice. An electronic search yielded 39 journal articles that met the review criteria. Findings demonstrate that a single definition of absconding remains elusive, making the prevalence of absconding difficult to establish. Absconding events are multifactorial, with environmental, psychosocial, and organic aspects. Negative consequences exist including violence, aggression, and self-neglect and harm to self and others. Papers are clustered around the following themes: harm and risk, absconder profiles, absconding rates, and perceptions of nurses and patients. Nursing interventions designed to decrease absconding have been implemented with success, but only in a few studies and in Australia, none have been reported in the literature to date. Further research is required to identify appropriate nursing-based interventions that may prove useful in reducing the risk of absconding.


The influence of testosterone on territorial defence and parental behavior in male free-living rufous whistlers, Pachycephala rufiventris.
We studied a population of rufous whistlers, Pachycephala rufiventris, throughout a single breeding season in central New South Wales, Australia. We evaluated the relation between plasma testosterone (T) and reproductive behaviors using both simulated territorial intrusions (STIs) and subcutaneous T implants. We compared circulating T values to aggression levels of males (using STI) during pair bond and territory establishment and again during incubation. Although plasma T levels were significantly lower in the latter period, male responsiveness to STI, in terms of proximity to decoy, call rate, and number of attacks on the decoy, was indistinguishable between the two breeding stages. T levels of males exposed to STI were not different from the levels of unexposed free-living males at the same breeding stage. The effect of exogenous T on parental behavior was examined by comparing duration of incubation bouts of males and their mates prior to and after T treatment. T males significantly reduced the amount of time they incubated following implantation, whereas Control males maintained their incubation effort. After cessation of breeding activities, T males displayed significantly higher call rates due to increased use of the primary intersexual advertisement call in this species. The reduction of incubation behavior following T implantation emphasises the functional significance of the rapid decline in T in free-living males during incubation. The results from both experiments suggest that intersexual advertisement, rather than territorial aggression, may be dependent on high T levels in this species.


Effects of N-acetylcysteine and ethyl pyruvate on ischemia-reperfusion injury in experimental electrical burn model.
This study was planned as a histopathologic evaluation of the effectiveness of ethyl pyruvate (EP) and N-acetylcysteine (NAC) in reducing electric burn-related organ damage in an experimental model. Four groups of 7 female Wister rats were established. The first was a sham group, the second an electrical burn control group receiving 600 V, the third group received NAC therapy of 20 mg/kg 1 hour after 600 V electrical burn, and the fourth group received 50 mg/kg EP 1 hour after 600 V electrical burn. Heart, kidney, striated muscle, brain, and lung tissues obtained 24 hours postprocedurally were subjected to histopathologic examination, and injury scores were determined. The values determined were then subjected to statistical analysis. Electrical fire caused significant damage in heart, striated muscle, kidney, and brain tissues. A statistically significant decrease in injury scores in total striated muscle and heart tissue was observed in the 2 treatment groups administered NAC or EP compared to the control group (P= .001). Total kidney injury scores among the groups were significantly lower in the NAC and EP groups compared to the control group (P= .002 and P= .001, respectively). Brain injury examination revealed a significant decrease in injury scores with NAC and EP therapy, both antioxidant agents, in terms of neuron degeneration (P= .004 and P= .001, respectively). Electrical burn was observed to cause injury in heart, striated muscle, kidney, and brain tissue. This injury was reduced by the administration of NAC and EP.


Differential Response of Mouse Thymic Epithelial Cell Types to Ionizing Radiation-Induced DNA Damage.
Thymic epithelial cells (TECs) are the main components of the thymic stroma that support and control T-cell development. Preparative regimens using DNA-damaging agents, such as total body irradiation and/or chemotherapeutic drugs, that are necessary prior to bone marrow transplantation (BMT) have profound deleterious effects on the hematopoietic system, including the thymic stroma, which may be one of the main causes for the prolonged periods of T-cell deficiency and the inefficient T cell reconstitution that are common following BMT. The DNA damage response (DDR) is a complex signaling network that allows cells to respond to all sorts of genotoxic insults. Hypoxia is known to modulate the DDR and play a role affecting the survival capacity of different cell types. In this study, we have characterized in detail the DDR of cortical and medullary TEC lines and their response to ionizing radiation, as well as the effects of hypoxia on their DDR. Although both mTECs and cTECs display relatively high radio-resistance, mTEC cells have an increased survival capacity to ionizing radiation (IR)-induced DNA damage, and hypoxia specifically decreases the radio-resistance of mTECs by upregulating the expression of the pro-apoptotic factor Bim. Analysis of the expression of TEC functional factors by primary mouse TECs showed a marked decrease of highly important genes for TEC function and confirmed cTECs as the most affected cell type by IR. These findings have important implications for improving the outcomes of BMT and promoting successful T cell reconstitution.


Protein conjugation with amphiphilic block copolymers for enhanced cellular delivery.
Modification of a model protein, horseradish peroxidase (HRP), with amphiphilic block copolymer poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic), was previously shown to enhance the transport of this protein across the blood-brain barrier in vivo and brain microvessel endothelial cells in vitro. This work develops procedures for synthesis and characterization of HRP with Pluronic copolymers, having different lengths of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) blocks. Four monoamine Pluronic derivatives (L81, P85, L121, P123) were synthesized and successfully conjugated to a model protein, HRP, via biodegradable or nondegradable linkers (dithiobis(succinimidyl propionate) (DSP), dimethyl 3,3'-dithiobispropionimidate (DTBP), and disuccinimidyl propionate (DSS)). The conjugation was confirmed by HRP amino group titration, matrix-assisted laser desorption/ionization-time of flight spectroscopy, and cation-exchange chromatography. HRP conjugates containing an average of one to two Pluronic moieties and retaining in most cases over 70% of the activity were synthesized. Increased cellular uptake of these conjugates was demonstrated using the Mardin-Derby canine kidney cell line and primary bovine brain microvessel endothelial cells. The optimal modifications included Pluronic L81 and P85. These copolymers have shorter PPO chains compared to Pluronic P123 and L121, which were less efficient. There was little if any dependence of the uptake on the length of the hydrophilic PEO block for the optimal modifications. The proposed modifications may be used to increase cellular uptake of other proteins.


