Search

Abstract Background Single-cell technologies to analyze transcription and chromatin structure have been widely used in many research areas to reveal the functions and molecular properties of cells at single-cell resolution. Sample multiplexing techniques are valuable when performing single-cell analysis, reducing technical variation and permitting cost efficiencies. Several commercially available methods have been used in many scRNA-seq studies. On the other hand, while several methods have been published, multiplexing techniques for single nuclear assay for transposase-accessible chromatin (snATAC)-seq assays remain under development. We developed a simple nucleus hashing method using oligonucleotide-conjugated antibodies recognizing nuclear pore complex proteins, NuHash, to perform snATAC-seq library preparations by multiplexing. Results We performed multiplexing snATAC-seq analyses on a mixture of human and mouse cell samples (two samples, 2-plex, and four samples, 4-plex) using NuHash. The analyses on nuclei with at least 10,000 read counts showed that the demultiplexing accuracy of NuHash was high, and only ten out of 9144 nuclei (2-plex) and 150 of 12,208 nuclei (4-plex) had discordant classifications between NuHash demultiplexing and discrimination using reference genome alignments. The differential open chromatin region (OCR) analysis between female and male samples revealed that male-specific OCRs were enriched in chromosome Y (four out of nine). We also found that five female-specific OCRs (20 OCRs) were on chromosome X. A comparative analysis between snATAC-seq and deeply sequenced bulk ATAC-seq on the same samples revealed that the bulk ATAC-seq signal intensity was positively correlated with the number of cell clusters detected in snATAC-seq. Moreover, when we categorized snATAC-seq peaks based on the number of cell clusters in which the peak was present, we observed different distributions over different genomic features between the groups. This result suggests that the peak intensities of bulk ATAC-seq can be used to identify different types of functional loci. Conclusions Our multiplexing method using oligo-conjugated anti-nuclear pore complex proteins, NuHash, permits high-accuracy demultiplexing of samples. The NuHash protocol is straightforward, works on frozen samples, and requires no modifications for snATAC-seq library preparation.

Background and Aims: Individuals of African (AFR) ancestry have a higher incidence of colorectal cancer (CRC) than those of European (EUR) ancestry and exhibit significant health disparities. Previous studies have noted differences in the tumor microenvironment between AFR and EUR patients with CRC. However, the molecular regulatory processes that underpin these immune differences remain largely unknown. Methods: Multiomics analysis was carried out for 55 AFR and 456 EUR patients with microsatellite-stable CRC using The Cancer Genome Atlas. We evaluated the tumor microenvironment by using gene expression and methylation data, transcription factor, and master transcriptional regulator analysis to identify the cell signaling pathways mediating the observed phenotypic differences. Results: We demonstrate that downregulated genes in AFR patients with CRC showed enrichment for canonical pathways, including chemokine signaling. Moreover, evaluation of the tumor microenvironment showed that cytotoxic lymphocytes and neutrophil cell populations are significantly decreased in AFR compared with EUR patients, suggesting AFR patients have an attenuated immune response. We further demonstrate that molecules called “master transcriptional regulators” (MTRs) play a critical role in regulating the expression of genes impacting key immune processes through an intricate signal transduction network mediated by disease-associated transcription factors (TFs). Furthermore, a core set of these MTRs and TFs showed a positive correlation with levels of cytotoxic lymphocytes and neutrophils across both AFR and EUR patients with CRC, thus suggesting their role in driving the immune infiltrate differences between the two ancestral groups. Conclusion: Our study provides an insight into the intricate regulatory landscape of MTRs and TFs that orchestrate the differences in the tumor microenvironment between patients with CRC of AFR and EUR ancestry.

As sequencing and analysis techniques provide increasingly detailed data at a plummeting cost, it is increasingly popular to seek the answers to medical and public health challenges in the DNA sequences of affected populations. This is methodologically attractive in its simplicity, but a genomics-only approach ignores environmentally mediated health disparities, which are well-documented at multiple national and global scales. While genetic differences exist among populations, it is unlikely that these differences overcome social and environmental factors in driving the gap in health outcomes between privileged and oppressed communities. We advocate for following the lead of communities in addressing their self-identified interests, rather than treating widespread suffering as a convenient natural experiment.

The prevalence of frailty across the world in older adults is increasing dramatically and having frailty places a person at increased risk for many adverse health outcomes, including impaired mobility, falls, hospitalizations, and mortality. Globally, the concept of frailty is gaining attention and the scientific field has made great strides in identifying and conceptually defining frailty through consensus conferences, in advancing the overall science of frailty by drawing on basic science discoveries including concepts surrounding the hallmarks of aging, resilience, and intrinsic capacities, and in identifying the many challenges faced by professionals within diverse clinical settings. Currently, it is thought that frailty is preventable, thus the identification of a person's degree of frailty is vital. Identification of frailty is achievable through widely used frailty screening tools, which are valid, reliable, and easy to use. Following the identification of a person's degree of frailty, targeted intervention strategies, such as physical activity programs must be implemented. In this perspective, we provide a historical perspective of the frailty field since the last quarter of the 20th century to present. We identify the proposed underlying pathophysiology of multiple physiological systems, including compromised homeostasis and resilience. Next, we outline the available screening tools for frailty with a physical performance assessment and highlight specific benefits of physical activity. Lastly, we discuss current scientific evidence supporting the physical activity recommendations for the aging population and for older adults with frailty. The goal is to emphasize early detection of frailty and stress the value of physical activity.

