Association between change in alcohol use reported during routine healthcare screening and change in subsequent hospitalization: A retrospective cohort study.

Background And Aims: Primary care systems often screen for unhealthy alcohol use with brief self-report tools such as the 3-item Alcohol Use Disorders Identification Test for consumption (AUDIT-C). There is little research examining whether change in alcohol use measured on the AUDIT-C captures meaningful change in outcomes affected by alcohol use. This study aimed to measure the association between change in AUDIT-C and change in all-cause hospitalization risk, measured in the year after each AUDIT-C.

Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.

The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Prevalence of probable post-traumatic stress disorder and experiences of trauma in emerging adults living with HIV in Zimbabwe.

Background: Little is known about the prevalence of post-traumatic stress disorder (PTSD) in emerging adults living with HIV in low-income countries.

Aims: Determine prevalence of trauma exposure, prevalence of probable PTSD and conditional prevalence of probable PTSD for different traumatic events; and better understand the experiences of individuals with HIV and PTSD.

Method: This mixed method study used secondary data from a cross-sectional survey of people ( = 222) aged 18 to 29 living with HIV in Zimbabwe and primary qualitative data collection.

Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.

Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes.

Association of Clinical, Biomechanical, and Psychosocial Factors with Smile Dynamics in Unilateral Cleft Lip: A Multicenter Observational Study.

Objective: To investigate the association between clinical, biomechanical, and psychosocial factors and smiling behavior in individuals with treated unilateral cleft lip with or without cleft palate (UCL ± P) compared to non-cleft controls.

Design: Multicenter observational study in New Zealand.

Participants: Individuals aged ≥15 ( = 42) comprised 2 study groups: a UCL ± P group ( = 21) and a non-cleft control group ( = 21).

Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1.

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.

ACE2-independent sarbecovirus cell entry can be supported by TMPRSS2-related enzymes and can reduce sensitivity to antibody-mediated neutralization.

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract.

Participation With Compensation: Ethical Considerations for Research Payment Practices With People Who Are Incarcerated.

The participation of incarcerated individuals in research is necessary to appropriately address the health disparities that affect them and to adapt and implement health services for the carceral setting. Incarceration significantly impacts health, leading to negative outcomes including accelerated aging and increased mortality, with these effects disproportionately impacting communities of color. The U.

An Enhanced Retroviral Vector for Efficient Genetic Manipulation and Selection in Mammalian Cells.

Introducing genetic material into hard-to-transfect mammalian cell lines and primary cells is often best achieved through retroviral infection. An ideal retroviral vector should offer a compact, selectable, and screenable marker while maximizing transgene delivery capacity. However, a previously published retroviral vector featuring an EGFP/Puromycin fusion protein failed to meet these criteria in our experiments.

Peer support for patients with opioid use disorder in the emergency department: A narrative review.

Faced with a growing opioid overdose crisis, emergency departments (EDs) are increasingly hiring peers-people with lived experiences of addiction and recovery-to work with patients in the ED who have opioid use disorders (OUDs) or who have experienced an opioid overdose. Despite a clear need for more support for patients with OUD and rapid expansion in grant funding for peer programs, there are limited data on how these programs affect clinical outcomes and how they are best implemented within the ED. In this narrative review, we synthesize the existing evidence on how to develop and implement peer programs for OUD in the ED setting.

Metabolic profiling of single cells by exploiting NADH and FAD fluorescence via flow cytometry.

Objective: The metabolism of different cells within the same microenvironment can differ and dictate physiological or pathological adaptions. Current single-cell analysis methods of metabolism are not label-free.

Methods: The study introduces a label-free, live-cell analysis method assessing endogenous fluorescence of NAD(P)H and FAD in surface-stained cells by flow cytometry.

Mutual capacity building model for adaptation (MCB-MA): a seven-step procedure bidirectional learning and support during intervention adaptation.