[The system of medical evacuation support for the troops at the present stage of development of military medicine].
The authors analyse the former and actual state of evacuation support of troops. Having been finally formed during the Great Patriotic War as the system of casualty staging it proved to be correct. At the same time this system has some deficiencies, namely: the repeated surgical intervention, multistaged character of evacuation, medical care and treatment. In the post-war period the improvement of this system is connected with a radical technical re-equipment of medical service, including modern evacuation facilities, as well as with rational assignment of medical specialists. Actually the assurance of an early (within first 6 hours) specialized medical care is considered to be the main task and the basic principle in the improvement of medical evacuation in troops.


Multi-element determination in acid-digested soy protein formulations by inductively coupled plasma-optical emission spectrometry.
The concentrations of major (Ca, K, Mg, Na and P) and trace elements (Al, Cu and Fe) in soy protein formulations sold in Bahia (Brazil) were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES). Liquid and powdered soy protein formulation samples, both whole and light, were digested using a conventional heating program on a hot-plate. The powdered samples were prepared according to the label instructions for human consumption. A 5.0-ml aliquot of the soy protein emulsion was transferred to a borosilicate Erlenmeyer and concentrated nitric and sulfuric acid added. After a digestion time of approximately 50 min, hydrogen peroxide was added and heating continued to give a final volume of approximately 5 ml; the colorless digests were then made up to 15.0 ml with deionised water. Residual acid content was determined by acid-base titration. Good agreement between measured and certified values for all analytes in a non-fat milk powder (NIST SRM 1549) indicated that the method was suitable for major and trace elements determination in soy protein formulations.


New method to disaggregate and analyze single isolated helminthes cells using flow cytometry: proof of concept.
In parasitology, particularly in helminthes studies, several methods have been used to look for the expression of specific molecules, such as RT-PCR, western blot, 2D-electrophoresis, and microscopy, among others. However, these methods require homogenization of the whole helminth parasite, preventing evaluation of individual cells or specific cell types in a given parasite tissue or organ. Also, the extremely high interaction between helminthes and host cells (particularly immune cells) is an important point to be considered. It is really hard to obtain fresh parasites without host cell contamination. Then, it becomes crucial to determine that the analyzed proteins are exclusively from parasitic origin, and not a consequence of host cell contamination. Flow cytometry is a fluorescence-based technique used to evaluate the expression of extra-and intracellular proteins in different type cells, including protozoan parasites. It also allows the isolation and recovery of single-cell populations. Here, we describe a method to isolate and obtain purified helminthes cells.


Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in advanced prostate cancer: a marked improvement in response and survival.
Eighty-seven previously untreated patients with clinical stage D2 (bone metastases) prostate cancer have received the combination therapy with a pure antiandrogen and an LHRH agonist (or orchiectomy) as first treatment in a multicentre study for up to 34 months (average = 16.2 months). A positive objective response assessed according to the criteria of the US NPCP has been observed in all cases. Pain disappeared in all patients within 1 month and performance become normal in all (including 2 bedridden patients) within 4 months. Progression of the disease after a period of remission has been observed in only 8 patients. Only one patient has died from prostate cancer while 3 have died from other causes. The probability of continuing response and survival at 2 years for the patients who receive the combination treatment (Kaplan-Meier's method) is 81 and 91%, respectively. By contrast, in the randomized group who had orchiectomy alone, 4 of 7 have died from prostate cancer (P less than 0.05 as compared to combination therapy). In addition to a marked improvement in the remission rate and survival, combination therapy maintains a good quality of life, hot flashes and a decrease or loss of libido being the only side-effects.


Modulation of Bacillus subtilis levansucrase gene expression by sucrose and regulation of the steady-state mRNA level by sacU and sacQ genes.
In Bacillus subtilis, the extracellular enzyme levansurcrase is synthesized in the presence of sucrose. A termination structure between the transcription start site and the structural gene was the apparent site for regulation by sucrose of transcription into the structural gene. Sequence analysis of the sacB leader region from two strains constitutive for levansucrase synthesis showed a single base change in the stem of this termination structure. This single base change also led to the constitutive synthesis of a sacB'-'lacZ fusion, whereas the wild-type sacB'-'lacZ fusion was induced by the addition of sucrose. S1 nuclease mapping of sacB transcripts with probes labeled either within the termination structure or 3' to the termination structure showed that sucrose did not increase the number of transcripts extending into the termination structure; however, sucrose did increase the number of transcripts extending past the termination structure. Two pleiotropic mutations which affect the expression of levansucrase, sacQ36 hyperproducing [sacQ36(Hy)] and sacU32(Hy), were separately introduced into the strain carrying the sacB'-'lacZ fusion. These mutations each increased the expression levels of the sacB'-'lacZ fusion. S1 mapping showed increased levels of transcript initiating at the sacB promoter in strains with the sacQ36(Hy) and sacU32(Hy) mutations. This increased transcription appeared to be independent of the sucrose-regulated transcription termination, suggesting the existence of at least two different mechanisms for the regulation of sacB expression.