Abstract Background and aim Fecal incontinence and/or evacuation difficulty are common after ileoanal pouch surgery. This study aimed to determine whether the development of these symptoms can be predicted so that preventive measures might be instituted. Methods A consecutive series of 46 patients with ulcerative colitis (median age at surgery, 41 years; 50% female) and a functioning pouch for a duration ≥12 months was included. Assessment utilized medical record review and questionnaires on pre‐ and postoperative bowel function, quality of life, and psychological well‐being. Pouch function was assessed by the Colorectal Functional Outcome score (0 = no impairment, 100 = worst impairment). Good pouch function was defined as a score ≤24. Results Fecal incontinence occurred in 67% preoperatively and 54% postoperatively; evacuation difficulty occurred in 65% and preoperatively and 85% postoperatively. The postoperative median Colorectal Functional Outcome score was 20 (range 2–74), with 44% of patients >24 (poor pouch function). Preoperative nocturnal fecal incontinence (odds ratio [OR] 4.92, 95% confidence interval [CI] 1.2–19.4, P = 0.02) and pouchitis (OR 5.41, 95% CI 1.2–23.7, P = 0.02) were associated with poor pouch function after multivariable regression analysis. Postoperative satisfaction, psychological well‐being, and quality of life were significantly better in those with good pouch function, while poor sleep, impaired work, and sexual dysfunction were independently associated with poor pouch function. Conclusions Functional bowel symptoms are common before and after pouch surgery and are associated with the impairment of patient‐reported outcomes. Preoperative nocturnal fecal incontinence predicts poor pouch function. Therapeutic focus on continence, bowel evacuation, psychological well‐being, and quality of life should begin before surgery.

Introduction: The effect of various types of dietary fat on cardiometabolic health continues to be debated, due in part to the high heterogeneity of results following clinical trials investigating the effects of saturated (SFA) and unsaturated fat intake. This variability may be due to genetic differences. Individuals with obesity are at an increased risk for adverse cardiometabolic health and dyslipidemia, and often present with the combined phenotype of elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) cholesterol concentrations. Studying genetic variants relevant to lipid and lipoprotein metabolism can elucidate the mechanisms by which diet might interact with genotype to influence these phenotypes. The objective of this study was to determine relationships of genetic variation, dietary fat intake, and blood lipid concentrations in adults with overweight and obesity. Methods: Genomic DNA, blood lipid concentrations (HDL and TG), and 7-day diet records were obtained from 101 adults (25–45 years of age) with overweight or obesity. Resting energy expenditure (REE) was measured using indirect calorimetry and used to determine implausible intakes using a modified Goldberg method (kilocalories/REE). Genetic variants included 23 single-nucleotide polymorphisms (SNPs) from 15 genes in lipid metabolism pathways. Variants were analyzed with dietary fat intake (total fat, SFA, monounsaturated fat [MUFA], and polyunsaturated fat [PUFA]) via regression analyses. All models were adjusted for age, sex, ancestry, visceral adipose tissue mass, and total kilocalorie intake. The Bonferroni correction was applied for multiple comparisons. Results: Two interactions were detected for TG concentrations. Five gene-diet interactions were associated with HDL concentrations. There was a significant interaction detected between the rs5882 variant of cholesterol-esterase transfer protein (CETP) and MUFA intake to associate with TG concentrations (interaction p = 0.004, R2 = 0.306). Among carriers of the CETP-rs5882 major allele (G), TG concentrations were significantly lower in individuals consuming more than the median MUFA intake (31 g/day) than in those with an intake below the median. Total dietary fat intake interacted with the rs13702 polymorphism of lipoprotein lipase (LPL) to associate with HDL concentrations (interaction p = 0.041, R2 = 0.419), by which individuals with the risk allele (G) had significantly higher HDL concentrations when consuming a higher-fat diet (>92 g/day) than those with a lower-fat diet (56 ± 3 vs. 46 ± 2 mg/dL, p = 0.033). Conclusions: Interactions between dietary intake and genes in lipid metabolism pathways were found to be associated with blood lipid concentrations in adults with overweight and obesity. Fatty acid intake may not modulate blood lipid concentrations uniformly across all individuals. Additional research is needed to determine the biological causes of individual variability in response to dietary intake. Understanding the influence of nutrigenetic interactions on dyslipidemia can aid in the development and implementation of personalized dietary strategies to improve health.

Background and Aim Large bowel functional symptoms are common in patients with inflammatory bowel disease (IBD) who are in disease remission. The efficacy of pelvic floor muscle training for symptoms of evacuation difficulty or fecal incontinence is well established in patients without organic bowel disease but is unknown in these patients. This study aimed to systematically evaluate the published evidence in this group of patients. Methods A systematic review was conducted of articles evaluating pelvic floor muscle training, with or without biofeedback, to improve bowel function in patients with quiescent IBD, including those with an ileoanal pouch. The outcome of interest was improved bowel function measured by bowel diary, patient report, or validated questionnaire in randomized controlled studies, cohort studies, or case series. Results Two randomized controlled trials, four retrospective case series, and one prospective study met eligibility criteria. Pelvic floor muscle training for patients with quiescent IBD improved symptoms in 51 of 76 (68%) patients with evacuation difficulty and 20 of 25 (80%) patients with fecal incontinence. Pelvic floor muscle training for patients with an ileoanal pouch, prior to stoma closure, did not appear to reduce the risk or severity of fecal incontinence following stoma closure. Studies were limited by small numbers, study design, methodological quality, and lack of long‐term follow‐up. Conclusion Pelvic floor muscle training appears to be of therapeutic value in some patients with quiescent IBD and evacuation difficulty or fecal incontinence. The effectiveness of this approach warrants further investigation.

