Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data.
Little is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns. The MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme's first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%-75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients' length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes. Good treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.


Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT.
Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.


Identification of genome regions controlling cotyledon, pod wall/seed coat and pod wall resistance to pea weevil through QTL mapping.
Pea weevil, Bruchus pisorum, is one of the limiting factors for field pea (Pisum sativum) cultivation in the world with pesticide application the only available method for its control. Resistance to pea weevil has been found in an accession of Pisum fulvum but transfer of this resistance to cultivated pea (P. sativum) is limited due to a lack of easy-to-use techniques for screening interspecific breeding populations. To address this problem, an interspecific population was created from a cross between cultivated field pea and P. fulvum (resistance source). Quantitative trait locus (QTL) mapping was performed to discover the regions associated with resistance to cotyledon, pod wall/seed coat and pod wall resistance. Three major QTLs, located on linkage groups LG2, LG4 and LG5 were found for cotyledon resistance explaining approximately 80 % of the phenotypic variation. Two major QTLs were found for pod wall/seed coat resistance on LG2 and LG5 explaining approximately 70 % of the phenotypic variation. Co-linearity of QTLs for cotyledon and pod wall/seed coat resistance suggested that the mechanism of resistance for these two traits might act through the same pathways. Only one QTL was found for pod wall resistance on LG7 explaining approximately 9 % of the phenotypic variation. This is the first report on the development of QTL markers to probe Pisum germplasm for pea weevil resistance genes. These flanking markers will be useful in accelerating the process of screening when breeding for pea weevil resistance.


Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.
The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine.


Generalized Beta Mixtures of Gaussians.
In recent years, a rich variety of shrinkage priors have been proposed that have great promise in addressing massive regression problems. In general, these new priors can be expressed as scale mixtures of normals, but have more complex forms and better properties than traditional Cauchy and double exponential priors. We first propose a new class of normal scale mixtures through a novel generalized beta distribution that encompasses many interesting priors as special cases. This encompassing framework should prove useful in comparing competing priors, considering properties and revealing close connections. We then develop a class of variational Bayes approximations through the new hierarchy presented that will scale more efficiently to the types of truly massive data sets that are now encountered routinely.


Demonstration of portfolios to assess competency of residents.
Residency educators are identifying approaches to measure resident competence. Portfolios are well suited since they require work already completed as part of patient care where competency must be demonstrated. This paper describes assessment of the reliability and validity of portfolios in a psychiatry residency program. This was a cross-sectional study across 4years of residency education. Using guidelines, 18 residents assembled portfolios containing five entries chosen from 13 skills. Trained raters scored the portfolios. Residents and faculty were interviewed about their perceptions. Generalizability results indicated five entries and two raters were sufficient for relative decisions. Six entries or a third rater would be sufficient for absolute decisions. Portfolio scores tended to improve with years of training and correlated with psychiatric knowledge but not clinical performance. Residents and faculty identified benefits to assembling a portfolio. Portfolios incorporate tasks embedded in the residency to provide evidence of resident competency. The results support that the score is reliable and valid.


Where should health services go: local authorities versus the NHS?
The Association of Metropolitan Authorities has recently proposed that responsibility for the NHS should pass from health authorities to local authorities. One of the fiercest debates at the outset of the NHS was whether the hospitals should be run by local authorities. In the end the minister for health, Aneurin Bevan, decided against local democracy and in favour of a national health service. His arguments included the fact that equality of treatment could not be guaranteed if facilities varied with local finances and that even the largest authorities were not big enough to pool risks and expertise. All these arguments still apply today, and the recent changes in community care provide an insight into how a market model of local authority control might work. The changes have been accompanied by a shift from public to private sector provision and the introduction of charges for services that the NHS once provided free. As important, the willingness and ability of local authorities to raise extra revenue from local taxes and charges affect the service they can provide, so leading to inequalities of provision. Local authorities have yet to make the case that they can preserve the fundamental principles and benefits of the NHS, including its reliance on central taxation and unified funding formulas.


Whole body autoregulation in reduced renal mass hypertension.
Whole body autoregulation in conscious rats can be shown in the absence of the rapid acting neural and hormonal controllers of blood pressure. It is hypothesized that this phenomenon is responsible for the gradual rise of vascular resistance observed in volume-dependent forms of hypertension such as reduced renal mass-salt-induced hypertension. To examine the hypothesis, we evaluated the gain of whole body autoregulation at various stages of reduced renal mass hypertension to determine if acute autoregulatory capacity is altered during chronic hypertension. Rats underwent reduced renal mass surgery (nephrectomy plus 70% reduction of remaining kidney) and were studied at 2 (n = 8), 4 (n = 6), and 6 (n = 7) weeks after high salt diet. Control rats (n = 6) underwent nephrectomy and sham surgery and were studied after 2 weeks of high salt diet. All reduced renal mass rats showed progressive hypertension (2 weeks, 136 +/- 5; 4 weeks, 157 +/- 8; and 6 weeks, 171 +/- 10 mm Hg) compared with sham rats (113 +/- 4 mm Hg). We observed an increase in basal level of total peripheral resistance index after neurohumoral blockade in reduced renal mass rats (2 weeks, 1.64 +/- 0.06; 4 weeks, 1.79 +/- 0.10; and 6 weeks, 1.89 +/- 0.09 mm Hg.100 g-1.min-1.ml-1) compared with sham rats (1.56 +/- 0.10 mm Hg.100 g-1.min-1.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)


High throughput assay for evaluation of reactive carbonyl scavenging capacity.
Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.


Phylogenetic analysis of trophic associations.
Ecologists frequently collect data on the patterns of association between adjacent trophic levels in the form of binary or quantitative food webs. Here, we develop statistical methods to estimate the roles of consumer and resource phylogenies in explaining patterns of consumer-resource association. We use these methods to ask whether closely related consumer species are more likely to attack the same resource species and whether closely related resource species are more likely to be attacked by the same consumer species. We then show how to use estimates of phylogenetic signals to predict novel consumer-resource associations solely from the phylogenetic position of species for which no other (or only partial) data are available. Finally, we show how to combine phylogenetic information with information about species' ecological characteristics and life-history traits to estimate the effects of species traits on consumer-resource associations while accounting for phylogenies. We illustrate these techniques using a food web comprising species of parasitoids, leaf-mining moths, and their host plants.


Antitumor Activity of KW-2450 against Triple-Negative Breast Cancer by Inhibiting Aurora A and B Kinases.
Currently, no targeted drug is available for triple-negative breast cancer (TNBC), an aggressive breast cancer that does not express estrogen receptor, progesterone receptor, or HER2. TNBC has high mitotic activity, and, because Aurora A and B mitotic kinases drive cell division and are overexpressed in tumors with a high mitotic index, we hypothesized that inhibiting Aurora A and B produces a significant antitumor effect in TNBC. We tested this hypothesis by determining the antitumor effects of KW-2450, a multikinase inhibitor of both Aurora A and B kinases. We observed significant inhibitory activities of KW-2450 on cell viability, apoptosis, colony formation in agar, and mammosphere formation in TNBC cells. The growth of TNBC xenografts was significantly inhibited with KW-2450. In cell-cycle analysis, KW-2450 induced tetraploid accumulation followed by apoptosis or surviving octaploid (8N) cells, depending on dose. These phenotypes resembled those of Aurora B knockdown and complete pharmaceutical inhibition of Aurora A. We demonstrated that 8N cells resulting from KW-2450 treatment depended on the activation of mitogen-activated protein kinase kinase (MEK) for their survival. When treated with the MEK inhibitor selumetinib combined with KW-2450, compared with KW-2450 alone, the 8N cell population was significantly reduced and apoptosis was increased. Indeed, this combination showed synergistic antitumor effect in SUM149 TNBC xenografts. Collectively, Aurora A and B inhibition had a significant antitumor effect against TNBC, and this antitumor effect was maximized by the combination of selumetinib with Aurora A and B inhibition.


Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.
4'-Demethoxydaunorubicin (idarubicin [IDR]) is a new anthracycline that differs from its parent compound by the deletion of a methoxy group at position 4 of the chromophore ring. This minor structural modification results in a more lipophilic compound with a unique metabolite that has a prolonged plasma half-life as well as in vitro and in vivo antileukemia activity. To determine its activity in acute myelogenous leukemia (AML), 130 consecutive adult patients between the ages of 16 and 60 with newly diagnosed disease were randomized in a single institution study to receive either IDR in combination with cytosine arabinoside (Ara-C) or standard therapy with daunorubicin (DNR) and Ara-C. The trial was analyzed using the O'Brien-Fleming multiple testing design that allowed for periodic inspection of the data at specific patient accession points. After accrual of 60 patients per arm, analysis showed that patients who received IDR/Ara-C had a superior response compared with those who received standard therapy: 48 of 60 patients (80%) achieved complete remission on the former arm compared with 35 of 60 patients on the latter (58%, P = .005). Logistic regression analysis of factors associated with complete response indicated that treatment with IDR/Ara-C offered a significant advantage to patients who presented with a high initial white blood cell count compared with treatment with DNR/Ara-C. The degree of marrow aplasia was approximately the same on each arm as was nonhematologic toxicity. Overall survival for patients on the IDR/Ara-C arm was 19.5 months compared with 13.5 months on the DNR/Ara-C arm (P = .025) at a median follow-up of 2.5 years. We conclude that IDR/Ara-C can effectively replace standard therapy with DNR/Ara-C in adult patients less than age 60 with newly diagnosed AML.


Structure determination of a DNA crystal by MicroED.
Microcrystal electron diffraction (MicroED) is a powerful tool for determining high-resolution structures of microcrystals from a diverse array of biomolecular, chemical, and material samples. In this study, we apply MicroED to DNA crystals, which have not been previously analyzed using this technique. We utilized the d(CGCGCG) 2 DNA duplex as a model sample and employed cryo-FIB milling to create thin lamella for diffraction data collection. The MicroED data collection and subsequent processing resulted in a 1.10 Å resolution structure of the d(CGCGCG) 2 DNA, demonstrating the successful application of cryo-FIB milling and MicroED to the investigation of nucleic acid crystals.


Objectives, criteria and methods for using molecular genetic data in priority setting for conservation of animal genetic resources.
The genetic diversity of the world's livestock populations is decreasing, both within and across breeds. A wide variety of factors has contributed to the loss, replacement or genetic dilution of many local breeds. Genetic variability within the more common commercial breeds has been greatly decreased by selectively intense breeding programmes. Conservation of livestock genetic variability is thus important, especially when considering possible future changes in production environments. The world has more than 7500 livestock breeds and conservation of all of them is not feasible. Therefore, prioritization is needed. The objective of this article is to review the state of the art in approaches for prioritization of breeds for conservation, particularly those approaches that consider molecular genetic information, and to identify any shortcomings that may restrict their application. The Weitzman method was among the first and most well-known approaches for utilization of molecular genetic information in conservation prioritization. This approach balances diversity and extinction probability to yield an objective measure of conservation potential. However, this approach was designed for decision making across species and measures diversity as distinctiveness. For livestock, prioritization will most commonly be performed among breeds within species, so alternatives that measure diversity as co-ancestry (i.e. also within-breed variability) have been proposed. Although these methods are technically sound, their application has generally been limited to research studies; most existing conservation programmes have effectively primarily based decisions on extinction risk. The development of user-friendly software incorporating these approaches may increase their rate of utilization.


Improving the estimation accuracy of rapeseed leaf photosynthetic characteristics under salinity stress using continuous wavelet transform and successive projections algorithm.
Soil salinization greatly restricts crop production in arid areas for salinity stress can inhibit crop photosynthesis and growth. Chlorophyll fluorescence and photosynthetic gas exchange (CFPGE) parameters are important indicators of crop photosynthesis and have been widely used to evaluate the impacts of salinity stress on crop photosynthesis and growth. Remote sensing technology can quickly and non-destructively obtain crop information under salinity stress, however, at present, the distribution of spectral features of CFPGE parameters in different regions is still unclear. In this study (2019-2020), under salinity stress conditions, the spectral data of rapeseed leaves were acquired and the CFPGE parameters were simultaneously determined. Then, continuous wavelet transformation (CWT) and standard normal variate (SNV) transformation were utilized to preprocess the raw spectral data. After that, a CFPGE parameter estimation model was constructed by using the partial least squares regression (PLSR) algorithm and the support vector machines (SVM) algorithm based on the spectral features in the red region (600-800 nm) and those in the red, blue-green (350-600 nm), and near-infrared (800-2500 nm) regions. The results showed that the spectral features of CFPGE parameters could be extracted by successive projections algorithm (SPA) based on the CWT preprocessing. The CFPGE parameter estimation model constructed based on the spectral features in the red region (675 nm, 680 nm, 688 nm, 749 nm, and 782 nm) had the highest Fv/Fm estimation accuracy on day 30, with R2c, R2p, and RPD of 0.723, 0.585, and 1.68, respectively. Based on this, the spectral features (578 nm, 976 nm, 1088 nm, 1476 nm, and 2250 nm) in the blue-green and near-infrared regions were added in the variables for modeling, which significantly improved the accuracy and stability of the model, with R2c, R2p, and RPD of 0.886, 0.815, and 2.58, respectively. Therefore, the fusion of the spectral features in the red, blue-green, and near-infrared regions could improve the estimation accuracy of rapeseed leaf CFPGE parameters. This study will provide technical reference for rapid estimation of photosynthetic performance of crops under salinity stress in arid and semi-arid areas.


Attachment factors.
As obligate intracellular parasites, viruses must bind to, and enter, permissive host cells in order to gain access to the cellular machinery that is required for their replication. The very large number of mammalian viruses identified to date is reflected in the fact that almost every human and animal cell type is a target for infection by one, or commonly more than one, species of virus. As viruses have adapted to target certain cell types for their propagation, there is exquisite specificity in cellular tropism. This specificity is frequently, but not always, mediated by the first step in the viral replication cycle: attachment of viral surface proteins to receptors expressed on susceptible cells. Viral receptors may be protein, carbohydrate, and/or lipid. Many viruses can use more than one attachment receptor, and indeed may sequentially engage multiple receptors to infect a cell. Thus, it is useful to differentiate between attachment receptors, that simply allow viruses a foothold at the limiting membrane of a cell, and entry receptors that mediate delivery the viral genome into the cytoplasm. For some viruses the attachment factors that promote binding to permissive cells are very well defined, but the sequence of events that triggers viral entry is only now beginning to be understood. For other viruses, despite many efforts, the receptors remain elusive. In this chapter we will confine our review to viruses that infect mammals, with particular focus on human pathogens. We do not intend that this will be an exhaustive overview of viral attachment receptors; instead we will take a number of examples of well-characterized virus-receptor interactions, discuss supporting evidence, and highlight any controversies and uncertainties in the field. We will then conclude with a reflection on general principles of viral attachment, consider some exceptions to these principles, and make some suggestion for future research.


A global meta-analysis of the relative extent of intraspecific trait variation in plant communities.
Recent studies have shown that accounting for intraspecific trait variation (ITV) may better address major questions in community ecology. However, a general picture of the relative extent of ITV compared to interspecific trait variation in plant communities is still missing. Here, we conducted a meta-analysis of the relative extent of ITV within and among plant communities worldwide, using a data set encompassing 629 communities (plots) and 36 functional traits. Overall, ITV accounted for 25% of the total trait variation within communities and 32% of the total trait variation among communities on average. The relative extent of ITV tended to be greater for whole-plant (e.g. plant height) vs. organ-level traits and for leaf chemical (e.g. leaf N and P concentration) vs. leaf morphological (e.g. leaf area and thickness) traits. The relative amount of ITV decreased with increasing species richness and spatial extent, but did not vary with plant growth form or climate. These results highlight global patterns in the relative importance of ITV in plant communities, providing practical guidelines for when researchers should include ITV in trait-based community and ecosystem studies.


Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening.
Cells are complex systems with concurrent multi-physical responses, and cell physiological signals are often encoded with spatiotemporal dynamics and further coupled with multiple cellular activities. However, most existing electronic sensors are only single-modality and cannot capture multi-parametric cellular responses. In this paper, a 1024-pixel CMOS quad-modality cellular interfacing array that enables multi-parametric cell profiling for drug development is presented. The quad-modality CMOS array features cellular impedance characterization, optical detection, extracellular potential recording, and biphasic current stimulation. The fibroblast transparency and surface adhesion are jointly monitored by cellular impedance and optical sensing modalities for comprehensive cell growth evaluation. Simultaneous current stimulation and opto-mechanical monitoring based on cardiomyocytes are demonstrated without any stimulation/sensing dead-zone. Furthermore, drug dose-dependent multi-parametric feature extractions in cardiomyocytes from their extracellular potentials and opto-mechanical signals are presented. The CMOS array demonstrates great potential for fully automated drug screening and drug safety assessments, which may substantially reduce the drug screening time and cost in future new drug development.