Sertraline induces endoplasmic reticulum stress in hepatic cells.
Sertraline is used for the treatment of depression, and is also used for the treatment of panic, obsessive-compulsive, and post-traumatic stress disorders. Previously, we have demonstrated that sertraline caused hepatic cytotoxicity, with mitochondrial dysfunction and apoptosis being underlying mechanisms. In this study, we used microarray and other biochemical and molecular analyses to identify endoplasmic reticulum (ER) stress as a novel molecular mechanism. HepG2 cells were exposed to sertraline and subjected to whole genome gene expression microarray analysis. Pathway analysis revealed that ER stress is among the significantly affected biological changes. We confirmed the increased expression of ER stress makers by real-time PCR and Western blots. The expression of typical ER stress markers such as PERK, IRE1α, and CHOP was significantly increased. To study better ER stress-mediated drug-induced liver toxicity; we established in vitro systems for monitoring ER stress quantitatively and efficiently, using Gaussia luciferase (Gluc) and secreted alkaline phosphatase (SEAP) as ER stress reporters. These in vitro systems were validated using well-known ER stress inducers. In these two reporter assays, sertraline inhibited the secretion of Gluc and SEAP. Moreover, we demonstrated that sertraline-induced apoptosis was coupled to ER stress and that the apoptotic effect was attenuated by 4-phenylbutyrate, a potent ER stress inhibitor. In addition, we showed that the MAP4K4-JNK signaling pathway contributed to the process of sertraline-induced ER stress. In summary, we demonstrated that ER stress is a mechanism of sertraline-induced liver toxicity.


Cognitive gender differences in very young children parallel biologically based cognitive gender differences in monkeys.
Infant humans were trained on 2 cognitive tests that have previously revealed, in infant monkeys, a double dissociation that was reversible by perinatal manipulations of androgens and ablations of specific brain sites. Children showed the same sex-linked behavior found with infant monkeys: young boys were superior on the object reversal task and young girls were superior on the concurrent discrimination task. As happened previously with infant monkeys, the gender difference was not apparent in older human subjects. Thus, early in ontogeny, cognitive gender differences have now been discovered in both humans and monkeys, probably a result of gender differences in androgens that influence the maturation rate of specific brain systems.


Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens.


Bispectral index-guided anaesthesia for off-pump coronary artery bypass grafting.
Bispectral index (BIS) monitoring may assist reduction in utilisation of anaesthetic agents during general surgical procedures. This study was designed to test whether the use of BIS monitoring reduces the anaesthetic requirements during off-pump coronary artery bypass grafting (CABG). This prospective - clinical trial was conducted on 40 adult patients undergoing elective off-pump CABG. Patients received either isoflurane or propofol anaesthesia. BIS monitoring, which guided the dose of anaesthetic, was carried out in 50 percent of the patients. The amount of anaesthetic agent (isoflurane or propofol) administered from the start of anaesthesia to the end of surgical procedure was calculated and were compared in four groups of patients - namely Group A (I-no BIS) received isoflurane; end tidal concentration was maintained at 1-1.2% in a low flow technique throughout the procedure, Group B (I-BIS) received isoflurane in a low flow technique; inspired concentration was dictated by BIS value maintained at 50; Group C (P-no BIS) received propofol at a dose range of 4-8 mg/kg/hr and in Group D(P-BIS) the propofol infusion rate was dictated by BIS value maintained at 50. The quantity of isoflurane was significantly less for Group B (I-BIS) as compared with Group A (I-no BIS) (37 +/- 4 vs. 24 +/- 4 ml; p< 0.05) and similarly the amount of propofol infused was significantly less in Group D (P-BIS) as compared with Group C (P-no BIS) (176 +/- 9 vs. 120 +/- 6 ml; p< 0.05). BIS guided anaesthesia reduces the anaesthetic agent required for the performance of off-pump CABG. This can be extrapolated in terms of saving agent and reduced cardiac depression during off-pump CABG.


Analysis of leukemia inhibitory factor, type 1 and type 2 cytokine production in patients with eosinophilic fasciitis.
Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by skin induration, elevated immune globulins, and peripheral eosinophilia. The hallmarks of the chronic cutaneous involvement in this syndrome are inflammation and fibrosis of the fascia. To determine how the inflammatory process in EF may be regulated, we investigated the spontaneous and mitogen induced [lipopolysaccharide (LPS), phytohemagglutinin (PHA) or both LPS+PHA] syntheses of interleukins (IL)-2, 5 and 10, interferon-gamma (IFN-gamma), and leukemia inhibitory factor (LIF) cytokines by peripheral blood mononuclear cells (PBMC) from 4 patients with active EF and compared them to those of 10 healthy individuals. We used a short term whole blood assay and culture supernatants were collected after 24 h to measure the IL-2 and IFN-gamma contents and after 48 h to evaluate IL-5, IL-10, and LIF. Supernatant cytokine concentrations were determined by ELISA. All 4 patients had similar patterns of cytokine secretion. Cytokine production did not differ between patients and controls under basal conditions or when LPS was added to the cultures. In contrast, under PHA or LPS+PHA stimulation, significantly higher amounts of all 5 cytokines were detected in samples from patients compared to those from controls. Overall, our data suggest that EF is characterized by an increased capacity of PBMC to produce IL-5 and IL-10, possibly leading to eosinophilia and immune globulin overexpression. In this context, the simultaneous elevations of type 1 cytokines (IL-2 and IFN-gamma) and LIF production by the same cells may be an attempt by the immune system to limit the exacerbation of a type 2 dominant response.