The New York State (NYS) Office of Mental Health created the NYS COVID-19 Emotional Support Helpline and enlisted graduate students to provide phone-based emotional support initially to the NYS community. This NYS-funded initiative transformed into providing psychosocial support for callers across the United States. Four NYS doctoral students acted as the helpline agents and received 251 individual calls from May–August 2020. The agents documented the calls with clinical notes which cannot be traced back to specific callers. The purpose of this retrospective qualitative study was to explore the themes that emerged from the calls to give voice to the trauma that callers were reporting during the early phases of the pandemic, and the resilience they demonstrated as they engaged with the Helpline. The agents’ clinical transcripts were converted into codes using a critical-constructivist grounded theory approach with the NVIVO qualitative data analysis software. A second research team audited the initial codes for construct clarity. Emergent themes detailed the unique traumas that helpline callers divulged, how the agents provided support, and the callers’ capacities for resilience. Recommendations are suggested to inform clinicians working with pandemic survivors, to offer guidance on providing distance or virtual interventions as well as to enhance policymakers’ understanding of addressing mental health needs across populations served via the NYS COVID-19 Emotional Support Helpline.

Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

Postprandial glycemic and insulinemic effects of three black bean pastas were evaluated among eighteen normoglycemic adults (8 men, 10 women) in a randomized crossover trial. Black beans were milled into flour using a commercial Knife or compression/decompression mill (C/D mill). The C/D-mill-derived pastas had medium protein (Combo-MP) and low protein (Cyclone-LP) concentrations. Three black bean flour pastas (Knife, Combo-MP, and Cyclone-LP) were compared to two controls: white bread and whole black beans. Treatments contained 50 g of available carbohydrate. Plasma glucose, serum insulin, and appetite measures were collected at fasting and 30, 60, 90, 150, and 180 min postprandial. Gastrointestinal symptoms were evaluated 10–12 h postprandial. ANOVA (one-way, repeated measures) was used to evaluate satiety, gastrointestinal symptoms, sensory variables, glucose and insulin differences from baseline, and incremental area under the curve (iAUC) by time and/or treatment. Three-hour glucose and insulin iAUCs were lower with whole black beans than white bread. Black bean pasta meals increased satiety, reduced appetite, and produced numerically lower glucose and insulin responses than white bread. However, no differences were observed between pasta types, indicating a similar metabolic response regardless of milling technique. Our results provide evidence for dietary guidance to reduce postprandial glucose and related health risks through pulse food products.

Objective: The aim of this study was to present safety, health and well-being profiles of workers within five occupations: call center work (N = 139), corrections (N = 85), construction (N = 348), homecare (N = 149), and parks and recreation (N = 178).Methods: Baseline data from the Data Repository of Oregon's Healthy Workforce Center were used. Measures were compared with clinical healthcare guidelines and national norms.Results: The prevalence of health and safety risks for adults was as follows: overweight (83.2%), high blood pressure (16.4%), injury causing lost work (9.9%), and reported pain (47.0%). Young workers were least likely to report adequate sleep (46.6%). Construction workers reported the highest rate of smoking (20.7%). All of the adult workers reported significantly lower general health than the general population.Conclusion: The number of workers experiencing poor safety, health and well-being outcomes suggest the need for improved working conditions.

Background The coronavirus disease 2019 (COVID-19) pandemic is likely to lead to a significant increase in mental health disorders among healthcare workers (HCW). Aims We evaluated the rates of anxiety, depressive and post-traumatic stress disorder (PTSD) symptoms in a population of HCW in the UK. Method An electronic survey was conducted between the 5 June 2020 and 31 July 2020 of all hospital HCW in the West Midlands, UK using clinically validated questionnaires: the 4-item Patient Health Questionnaire(PHQ-4) and the Impact of Event Scale-Revised (IES-R). Univariate analyses and adjusted logistic regression analyses were performed to estimate the strengths in associations between 24 independent variables and anxiety, depressive or PTSD symptoms. Results There were 2638 eligible participants who completed the survey (female: 79.5%, median age: 42 years, interquartile range: 32–51). The rates of clinically significant symptoms of anxiety, depression and PTSD were 34.3%, 31.2% and 24.5%, respectively. In adjusted analysis a history of mental health conditions was associated with clinically significant symptoms of anxiety (odds ratio (OR) = 2.3, 95% CI 1.9–2.7, P < 0.001), depression (OR = 2.5, 95% CI 2.1–3.0, P < 0.001) and PTSD (OR = 2.1, 95% CI 1.7–2.5, P < 0.001). The availability of adequate personal protective equipment (PPE), well-being support and lower exposure to moral dilemmas at work demonstrated significant negative associations with these symptoms (P ≤ 0.001). Conclusions We report higher rates of clinically significant mental health symptoms among hospital HCW following the initial COVID-19 pandemic peak in the UK. Those with a history of mental health conditions were most at risk. Adequate PPE availability, access to well-being support and reduced exposure to moral dilemmas may protect hospital HCW from mental health symptoms.

