Integrated analysis of rectal mucosal microbiome and transcriptome reveals a distinct microenvironment among young MSM.

Crosstalk between the microbiome and gut mucosa-resident immune cells plays a pivotal role in modulating immune responses to pathogens, including responses to HIV infection. However, how these interactions may differ between young men who have sex with men (YMSM) disproportionately impacted by HIV, as compared with older adult MSM (AMSM), is not well understood. A broad analysis of associations between the microbiome and rectal transcriptome revealed 10 microbial families/genera correlated with immunologic gene pathways.

Using policy codesign to achieve multi-sector alignment in adolescent behavioral health: a study protocol.

Background: Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies.

Reaching and Re-Engaging People Living with HIV Who Are Out of Care: A Mixed-Methods Exploration of Patient Preferences for Strategies to Enhance Clinic Communication and Outreach.

Half of all people living with HIV (PLWH) in the United States are not retained in HIV medical care. The utility of appointment reminders and clinic-based retention support services is often limited by the inability to contact PLWH who are out of care (PLWH-OOC) due to disconnected phone lines, full voice mails, and housing instability. Between June 2019 and May 2021, as part of a larger mixed-methods study in Metro Atlanta, Georgia, we conducted surveys with 50 PLWH-OOC and interviews with 13 PLWH holding a variety of clinic stakeholder roles (patients, Community Advisory Board members, and peer navigators) to explore preferences for clinic communication and peer outreach and factors impacting uptake.

T-cell activation and B-cell interaction signatures in rectal tissues are associated with HIV replication in ex-vivo model of infection.

Objective: The rectal mucosa is a critical site of HIV vulnerability. We sought to identify transcriptomic features of rectal mucosal tissue prior to exposure associated with support or restriction of HIV replication.

Design: Rectal tissue from HIV-negative cis gender men ( n  = 57) underwent concurrent RNAseq transcriptomic analyses (two biopsies/participant) and challenge with HIV in the ex-vivo explant model of infection (three biopsies challenged/participant) as part of a larger cohort study to understand the rectal mucosal immune environment among MSM.

Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection.

Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally.

Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the effect of SARS-CoV-2 variants B.1.

Aberrant lung lipids cause respiratory impairment in a Mecp2-deficient mouse model of Rett syndrome.

Severe respiratory impairment is a prominent feature of Rett syndrome, an X-linked disorder caused by mutations in methyl CpG-binding protein 2 (MECP2). Despite MECP2's ubiquitous expression, respiratory anomalies are attributed to neuronal dysfunction. Here, we show that neutral lipids accumulate in mouse Mecp2-mutant lungs, whereas surfactant phospholipids decrease.

TP63 basal cells are indispensable during endoderm differentiation into proximal airway cells on acellular lung scaffolds.

The use of decellularized whole-organ scaffolds for bioengineering of organs is a promising avenue to circumvent the shortage of donor organs for transplantation. However, recellularization of acellular scaffolds from multicellular organs like the lung with a variety of different cell types remains a challenge. Multipotent cells could be an ideal cell source for recellularization.

Identification of RSV Fusion Protein Interaction Domains on the Virus Receptor, Nucleolin.

Nucleolin is an essential cellular receptor to human respiratory syncytial virus (RSV). Pharmacological targeting of the nucleolin RNA binding domain RBD1,2 can inhibit RSV infections in vitro and in vivo; however, the site(s) on RBD1,2 which interact with RSV are not known. We undertook a series of experiments designed to: document RSV-nucleolin co-localization on the surface of polarized MDCK cells using immunogold electron microscopy, to identify domains on nucleolin that physically interact with RSV using biochemical methods and determine their biological effects on RSV infection in vitro, and to carry out structural analysis toward informing future RSV drug development.

Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection.

Our understanding of innate immune responses in human rectal mucosal tissues (RM) and their contributions to promoting or restricting HIV transmission is limited. We defined the RM composition of innate and innate-like cell subsets, including plasmacytoid dendritic cells; CD1c + myeloid DCs; neutrophils; macrophages; natural killer cells (NK); Marginal Zone-like B cells (MZB); γδ T cells; and mucosal-associated invariant T cells in RM from 69 HIV-negative men by flow cytometry. Associations between these cell subsets and HIV-1 replication in ex vivo RM explant challenge experiments revealed an inverse correlation between RM-NK and p24 production, in contrast to a positive association between RM-MZB and HIV replication.

