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Reporter-based assays underlie many high-throughput screening (HTS) platforms, but most are limited to in vitro applications. Here, we report a simple whole-organism HTS method for quantifying changes in reporter intensity in individual zebrafish over time termed, Automated Reporter Quantification in vivo (ARQiv). ARQiv differs from current \"high-content\" (e.g., confocal imaging-based) whole-organism screening technologies by providing a purely quantitative data acquisition approach that affords marked improvements in throughput. ARQiv uses a fluorescence microplate reader with specific detection functionalities necessary for robust quantification of reporter signals in vivo. This approach is: 1) Rapid; achieving true HTS capacities (i.e., >50,000 units per day), 2) Reproducible; attaining HTS-compatible assay quality (i.e., Z'-factors of ≥0.5), and 3) Flexible; amenable to nearly any reporter-based assay in zebrafish embryos, larvae, or juveniles. ARQiv is used here to quantify changes in: 1) Cell number; loss and regeneration of two different fluorescently tagged cell types (pancreatic beta cells and rod photoreceptors), 2) Cell signaling; relative activity of a transgenic Notch-signaling reporter, and 3) Cell metabolism; accumulation of reactive oxygen species. In summary, ARQiv is a versatile and readily accessible approach facilitating evaluation of genetic and/or chemical manipulations in living zebrafish that complements current \"high-content\" whole-organism screening methods by providing a first-tier in vivo HTS drug discovery platform.

PurposePsychiatric emergency hospital admissions for distinct psychiatric disorders and length of inpatient stay in the hospital during the Coronavirus disease 2019 (COVID-19) outbreak have not been thoroughly assessed.MethodsA retrospective study was performed analyzing claims data from a large German Hospital network during the COVID-19 outbreak (study period: March 13–May 21, 2020) as compared to periods directly before the outbreak (same year control: January 1–March 12, 2020) and one year earlier (previous year control: March 13–May 21, 2019).ResultsA total of 13,151 emergency hospital admissions for psychiatric diagnoses were included in the analysis. For all psychiatric diagnoses combined, emergency admissions significantly decreased during the study period with mean (interquartile range) incidence rate ratios (IRRs) of 0.68 (0.65, 0.71) and 0.70 (0.67, 0.73) as compared to the same and previous year controls, respectively (both p < 0.00001). IRR ranged from 0.56 for mood affective disorders (F30-F39) to 0.75 for mental disorders due to psychoactive substance use (F10-F19; all p < 0.00001). Mean (standard deviation) length of hospital stay for all psychiatric diagnoses was significantly shorter during the study period [9.8 (11.6) days] as compared to same [14.7 (18.7) days] and previous [16.4 (23.9) days] year controls (both p < 0.00001).ConclusionBoth emergency hospital admissions and length of hospital stay significantly decreased for psychiatric disorders during the COVID-19 outbreak. It needs to be assessed in further studies whether healthcare systems will face increased demand for the provision of mental health care in the nearer future.

Black same-gender-loving (SGL) men (BSGLM) bear a disproportionate burden of depression. Adverse childhood experiences (ACEs) have been found to predict depression among this group. However, little research has examined the mechanisms that may account for this relationship. This study aimed to examine how stress appraisal explained the association between ACEs and depression. This cross-sectional study leveraged survey data from 169 BSGLM residing in the United States. Utilizing Hayes’ PROCESS Macro (Model 4), we found that five different dimensions of stress appraisal were significant partial mediators of the association between ACEs and depression. Specifically, ACEs predicted lower levels of stress appraisal dimensions consistent with an optimal worldview, which in turn were inversely associated with depressive symptoms. ACEs predicted higher levels of stress appraisal dimensions consistent with a suboptimal worldview, which in turn were positively associated with depressive symptoms. Effects sizes ranged from small to large. Implications of these findings for clinical care and research with BSGLM were discussed.