We describe here the first reported case of compartment syndrome complicating malaria. Compartment syndrome has previously been reported secondary to a number of infectious aetiologies including meningococcal septicaemia, dengue fever, and primary infection of muscles in affected compartments. Capillary leakage in sepsis and localised inflammation in myositis have previously been hypothesised as pathophysiological mechanisms. The patient's muscular physique, owing to his bodybuilding hobby, likely predisposed to compartment syndrome in this case. Whilst sequestration of parasitized red blood cells in skeletal muscle has been previously reported it is unclear whether this could have contributed to the development of this unusual complication.

In this paper we discuss results from the study of the energy balance in JET based on calculated heating energies, radiated energy from bolometry and tile calorimetry. Recent data enables us to be more confident in the numbers used and to exclude certain possibilities but the overall energy imbalance which typically amounts to 25% of total input remains unexplained. This shows that caution is required in interpreting fractional radiated powers which are commonly used to measure the effectiveness of impurity seeded scenarios at reducing divertor heat load. Keywords: ILW, JET

Disuse induces adaptations in skeletal muscle, which lead to muscle deterioration. Hindlimb-unloading (HU) is a well-established model to investigate cellular mechanisms responsible for disuse-induced skeletal muscle dysfunction. In myosin heavy chain (MHC) type IIB fibers HU induces a reduction in contraction speed (Vo) and a reduction in the relative myosin light chain 3f (MLC3f) protein content compared with myosin light chain 1f (MLC1f) protein. This study tested the hypothesis that increasing the relative MLC3f protein content via rAd-MLC3f vector delivery would attenuate the HU-induced decline in Vo in single MHC type IIB fibers. Fischer-344 rats were randomly assigned to one of three groups: control, HU for 7 days, and HU for 7 days plus rAd-MLC3f. The semimembranosus muscles were injected with rAd-MLC3f (3.75 x 1011-5 x 1011 ifu/ml) at four days after the initiation of HU. In single MHC type IIB fibers the relative MLC3f content decreased by 25% (12.00±0.60% to 9.06±0.66%) and Vo was reduced by 29% (3.22±0.14fl/s vs. 2.27±0.08fl/s) with HU compared to the control group. The rAd-MLC3f injection resulted in an increase in the relative MLC3f content (12.26±1.19%) and a concomitant increase in Vo (2.90±0.15fl/s) of MHC type IIB fibers. A positive relationship was observed between the percent of MLC3f content and Vo. Maximal isometric force and specific tension were reduced with HU by 49% (741.45±44.24μN to 379.09±23.77μN) and 33% (97.58±4.25kN/m2 to 65.05±2.71kN/m2), respectively compared to the control group. The rAd-MLC3f injection did not change the HU-induced decline in force or specific tension. Collectively, these results indicate that rAd-MLC3f injection rescues hindlimb unloading-induced decline in Vo in MHC type IIB single muscle fibers.

Objective: To investigate the relationship between retinal morphometric measures and intellectual abilities among adults with overweight and obesity.Methods: Adults between 25 and 45 years (N = 55, 38 females) with overweight or obesity (BMI ≥ 25.0 kg/m2) underwent an optical coherence tomography (OCT) scan to assess retinal nerve fiber layer (RNFL) volume, ganglion cell layer (GCL) volume, macular volume, and central foveal thickness. Dual-Energy X-ray absorptiometry was used to assess whole-body adiposity (% Fat). The Kaufman Brief Intelligence Test-2 was used to assess general intelligence (IQ), fluid, and crystallized intelligence. Hierarchical linear regression analyses were performed to examine relationships between adiposity and intelligence measures following adjustment of relevant demographic characteristics and degree of adiposity (i.e., % Fat).Results: Although initial bivariate correlations indicated that % Fat was inversely related to fluid intelligence, this relationship was mitigated by inclusion of other demographic factors, including age, sex, and education level. Regression analyses for primary outcomes revealed that RNFL was positively related to IQ and fluid intelligence. However, only GCL was positively related to crystallized intelligence.Conclusion: This work provides novel data linking specific retinal morphometric measures – assessed using OCT – to intellectual abilities among adults with overweight and obesity.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02740439.

BackgroundSudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. Methods and ResultsOverall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P

Misconceptions, also known as alternate conceptions, about key concepts often hinder the ability of students to learn new knowledge. Concept inventories (CIs) are designed to assess students’ understanding of key concepts, especially those prone to misconceptions. Two-tiered CIs include prompts that ask students to explain the logic behind their answer choice. Such two-tiered CIs afford an opportunity for faculty to explore the student thinking behind the common misconceptions represented by their choice of a distractor. In this study, we specifically sought to probe the misconceptions that students hold prior to beginning an introductory microbiology course (i.e., preconceptions). Faculty-learning communities at two research-intensive universities used the validated Host-Pathogen Interaction Concept Inventory (HPI-CI) to reveal student preconceptions. Our method of deep analysis involved communal review and discussion of students’ explanations for their CI answer choice. This approach provided insight valuable for curriculum development. Here the process is illustrated using one question from the HPI-CI related to the important topic of antibiotic resistance. The frequencies with which students chose particular multiple-choice responses for this question were highly correlated between institutions, implying common underlying misconceptions. Examination of student explanations using our analysis approach, coupled with group discussions within and between institutions, revealed patterns in student thinking to the participating faculty. Similar application of a two-tiered concept inventory by general microbiology instructors, either individually or in groups, at other institutions will allow them to better understand student thinking related to key concepts in their curriculum.

