Emergency and postoperative access to critical and enhanced care: a multicentre prospective observational study.

Introduction: The ability to admit patients to enhanced or critical care may be limited by bed availability. In a network with low provision of critical and enhanced care beds, we aimed to assess the proportion of patients having surgery with moderate (1%-< 5%) or high (≥ 5%) predicted risk of 30-day postoperative mortality and their postoperative care location. We also aimed to study referral and admission outcomes to critical care.

An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.

Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation.

An Adaptive Antiretroviral Therapy Adherence Intervention for Youth with HIV Through Text Message and Cell Phone Support with and without Incentives: A Sequential Multiple Assignment Randomized Trial (SMART).

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months.

Peer social support moderates the impact of ethnoracial discrimination on mental health among young sexual minority men of color.

Few studies have examined developmentally relevant sources of resilience, such as peer social support, among young sexual minority men (SMM) of color experiencing discrimination and mental health distress. To address this gap in the literature, we examined the role of peer social support in the association between discrimination and mental health distress in a sample of young SMM of color. Ninety-four cisgender young SMM of color (aged 16-29) were recruited through community-based organizations in the New York City metropolitan area as part of an effectiveness trial of a tailored Motivational Interviewing intervention.

A protocol for a randomized controlled trial of couples motivational interviewing to reduce drug use and HIV transmission risk among male couples in the US: the Couples Health Project.

Background: To reduce substance use and sexual HIV transmission risk among sexual minority men (SMM) requires the development of interventions tailored for those in relationships. In the past 5 years, there have been considerable advances in the development of motivational nterviewing (MI) with couples. The Couples Health Project (CHP) is the first multi-session risk reduction protocol built on this formative research.

In utero human cytomegalovirus infection expands NK-like FcγRIII+CD8+ T cells that mediate Fc antibody functions.

Human cytomegalovirus (HCMV) profoundly impacts host T and NK cells across the lifespan, yet how this common congenital infection modulates developing fetal immune cell compartments remains underexplored. Using cord blood from neonates with and without congenital HCMV (cCMV) infection, we identify an expansion of Fcγ receptor III-expressing (FcγRIII-expressing) CD8+ T cells following HCMV exposure in utero. Most FcγRIII+CD8+ T cells express the canonical αβ T cell receptor (TCR), but a proportion express noncanonical γδ TCR.

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).

Technology-Based Interventions, with a Stepped Care Approach, for Reducing Sexual Risk Behaviors and Increasing PrEP Initiation Among Transgender and Gender Expansive Youth and Young Adults.

TechStep was a technology-based trial, with a stepped care approach, to reduce sexual risks and increase PrEP uptake among transgender and gender expansive youth and young adults (15-24 years old). From October 2019 to September 2021, 254 participants were randomized into: 1) Text (n = 82), or 2) Webapp (n = 87), or 3) Control (n = 85). At the 3-month follow-up assessment, those randomized to Text and Webapp and did not demonstrate improvement on primary outcomes were re-randomized to receive virtual eCoaching (Text + or Webapp +), or to remain in their initial condition without eCoaching.

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design.

A Qualitative Analysis of Shared Values and Motivation for Change Expressed by Sexual Minority Men in Relationships: Use of the Personal Values Card Sort Activity During Motivational Interviewing Sessions Addressing Drug Use and Sexual Health.

The development of tailored interventions that address drug use and sexual risk taking among sexual minority men (SMM) in relationships has garnered increasing interest over the past 20 years. Motivational interviewing (MI) has demonstrated promise in both individual and couples-based applications. The Personal Values Card Sort activity is commonly employed in these interventions; however, relatively little is known about the content of client responses evoked by this intervention task.

Five historical innovations that have shaped modern otolaryngological surgery.

Throughout history, many innovations have contributed to the development of modern otolaryngological surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern otolaryngological surgery: Operative Microscope, Hopkins Rigid Endoscope, Laryngeal Nerve monitoring, Cochlear implants and Laser surgery. The selection of innovations for inclusion in this article was meticulously determined through expert consensus and an extensive literature review.

Optimizing Individual HIV Testing and Counseling for Emerging Adult Sexual Minority Men (Aged 18 to 24) in Relationships: A Pilot Randomized Controlled Trial of Adjunct Communication Components.

The majority of new HIV infections in the US occur among sexual minority men (SMM) with older adolescent and emerging adult SMM at the highest risk. Those in relationships face unique HIV prevention challenges. Existing sexual HIV transmission risk interventions for male couples often encounter implementation challenges and engaging younger SMM early in relationships may be particularly difficult.

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541).

Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial.

Importance: The prevalence of e-cigarette use among US adults, especially young adults, is rising. Many would like to quit vaping nicotine but are unable to do so. Cytisinicline, a plant-based alkaloid, targets nicotinic acetylcholine receptors, reduces nicotine dependence, and helps adults to stop smoking cigarettes.

Main Partner Relationships and the HIV Care Cascade: Examining the Predictive Utility of Sexual Agreements, Partner Concordance, and Drug Use Among Sexual Minority Men Living With HIV in the USA.

Background: The past 15 years have seen increasing attention to relationship factors among sexual minority male (SMM) couples at high risk for HIV infection. Research has largely focused on HIV prevention outcomes. Outcomes relevant to SMM living with HIV have received relatively less attention.

A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals.

Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys.

Comparing Repeated (Annual) Couples HIV Testing and Counseling to Individual HIV Testing and Counseling Among Male Couples at High Risk of HIV Infection: Protocol for a Randomized Control Trial.

Background: Couples HIV testing and counseling (CHTC) is now a standard of care prevention strategy recommended by the Centers for Disease Control and Prevention for sexual minority men (SMM) in relationships. Despite standard recommendations that couples complete CHTC every 6-12 months, no study has empirically evaluated the effects associated with CHTC retesting.

Objective: This study aims to understand the benefits associated with continued dyadic engagement in the HIV prevention continuum through routine CHTC retesting, which is of particular importance for emerging-adult SMM in relationships who use drugs.

Drug use during the second year of the COVID-19 pandemic: observations from repeated cross-sectional surveys of sexual minority men in the US active on social networking applications.

Studies conducted early in the COVID-19 pandemic - before vaccines were widely available - indicated that drug use may have declined among sexual minority men (SMM). This study evaluated drug use trends in the second year of the pandemic. Cross-sectional responses from cisgender SMM living in the US and recruited online (= 15,897) were grouped for analyses: Time 1: 3/1/2021-5/30/2021; Time 2: 6/1/2021-8/31/2021; Time 3: 9/1/2021-11/30/2021; and Time 4: 12/1 2021-2/28/2022.

The intersectional social patterning of early-COVID-era digital intimacies among transgender and gender-diverse young adults: effects on peri-pandemic sexual decision-making.

Interactive communications technologies facilitate identity formation and socio-sexual connection among transgender and gender-diverse young people. However, within their communities, variations in technology use along ethno-racial, sexual and gendered lines, and as facilitators of sexual resilience during the early COVID-19 pandemic, remain under-studied. Among  = 230 transgender and gender-diverse young adults, surveyed between October 2020 and September 2021, latent class analyses characterised participants by preferred functional affordances, such as finding dates, sex and friends (Model 1), and by simultaneous account-keeping across social, dating and 'hookup' apps (Model 2).

Biomarkers in Prostate Cancer: A Review.

Background: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2.

Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages.

Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.

The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs.

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. To precisely engineer bnAb boosting immunogens, we used molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).