Exaggerated High-Beta Oscillations are Associated with Cortical Thinning at the Motor Cortex in Parkinson's Disease.
Elevated β oscillations (13-35 Hz) are characteristic pathophysiology in Parkinson's Disease (PD). Cortical thinning has also been reported in the disease, however the relationship between these biomarkers of PD has not been established. By comparing electrophysiological measurements with cortical thickness, this study aims to reveal the pathoetiology of disease and symptoms in PD. Preoperative magnetic resonance imaging (MRI) and intraoperative local field potentials (LFPs) were collected from 34 subjects diagnosed with PD. Cortical surfaces were reconstructed from the images, and cortical thickness was extracted from the subregions where the recording electrode was placed in M1. LFPs were preprocessed and cleaned using a semiautomatic artifact detection algorithm, then power spectral densities (PSD) were computed and periodic and aperiodic frequency components were calculated. Nonparametric Spearman rank correlations assessed the relationship between electrophysiological components (i.e. center frequency (CF), power, bandwidth, 1/f exponent, knee), with cortical thickness. According to the CF of each subject's PSD, the cohort was split into two sub-groups: low-β peak (13-20 Hz) and high-β peak (20-35 Hz) groups. There was a significant negative correlation between power and cortical thickness only in the high-β subgroup (r=-0.48, p(corrected)=0.049). This relationship remained significant when correcting for age (r=-0.52,p=0.015), indicating that the effect of age on cortical thinning was not the determining factor. We did not find significant differences between UPDRS-III motor symptom scores for the low-and high-β subgroups. Of note is the dominance of high-β oscillatory power and its relationship with cortical thickness. As suggested by the literature, increased high-β activity during movement may be exaggerated in PD. These findings suggest that the characteristic cortical thinning in PD causes variation in electrical activity, leading to elevated high-β activity.Clinical relevance- This multimodal study provides additional insights on the pathophysiology and its relevance with morphology of Parkinson's Disease.


Cell Wall Polysaccharide-Mediated Cadmium Tolerance Between Two Arabidopsis thaliana Ecotypes.
Cadmium (Cd) is a toxic metal element and the mechanism(s) underlying Cd tolerance in plants are still unclear. Increasingly more studies have been conducted on Cd binding to plant cell walls (CW) but most of them have focused on Cd fixation by CW pectin, and few studies have examined Cd binding to cellulose and hemicellulose. Here we found that Cd binding to CW pectin, cellulose, and hemicellulose was significantly higher in Tor-1, a Cd tolerant A. thaliana ecotype, than in Ph2-23, a sensitive ecotype, as were the concentrations of pectin, cellulose, and hemicellulose. Transcriptome analysis revealed that the genes regulating CW pectin, cellulose, and hemicellulose polysaccharide concentrations in Tor-1 differed significantly from those in Ph2-23. The expressions of most genes such as pectin methyl esterase inhibitors (PMEIs), pectin lyases, xyloglucan endotransglucosylase/hydrolase, expansins (EXPAs), and cellulose hydrolase were higher in Ph2-23, while the expressions of cellulose synthase-like glycosyltransferase 3 (CSLG3) and pectin ethyl esterase 4 (PAE4) were higher in Tor-1. The candidate genes identified here seem to regulate CW Cd fixation by polysaccharides. In conclusion, an increase in pectin demethylation activity, the higher concentration of cellulose and hemicellulose, regulated by related genes, in Tor-1 than in Ph2-23 are likely involved in enhanced Cd CW retention and reduce Cd toxicity.


Nursing students' prosocial motivation: does it predict professional commitment and involvement in the job?
This study investigated how prosocial motivation reported by nursing students in their final year of academic studies relates to career commitment and job involvement three years after graduation. Most studies investigating nurses' prosocial motivation for choosing the nursing profession examine only their prosocial motivation for entering nursing training; they do not investigate whether this motivation is associated with job involvement or commitment to the profession. A longitudinal survey design was used. The present longitudinal study included 160 nurses. In their final academic year of spring 2007, the nurses received a questionnaire about their motivation for entering nursing. Three years after graduation, spring 2010, they received another questionnaire about their level of job involvement and career commitment. The results showed that prosocial motivation measured in their last academic year was related to career commitment three years after graduation, but unrelated to job involvement. The results indicated that prosocial motivation is important in identifying with the profession but not necessarily for personal involvement in the job. The study gives important knowledge on how a commonly reported motivation for entering nursing relates to the nurses' attitudes about their work life.


Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions.
The prevailing model of cerebellar learning states that climbing fibers (CFs) are both driven by, and serve to correct, erroneous motor output. However, this model is grounded largely in studies of behaviors that utilize hardwired neural pathways to link sensory input to motor output. To test whether this model applies to more flexible learning regimes that require arbitrary sensorimotor associations, we developed a cerebellar-dependent motor learning task that is compatible with both mesoscale and single-dendrite-resolution calcium imaging in mice. We found that CFs were preferentially driven by and more time-locked to correctly executed movements and other task parameters that predict reward outcome, exhibiting widespread correlated activity in parasagittal processing zones that was governed by these predictions. Together, our data suggest that such CF activity patterns are well-suited to drive learning by providing predictive instructional input that is consistent with an unsigned reinforcement learning signal but does not rely exclusively on motor errors.


Predictors of Postdischarge Surgical Recovery Following Laparoscopic Sacrocolpopexy: A Prospective Cohort Study.
Our aim was to identify sociodemographic/clinical, surgical, and psychosocial predictors of postdischarge surgical recovery after laparoscopic sacrocolpopexy. Study participants (N = 171) with at least stage 2 pelvic organ prolapse completed a preoperative survey measuring hypothesized sociodemographic/clinical, surgical, and psychosocial recovery predictors followed by a postoperative survey at 4 time points (days 7, 14, 42, and 90) that included the Postdischarge Surgical Recovery 13 scale. One multivariate linear regression model was constructed for each time point to regress Postdischarge Surgical Recovery 13 scores on an a priori set of hypothesized predictors. All variables that had P < 0.1 were considered significant predictors of recovery because of the exploratory nature of this study and focus on model building rather than model testing. Predictors of recovery at 1 or more time points included the following: sociodemographic/clinical predictors: older age, higher body mass index, fewer comorbidities, and greater preoperative pain predicted greater recovery; surgical predictors: fewer perioperative complications and greater change in the leading edge of prolapse after surgery predicted greater recovery; psychosocial predictors: less endorsement of doctor's locus of control, greater endorsement of other's locus of control, and less sick role investment predicted greater recovery. Identified sociodemographic/clinical, surgical, and psychosocial predictors should provide physicians with evidence-based guidance on recovery times for patients and family members. This knowledge is critical for informing future research to determine if these predictors are modifiable by changes to our narrative during the preoperative consultation visit. These efforts may reduce the postdischarge surgical recovery for patients with pelvic organ prolapse after laparoscopic sacrocolpopexy, accepting the unique demands on each individual's time.