The Sexual Health in Faith Traditions Study evaluated the relationships between religiosity, spirituality, internalized homonegativity, and sexual risk behaviors among a sample of African American men who have sex with men living in the Deep South. Participants were recruited primarily from Black Gay Pride celebrations to complete a self-administered, paper-and-pencil survey. Structural equation modeling was used to determine relationships between key constructs and condom use for insertive ( n = 285) and receptive ( n = 263) anal intercourse in the past 3 months. Almost half of respondents reported using condoms “every time” when engaging in insertive (48.3%) or receptive (45.1%) anal intercourse. Religiosity and spirituality were differentially associated with dimensions of internalized homonegativity. While no significant direct relationships were reported between either religiosity or spirituality and condom use, dimensions of internalized homonegativity mediated significant indirect relationships. Findings suggest that religiosity and spirituality influence African American men who have sex with men’s internalized homonegativity and, subsequently, engagement in safer sex behaviors.

Dietary carotenoids, plant pigments with anti-oxidant properties, accumulate in neural tissue and are often found in lower concentrations among individuals with obesity. Given previous evidence of negative associations between excess adiposity and memory, it is possible that greater carotenoid status may confer neuroprotective effects among persons with overweight or obesity. This study aimed to elucidate relationships between carotenoids assessed in diet, serum, and the macula (macular pigment optical density (MPOD)) and relational memory among adults who are overweight or obese. Adults aged 25–45 years (N = 94) completed a spatial reconstruction task. Task performance was evaluated for accuracy of item placement during reconstruction relative to the location of the item during the study phase. Dietary carotenoids were assessed using 7-day diet records. Serum carotenoids were measured using high-performance liquid chromatography. Hierarchical linear regression analyses were used to determine the relationship between carotenoids and task performance. Although initial correlations indicated that dietary lutein, beta-carotene, and serum beta-carotene were positively associated with memory performance, these relationships were not sustained following adjustment for age, sex, and BMI. Serum lutein remained positively associated with accuracy in object binding and inversely related to misplacement error after controlling for covariates. Macular carotenoids were not related to memory performance. Findings from this study indicate that among the carotenoids evaluated, lutein may play an important role in hippocampal function among adults who are overweight or obese.

Background: While left ventricular ejection fraction (LVEF) has been shown to have prognostic value in ischemic cardiomyopathy (ICMX) patients, right ventricular ejection fraction (RVEF) has not been systematically evaluated in either ICMX or non-ischemic cardiomyopathy (NICMX) patients. Moreover, an accurate estimation of RVEF is problematic due to the geometry of the right ventricle (RV). Over the years, there have been improvements in the resolution, image acquisition and post-processing software for cardiac magnetic resonance imaging (CMR), such that CMR has become the “gold standard„ for measuring RV volumetrics and RVEF. We hypothesize that CMR defines RVEF more so than LVEF and might have prognostic capabilities in ischemic and non-ischemic cardiomyopathy patients (ICMX and NICMX). Methods: Patients that underwent CMR at our institution between January 2005 and October 2012 were retrospectively selected if three-dimensional (3D) LVEF < 35%. Patients were further divided into ICMX and NICMX groups. The electronic medical record (EMR) database inquiry determined all-cause mortality and major adverse cardiovascular events (MACE). Additionally, a Social Security Death Index (SSI) database inquiry was performed to determine all-cause mortality in patients who were lost to follow-up. Patients were further sub-grouped on the basis of 3D RVEF ≥ 20%. Separately, patients were sub-grouped by LVEF ≥ 20% in both ICMX and NICMX cases. A cut-off of ≥20% was chosen for the RVEF based on the results of prior studies showing significance based on Kaplan⁻Meier (KM) survival curves. Cumulative event rates were estimated for each subgroup using the KM analysis and were compared using the log-rank test. The 3D RV/LVEFs were compared to all-cause mortality and MACE. ICMX patients were defined using the World Health Organization (WHO) criteria. Results: From a 7000-patient CMR database, 753 heart failure patients were selected. Eighty-seven patients met WHO definition of ICMX and NICMX (43 ICMX and 44 NICMX). The study patients were followed for a median of 3 years (Interquartile range or IQR 1.5⁻6.5 years). The mean age of patients was 58 ± 13 years; 79% were male. In ICMX, mean 3D LVEF was 21% ± 6% and mean 3D RVEF was 38% ± 14%, while for NICMX, mean 3D LVEF was 16% ± 6% and mean 3D RVEF was 30% ± 14% (p < 0.005 for intra- and inter-group comparison). It should be noted that LVEF < RVEF in both groups and the ejection fraction (EF) in NICMX was less than the corresponding EF in ICMX. Overall mortality was higher in ICMX than NICMX (12/40, 30% vs. 7/43, 16%; p < 0.05). Patients were stratified based on both RVEF and LVEF with a threshold of EF ≥ 20% separately. RVEF but not LVEF was a significant predictor of death for NICMX (χ2 = 8; p < 0.005), while LVEF did not predict death in ICMX (χ2 = 2, p = not significant). Similarly, time to MACE was predicted by RVEF for NICMX (χ2 = 9; p < 0.005) but not by LVEF in ICMX (χ2 = 1; p = NS). Importantly, RVEF, while predictive of NICMX MACE, did not emerge as a predictor of survival or MACE in ICMX. Conclusions: Via 3D CMR in non-ischemic CMX patients, RVEF has important value in predicting death and time to first MACE while 3D LVEF is far less predictive.