Previous research has highlighted the homonegative atmospheres of many religious communities in Western society and their harmful impact on Black sexual minority (SM) people’s mental and physical health. However, few studies have examined the relationship between sexual orientation disclosure to church members and exposure to homonegative religious messages in religious settings. This online quantitative study investigated this relationship among a sample of 320 Black SM men. The participants for this study were recruited nationally from across the United States and had a mean age of 34 years. Descriptive statistics and linear regression analyses were conducted. Findings indicated that sexual orientation disclosure to church members was significantly associated with exposure to homonegative religious messages, even when controlling for geographic region of residence and denominational affiliation. Black SM men who had higher levels of disclosure were exposed to fewer homonegative religious messages. The implications of these findings for health research and clinical work with Black SM men are discussed in detail.

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services. Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments. Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Clinicaltrials.gov NCT01600391.

\"Black LGBT Health in the United States: The Intersection of Race, Gender, and Sexual Orientation focuses on the mental, physical, and spiritual aspects of health, and considers both risk and resiliency factors for the Black LGBT population. Contributors to this collection intimately understand the associations between health and intersectional anti-Black racism, heterosexism, homonegativity, biphobia, transphobia, and social class. This collection fills a gap in current scholarship by providing information about an array of health issues like cancer, juvenile incarceration, and depression that affect all subpopulations of Black LGBT people, especially Black bisexual-identified women, Black bisexual-identified men, and Black transgender men. This book is recommended for readers interested in psychology, health, gender studies, race studies, social work, and sociology\"

Attenuated retinal vasoreactivity in patients with type 2 diabetes preceding diabetic retinopathy development has been proposed to reflect local endothelial dysfunction. Whether retinal vessel reactivity is associated with peripheral endothelial dysfunction and large artery stiffness in patients with type 2 diabetes remains to be elucidated. Twenty patients with type 2 diabetes without retinopathy and 20 sex- and age matched controls (diabetes duration: 9.9 years (range 6.0;12.4), 40% male, age: 66.5 ± 7.3 (diabetes) and 65.2 ± 7.6 years (controls)) were included. Endothelial function was assessed using EndoPAT. Arterial stiffness was assessed by carotid-femoral pulse wave velocity using the SphygmoCor. Retinal blood supply regulation was examined by retinal arteriolar diameter change during 1) isometric exercise (hand-weight lifting), 2) exposure to flickering lights, and 3) a combined stimulus of 1) + 2) using the Dynamic Vessel Analyzer. No significant differences were observed in retinal vessel reactivity in T2DM patients compared to controls. Endothelial function was associated with mean arteriolar diameter change during only the combination intervention, (Beta = 0.033 [0.0013;0.064], p = 0.042) in the overall population of patients and controls. When groups were analyzed separately, the associations was statistically significant only in controls. However, formal test for interaction was not statistically significant, p = 0.40. No association was observed between pulse wave velocity and retinal arteriolar %-diameter change in patients or controls. Peripheral endothelial function was associated with retinal arteriolar diameter change in the combined sample. The association seemed to be driven primarily by the controls. Our findings indicate that peripheral endothelial function is reflective of endothelial function in the retina mainly in subjects without T2DM, whereas an association in T2DM without retinopathy was not observed. Further studies are needed in T2DM patients with more advanced retinopathy.

Across a range of studies, health scientists have found that being in a romantic relationship can have positive and negative influences on one's health. A couple's health outcomes are often influenced by relationship quality-or how they perceive the positive or negative character of their relationship. These findings have important implications for how scientists and interventionists may leverage romantic relationships facilitating good health among couples. However, in general, couples research has not included Black same-sex male couples in large enough numbers to make previous studies' findings relevant to them. This represents a gap in the scientific literature and, more importantly, a missed opportunity to understand how romantic relationships influence health for a group that must navigate distinct, multilevel health and social inequities. This study aims to (1) decode and understand the ways in which Black same-sex male couples express their romantic relationships in virtual contexts via symbolic indicators, (2) determine how Black same-sex male couples describe the quality of their romantic relationships, and (3) explore how Black same-sex male couples make meaning of their relationship quality and its impact on their relational and individual health. We will use joint dyadic interviews embedded within a symbolic netnography research design to accomplish our aims. We will use grounded theory to analyze our qualitative data. We will then triangulate our findings to determine how well they answer our research questions. This study received ethical approval on October 8, 2020 and we began data collection in November 2020. Results are expected to be available no later than December 31, 2022. This study will apply novel symbolic netnographic qualitative methods to further our understanding of Black same-sex male couples' romantic relationships and how they contribute to their health. The findings will be used to develop programs to improve Black same-sex male couples' health in community and virtual settings. DERR1-10.2196/29589.