Developing and Demonstrating the Viability and Availability of the Multilevel Implementation Strategy for Syncope Optimal Care Through Engagement (MISSION) Syncope App: Evidence-Based Clinical Decision Support Tool.
Syncope evaluation and management is associated with testing overuse and unnecessary hospitalizations. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Syncope Guideline aims to standardize clinical practice and reduce unnecessary services. The use of clinical decision support (CDS) tools offers the potential to successfully implement evidence-based clinical guidelines. However, CDS tools that provide an evidence-based differential diagnosis (DDx) of syncope at the point of care are currently lacking. With input from diverse health systems, we developed and demonstrated the viability of a mobile app, the Multilevel Implementation Strategy for Syncope optImal care thrOugh eNgagement (MISSION) Syncope, as a CDS tool for syncope diagnosis and prognosis. Development of the app had three main goals: (1) reliable generation of an accurate DDx, (2) incorporation of an evidence-based clinical risk tool for prognosis, and (3) user-based design and technical development. To generate a DDx that incorporated assessment recommendations, we reviewed guidelines and the literature to determine clinical assessment questions (variables) and likelihood ratios (LHRs) for each variable in predicting etiology. The creation and validation of the app diagnosis occurred through an iterative clinician review and application to actual clinical cases. The review of available risk score calculators focused on identifying an easily applied and valid evidence-based clinical risk stratification tool. The review and decision-making factors included characteristics of the original study, clinical variables, and validation studies. App design and development relied on user-centered design principles. We used observations of the emergency department workflow, storyboard demonstration, multiple mock review sessions, and beta-testing to optimize functionality and usability. The MISSION Syncope app is consistent with guideline recommendations on evidence-based practice (EBP), and its user interface (UI) reflects steps in a real-world patient evaluation: assessment, DDx, risk stratification, and recommendations. The app provides flexible clinical decision making, while emphasizing a care continuum; it generates recommendations for diagnosis and prognosis based on user input. The DDx in the app is deemed a pragmatic model that more closely aligns with real-world clinical practice and was validated using actual clinical cases. The beta-testing of the app demonstrated well-accepted functionality and usability of this syncope CDS tool. The MISSION Syncope app development integrated the current literature and clinical expertise to provide an evidence-based DDx, a prognosis using a validated scoring system, and recommendations based on clinical guidelines. This app demonstrates the importance of using research literature in the development of a CDS tool and applying clinical experience to fill the gaps in available research. It is essential for a successful app to be deliberate in pursuing a practical clinical model instead of striving for a perfect mathematical model, given available published evidence. This hybrid methodology can be applied to similar CDS tool development.


Can spray freeze-drying improve the re-dispersion of crystalline nanoparticles of pure naproxen?
Spray freeze drying (SFD) was used to prepare re-dispersible powders of crystalline, pure-drug nanodispersions of naproxen in lactose and stabilized with hydroxypropyl cellulose. The particle size of the rehydrated powders was determined using static light scattering/Mie analysis. The nanoparticles present in the SFD powders were aggregated but could be dispersed on re-dispersion with water and stirring either with or without additional ultrasonic treatment. The disaggregation of the SFD nanoparticles was superior to that reported in the literature for spray dried nanoparticles of the same composition. It appears that the moderately-rapid freezing of the large spray droplets in LN2 during SFD produces less aggregation than does evaporative drying of the much smaller droplets during spray drying. Re-dispersion was also found to depend strongly on the pH of the original nanodispersion. The solubility of this weak acid is greater at higher pH which resulted in formation of a dissolved fraction of drug in the nanodispersions during media milling. After SFD, the dissolved naproxen fraction formed an amorphous solid which re-dissolves on re-hydration whereas the crystalline nanoparticles disaggregate.


Are Prolactin Levels Linked to Suction Pressure?
Suction pressure has been reported to be a key driving force of lactation. An infant's sucking at its mother's breasts is the major stimulus to post-natal prolactin (PRL) secretion, and PRL is the essential hormone for lactation and milk production. It is unknown what role suction pressure has in PRL secretion and milk supply postnatally. To explore the relationship between the suction pressure, PRL level, lactation, and milk supply in breastfeeding mother-infant dyads. Healthy women with normal full-term infants were enrolled (n = 122). Data collection included suction pressure, PRL level, and the mother's perception of both the onset of her lactation and her milk supply at 1 month. Suction pressure was measured with a pressure sensor connected to a tube placed alongside the nipple. The chemiluminescence method was used to quantify maternal serum PRL level both before and after a breastfeed to explore the effect of suckling on PRL increment. The mother's perception of the onset of her lactation was evaluated by the mother's sense of fullness in her breast. The mother's perception of milk supply was evaluated by using the H&H Lactation Scale. Data from 117 participants were included in this analysis. Low suction pressure, a shorter gestational age, a high pre-gestational body mass index (BMI), and high infant birth weight were associated with a smaller than average PRL increment. High suction pressure, longer sucking duration, and a low gestational weight gain were related to a mother's perception of an earlier onset of her lactation. However, low suction pressure, a high frequency of giving formula, a small PRL increment, and the mother's perception of a later onset of her lactation were correlated with her perception of an insufficient milk supply. Suction pressure varied directly with the post-natal PRL increment. Suction pressure was associated with the timing of the mother's perception of her lactation. Strong suction pressure by the infant is likely to enhance the mother's confidence in her lactation. Additionally, sucking duration, frequency of giving formula, maternal BMI, and infant birth weight played a role in early breastfeeding success.