Three methods were used to fabricate ZnO-based room temperature liquid petroleum gas (LPG) sensors having interdigitated metal-semiconductor-metal (MSM) structures. Specifically, devices with Pd Schottky contacts were fabricated with: (1) un-doped ZnO active layers; (2) Pd-doped ZnO active layers; and (3) un-doped ZnO layers on top of Pd microstructure arrays. All ZnO films were grown on p-type Si(111) substrates by the sol-gel method. For devices incorporating a microstructure array, Pd islands were first grown on the substrate by thermal evaporation using a 100 μm mesh shadow mask. We have estimated the sensitivity of the sensors for applied voltage from

Impairment in cognitive flexibility is a trait characteristic among individuals with diagnosed eating disorders. However, the extent to which these relationships exist in individuals with overweight or obesity remains unclear. Furthermore, there is a lack of knowledge characterizing the neural underpinnings of these relationships. The current study aimed to investigate disordered eating attitudes and cognitive flexibility among adults with overweight and obesity. The Eating Attitudes Test (EAT-26) and a task-switching paradigm were collected from 132 adults (50 males, Body Mass Index (BMI) = 32.0 ± 5.8 kg/m2). Behavioral measures (accuracy and reaction time (RT)) and neuroelectric indices (amplitude and latency) of the P3 component were assessed. Hierarchical linear regressions, following adjustment of age, sex, intelligence quotient (IQ), weight status, and diet quality were developed using summative and subscale scores of the EAT-26. Higher EAT-26 summative scores, and the Dieting subscale, were related to longer RT. Only the Bulimia and Food Preoccupation subscale was related to longer P3 latency. The relationship between disordered eating attitudes and cognitive flexibility extends to individuals with overweight and obesity and is independent of age, sex, IQ, weight status, and diet quality. These findings are important, as differences in cognitive flexibility can lead to behavioral rigidity. Future work should aim to examine other neuroelectric components to identify where differences driving behavioral latencies may be occurring.

We present a phenomenological model for the photocurrent transient relaxation observed in ZnO-based metal-semiconductor-metal (MSM) planar photodetector devices based on time-resolved surface band bending. Surface band bending decreases during illumination, due to migration of photogenerated holes to the surface. Immediately after turning off illumination, conduction-band electrons must overcome a relatively low energy barrier to recombine with photogenerated holes at the surface; however, with increasing time, the adsorption of oxygen at the surface or electron trapping in the depletion region increases band bending, resulting in an increased bulk/surface energy barrier that slows the transport of photogenerated electrons. We present a complex rate equation based on thermionic transition of charge carriers to and from the surface and numerically fit this model to transient photocurrent measurements of several MSM planar ZnO photodetectors at variable temperature. Fitting parameters are found to be consistent with measured values in the literature. An understanding of the mechanism for persistent photoconductivity could lead to mitigation in future device applications.

Dislocations are known to be associated with both physical and electrical degradation mechanisms of AlGaN/GaN-on-Si high electron mobility transistors (HEMTs). We have observed threading dislocation movement toward the gate-edges in AlGaN/GaN-on-Si HEMT under high reverse bias stressing. Stressed devices have higher threading dislocation densities (i.e. ∼5 × 109/cm2) at the gate-edges, as compared to unstressed devices (i.e. ∼2.5 × 109/cm2). Dislocation movement correlates well with high tensile stress (∼1.6 GPa) at the gate-edges, as seen from inverse piezoelectric calculations and x-ray synchrotron diffraction residual stress measurements. Based on Peierls stress calculation, we believe that threading dislocations move via glide in 〈 11 2 ¯ 0 〉 / { 1 1 ¯ 00 } and 〈 11 2 ¯ 0 〉 / { 1 1 ¯ 01 } slip systems. This result illustrates the importance of threading dislocation mobility in controlling the reliability of AlGaN/GaN-on-Si HEMTs.

BACKGROUND:Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. METHODS AND FINDINGS:We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. CONCLUSIONS:Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35).

The standard 26S proteasome is responsible for the majority of myofibrillar protein degradation leading to muscle atrophy. The immunoproteasome is an inducible form of the proteasome. While its function has been linked to conditions of atrophy, its contribution to muscle proteolysis remains unclear. Therefore, the purpose of this study was to determine if the immunoproteasome plays a role in skeletal muscle atrophy induced by denervation. Adult male C57BL/6 wild type (WT) and immunoproteasome knockout lmp7-/-/mecl-1-/- (L7M1) mice underwent tibial nerve transection on the left hindlimb for either 7 or 14 days, while control mice did not undergo surgery. Proteasome activity (caspase-, chymotrypsin-, and trypsin- like), protein content of standard proteasome (β1, β5 and β2) and immunoproteasome (LMP2, LMP7 and MECL-1) catalytic subunits were determined in the gastrocnemius muscle. Denervation induced significant atrophy and was accompanied by increased activities and protein content of the catalytic subunits in both WT and L7M1 mice. Although denervation resulted in a similar degree of muscle atrophy between strains, the mice lacking two immunoproteasome subunits showed a differential response in the extent and duration of proteasome features, including activities and content of the β1, β5 and LMP2 catalytic subunits. The results indicate that immunoproteasome deficiency alters the proteasome's composition and activities. However, the immunoproteasome does not appear to be essential for muscle atrophy induced by denervation.