Background We have investigated a simple strategy for enhancing transgene expression specificity by leveraging genetic silencer elements. The approach serves to restrict transgene expression to a tissue of interest - the nervous system in the example provided here - thereby promoting specific/exclusive targeting of discrete cellular subtypes. Recent innovations are bringing us closer to understanding how the brain is organized, how neural circuits function, and how neurons can be regenerated. Fluorescent proteins enable mapping of the 'connectome', optogenetic tools allow excitable cells to be short-circuited or hyperactivated, and targeted ablation of neuronal subtypes facilitates investigations of circuit function and neuronal regeneration. Optimally, such toolsets need to be expressed solely within the cell types of interest as off-site expression makes establishing causal relationships difficult. To address this, we have exploited a gene 'silencing' system that promotes neuronal specificity by repressing expression in non-neural tissues. This methodology solves non-specific background issues that plague large-scale enhancer trap efforts and may provide a means of leveraging promoters/enhancers that otherwise express too broadly to be of value for in vivo manipulations. Results We show that a conserved neuron-restrictive silencer element (NRSE) can function to restrict transgene expression to the nervous system. The neuron-restrictive silencing factor/repressor element 1 silencing transcription factor (NRSF/REST) transcriptional repressor binds NRSE/repressor element 1 (RE1) sites and silences gene expression in non-neuronal cells. Inserting NRSE sites into transgenes strongly biased expression to neural tissues. NRSE sequences were effective in restricting expression of bipartite Gal4-based 'driver' transgenes within the context of an enhancer trap and when associated with a defined promoter and enhancer. However, NRSE sequences did not serve to restrict expression of an upstream activating sequence (UAS)-based reporter/effector transgene when associated solely with the UAS element. Morpholino knockdown assays showed that NRSF/REST expression is required for NRSE-based transgene silencing. Conclusions Our findings demonstrate that the addition of NRSE sequences to transgenes can provide useful new tools for functional studies of the nervous system. However, the general approach may be more broadly applicable; tissue-specific silencer elements are operable in tissues other than the nervous system, suggesting this approach can be similarly applied to other paradigms. Thus, creating synthetic associations between endogenous regulatory elements and tissue-specific silencers may facilitate targeting of cellular subtypes for which defined promoters/enhancers are lacking.

Background The long-term association between physical activity and endothelial function has not previously been investigated in patients with type 2 diabetes. Therefore, we aimed to evaluate the relationship between physical activity and endothelial function, assessed by peripheral arterial tonometry, in patients with type 2 diabetes and non-diabetic controls after 5 years of follow-up. Methods We included 51 patients with newly diagnosed type 2 diabetes and 53 sex- and age matched controls. Participants underwent baseline clinical characterization including objective measurement of physical activity level using accelerometery. After 5 years of follow-up, participants were re-examined, and endothelial function was assessed as natural logarithm of reactive hyperemia index (lnRHI). Results Physical activity at baseline was associated with lnRHI after 5 years of follow-up in both patients with type 2 diabetes and controls. An increase of 1 standard deviation (SD) in daytime physical activity corresponded to a 6.7 % increase in RHI (95 % confidence interval: 1.1;12.5 %, p  = 0.02). We found no difference in lnRHI between patients with diabetes and controls (0.67 ± 0.29 vs. 0.73 ± 0.31, p  = 0.28). Conclusions Daytime physical activity is associated with endothelial function after 5 years of follow-up in patients with type 2 diabetes and controls.