Pediatric Liver Transplant: Techniques and Complications.
Liver transplant is considered to be the last-resort treatment approach for pediatric patients with end-stage liver disease. Despite the remarkable advance in survival rates, liver transplant remains an intricate surgery with significant morbidity and mortality. Early diagnosis of complications is crucial for patient survival but is challenging given the lack of specificity in clinical presentation. Knowledge of the liver and vascular anatomy of the donor and the recipient or recipients before surgery is also important to avoid complications. In this framework, radiologists play a pivotal role on the multidisciplinary team in both pre- and postoperative scenarios by providing a road map to guide the surgery and by assisting in diagnosis of complications. The most common complications after liver transplant are (a) vascular, including the hepatic artery, portal vein, hepatic veins, and inferior vena cava; (b) biliary; (c) parenchymal; (d) perihepatic; and (e) neoplastic. The authors review surgical techniques, the role of each imaging modality, normal posttransplant imaging features, types of complications after liver transplant, and information required in the radiology report that is critical to patient care. They present an algorithm for an imaging approach for pediatric patients after liver transplant and describe key points that should be included in radiologic reports in the pre- and postoperative settings. Online supplemental material is available for this article. ©RSNA, 2017.


A network analysis of female sexual function: comparing symptom networks in women with decreased, increased, and stable sexual desire.
Problems related to low sexual desire in women are common clinical complaints, and the aetiology is poorly understood. We investigated predictors of change in levels of sexual desire using a novel network approach, which assumes that mental disorders arise from direct interactions between symptoms. Using population-based data from 1,449 Finnish women, we compared between-subject networks of women whose sexual desire decreased, increased, or remained stable over time. Networks were estimated and analyzed at T1 (2006) and replicated at T2 (2013) using R. Domains included were, among others, sexual functions, sexual distress, anxiety, depression, body dissatisfaction, and relationship status. Overall, networks were fairly similar across groups. Sexual arousal, satisfaction, and relationship status were the most central variables, implying that they might play prominent roles in female sexual function; sexual distress mediated between general distress and sexual function; and sexual desire and arousal showed different patterns of relationships, suggesting that they represent unique sexual function aspects. Potential group-differences suggested that sex-related pain and body dissatisfaction might play roles in precipitating decreases of sexual desire. The general network structure and similarities between groups replicated well; however, the potential group-differences did not replicate. Our study sets the stage for future clinical and longitudinal network modelling of female sexual function.


Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine.
The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.


Vaccinia virus virulence factor N1L is a novel promising target for antiviral therapeutic intervention.
The 14 kDa homodimeric N1L protein is a potent vaccinia and variola (smallpox) virulence factor. It is not essential for viral replication, but it causes a strong attenuation of viral production in culture when deleted. The N1L protein is predicted to contain the BH3-like binding domain characteristic of Bcl-2 family proteins, and it is able to bind the BH3 peptides. Its overexpression has been reported to prevent infected cells from committing apoptosis. Therefore, interfering with the N1L apoptotic blockade may be a legitimate therapeutic strategy affecting the viral growth. By using in silico ligand docking and an array of in vitro assays, we have identified submicromolar (600 nM) N1L antagonists belonging to the family of polyphenols. Their affinity is comparable to that of the BH3 peptides (70-1000 nM). We have also identified the natural polyphenol resveratrol as a moderate N1L inhibitor. Finally, we show that our ligands efficiently inhibit growth of vaccinia virus.


Telmisartan-induced sprue-like enteropathy: a case report.
A possible case of sprue-like enteropathy (SLE) induced by the use of telmisartan is reported. Telmisartan is an angiotensin-receptor II blocker (type 1) used for the treatment of hypertension. Several cases of SLE associated with olmesartan and other drugs of the same group have been reported. In all cases, SLE resolved following therapy withdrawal. We describe the case of an 80-year-old woman who presented with diarrhoea and abdominal pain. In the past 5 years she had been treated with telmisartan 40 mg once a day for hypertension, so we hypothesised that symptoms might be caused by telmisartan. After treatment discontinuation, diarrhoea disappeared. Three causality algorithms were applied and revealed a possible or likely causal relationship. At present, the patient remains asymptomatic. There is a causal relationship between the use of telmisartan and SLE. This association should be taken into account by physicians when prescribing and reviewing drug therapies.


Rossella podagrosa Kirkpatrick, 1907-A valid species after all.
In this study we provide evidence that the species Rossella podagrosa Kirkpatrick, 1907, commonly considered a synonym of Rossella racovitzae Topsent, 1901, is truly a valid species. We show that it can be clearly distinguished from other species especially when taking into consideration the in situ habitus of the sponge in combination with the spicules. Furthermore we demonstrate the weaknesses in the so far published synonymy concept for the very complicated genus Rossella Carter, 1872. From this we conclude that the best strategy for further analysis of Rossella and establishment of acceptable synonymies will need to be based on detailed examination of the spicules, the holotypes, and in situ habitus. When possible it will be useful to analyze specimens from all Antarctic oceanographic regions.


Effect of Escherichia coli alpha-hemolysin on human peripheral leukocyte function in vitro.
To gain further evidence for the role of the Escherichia coli alpha-hemolysin in pathogenesis, its in vitro effects on human peripheral leukocyte function were studied. Leukocytes exposed to low doses of alpha-hemolysin responded with a marked chemiluminescence response, indicating activation of oxidative metabolism. This response was time and dose dependent. Pretreatment of leukocytes with doses of alpha-hemolysin at which nearly 80% of the cells survived decreased the ability of the cells to phagocytize bacteria and particles and to undergo chemotaxis. Premature activation of leukocytes and inhibition of phagocytosis and chemotaxis by alpha-hemolysin, if they occur in vivo, would greatly enhance the survival of an invading E. coli strain.


Low seroprevalence rates of Zika virus in Kuala Lumpur, Malaysia.
Zika virus (ZIKV) is believed to be endemic in Southeast Asia. However, there have been few Zika cases reported to date in Malaysia, which could be due to high pre-existing levels of population immunity. To determine Zika virus (ZIKV) seroprevalence in Kuala Lumpur, Malaysia, 1085 serum samples from 2012, 2014-2015 and 2017 were screened for anti-ZIKV antibodies using a ZIKV NS1 blockade-of-binding assay. Reactive samples were confirmed using neutralization assays against ZIKV and the four dengue virus (DENV) serotypes. A sample was possible ZIKV seropositive with a ZIKV 50% neutralization (NT50) titre ≥20. A sample was probable ZIKV seropositive if, in addition, all DENV NT50 titres were <20 or the ZIKV NT50 titre was >4-fold greater than the highest DENV NT50 titre. We found low rates of possible ZIKV seropositivity (3.3% [95% confidence interval {CI} 2.4 to 4.6]) and probable ZIKV seropositivity (0.6% [95% CI 0.3 to 1.4]). Possible ZIKV seropositivity was independently associated with increasing age (odds ratio [OR] 1.04 [95% CI 1.02 to 1.06], p<0.0001) and male gender (OR 3.5 [95% CI 1.5 to 8.6], p=0.005). The low ZIKV seroprevalence rate, a proxy for population immunity, does not explain the low incidence of Zika in dengue-hyperendemic Kuala Lumpur. Other factors, such as the possible protective effects of pre-existing flavivirus antibodies or reduced transmission by local mosquito vectors, should be explored. Kuala Lumpur is at high risk of a large-scale Zika epidemic.


High Temperature Absorption in CO(2) at 10.6 microm.
Measurements of the temperature variation of the resonant absorption coefficient in shock heated CO(2) gas (350-1600 K) using a laser source operating on the P(20) or P(18) transition are reported. Values obtained are compared with theory allowing for mixed mode contributions to absorption as well as dependence of the optical broadening cross section on temperature.


