Randomized controlled trial of a pilot PrEP linkage intervention for individuals leaving incarceration in a southern state: Design and baseline characteristics.

Objective: We report baseline characteristics of a pilot intervention, PrEP-Link, which uses a community health worker (CHW) model to provide navigation to PrEP, the daily HIV preventative medication, and other medical and social services upon release from incarceration.

Trial Design And Methods: This pilot study uses a randomized controlled trial design. The control group receives enhanced standard of care, and the intervention receives enhanced standard of care plus personalized navigation services from the CHW for up to one year.

Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population-based survey setting.

Introduction: The apolipoprotein E (APOE) ε4 allele carries risk for cognitive impairment, but whether the level of circulating apoE4 protein in carriers affects cognition is unclear, as is how health and lifestyle impact circulating apoE4 levels.

Methods: We assayed apoE4 protein levels in dried blood spots of 12,532 adults aged 50+. Regression analyses tested the likelihood of cognitive impairment between groups and within those with detected apoE4 protein.

Antigen specificities and proviral integration sites differ in HIV-infected cells by timing of antiretroviral treatment initiation.

Despite effective antiretroviral therapy (ART), persons living with HIV harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure. Initiation of ART during acute infection reduces the size of the HIV reservoir, and we hypothesized that in addition, it would favor integration of proviruses in HIV-specific CD4+ T cells, while initiation of ART during chronic HIV infection would favor relatively more proviruses in herpesvirus-specific cells. We further hypothesized that proviruses in acute ART initiators would be integrated into antiviral genes, whereas integration sites (ISs) in chronic ART initiators would favor genes associated with cell proliferation and exhaustion.

Optimizing a linear 'Doggybone' DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen.

Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase the breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realize their potential.

National and state-level trends in the availability of mental health treatment services tailored to individuals ordered to treatment by a court: United States, 2016, 2018, and 2020.

Purpose: We sought to identify trends and characteristics associated with the availability of tailored mental health services for individuals involved in the criminal justice system and ordered to treatment by a court, nationally in the US and by state.

Methods: We used National Mental Health Services Survey to identify outpatient mental health treatment facilities in the US (2016 n = 4744; 2018 n = 4626; 2020 n = 4869). We used clustered multiple logistic regression to identify changes over time as well as facility- and state-level factors associated with the availability of specialty court-ordered services.

Functional enhancement of mesothelin-targeted TRuC-T cells by a PD1-CD28 chimeric switch receptor.

T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. However, they are susceptible to suppression by the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis and lack intrinsic costimulatory signaling elements. To enhance the function of anti-MSLN TRuC-T cells, chimeric switch receptors (CSRs) have been designed to co-opt the immunosuppressive PD-1/PD-L1 axis and to deliver a CD28-mediated costimulatory signal.

Tibial Plateau and Stifle Joint Invasion with a Subcutaneous Mast Cell Tumor.

A 4 yr old female neutered Labrador retriever was referred with a history of left hind-limb lameness and an acute, nonpainful, subcutaneous mass on the medial aspect of the left stifle. Stifle radiographs and fine needle aspirates of the soft tissue mass performed by the referring veterinarian confirmed the presence of predominantly highly granulated mast cells, consistent with a mast cell tumor. Computed tomography demonstrated a soft tissue mass centered on the left medial stifle, with associated joint effusion and polyostotic lytic lesions on the tibial plateau and distal patella.

Successful treatment of perianal fistulas in two dogs with oclacitinib.

Perianal fistula (PAF) formation in dogs is a frustrating and painful disease, occurring primarily in German shepherd dogs. Ciclosporin has become the recommended treatment of choice yet may be associated with numerous adverse effects. This case report describes the successful treatment of two cases of PAF with oclacitinib.

The Restorative Integral Support (RIS) Model: Community-Based Integration of Trauma-Informed Approaches to Advance Equity and Resilience for Boys and Men of Color.

Mental health and health promotion research and practice have consistently revealed the social and structural inequities that boys and men of color (BMoC) face. Moreover, scholarship highlights the importance of gender, especially the concepts of masculinity and manhood, in understanding inequities that are experienced. Providers and community leaders are finding culturally relevant ways to foster healing and restoration while addressing racial trauma and the adverse community environments tied to adverse childhood experiences (ACEs).

Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors.

T cell Receptor (TCR) Fusion Construct (TRuC®) T cells harness all signaling subunits of the TCR to activate T cells and eliminate tumor cells, with minimal release of cytokines. While adoptive cell therapy with chimeric antigen receptor (CAR)-T cells has shown unprecedented clinical efficacy against B-cell malignancies, monotherapy with CAR-T cells has suboptimal clinical efficacy against solid tumors, probably because of the artificial signaling properties of the CAR. TRuC-T cells may address the suboptimal efficacy of existing CAR-T therapies for solid tumors.

The Long Arm of childhood hypothesis and systematic low-grade inflammation: Evidence from parental education of older European adults.