It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle's intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6-8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling.

BACKGROUND:Bean consumption can reduce chronic disease risk and improve nutrition status. Consumer knowledge of bean health benefits could lead to increased intakes. Low-income women have poorer health and nutrition, but their level of knowledge about bean health benefits is unknown. Beans are a familiar food of reasonable cost in most settings and are cultural staples for Hispanics and other ethnicities. Study objectives were to assess awareness of bean health benefits among low-income women, and to evaluate any differences by acculturation status for Hispanic women in the Southwestern United States. METHODS:A convenience sample of 406 primarily Mexican-origin (70%) low-income women completed a survey on knowledge of bean health benefits and general food behaviors. Principal components analysis of responses identified two summary scale constructs representing "bean health benefits" and "food behaviors." Acculturation level was the main independent variable in chi-square or ANOVA. RESULTS:The survey completion rate was 86% (406/471). Most women agreed or strongly agreed that beans improved nutrition (65%) and were satiating (62%). Over 50% answered 'neutral' to statements that beans could lower LDL cholesterol (52%), control blood glucose (56%) or reduce cancer risk (56%), indicating indifference or possible lack of knowledge about bean health benefits. There were significant differences by acculturation for beliefs that beans aid weight loss and intestinal health. Scores on the bean health benefits scale, but not the food behavior scale, also differed by acculturation. CONCLUSIONS:Limited resource women have a favorable view of the nutrition value of beans, but the majority did not agree or disagreed with statements about bean health benefits. Greater efforts to educate low-income women about bean health benefits may increase consumption and improve nutrition.

Registered Dietitians (RDs) promote nutrition practices and policies and can influence food consumption patterns to include nutrient dense foods such as beans. Although many evidence-based health benefits of bean consumption (e.g., cholesterol reduction, glycemic control) have been demonstrated, there is limited research on the knowledge, attitudes, and perceptions of RDs regarding the inclusion of beans in a healthy diet. To fill this existing research gap, this cross-sectional survey explored the perceptions, knowledge, and attitudes of 296 RDs in Arizona, USA, toward beans. The RDs largely held positive attitudes toward the healthfulness of beans and were aware of many health benefits. Some gaps in awareness were evident, including effect on cancer risk, intestinal health benefits, folate content, and application with celiac disease patients. RDs with greater personal bean consumption had significantly higher bean health benefit knowledge. Twenty-nine percent of the RDs did not know the meaning of ‘legume’, and over two-thirds could not define the term ‘pulse’. It is essential that RDs have up-to-date, evidence-based information regarding bean benefits to provide appropriate education to patients, clients, and the public.

Legumes, such as black beans (Phaseolus vulgaris L.) and chickpeas (Cicer arietinum L.), have a low glycemic index, and may reduce the glycemic load of meals in which they are included. Although the low glycemic response of beans consumed alone has been documented, few studies have examined the glycemic response to traditional food combinations such as black beans and rice or chickpeas and rice. This randomized cross-over study examined the glycemic and insulinemic impact of 50 grams of available carbohydrate from three test meals: plain white rice (control), black beans with rice, and chickpeas with rice among healthy adult women (n = 12, 18–65 years). Treatments were consumed on different mornings, a minimum of 7 days apart. Blood samples were collected at time 0 (fasting), and at 30, 60, 90, and 120 min postprandial, and were subsequently analyzed for glucose and insulin concentrations. Glucose response based on the incremental area under the curve showed a significant difference by treatment (p = 0.027). Changes in blood glucose concentrations were significantly different for the black bean meal and the chickpea meal in comparison to rice alone at 60 min (p = 0.026 and p = 0.024), 90 min (p = 0.001 and p = 0.012) and 120 min post prandial (p = 0.024; black bean meal). Findings indicate that combinations of black beans and chickpeas with white rice improve glycemic response, providing evidence that has promising implications for dietary guidance to reduce postprandial glucose and related health risks through traditional food patterns.