Optoacoustic mesoscopy analysis and quantitative estimation of specific imaging metrics in Fitzpatrick skin phototypes II to V.
Raster Scanning Optoacoustic Mesoscopy (RSOM) is a novel optoacoustic imaging modality that offers non-invasive, label-free, high resolution (~7 μm axial, ~30 μm lateral) imaging up to 1 to 2 mm below the skin, providing novel quantitative insights into skin pathophysiology. As the RSOM image contrast mechanism is based on light absorption, it is expected that the amount of melanin present in the skin will affect RSOM images. However, the effect of skin tone in the performance of RSOM has not been addressed so far. Herein, we present the efficiency of RSOM for in vivo skin imaging of human subjects with Fitzpatrick (FP) skin types between II to V. RSOM images acquired from the volar forearms of the subjects were used to derive metrics used in RSOM studies, such as total blood volume, vessel diameter and melanin signal intensity. Our study shows that the melanin signal intensity derived from the RSOM images exhibited an excellent correlation with that obtained from a clinical colorimeter for the subjects of varying FP skin types. We could successfully estimate the vessel diameter at different depths of the dermis. Furthermore, our study shows that there is a need to compensate for total blood volume calculated for subjects with higher FP skin types due to the lower signal-to-noise ratio in dermis, owing to strong absorption of light by melanin. This study sheds light into how RSOM can be used for studying various skin conditions in populations with different skin phenotypes.


A new genus with two new species of lecanicephalidean tapeworms (Cestoda) from the mangrove whipray, Urogymnus granulatus (Myliobatiformes: Dasyatidae),from the Solomon Islands and northern Australia.
A new lecanicephalidean genus is erected for cestodes previously recognised as "New Genus 12" (Polypocephalidae) in a phylogenetic analysis of the interrelationship of members of this order. Examination of the cestode fauna of the mangrove whipray, Urogymnus granulatus (Macleay) (Myliobatiformes: Dasyatidae) from the Solomon Islands and northern Australia revealed the existence of specimens representing two new species, consistent in morphology with "New Genus 12." Corollapex gen. n. is unique among the 24 valid lecanicephalidean genera in its possession of an apical organ in the form of an external retractable central disk surrounded by eight concave muscular, membrane-bound pads and an internal heterogeneous glandular component. The two new species described herein, Corollapex cairae sp. n. (type species) and Corollapex tingoi sp. n., differ from one another in overall size and number of mature and immature proglottids, and are noted to demonstrate a differential distribution between mature and juvenile host individuals. Additional species diversity in the new genus, beyond C. cairae sp. n., C. tingoi sp. n., and "New Genus 12 n. sp. 1" of Jensen et al. (2016) is suggested. Corollapex gen. n. appears to be restricted to dasyatid hosts in the Indo-West Pacific region.


Three-dimensional diffraction of a thin metallic cylinder illuminated in conical incidence: application to diameter estimation.
We present a model to determine the far-field diffraction pattern of a metallic cylinder of infinite length when it is illuminated in oblique incidence. This model is based on the Helmholtz-Kirchhoff integral using the Beckmann conditions for reflection. It considers the three-dimensional nature of the diffracting object as well as the material of which the cylinder is made. This model shows that the diffraction orders are placed in a cone of light. The amplitude at the far field can be divided into three terms: the first term accounts for Babinet's principle, that is, the contribution of the cylinder projection; the second term accounts for the three dimensionality of the cylinder; and the third term accounts for the material of which the cylinder is made. This model is applied to the diameter estimation of the cylinder. Since the amplitude of the Babinet contribution is much larger than the light reflected by the surface, the cylinder diameter can be obtained in a simple way. With this approximation, the locations of the diffraction minima do not vary when the cylinder is inclined. On the other hand, when the reflected light is considered the location of the minima and, hence, the estimation of the diameter, varies. Also, a modification of the diffraction minima is produced by the material of which the cylinder is made. Experimental results are also obtained that corroborate the theoretical approach.


Complementary on-line preconcentration strategies for steroids by capillary electrophoresis.
Complementary on-line preconcentration strategies are needed when analyzing different classes of solutes in real samples by capillary electrophoresis (CE) with UV detection. The performance of three different on-line preconcentration (focusing) techniques under alkaline conditions was examined in terms of their selectivity and sensitivity enhancement for a group of steroids, including classes of androgens, corticosteroids and estrogens. Electrokinetic focusing of large sample injection plugs (up to 28% of effective capillary length or 22.1 cm) directly on-capillary can be tuned for specific classes of steroids based on changes in their mobility (velocity) using a multi-section electrolyte system in CE. A dynamic pH junction was applied for the selective resolution and focusing of weakly acidic estrogens using borate, pH 11.0 and pH 8.0 in the background electrolyte and the sample, respectively. Sweeping, using an anionic bile acid surfactant and neutral gamma-cyclodextrin (gamma-CD) under alkaline conditions (pH 8), resulted in focusing and separation of the moderately hydrophobic (non-ionic) classes of steroids, such as androgen and corticosteroids. Optimal focusing and resolution of all test steroids under a single buffer condition was realized by a dynamic pH junction-sweeping format using borate, pH 11.0 and bile acid surfactant with gamma-CD in the BGE, whereas the sample is devoid of surfactant at pH 8.0. The design of selective on-line focusing strategies in CE is highlighted by the analysis of microgram amounts of ethynyl estradiol derived from a female contraceptive pill extract using the dynamic pH junction method, which resulted in over a 100-fold enhancement in concentration sensitivity.


Enamel resistance to demineralisation around orthodontic brackets after CO2 laser irradiation: a randomised clinical trial.
To evaluate the clinical effect of 10.6 µm CO2 laser irradiation on the formation of demineralised lesions (DLs) around orthodontic brackets. A two-arm, split-mouth, randomised clinical trial (RCT). The Orthodontic Department, Faculty of Dentistry, Damascus University, Syria. Twenty-six patients with a total of 520 teeth were recruited into the trial. Two reversed quadrants of the dental arches in each patient were randomly allocated to CO2 laser application around the orthodontic brackets. The other two quadrants received a control non-therapeutic light. There was blinding of both patients and assessors in the study. The primary outcome was the presence or absence of at least one new DL observed by clinical and photographic examinations. Secondary outcomes included the degree and area of DLs measured on digital images and DIAGNOdent assessment. Teeth were examined before bonding (T0), after bonding and laser irradiation (T1), after 1 month (T2), 2 months (T3) and 6 months (T4). The presence of at least new DL was significantly lower in the laser group when observed at 2 and 6 months (P < .0001), the DLs degree and area were also significantly lower in the laser group at 2 and 6 months (P ≤ .005), and DIAGNOdent values were significantly lower in the laser group (P < .0001) at all observation times. Enamel irradiation with a CO2 laser (at the wavelength of 10.6 µm) has an inhibitory effect on DL formation during orthodontic treatments. Registration: The trial was registered at ClinicalTrials.gov, number NCT03114475.


Density functional theory (DFT) study of edaravone derivatives as antioxidants.
Quantum chemical calculations at the B3LYP/6-31G* level of theory were employed for the structure-activity relationship and prediction of the antioxidant activity of edaravone and structurally related derivatives using energy (E), ionization potential (IP), bond dissociation energy (BDE), and stabilization energies (ΔE(iso)). Spin density calculations were also performed for the proposed antioxidant activity mechanism. The electron abstraction is related to electron-donating groups (EDG) at position 3, decreasing the IP when compared to substitution at position 4. The hydrogen abstraction is related to electron-withdrawing groups (EDG) at position 4, decreasing the BDE(CH) when compared to other substitutions, resulting in a better antioxidant activity. The unpaired electron formed by the hydrogen abstraction from the C-H group of the pyrazole ring is localized at 2, 4, and 6 positions. The highest scavenging activity prediction is related to the lowest contribution at the carbon atom. The likely mechanism is related to hydrogen transfer. It was found that antioxidant activity depends on the presence of EDG at the C(2) and C(4) positions and there is a correlation between IP and BDE. Our results identified three different classes of new derivatives more potent than edaravone.


Octreotide: a clinical update.
Somatostatin is found in the pancreas and gastrointestinal tract, including the visceral autonomic nervous system, the endocrine D cells and the gut lumen. Somatostatin peptides may act differently at different sites as hormones, as paracrine substances or neurotransmitters. So far not much is known on the physiological effects of somatostatin in the gastrointestinal tract. Somatostatin and octreotide, a synthetic analogue with a longer half-life and higher potency, inhibit the neuroendocrine and exocrine gastrointestinal secretion, intestinal glucose, fat and amino acid transport, intestinal propulsive and gallbladder motility, splanchnic blood flow in volunteers and hepatic venous pressure in cirrhotic patients. The inhibition occurs to various extents depending on the target organ. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions and describes the therapeutic role in different gastrointestinal disorders.