Global health reciprocal innovation emphasizes the movement of technologies or interventions between high- and low-income countries to address a shared public health problem, in contrast to unidirectional models of "development aid" or "reverse innovation". Evidence-based interventions are frequently adapted from the setting in which they were developed and applied in a new setting, presenting an opportunity for learning and partnership across high- and low-income contexts. However, few clear procedures exist to guide researchers and implementers on how to incorporate equitable and learning-oriented approaches into intervention adaptation across settings.

Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model.

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection , we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant.

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.

Identification of TFG- and Autophagy-Regulated Proteins and Glycerophospholipids in B Cells.

Autophagy supervises the proteostasis and survival of B lymphocytic cells. (TFG) promotes autophagosome-lysosome flux in murine CH12 B cells, as well as their survival. Hence, quantitative proteomics of CH12KO and WT B cells in combination with lysosomal inhibition should identify proteins that are prone to lysosomal degradation and contribute to autophagy and B cell survival.

Global Is Local: Leveraging Global Mental-Health Methods to Promote Equity and Address Disparities in the United States.

Structural barriers perpetuate mental health disparities for minoritized US populations; global mental health (GMH) takes an interdisciplinary approach to increasing mental health care access and relevance. Mutual capacity building partnerships between low and middle-income countries and high-income countries are beginning to use GMH strategies to address disparities across contexts. We highlight these partnerships and shared GMH strategies through a case series of said partnerships between Kenya-North Carolina, South Africa-Maryland, and Mozambique-New York.

Rural Friendship Bench: A qualitative study in Zaka district, Zimbabwe.

Background: We piloted the Friendship Bench-an evidence-based, urban-area task sharing intervention for common mental disorders-in rural Zimbabwe. The intervention combines problem solving therapy with income generating activities. This study sought to understand the intervention's implementation in terms of acceptability, feasibility, and sustainability as well as local attitudes towards mental wellbeing in rural Zimbabwe.

Raising the issue of quality in implementation science reporting in global health: Implications for health planning and practice.

Implementation outcomes, which focus on the barriers to, and facilitators and processes of healthcare delivery, are critical to translating research evidence to health planning and practice and to improving healthcare delivery. This article summarises key quality issues in reporting of implementation science outcomes within global health and describes the ways in which this presents a challenge for shifting health planning and practice across low-resource health systems. This article also suggests that the wider use of reporting guidelines for implementation outcomes could help address this issue.

GLUT1-mediated glucose import in B cells is critical for anaplerotic balance and humoral immunity.

Glucose uptake increases during B cell activation and antibody-secreting cell (ASC) differentiation, but conflicting findings prevent a clear metabolic profile at different stages of B cell activation. Deletion of the glucose transporter type 1 (GLUT1) gene in mature B cells (GLUT1-cKO) results in normal B cell development, but it reduces germinal center B cells and ASCs. GLUT1-cKO mice show decreased antigen-specific antibody titers after vaccination.

SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency.

BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.

Equity M&M - Adaptation of the Morbidity and Mortality Conference to Analyze and Confront Structural Inequity in Internal Medicine.

Background: At morbidity and mortality (M&M) conferences, medical teams review cases for medical education and system improvement. Adverse outcomes are often driven by social inequity, but processes to analyze such outcomes are lacking.

Aim: Adapt quality improvement and patient safety (QIPS) tools in the M&M format to systematically analyze adverse patient outcomes rooted in social and structural determinants of health (SSDH).

Identification of miR-128 Target mRNAs That Are Expressed in B Cells Using a Modified Dual Luciferase Vector.

MicroRNAs (miRNAs) are 21-25 nucleotide long non-coding ribonucleic acids that modulate gene expression by degrading transcripts or inhibiting translation. The miRNA miR-128, originally thought to be brain-specific, was later also found in immune cells. To identify a valuable immune cell model system to modulate endogenous miR-128 amounts and to validate predicted miR-128 target mRNAs in B cells, we first investigated miR-128 expression using Northern blot analysis in several cell lines representing different stages of B cell development.