Therapeutic Efficacy of a Subunit Vaccine in Controlling Chronic Trypanosoma cruzi Infection and Chagas Disease Is Enhanced by Glutathione Peroxidase Over-Expression.
Trypanosoma cruzi-induced oxidative and inflammatory responses are implicated in chagasic cardiomyopathy. In this study, we examined the therapeutic utility of a subunit vaccine against T. cruzi and determined if glutathione peroxidase (GPx1, antioxidant) protects the heart from chagasic pathogenesis. C57BL/6 mice (wild-type (WT) and GPx1 transgenic (GPxtg) were infected with T. cruzi and at 45 days post-infection (dpi), immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach. The plasma and tissue-sections were analyzed on 150 dpi for parasite burden, inflammatory and oxidative stress markers, inflammatory infiltrate and fibrosis. WT mice infected with T. cruzi had significantly more blood and tissue parasite burden compared with infected/GPxtg mice (n = 5-8, p<0.01). Therapeutic vaccination provided >15-fold reduction in blood and tissue parasites in both WT and GPxtg mice. The increase in plasma levels of myeloperoxidase (MPO, 24.7%) and nitrite (iNOS activity, 45%) was associated with myocardial increase in oxidant levels (3-4-fold) and non-responsive antioxidant status in chagasic/WT mice; and these responses were not controlled after vaccination (n = 5-7). The GPxtg mice were better equipped than the WT mice in controlling T. cruzi-induced inflammatory and oxidative stress markers. Extensive myocardial and skeletal tissue inflammation noted in chagasic/WT mice, was significantly more compared with chagasic/GPxtg mice (n = 4-6, p<0.05). Vaccination was equally effective in reducing the chronic inflammatory infiltrate in the heart and skeletal tissue of infected WT and GPxtg mice (n = 6, p<0.05). Hypertrophy (increased BNP and ANP mRNA) and fibrosis (increased collagen) of the heart were extensively present in chronically-infected WT and GPxtg mice and notably decreased after therapeutic vaccination. We conclude the therapeutic delivery of D/P vaccine was effective in arresting the chronic parasite persistence and chagasic pathology; and GPx1 over-expression provided additive benefits in reducing the parasite burden, inflammatory/oxidative stress and cardiac remodeling in Chagas disease.


Routine quantification of rheumatoid factor by rate nephelometry.
In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid factor (RF) measured by rate nephelometry (Beckman ICS II) were compared with values obtained by the more traditional methods of sheep cell agglutination (Rose-Waaler) and latex agglutination. Similar values for sensitivity and specificity were found for all three methods for rheumatoid arthritis, with nephelometry giving slightly higher levels of sensitivity for other rheumatic disorders. A significant correlation (r = 0.46, p less than 0.01) was found between the nephelometric and Rose-Waaler method for 147 consecutive seropositive specimens. Of interest, however, several disparate results were observed, and explanations for these were sought. Longitudinal studies of RF were performed in 49 seropositive patients over a two-year period. The nephelometric method was considered superior compared with the other techniques because of its ability to detect changes in absolute levels at earlier stages and its low interassay coefficient of variance (11%). We conclude that the nephelometric technique appears suitable for routine diagnostic use, offers several advantages compared with more traditional methods, and is no more expensive per test specimen than the Rose-Waaler technique.


Structural investigation of zymogenic and activated forms of human blood coagulation factor VIII: a computational molecular dynamics study.
Human blood coagulation factor VIII (fVIII) is a large plasma glycoprotein with sequential domain arrangement in the order A1-a1-A2-a2-B-a3-A3-C1-C2. The A1, A2 and A3 domains are interconnected by long linker peptides (a1, a2 and a3) that possess the activation sites. Proteolysis of fVIII zymogen by thrombin or factor Xa results in the generation of the activated form (fVIIIa) which serves as a critical co-factor for factor IXa (fIXa) enzyme in the intrinsic coagulation pathway. In our efforts to elucidate the structural differences between fVIII and fVIIIa, we developed the solution structural models of both forms, starting from an incomplete 3.7 A X-ray crystal structure of fVIII zymogen, using explicit solvent MD simulations. The full assembly of B-domainless single-chain fVIII was built between the A1-A2 (Ala1-Arg740) and A3-C1-C2 (Ser1669-Tyr2332) domains. The structural dynamics of fVIII and fVIIIa, simulated for over 70 ns of time scale, enabled us to evaluate the integral motions of the multi-domain assembly of the co-factor and the possible coordination pattern of the functionally important calcium and copper ion binding in the protein. MD simulations predicted that the acidic linker peptide (a1) between the A1 and A2 domains is largely flexible and appears to mask the exposure of putative fIXa enzyme binding loop (Tyr555-Asp569) region in the A2 domain. The simulation of fVIIIa, generated from the zymogen structure, predicted that the linker peptide (a1) undergoes significant conformational reorganization upon activation by relocating completely to the A1-domain. The conformational transition led to the exposure of the Tyr555-Asp569 loop and the surrounding region in the A2 domain. While the proposed linker peptide conformation is predictive in nature and warrants further experimental validation, the observed conformational differences between the zymogen and activated forms may explain and support the large body of experimental data that implicated the critical importance of the cleavage of the peptide bond between the Arg372 and Ser373 residues for the full co-factor activity of fVIII.


Left ventricular volume analysis as a basic tool to describe cardiac function.
The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.


Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli.
A structural gene for isocitrate lyase was isolated from a cosmid containing an ace locus of the Escherichia coli chromosome. Cloning and expression under control of the tac promoter in a multicopy plasmid showed that a 1.7-kilobase-pair DNA segment was sufficient for complementation of an aceA deletion mutation and overproduction of isocitrate lyase. DNA sequence analysis of the cloned gene and N-terminal protein sequencing of the cloned and wild-type enzymes revealed an entire aceA gene which encodes a 429-amino-acid residue polypeptide whose C-terminus is histidine. The deduced amino acid sequence for the 47.2-kilodalton subunit of E. coli isocitrate lyase could be aligned with that for the 64.8-kilodalton subunit of the castor bean enzyme with 39% identity except for limited N- and C-terminal regions and a 103-residue stretch that was unique for the plant enzyme and started approximately in the middle of that peptide.


The PAR proteins: fundamental players in animal cell polarization.
The par genes were discovered in genetic screens for regulators of cytoplasmic partitioning in the early embryo of C. elegans, and encode six different proteins required for asymmetric cell division by the worm zygote. Some of the PAR proteins are localized asymmetrically and form physical complexes with one another. Strikingly, the PAR proteins have been found to regulate cell polarization in many different contexts in diverse animals, suggesting they form part of an ancient and fundamental mechanism for cell polarization. Although the picture of how the PAR proteins function remains incomplete, cell biology and biochemistry are beginning to explain how PAR proteins polarize cells.


Paternity testing: analysis of six blood groups and HLA markers, with particular reference to comparison of races.
Blood groups (ABO, Rh, MNSs, Kell, Duffy, and Kidd) and HLA markers were tested in cases involving 563 children of disputed parentage. In 149 (26.5%) cases, the accused men were excluded as the biologic fathers of the children in question. One hundred forty of the 149 exclusions were direct exclusions. Five exclusions were based on red blood cell data alone, i.e., HLA was non-exclusionary. Of the remaining 414 cases in which the alleged father could not be excluded as the biologic father, in 361 (87.2%) instances, the plausibility of paternity ws 95% or greater, and in 385 (93.0%) instances the comparison of men value was 20 or greater. Caucasians, blacks, and men of other races were involved in 367 (65.1%), 185 (33%), and 11 (1.9%) cases, respectively. No significant difference among races was observed in the rate of exclusion of accused men. However, of the non-excluded men, in a significantly greater proportion of black men than white men, the plausibility of paternity was below 95%. The difference was probably due to lower polymorphism of the markers tested in blacks than in whites. It is suggested that tests for additional polymorphic genes be directed towards the 12-15% of the nonexclusionary cases with plausibility of paternity values below 95%.


[Changes in the functional state of the cardiovascular system as an indicator of the general reaction of the body to the application of therapeutic mud].
Multimodality clinical and physiological studies on the CVS in patients with rheumatoid arthritis (56), deforming osteoarthrosis (97) and systemic scleroderma (29) before and after various mud application procedures during the entire course of treatment showed that the CVS sensitively responded to the mud effect. As to the nature and expression of reactions peloid applications produced a general effect on the body; the most informative reactions were hemodynamic effects, changes of indices of intervalograms and the capillary blood flow. The hemodynamic effect was of a hypodynamic type of the CVS adaptation response to mud therapy. The author proposed that these indices should be used as tests for working out methods of control of the process of mud therapy and for other practical problems of pelotherapy.


[Changes in the actin cytoskeleton during transformation and tumor progression in liver epithelium in culture].
Two patterns of actin distribution were revealed by indirect immunofluorescence in non-tumorigenic cell lines of cultured liver epithelium. The first one was represented by large marginal cable, lining the active edge of epithelial sheet. The second one was represented by numerous inner bundles randomly distributed in all cells. The following changes in actin pattern were detected in cultures of transformed epithelium: A) The reduction of inner bundles in all cells and the appearance of the marginal actin cable in central cells of the sheet, and B) The reduction of marginal cable and the presence of inner bundles, preferentially oriented along the longer axis of cells which became more polarized. In tumor cells, arising from transformed epithelium with A-type of actin pattern alteration, a secondary redistribution of actin bundles towards B-type occurred. Histochemical staining of such cells revealed a high activity of gamma-glutamyltranspeptidase, a marker enzyme for transformed cultures. The complete loss of actin bundles was observed in soft agar clone originated from cells with B-type alteration of actin pattern.


A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems.
The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.


Gastroduodenal major haemorrhages in critical patients: an original surgical technique.
Upper gastrointestinal bleeding represents today a serious pathology with two important problems: mortality and correct management. Our study is a review of recent and past licterature about causes, diagnosis and treatment of upper gastrointestinal bleeding. The Authors describe an original surgical technique in treating patients with gastroduodenal haemorrhages and critical circulatory-coagulative conditions. Any surgical resective procedure could be absolutely inacceptable for the rates in morbility and mortality in these absolutely instable patients. We approached the problem with a control damage surgery by endoluminal packing of the stomach or the duodenum.


Porous Organic Frameworks: Advanced Materials in Analytical Chemistry.
Porous organic frameworks (POFs), a general term for covalent-organic frameworks (COFs), covalent triazine frameworks (CTFs), porous aromatic frameworks (PAFs), etc., are constructed from organic building monomers with strong covalent bonds and have generated great interest among researchers. The remarkable features, such as large surface areas, permanent porosity, high thermal and chemical stability, and convenient functionalization, promote the great potential of POFs in diverse applications. A critical overview of the important development in the design and synthesis of COFs, CTFs, and PAFs is provided and their state-of-the-art applications in analytical chemistry are discussed. POFs and their functional composites have been explored as advanced materials in "turn-off" or "turn-on" fluorescence detection and novel stationary phases for chromatographic separation, as well as a promising adsorbent for sample preparation methods. In addition, the prospects for the synthesis and utilization of POFs in analytical chemistry are also presented. These prospects can offer an outlook and reference for further study of the applications of POFs.