An analysis of state legislation on community trails.
Trails provide opportunities for recreation, transportation and activity. The purpose of this article is to describe state legislation related to community trails, to analyze legislation content, and to evaluate legislation on inclusion of evidence-informed elements. State trail legislation from 2001 to 2008 was identified using online legislative databases. An analysis of evidence-informed elements included in the legislation was conducted. These elements included: funding, liability, accessibility, connectivity, and maintenance. Of the total 991 trail bills, 516 (52.0%) were appropriations bills, of which 167 (32.2%) were enacted. We analyzed 475 (48%) nonappropriation trail bills of which 139 (29.3%) were enacted. The percentage of enactment of appropriations bills decreased over time while enactment of nonappropriations trail bills increased. Over half of the nonappropriations trail bills included at least 1 evidence-informed element, most commonly funding. Few bills contained liability, connectivity, accessibility, or maintenance. There is opportunity for providing evidence-informed information to policy-makers to potentially influence bill content. The number of bills with a funding element demonstrates that fiscal support for trails is an important policy lever that state legislatures may use to support trails. Lastly, trails should be considered in over-all state-level physical activity legislation to provide opportunities for communities to be active.


Whey protein improves exercise performance and biochemical profiles in trained mice.
The objective of this study is to verify the beneficial effects of whey protein (WP) supplementation on health promotion and enhance exercise performance in an aerobic-exercise training protocol. In total, 40 male Institute of Cancer Research mice (4 wk old) were divided into four groups (n = 10 per group): sedentary control with vehicle (SC) or WP supplementation (4.1 g·kg, SC + WP), and exercise training with vehicle (ET) or WP supplementation (4.1 g·kg, ET + WP). Animals in the ET and ET + WP groups underwent swimming endurance training for 6 wk, 5 d·wk. Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time as well as by changes in body composition and biochemical parameters at the end of the experiment. ET significantly decreased final body and muscle weight and levels of albumin, total protein, blood urea nitrogen, creatinine, total cholesterol, and triacylglycerol. ET significantly increased grip strength; relative weight (%) of liver, heart, and brown adipose tissue (BAT); and levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and total bilirubin. WP supplementation significantly decreased final body, muscle, liver, BAT, and kidney weight and relative weight (%) of muscle, liver, and BAT as well as levels of aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and uric acid. In addition, WP supplementation slightly increased endurance time and significantly increased grip strength and levels of albumin and total protein. WP supplementation improved exercise performance, body composition, and biochemical assessments in mice and may be an effective ergogenic aid in aerobic exercise training.


Improving driving advice provided to cardiology patients on discharge.
Certain cardiac conditions can limit patients' ability to drive. It remains the doctors' responsibility to advise patients of any driving restrictions and is particularly important after certain diagnoses or procedures. We identified that the quality of documented advice was variable and frequently no written driving advice was recorded on discharge. It was apparent that there was a lack of awareness and knowledge of the current Driving and Vehicle Licensing Agency (DVLA) guidance among junior doctors. We therefore designed a quality improvement project using Plan-Do-Study-Act (PDSA) methodology to improve the provision of driving advice on discharge from a cardiology ward by focusing on staff education. After collecting baseline data, we created a template with cardiology-specific DVLA advice. During the second PDSA cycle, we improved the electronic template and also introduced a hard copy on the ward. During the third PDSA cycle, we incorporated information on DVLA guidance in the specialty induction session. We also evaluated junior doctors' confidence of providing driving advice before and after this intervention. Baseline measurements showed that 10% (9/92) of all discharge summaries included driving advice. This improved to 49% (34/69) after the third PDSA cycle. Importantly, after receiving information on driving advice in the induction, junior doctors felt more confident in providing driving advice to cardiology patients on discharge. In conclusion, the provision of driving advice on discharge is an important element of patient safety. However, clinicians' knowledge and awareness of current DVLA guidance is often limited. We demonstrated a significant increase in the provision of driving advice by introducing a standardised template.


The effects of Curcuma longa and curcumin on reproductive systems.
Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-inflammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an effort on a detailed literature survey concentrated on the protective effects of C. longa and curcumin on the reproductive organs activity. The databases such as, PubMed, Web of Science, Google Scholar, Scopus, and Iran- Medex, were considered. The search terms were "testis" or "ovary" and "Curcuma longa", "curcumin", "antioxidant effect", "anti-inflammatory effect" and "anti-cancer effect". C. longa and curcumin inhibited the production of the tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) and increased the caspases (3, 8 and 9) activities in HL-60 prostate cancer. Furthermore, C. longa and curcumin suppressed the vascular endothelial growth factor (VEGF), phosphorylated signal transducers and activators of the transcription 3 (STAT) and matrix metalloproteinase-9 (MMP-9) in ovarian cancer cell line. C. longa and curcumin might decrease the risk of cancer and other malignant diseases in the reproductive system. C. longa and curcumin have a protective effect on the reproductive organs activity such as, anti-inflammatory, anti-apoptotic, and antioxidant effects in normal cells but showed pro-apoptotic effects in the malignant cells. Therefore, different effects of C. longa and curcumin are dependent on the doses and the type of cells used in various models studied.


Ex vivo Bone Models and Their Potential in Preclinical Evaluation.
Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems. Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.


A facile technology for the high-throughput sequencing of the paired VH:VL and TCRβ:TCRα repertoires.
Natively paired sequencing (NPS) of B cell receptors [variable heavy (VH) and light (VL)] and T cell receptors (TCRb and TCRa) is essential for the understanding of adaptive immunity in health and disease. Despite many recent technical advances, determining the VH:VL or TCRb:a repertoire with high accuracy and throughput remains challenging. We discovered that the recently engineered xenopolymerase, RTX, is exceptionally resistant to cell lysate inhibition in single-cell emulsion droplets. We capitalized on the characteristics of this enzyme to develop a simple, rapid, and inexpensive in-droplet overlap extension reverse transcription polymerase chain reaction method for NPS not requiring microfluidics or other specialized equipment. Using this technique, we obtained high yields (5000 to >20,000 per sample) of paired VH:VL or TCRb:a clonotypes at low cost. As a demonstration, we performed NPS on peripheral blood plasmablasts and T follicular helper cells following seasonal influenza vaccination and discovered high-affinity influenza-specific antibodies and TCRb:a.


A Targeted Literature Review of the Disease Burden in Patients With Symptomatic Peripheral Artery Disease.
Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle-brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.


Development of an algorithm using ultrasonography-assisted peripheral intravenous catheter placement for reducing catheter failure.
Up to 50% peripheral intravenous catheters (PIVs) are removed prematurely because of failures. Catheter failure (CF) leads to replacement and is a great concern for patients and medical staff. It is known that visualization of catheters and vessels with ultrasonography (US) during placement prevents CF. However, US is not a common technique for general nurses. In order to standardize US-assisted PIV placement techniques, an algorithm is needed. This study aimed to develop an algorithm using US-assisted PIV placement to reduce CF rate. Furthermore, to evaluate the effectiveness of the algorithm, CF rates were compared before and after intervention. A pretest-posttest study was performed. The intervention was PIV placement by 23 nurses undergoing training sessions for the algorithm. Intention to treat, per protocol analyses were applied. Logistic regression analysis was used for factor analysis. The CF rate in the pre-intervention group 35.2% (19/54) did not significantly differ from post-intervention group 33.6% (48/143) (p = 0.831), yet significantly differ from complete algorithm-use group 8.7% (2/23; p = 0.017). In factor analysis, compliance to the algorithm was significantly correlated with CF (p = 0.032). The compliance rate was low 16.1% (23/143). Algorithm compliance reduced CF by confirming appropriate catheter tip position from the insertion to the securement phase. This algorithm effectively reduced CF, however, the compliance rate was unacceptable. In order to increase the compliance rate, modified algorithm and new visualizing technology is required.