Childhood SES has been extensively studied as a predictor for health outcomes in adulthood, though the direct mechanisms remain unclear. The Long Arm of Childhood Model hypothesizes that this process is a chain of events, moderated by numerous factors such as family economic status and environment, health behaviors, as well as biological processes. We expand on this model with objective measures of health in older age, namely C-reactive protein (CRP), as chronic low grade inflammation, which has been found to be connected to both childhood SES as well as a number of cardiovascular diseases in adulthood.

Newfound features of meiotic chromosome organization that promote efficient congression and segregation in oocytes.

Although end-on microtubule-kinetochore attachments typically drive chromosome alignment, oocytes do not form these connections. Instead, microtubule bundles run laterally alongside chromosomes and a ring-shaped protein complex facilitates congression (the "ring complex", RC). Here, we report new aspects of RC and chromosome structure that are required for congression and segregation.

Barriers and facilitators to HIV care engagement: Recommendations from people with HIV in rural Arkansas.

Purpose: Little is known about factors affecting HIV care engagement and retention among rural people with HIV (PWH) in the South. About half of PWH in Arkansas reside in rural areas. The purpose of this study was to explore factors affecting engagement and retention in HIV care among PWH in rural areas of Arkansas.

SARS-CoV-2 Doggybone DNA Vaccine Produces Cross-Variant Neutralizing Antibodies and Is Protective in a COVID-19 Animal Model.

To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid vaccines have the advantage of rapid production, as they only require a viral antigen sequence and can readily be modified to detected viral mutations. Doggybone™ DNA vaccines targeting the spike protein of SARS-CoV-2 have been generated and compared with a traditionally manufactured, bacterially derived plasmid DNA vaccine that utilizes the same spike sequence.

Enzymatically amplified linear dbDNA as a rapid and scalable solution to industrial lentiviral vector manufacturing.

Traditional bacterial fermentation techniques used to manufacture plasmid are time-consuming, expensive, and inherently unstable. The production of sufficient GMP grade material thus imposes a major bottleneck on industrial-scale manufacturing of lentiviral vectors (LVV). Touchlight's linear doggybone DNA (dbDNA) is an enzymatically amplified DNA vector produced with exceptional speed through an in vitro dual enzyme process, enabling industrial-scale manufacturing of GMP material in a fraction of the time required for plasmid.

Response of Human Liver Tissue to Innate Immune Stimuli.

Precision-cut human liver slice cultures (PCLS) have become an important alternative immunological platform in preclinical testing. To further evaluate the capacity of PCLS, we investigated the innate immune response to TLR3 agonist (poly-I:C) and TLR4 agonist (LPS) using normal and diseased liver tissue. Pathological liver tissue was obtained from patients with active chronic HCV infection, and patients with former chronic HCV infection cured by recent Direct-Acting Antiviral (DAA) drug therapy.

Diagnosis and treatment impacts on wound care efficiency drivers: real-world analysis.

The prevalence and economic burden of wounds are growing. Any wound has the potential to become hard-to-heal and require frequent care. Clinicians need to find ways to absorb demand on services without compromising outcomes.

Methods for Rapid Protein Depletion in C. elegans using Auxin-Inducible Degradation.

Numerous methods have been developed in model systems to deplete or inactivate proteins to elucidate their functional roles. In Caenorhabditis elegans, a common method for protein depletion is RNA interference (RNAi), in which mRNA is targeted for degradation. C.

Myeloid-derived suppressor cells and their association with vaccine immunogenicity in South African infants.

The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year.

Functional responses of resident human T cells in intact liver tissue.

The liver contains a rich mix of T cells, including activated T cells, tissue-resident memory T cells and cells undergoing apoptosis. When antigens are presented in this milieu the default result is functional tolerance. T cell tolerance in the liver could be constitutive, or it could be adaptive, in which case liver cells would become unresponsive after encountering antigen in the liver context.

Human Liver Macrophage Subsets Defined by CD32.

Human liver myeloid cells are imperfectly defined, but it is broadly agreed that cells of stellate appearance , expressing the markers CD11b and CD68, are the liver's resident macrophages, classically termed Kupffer cells. Recent investigations using single cell RNA sequencing and unsupervised clustering algorithms suggest there are two populations of cells with the characteristics of tissue macrophages in human liver. We therefore analyzed dissociated human liver tissue using the markers CD11b and CD68 to define macrophage-like cells and found within this population two subsets that differ in their expression of multiple surface markers.

Barriers to linking high-risk jail detainees to HIV pre-exposure prophylaxis.

Individuals involved in the criminal justice (CJ) system continue to be at disproportionate risk for HIV infection, and often have a greater prevalence of substance use and sexual related risk behaviors relative to their non-CJ involved peers. Pre-exposure prophylaxis (PrEP), a once daily antiretroviral medicine, is an evidence-based approach for reducing the risk of contracting HIV but limited data exist regarding the use of PrEP among CJ populations, especially in the U.S.

Methyltransferase-like 21c methylates and stabilizes the heat shock protein Hspa8 in type I myofibers in mice.

Protein methyltransferases mediate posttranslational modifications of both histone and nonhistone proteins. Whereas histone methylation is well-known to regulate gene expression, the biological significance of nonhistone methylation is poorly understood. Methyltransferase-like 21c (Mettl21c) is a newly classified nonhistone lysine methyltransferase whose function has remained elusive.