Author Correction: Distribution of Functional CD4 and CD8 T cell Subsets in Blood and Rectal Mucosal Tissues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Repeat adverse drug events associated with outpatient medications: a descriptive analysis of 3 observational studies in British Columbia, Canada.

Background: Adverse drug events are an important cause of preventable emergency department visits and hospital admissions. We examined repeat adverse drug events associated with outpatient medications resulting in acute care utilization.

Methods: This descriptive analysis combined data from 3 prospective multicentre observational studies, in which clinical pharmacists and physicians independently evaluated patients who visited the emergency department for adverse drug events in 3 hospitals in British Columbia.

Autophagy is required for lung development and morphogenesis.

Bronchopulmonary dysplasia (BPD) remains a major respiratory illness in extremely premature infants. The biological mechanisms leading to BPD are not fully understood, although an arrest in lung development has been implicated. The current study aimed to investigate the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation.

Distribution of Functional CD4 and CD8 T cell Subsets in Blood and Rectal Mucosal Tissues.

A better understanding of the distribution and functional capacity of CD4 T helper (Th) and CD8 T cytotoxic (Tc) cell subsets in the rectal mucosa (RM), a major site for HIV acquisition and replication, in adults is needed. In this study, we compared the distribution of Th and Tc cell subsets between blood and RM compartments in 62 HIV negative men, focusing primarily on IL-17-producing CD4 and CD8 T cells due to their importance in establishing and maintaining mucosal defenses, and examined associations between the frequencies of Th17 and Tc17 cell subsets and the availability of highly HIV-susceptible target cells in the RM. The RM exhibited a distinct immune cell composition comprised of higher frequencies of Th2, Th17, and Tc17 cells compared to the peripheral blood.

Human Immunodeficiency Virus in Transgender Persons.

Worldwide, transgender populations are disproportionately affected by human immunodeficiency virus (HIV). Pervasive stigma and discrimination impact social and economic determinants of health, which perpetuate HIV disparities among transgender individuals. This article reviews the prevalence of HIV infection among transgender populations and presents psychosocial, behavioral, and individual level factors that contribute to HIV acquisition.

Acid Sphingomyelinase Inhibition Attenuates Cell Death in Mechanically Ventilated Newborn Rat Lung.

Rationale: Premature infants subjected to mechanical ventilation (MV) are prone to lung injury that may result in bronchopulmonary dysplasia. MV causes epithelial cell death and halts alveolar development. The exact mechanism of MV-induced epithelial cell death is unknown.

Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor resulting in high rates of morbidity and mortality. A strategy to increase the efficacy of available drugs and enhance the delivery of chemotherapeutics through the blood brain barrier (BBB) is desperately needed. We investigated the potential of Cisplatin conjugated gold nanoparticle (GNP-UP-Cis) in combination with MR-guided Focused Ultrasound (MRgFUS) to intensify GBM treatment.

Patient Perceptions About Data Sharing & Privacy: Insights from ActionADE.

Information communication technologies (ICTs) may improve health delivery by enhancing informational continuity of care and enabling secondary use of health data including public health surveillance and research. ICTs also introduce concerns related to privacy. In this paper, we examine and address this tension in the context of the development and implementation of a novel platform that will enable the documentation and communication of patient-specific ADE information, titled ActionADE.

Lafora disease in miniature Wirehaired Dachshunds.

Lafora disease (LD) is an autosomal recessive late onset, progressive myoclonic epilepsy with a high prevalence in the miniature Wirehaired Dachshund. The disease is due to a mutation in the Epm2b gene which results in intracellular accumulation of abnormal glycogen (Lafora bodies). Recent breed-wide testing suggests that the carrier plus affected rate may be as high as 20%.

Lafora disease.

Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype-phenotype differences between the two. Founder effects and recurrent mutations are common, and mostly isolated to specific ethnic groups and/or geographical locations. Pathologically, LD is characterized by distinctive polyglucosans, which are formations of abnormal glycogen.