Structural analysis of altered large-subunit loop-6/carboxy-terminus interactions that influence catalytic efficiency and CO2/O2 specificity of ribulose-1,5-bisphosphate carboxylase/oxygenase.
The loop between alpha-helix 6 and beta-strand 6 in the alpha/beta-barrel of ribulose-1,5-bisphosphate carboxylase/oxygenase plays a key role in discriminating between CO2 and O2. Genetic screening in Chlamydomonas reinhardtii previously identified a loop-6 V331A substitution that decreases carboxylation and CO2/O2 specificity. Revertant selection identified T342I and G344S substitutions that restore photosynthetic growth by increasing carboxylation and specificity of the V331A enzyme. In numerous X-ray crystal structures, loop 6 is closed or open depending on the activation state of the enzyme and the presence or absence of ligands. The carboxy terminus folds over loop 6 in the closed state. To study the molecular basis for catalysis, directed mutagenesis and chloroplast transformation were used to create T342I and G344S substitutions alone. X-ray crystal structures were then solved for the V331A, V331A/T342I, T342I, and V331A/G344S enzymes, as well as for a D473E enzyme created to assess the role of the carboxy terminus in loop-6 closure. V331A disturbs a hydrophobic pocket, abolishing several van der Waals interactions. These changes are complemented by T342I and G344S, both of which alone cause decreases in CO2/O2 specificity. In the V331A/T342I revertant enzyme, Arg339 main-chain atoms are displaced. In V331A/G344S, alpha-helix 6 is shifted. D473E causes disorder of the carboxy terminus, but loop 6 remains closed. Interactions between a transition-state analogue and several residues are altered in the mutant enzymes. However, active-site Lys334 at the apex of loop 6 has a normal conformation. A variety of subtle interactions must be responsible for catalytic efficiency and CO2/O2 specificity.


Atypical cortical connectivity and visuospatial cognitive impairments are related in children with chromosome 22q11.2 deletion syndrome.
Chromosome 22q11.2 deletion syndrome is one of the most common genetic causes of cognitive impairment and developmental disability yet little is known about the neural bases of those challenges. Here we expand upon our previous neurocognitive studies by specifically investigating the hypothesis that changes in neural connectivity relate to cognitive impairment in children with the disorder. Whole brain analyses of multiple measures computed from diffusion tensor image data acquired from the brains of children with the disorder and typically developing controls. We also correlated diffusion tensor data with performance on a visuospatial cognitive task that taps spatial attention. Analyses revealed four common clusters, in the parietal and frontal lobes, that showed complementary patterns of connectivity in children with the deletion and typical controls. We interpreted these results as indicating differences in connective complexity to adjoining cortical regions that are critical to the cognitive functions in which affected children show impairments. Strong, and similarly opposing patterns of correlations between diffusion values in those clusters and spatial attention performance measures considerably strengthened that interpretation. Our results suggest that atypical development of connective patterns in the brains of children with chromosome 22q11.2 deletion syndrome indicate a neuropathology that is related to the visuospatial cognitive impairments that are commonly found in affected individuals.


Adrenal insufficiency in a woman secondary to standard-dose inhaled fluticasone propionate therapy.
A 55-year-old woman with asthma presented with adrenal insufficiency of unknown origin. She was referred to our Division of Reproductive Endocrinology to further evaluate an undetectable morning cortisol level discovered during the evaluation of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue and weight gain. Her medication list included 220 μg of inhaled fluticasone propionate twice daily for asthma, which she was taking as prescribed. On presentation, the undetectable morning cortisol level was confirmed. A urinary measurement of fluticasone propionate 17β-carboxylic acid was markedly elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2 months. A repeat urinary fluticasone measurement 4 months after the discontinuation of fluticasone therapy was undetectably low and morning cortisol level was normal at 18.0 μg/dl. Inhaled fluticasone is generally considered to be minimally systemically absorbed. This patient's only clinical evidence suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S level. This case demonstrates that adrenal insufficiency can be caused by a routine dose of inhaled fluticasone. Missing this diagnosis could potentially result in adrenal crisis upon discontinuation of fluticasone therapy. Standard-dose inhaled fluticasone can cause adrenal insufficiency.Adrenal insufficiency should be considered in patients taking, or who have recently discontinued, inhaled fluticasone therapy and present with new onset of nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia, unexplained weight loss, and nausea that are suggestive of adrenal insufficiency.Adrenal insufficiency should be considered in postoperative patients who exhibit signs of hypoadrenalism after fluticasone therapy has been withheld in the perioperative setting.Routine screening for hypoadrenalism in patients without clinical signs or symptoms of adrenal insufficiency after the discontinuation of inhaled fluticasone therapy is not indicated due to the apparently low incidence of adrenal insufficiency caused by fluticasone.


Does implantation technique influence lead failure?
We aimed to analyse whether different lead implantation techniques influence lead failure based on implant duration. Eighty-two transvenous leads were extracted due to lead failure. Median implant duration (MID) of the extracted leads was 68 months. Failed leads were retrospectively divided into 5 subgroups according to predefined technical procedural aspects, potentially triggering lead failure: venous approach, lead disorder in the generator pocket, sharp lead angulation, lead-lead interaction and number of leads in situ. The subgroups were correlated to the MID and compared. The MID was 81 vs 59 months in medial vs lateral venous puncture (P=0.453). In subgroups without/with lead disorder the MID was 59 vs 107 months (P=0.006) and 57 vs 84 months (P=0.012) in subgroups without/with sharp lead angulation, respectively. In subgroups without/with more than 1 lead-lead interaction the MID was 59 vs 81 months (P=0.029) and 65 vs 86 months (P=0.128) without/with more than 2 lead-lead interactions, respectively. In subgroups without/with more than 1 lead in situ the MID was 73 vs 67 months (P=0.453), 81 vs 27 months (P=0.296) in subgroups without/with more than 2 leads in situ and 68 vs 77 months (P=0.264) in subgroups without/with more than 3 leads in situ, respectively. Although, we were able to confirm our hypothesis only partially, technical aspects of lead implantation technique should be kept in mind as a potential reason causing lead failure.


Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion.
Conditioning lesion of the peripheral branch of dorsal column axons is a well-known paradigm enabling the central branch to regenerate after injury to the spinal cord. However, only a small number of regenerating axons enter grafted substrates, and they do not grow beyond the lesion. We found that conditioning lesion induces, in addition to growth-stimulating genes, related to receptor tyrosine kinase (Ryk), a potent repulsive receptor for Wnts. Wnts are expressed around the site of spinal cord injury, and we found that grafted bone marrow stromal cells secreting the Wnt inhibitors secreted frizzled-related protein 2 or Wnt inhibitory factor 1 enhanced regeneration of the central branch after peripheral conditioning lesion. Furthermore, we found that Wnt4-expressing grafts caused dramatic long-range retraction of the injured central branch of conditioned dorsal root ganglion neurons. Macrophages accumulate along the path of receding axons but not around Wnt4-expressing cells, suggesting that the retraction of dorsal column axons is not a secondary effect of increased macrophages attracted by Wnt4. Therefore, Wnt-Ryk signaling is an inhibitory force co-induced with growth-stimulating factors after conditioning lesion. Overcoming Wnt inhibition may further enhance therapies being designed on the basis of the conditioning-lesion paradigm.


Low Dose Naltrexone and Lung Cancer: A Case Report and Discussion.
Low dose naltrexone (LDN) has been promising as a complementary medication for patients with a broad range of medical disorders. Although not a proven cure, evidence from clinical trials supports LDN as being a valuable adjunct for disorders in which the immune system plays a centralized role. Additionally, clinical trials have proposed a unique mechanism(s) allowing LDN to affect tumors including non-small cell lung cancer (NSCLC) at the cellular level by augmenting the immune system. We present a case of a 50-year-old male with a prolonged survival and a past medical history of prostate and lung cancer.


Surgical treatment of gynecomastia: complications and outcomes.
Gynecomastia is defined as the benign enlargement of the male breast. Multiple surgical options have been used to improve outcomes. The aim of this study was to analyze the surgical approaches to the treatment of gynecomastia and their outcomes over a 10-year period. All patients undergoing surgical correction of gynecomastia in our department between 2000 and 2010 were included for retrospective evaluation. The data were analyzed for etiology, stage of gynecomastia, surgical technique, complications, risk factors, and revision rate. The surgical result was evaluated with self-assessment questionnaires. A total of 41 patients with 75 operations were included. Techniques included subcutaneous mastectomy alone or with additional ultrasound-assisted liposuction (UAL) and isolated UAL. The surgical revision rate for all patients was 4.8%. The skin-sparing procedure gave good surgical results in grade IIb and grade III gynecomastia with low revision and complication rates. The self-assessment report revealed a good level of overall satisfaction and improvement in self-confidence (average scores 9.4 and 9.2, respectively, on a 10-point scale). The treatment of gynecomastia requires an individualized approach. Subcutaneous mastectomy combined with UAL could be used as the first choice for surgical treatment of grade II and III gynecomastia.