Two new arsenides, Eu7Cu44As23 and Sr7Cu44As23, with a new filled variety of the BaHg11 structure.
Two new ternary arsenides, namely, Eu7Cu44As23 and Sr7Cu44As23, were synthesized from elements at 800 °C. Their crystal structure represents a new filled version of the BaHg11 motif with cubic voids alternately occupied by Eu(Sr) and As atoms, resulting in a 2 × 2 × 2 superstructure of the aristotype: space group Fm3̅m, a = 16.6707(2) Å and 16.7467(2) Å, respectively. The Eu derivative exhibits ferromagnetic ordering below 17.5 K. In agreement with band structure calculations both compounds are metals, exhibiting relatively low thermopower, but high electrical and low thermal conductivity.


A review of Simulium damnosum s.l. and human onchocerciasis in Nigeria, with special reference to geographical distribution and the development of a Nigerian national control campaign.
The confirmed geographical distribution of human onchocerciasis and its Simulium damnosum complex vectors in Nigeria is reviewed with the aim of defining the endemic zones of the disease relevant to the planning of a Nigerian national onchocerciasis control campaign. Five major endemic zones are recognized, a terminology suggested for them, their sizes estimated and the disease and vector situation within each zone briefly described; four of the zones are in savanna areas of the north, and the fifth in forest-savanna mosaic and forest areas of the south-west. Other areas where disease and/or vectors have been reported are briefly considered. Maps are given of known vector breeding sites, of disease distribution, and of the approximate extent of the anticipated control zones. The scanty available data on cytospecies identity of the vectors, vector biting rates, and Onchocerca volvulus transmission potentials, are reviewed, and it is stressed that acquisition of distributional data for the individual members of the S. damnosum complex and of ATP data is essential for the planning of control. An historical resumé, accompanied by a comprehensive bibliography of the published literature, of the work to date in Nigeria is included.


A multicenter randomized controlled trial comparing absorbable barbed sutures versus conventional absorbable sutures for dermal closure in open surgical procedures.
Barbed sutures were developed to reduce operative time and improve security of wound closure. The authors compare absorbable barbed sutures (V-Loc, Covidien, Mansfield, Massachusetts) with conventional (smooth) absorbable sutures for soft tissue approximation. A prospective multicenter randomized study comparing barbed sutures with smooth sutures was undertaken between August 13, 2009, and January 31, 2010, in 241 patients undergoing abdominoplasty, mastopexy, and reduction mammaplasty. Each patient received barbed sutures on 1 side of the body, with deep dermal sutures eliminated or reduced. Smooth sutures with deep dermal and subcuticular closure were used on the other side as a control. The primary endpoint was dermal closure time. Safety was assessed through adverse event reporting through a 12-week follow-up. A total of 229 patients were ultimately treated (115 with slow-absorbing polymer and 114 with rapid-absorbing polymer). Mean dermal closure time was significantly quicker with the barbed suture compared with the smooth suture (12.0 vs 19.2 minutes; P<.001), primarily due to the need for fewer deep dermal sutures. The rapid-absorbing barbed suture showed a complication profile equivalent to the smooth suture, while the slow-absorbing barbed suture had a higher incidence of minor suture extrusion. Barbed sutures enabled faster dermal closure quicker than smooth sutures, with a comparable complication profile. 1.


Acoustic space learning for sound-source separation and localization on binaural manifolds.
In this paper, we address the problems of modeling the acoustic space generated by a full-spectrum sound source and using the learned model for the localization and separation of multiple sources that simultaneously emit sparse-spectrum sounds. We lay theoretical and methodological grounds in order to introduce the binaural manifold paradigm. We perform an in-depth study of the latent low-dimensional structure of the high-dimensional interaural spectral data, based on a corpus recorded with a human-like audiomotor robot head. A nonlinear dimensionality reduction technique is used to show that these data lie on a two-dimensional (2D) smooth manifold parameterized by the motor states of the listener, or equivalently, the sound-source directions. We propose a probabilistic piecewise affine mapping model (PPAM) specifically designed to deal with high-dimensional data exhibiting an intrinsic piecewise linear structure. We derive a closed-form expectation-maximization (EM) procedure for estimating the model parameters, followed by Bayes inversion for obtaining the full posterior density function of a sound-source direction. We extend this solution to deal with missing data and redundancy in real-world spectrograms, and hence for 2D localization of natural sound sources such as speech. We further generalize the model to the challenging case of multiple sound sources and we propose a variational EM framework. The associated algorithm, referred to as variational EM for source separation and localization (VESSL) yields a Bayesian estimation of the 2D locations and time-frequency masks of all the sources. Comparisons of the proposed approach with several existing methods reveal that the combination of acoustic-space learning with Bayesian inference enables our method to outperform state-of-the-art methods.


Morvan's fibrillary chorea: a paraneoplastic manifestation of thymoma.
Morvan's fibrillary chorea is a rare disease characterised by symptoms which include neuromyotonia, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. The first case of Morvan's fibrillary chorea to be associated with clinical manifestations of myasthenia gravis with thymoma, psoriasis, and atopic dermatitis is reported. Muscle histopathology disclosed chronic denervation and myopathic changes and in vitro electrophysiology demonstrated both presynaptic and postsynaptic defects in neuromuscular transmission. Serum antibodies to acetylcholine receptors, titin, N-type calcium channels, and voltage gated potassium channels were detected. Plasmapheresis, thymectomy, and long term immunosuppression induced a dramatic resolution of symptoms. The association of thymoma with other autoimmune disorders and autoantibodies, and prolonged and sustained remission with chronic immunosuppression, place Morvan's fibrillary chorea on the range of neurological diseases arising as a paraneoplastic complication of cortical thymomas.