The lomas formations of the Peruvian and Atacama deserts are characterized by both climatic and floristic spatial heterogeneity, as well as non-contiguous pockets of relatively distinct flora. We examined two distinct types of communities in Parque Nacional Pan de Azúcar in Chile, the low-elevation arroyo and bajada community, and the high-elevation fog-zone community. We determined the distribution with elevation of the dominant perennial plant species in a single arroyo community, as well as the distribution of associated climatic characteristics. Climatic conditions (including air temperature, relative humidity, and wind speed and direction) were recorded from June, 1999, to March, 2001, for the arroyo, as well as for a medium-elevation inland site with little vegetation, and a high-elevation fog-zone site with copious vegetation. The fog layer, or camanchaca, derived from the marine inversion layer ubiquitous to the Peruvian and Atacama deserts was found to be more persistent, though weaker, during the summer months and somewhat more condensed and shallower in the winter months, with uncharacteristically dry air and high temperatures occurring at and above 400 m elevation during the late fall and early winter of 2000. The reduction or increase in the maximum elevation of the camanchaca or a change in the rainfall regime of the park may have broad implications for the distribution or even presence of certain species in Parque Nacional Pan de Azúcar. Vegetation patterns appear to be strongly dependent on inversion layer development, and perhaps on its subsidence during the winter. A number of species prevalent at low-elevation sites may have little advantage at a high-elevation foggy site, whereas the consistently high humidity at low elevations would be a boon to any desert plant accustomed to low precipitation. If we are to successfully assess the effects of changes in southern Pacific weather patterns, it will become necessary to more closely examine the local variation in climate and plant distribution in these regions, on sets of species with known distributions and in environments whose climatic conditions are particularly well-characterizedLas "lomas", formaciones de los desiertos Peruano y de Atacama, se caracterizan por su heterogeneidad climática y florística, así como también por la discontinuidad de una vegetación relativamente distintiva y particular. Se investigaron dos grupos distintos de comunidades vegetales en el Parque Nacional Pan de Azúcar en Chile, las comunidades de baja elevación "arroyo" y "bajada", y la comunidad de la zona de niebla a mayor elevación. Se determinó la distribución altitudinal de las especies de plantas perennes dominantes en un arroyo, así como la distribución de las características climáticas asociadas. Las variables climáticas (incluyendo la temperatura ambiental, la humedad relativa, y la velocidad y dirección del aire) fueron registradas desde el mes de junio de 1999 hasta marzo de 2001, en el arroyo, así como en un sitio de elevación media en el interior del parque con poca vegetación y en otro sitio de alta elevación y vegetación abundante en la zona de niebla. El nivel de niebla, o camanchaca, derivada de la inversión marítima omnipresente en los desiertos Peruano y de Atacama, fue más persistente, aunque más débil, durante los meses de verano, y algo mas condensada y superficial durante los meses de invierno, con aire inusualmente seco y caliente sobre los 400 m durante el final del otoño e inicios del invierno de 2000. La reducción o el incremento en la elevación máxima de la camanchaca o un cambio en el régimen de precipitación podría tener grandes implicaciones en la distribución o aun más sobre la presencia de ciertas especies en el Parque. El patrón de distribución de las plantas parece ser fuertemente dependiente del desarrollo de la inversión marítima, y posiblemente de su descenso durante el invierno. Algunas especies comunes en sitios de baja elevación podrían tener poca ventaja en sitios altos y nublados, mientras que la alta humedad en los arroyos daría gran ventaja a cualquier planta desértica acostumbrada a la escasez de lluvias. Si quisiéramos discutir exitosamente los efectos de los cambios en los patrones climáticos del Pacifico Sur, sería necesario examinar cuidadosamente la variación climática local asociada a la distribución de la vegetación in estas regiones, considerando especies de distribución bien conocida y en ambientes cuyas condiciones climáticas estén particularmente bien caracterizadas

Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newly-diagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day × four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m2 × 4 rituximab was combined with three 4-day cycles of 28 mg/m2 (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥100×109/L) or partial (50–99×109/L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50×109/L at a median 17 months (range 4–67) projecting 44% event-free survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P

OBJECTIVE: To assess the reliability of magnetic resonance imaging (MRI) for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy. BACKGROUND: The Levrat model has proven utility in terms of its ability to replicate Barrett's carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting. METHODS: Chronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively. RESULTS: The accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p

Workers compensation statistics show high rates of fatalities, traumatic injuries and musculoskeletal disorders occur in the transport industry, particularly the road transport sub-sector. Safety initiatives and innovation are occurring although they tend not to be shared between operators. The Transport Strategy Group, Workplace Health and Safety Queensland is engaging with the industry, especially the heavy freight road transport sector, using action research to learn more about the health and safety systems in the industry and concurrently to improve health and safety outcomes. Industry networks are being established using concepts of collaborative governance to break down barriers, improve sharing of issues and solutions and to improve work health and safety outcomes.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

We study backward cooperative emissions from a dense sodium atomic vapor. Ultrashort pulses produced from a conventional amplified femtosecond laser system with an optical parametric amplifier are used to excite sodium atoms resonantly on the two-photon 3S $_{1/2}$ –4S $_{1/2}$ transition. Backward superfluorescent emissions (BSFEs), both on the 4S $_{1/2}$ –3P $_{3/2}$ and 4S $_{1/2}$ –3P $_{1/2}$ transitions, are observed. The picosecond temporal characteristics of the BSFE are observed using an ultrafast streak camera. The power laws for the dependencies of the average time delay and the intensity of the BSFEs on input power are analyzed in the sense of cooperative emission from nonidentical atomic species. As a result, an absolute (rather than relative) time delay and its fluctuations (free of any possible external noise) are determined experimentally. The possibility of a backward swept-gain superfluorescence as an artificial laser guide star in the sodium layer in the mesosphere is also discussed.

The medical records of 97 patients with alcoholic hepatitis, including 20 with coexisting bacterial infections and 77 with no evidence of bacterial infection, were reviewed to determine whether commonly employed tests would be useful in distinguishing between the two groups. The results of the study revealed that patients with alcoholic hepatitis and bacterial infections had higher temperatures (38.4±0.9°C versus 37.9±0.7°C, P