Relationship between CD4 count and quality of life over time among HIV patients in Uganda: a cohort study.
Immunological markers (CD4 count) are used in developing countries to decide on initiation of antiretroviral therapy and monitor HIV/AIDS disease progression. HIV is an incurable chronic illness, making quality of life paramount. The direct relationship between quality of life and CD4 count is unclear. The purpose of this study is to determine the relationship between change in CD4 count and quality of life measures in a Ugandan cohort of people living with HIV. We prospectively assessed quality of life among 1274 HIV patients attending an HIV clinic within a national referral hospital over a period of 6 months. Quality of life was measured using an objective measure, the Medical Outcomes Study HIV health survey summarized as Physical Health Score and Mental Health Score and a subjective measure, the Global Person Generated Index. Generalized estimating equations were used to analyze the data. The primary predictor variable was change in CD4 count, and the outcome was quality of life scores. We controlled for sociodemographic characteristics, clinical factors and behavioral factors. Twenty in-depth interviews were conducted to assess patient perception of quality of life and factors influencing quality of life. Of the 1274 patients enrolled 1159 had CD4 count at baseline and six months and 586 (51%) received antiretroviral therapy. There was no association found between change in CD4 count and quality of life scores at univariate and multivariate analysis among the study participants whether on or not on antiretroviral therapy. Participants perceived quality of life as happiness and well-being, influenced by economic status, psychosocial factors, and health status. Clinicians and policy makers cannot rely on change in immunological markers to predict quality of life in this era of initiating antiretroviral therapy among relatively healthy patients. In addition to monitoring immunological markers, socioeconomic and psychosocial factors should be underscored in management of HIV patients.


Alterations in triad ultrastructure following repetitive stimulation and intracellular changes associated with exercise in amphibian skeletal muscle.
This study used Rana temporaria sartorius muscles to examine the effect of fatiguing electrical stimulation on the gap between the T-tubular and sarcoplasmic reticular membranes (T-SR distance) and the T-tubule diameter and compared this with corresponding effects on resting fibres exposed to a range of extracellular conditions that each replicate one of the major changes associated with muscular activity: membrane depolarisation, isotonic volume increase, acidification and intracellular lactate accumulation. Following each treatment, muscles were immersed in isotonic fixative solution and processed for transmission electron microscopy (TEM). Mean T-SR distances were estimated from orthogonal intercepts to provide estimates of diffusion distances between T and SR membranes and T-tubule diameter was estimated by measuring its shortest axis in the sampled J-SR complexes. Measurements from muscles fatigued by low frequency intermittent stimulation showed significant (P << 0.05) reversible increases in both T-SR distance and T-tubule diameter from 15.97 +/- 0.37 nm to 20.15 +/- 0.56 nm and from 15.44 +/- 0.60 nm to 22.26 +/- 0.84 nm (n = 40, 30) respectively. Exposure to increasing concentrations of extracellular [K(+)] in the absence of Cl(-) to produce membrane depolarisation without accompanying cell swelling reduced T-SR distance and increased T-tubule diameter, whilst comparable increases in [K(+)](e) in the presence of Cl(-) suggested that isotonic cell swelling has the opposite effect. Acidification alone, produced by NH(4)Cl addition and withdrawal, also decreased T-SR distance and T-tubule diameter. A similar reduction in T-SR distance occurred following exposure to extracellular Na-lactate where such acidification was accompanied by elevations of intracellular lactate, but these conditions produced a significant swelling of T-tubules attributable to movement of lactate from the cell into the T-tubules. This study thus confirms previous reports of significant increases in T-SR distance and T-tubule diameter following stimulation. However, of membrane depolarisation, isotonic cell swelling, intracellular acidification and lactate accumulation, only isotonic cell swelling increases T-SR distance whilst membrane depolarisation and intracellular lactate likely contribute to the observed increases in T-tubule diameter.


Emotional valence and arousal interact in attentional control.
A recent study demonstrated that observers' ability to identify targets in a rapid visual sequence was enhanced when they simultaneously listened to happy music. In the study reported here, we examined how the emotion-attention relationship is influenced by changes in both mood valence (negative vs. positive) and arousal (low vs. high). We used a standard induction procedure to generate calm, happy, sad, and anxious moods in participants. Results for an attentional blink task showed no differences in first-target accuracy, but second-target accuracy was highest for participants with low arousal and negative affect (sad), lowest for those with strong arousal and negative affect (anxious), and intermediate for those with positive affect regardless of their arousal (calm, happy). We discuss implications of this valence-arousal interaction for the control of visual attention.


The inter-operator variability in measuring waist circumference and its potential impact on the diagnosis of the metabolic syndrome.
The International Diabetes Federation (IDF) has proposed ethnicity specific cut-off values for waist circumference, as an essential criterion for the diagnosis of the metabolic syndrome (MetS). However, before introducing waist circumference measurement as part of the clinical examination, or an obligatory criterion for MetS, it is important to ensure that the measurement is reliable and reproducible. The inter- and intra-operator variability in measuring waist circumference was assessed in a preliminary study of 10 health professionals and the inter-operator variability in clinical practice was assessed in a study of 102 patients. Repeated measures analysis of variance (ANOVA) was used to assess the significance of the inter- and intra-operator variability. Intra-operator variability was not found to be significant in the preliminary study (F = 0.15, p = 0.764). However, the inter-operator variability was significant in both studies (preliminary: F = 4.16, p<0.001, clinical practice study: F = 14.06, p<0.001). In clinical practice, this could lead to disagreement among operators regarding the presence of central obesity in 9% of the patients. After giving written instructions on how to measure waist circumference, the coefficient of variation was not significantly altered (p = 0.202) but the inter-operator variability lost significance (F = 2.34, p = 0.11), suggesting a reduction in systematic error. Measuring waist circumference is subject to significant inter-operator variability and could potentially lead to misclassifying patients as having the MetS, or not. Better training of health professionals on how to measure waist circumference properly is needed in order to ensure that patients are not misclassified and that international comparisons of the prevalence of the MetS are reliable.


Interferon gamma in successful pregnancies.
Interferon gamma (IFNG) is a proinflammatory cytokine secreted in the uterus during early pregnancy. It is abundantly produced by uterine natural killer cells in maternal endometrium but also by trophoblasts in some species. In normal pregnancies of mice, IFNG plays critical roles that include initiation of endometrial vasculature remodeling, angiogenesis at implantation sites, and maintenance of the decidual (maternal) component of the placenta. In livestock and in humans, deviations in these processes are thought to contribute to serious gestational complications, such as fetal loss or preeclampsia. Interferon gamma has broader roles in activation of innate and adaptive immune responses to viruses and tumors, in part through upregulating transcription of genes involved in cell cycle regulation, apoptosis, and antigen processing/presentation. Despite this, rodent and human trophoblast cells show dampened responses to IFNG that reflect the resistance of these cells to IFNG-mediated activation of major histocompatibility complex (MHC) class II transplantation antigen expression. Lack of MHC class II antigens on trophoblasts is thought to facilitate survival of the semiallogeneic conceptus in the presence of maternal lymphocytes. This review describes the dynamic roles of IFNG in successful pregnancy and briefly summarizes data on IFNG in gestational pathologies.


Efficacy and safety assessment of acute sports-related traumatic soft tissue injuries using a new ibuprofen medicated plaster: results from a randomized controlled clinical trial.
To investigate the efficacy and safety of a recently developed ibuprofen medicated plaster in the treatment of acute sports impact injuries/contusions. In this double-blind, multi-center, placebo-controlled, parallel group, phase 3 study (EudraCT Number: 2012-003257-2) patients (n = 132; ages 18 to 60 years) diagnosed with acute sports-related traumatic blunt soft tissue injury/contusion to the upper or lower limbs were randomized to receive either ibuprofen 200 mg plaster (n = 64) or placebo plaster (n = 68). Plasters were administered once daily for five consecutive days. The primary assessment was the area under the curve (AUC) of the visual analogue scale (VAS) of pain on movement (POM) over 0 to 72 h (VAS0-72). The ibuprofen medicated plaster was associated with a reduction in pain on movement (POM) based on lower VAS AUC0-72h (2399.4 mm*h) compared with placebo (4078.9 mm*h) (least squares mean difference: - 1679.5 mm*h; P < 0.0001). The reduction in AUC of POM was also significantly greater for the ibuprofen medicated plaster compared with placebo at 12, 48, 24, and 120 h (P < 0.0001). Algometry/tenderness measurements found that the ibuprofen medicated plaster was associated with greater reduction in tenderness/pain than placebo at each timepoint (P values <0.0001). Seven patients experienced drug-related adverse events (n = 1 [1.6%] for the ibuprofen plaster, and n = 6 [8.8%] for placebo). All drug-related AEs were administration site reactions and were mild in intensity. The results of this study indicate that ibuprofen medicated plaster results in rapid and clinically relevant reduction of pain in patients suffering from blunt musculoskeletal injuries or recurrent pain. The ibuprofen medicated plaster was well tolerated.


Reference Pose Generation for Long-term Visual Localization via Learned Features and View Synthesis.
Visual Localization is one of the key enabling technologies for autonomous driving and augmented reality. High quality datasets with accurate 6 Degree-of-Freedom (DoF) reference poses are the foundation for benchmarking and improving existing methods. Traditionally, reference poses have been obtained via Structure-from-Motion (SfM). However, SfM itself relies on local features which are prone to fail when images were taken under different conditions, e.g., day/night changes. At the same time, manually annotating feature correspondences is not scalable and potentially inaccurate. In this work, we propose a semi-automated approach to generate reference poses based on feature matching between renderings of a 3D model and real images via learned features. Given an initial pose estimate, our approach iteratively refines the pose based on feature matches against a rendering of the model from the current pose estimate. We significantly improve the nighttime reference poses of the popular Aachen Day-Night dataset, showing that state-of-the-art visual localization methods perform better (up to 47%) than predicted by the original reference poses. We extend the dataset with new nighttime test images, provide uncertainty estimates for our new reference poses, and introduce a new evaluation criterion. We will make our reference poses and our framework publicly available upon publication.


Five-year clinical effectiveness of a two-step self-etching adhesive.
The purpose of this prospective randomized controlled clinical study was to evaluate the clinical performance of a "mild" two-step self-etching adhesive, Clearfil SE, in Class V restorations after 5 years of clinical functioning. Twenty-nine patients received two or four restorations following two randomly assigned experimental protocols: (1) a mild self-etching adhesive (Clearfil SE, Kuraray) was applied following manufacturer's instructions on both enamel and dentin (C-SE non-etch); (2) similar application of Clearfil SE, but including prior selective acid-etching of the enamel cavity margins with 40% phosphoric acid (C-SE etch). Clearfil AP-X (Kuraray) was used as the restorative composite for all 100 restorations. The clinical effectiveness was recorded in terms of retention, marginal integrity, marginal discoloration, caries recurrence, postoperative sensitivity, and preservation of tooth vitality after 5 years of clinical service. The hypothesis tested was that selective acid etching of enamel with phosphoric acid improved retention, marginal integrity, and clinical microleakage of Class V restorations. Only one restoration of the C-SE non-etch group was lost at the 5-year recall. All other restorations were clinically acceptable. Marginal integrity deteriorated with time in both groups. The number of restorations with defect-free margins was significantly lower in the C-SE non-etch group (p = 0.0043). This latter group presented significantly more small incisal marginal defects on the enamel side (p = 0.0169). Superficial marginal discoloration increased in both groups, but was more pronounced in the C-SE non-etch group and was related to the higher frequency of small incisal marginal defects. The clinical effectiveness of the two-step self-etching adhesive Clearfil SE remained excellent after 5 years of clinical service. Additional etching of the enamel cavity margins resulted in an improved marginal adaptation on the enamel side; however, this was not critical for the overall clinical performance of the restorations.


A preliminary evaluation of repeated exposure for depersonalization and derealization.
Dissociative symptoms including depersonalization and derealization are commonly experienced by individuals suffering from panic disorder or posttraumatic stress disorder (PTSD). Few studies have been published investigating the specific treatment of these symptoms in individuals diagnosed with panic disorder or PTSD, despite evidence that the subset of individuals with panic disorder who experience depersonalization and derealization report more panic attacks as well as greater panic severity and functional impairment. Furthermore, it has been shown that these symptoms can impede treatment and recovery in PTSD. Finally, recent research has shown that interoceptive exposure generally enhances the efficacy of treatment outcome for PTSD and PTSD with comorbid panic. This study investigated the use of a novel interoceptive exposure technique for treatment of depersonalization and derealization in individuals with high anxiety sensitivity and/or symptoms of PTSD. Results indicated significant reductions on six of seven items as well as total score on an outcome measure of depersonalization and derealization. Thus, this technique appears to hold promise for utilization as a form of interoceptive exposure in the treatment of these symptoms.


Voluntary active euthanasia and doctor-assisted suicide: knowledge and attitudes of Dutch medical students.
The objective of the study was to gain insight into the knowledge of and attitudes towards voluntary active euthanasia and doctor-assisted suicide (EEDAS) of Dutch medical students, and to determine whether knowledge and attitudes change after a 1-day informative conference about EDAS. Data were collected by means of two self-administered questionnaires. Questionnaire 1 had to be completed before the start of the conference and questionnaire 2 after the conference. In both questionnaires, students were asked by means of two open-ended questions to define euthanasia and doctor-assisted suicide. They were also asked to indicate which of eight statements met with the requirements for prudent practice. Finally, the students were asked to what extent they agreed or disagreed with each of seven statements about attitudes towards EDAS. To determine if a selection occurred among students who returned both questionnaires, their background characteristics, and knowledge and attitudes towards EDAS were compared with those who returned only the first questionnaire. Forty-seven students returned only the first questionnaire, while both questionnaires were returned by 137 students. No differences were found between students who returned both questionnaires and those who returned only the first questionnaire with regard to age, religion, knowledge of and attitudes towards EDAS. Students' knowledge of the definitions of EDAS and the requirements for prudent practice improved significantly. Students' reactions to the statements on attitudes towards EDAS showed that a large majority had a fairly positive attitude towards EDAS. There was no significant difference before and after the conference. Male students and students with a religion were more opposed to EDAS than female students and students without a religion. The fact that the students' knowledge of EDAS improved after a 1-day conference does not imply sufficient understanding of the issue. Because EDAS is allowed only under strict conditions in the Netherlands, medical students require special training. Only then will they be equipped to deal with requests for EDAS during their future careers.


Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.
The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.


IR, Raman, and NMR studies of the short-range structures of 0.5Na2S + 0.5[xGeS2 + (1-x)PS(5/2)] mixed glass-former glasses.
A nonlinear and nonadditive composition-dependent change of the ionic conductivity in mixed glass-former (MGF) glasses when one glass former, such as PS(5/2), is replaced by a second glass former, such as GeS2, at constant alkali modifier concentrations, such as Na2S, is known as the mixed glass-former effect (MGFE). Alkali ion conducting glasses are of particular interest for use as solid electrolytes in alkali-based all-solid-state batteries because sulfide amorphous materials have significantly higher alkali ion conductivities than their oxide glass counterparts. In this study of the ternary MGF system Na2S + GeS2 + PS(5/2), we report the careful structural characterization of these glasses using a combination of vibrational, infrared (IR), Raman, and nuclear magnetic resonance (NMR) spectroscopies. Our measurements of the 0.5Na2S + 0.5[xGeS2 + (1-x)PS(5/2)] MGF system show that this glass system exhibits a strongly negative MGFE and non-Arrhenius ionic conductivities. While this negative MGFE in the Na(+) ion conductivity makes these glasses less attractive for use in solid-state Na batteries, the structural origin of this effect is important to better understand the mechanisms of ion conduction in the glassy state. For these reasons, we have examined the structures of ternary 0.5Na2S + 0.5[xGeS2 + (1-x)PS(5/2)] glasses using Raman, IR, and (31)P MAS NMR spectroscopies. In these studies, it is found that the substitution of PS(5/2) by GeS2, that is, increasing x, leads to unequal sharing of the Na(+) in these glasses. Thus, in all MGF compositions, phosphorus groups are associated with a disproportionately larger fraction, f(Na(P)) > 0.5(1 - x), of the Na(+) ions while the germanium groups are found to be Na(+)-deficient relative to the total amount of Na(+) present in the glass, that is, f(Na(Ge)) < 0.5x. From the spectroscopic study of these glasses, a short-range order (SRO) structural model is developed for these glasses and is based on the germanium and phosphorus SRO groups in these glasses as a first step in understanding the unique negative MGFE and non-Arrhenius behavior in the Na(+) ion conductivity in these glasses.