mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

Exploring physiotherapy staff's perceptions of physiotherapy delivery in acute stroke rehabilitation.

Objective: To explore physiotherapists' perspectives on current and alternative models of physiotherapy delivery in acute stroke rehabilitation.

Design: Qualitative service evaluation.

Setting: An acute stroke rehabilitation unit within a London teaching hospital in the UK.

A mobile app for chronic disease self-management for individuals with low health literacy: A multisite randomized controlled clinical trial.

The purpose of this study was to evaluate the effects of a mobile app designed to improve chronic disease self-management in patients 40 years and older with low health literacy and who had at least one chronic health condition, and to assess the impact of delivering information at different levels of reading difficulty. A randomized controlled trial was completed at two sites. Individuals aged 40 years and older screened for low health literacy who had at least one chronic health condition were randomly assigned to a tailored information multimedia app with text at one of three grade levels.

Correction Factor Evaluation and Between-System Comparison of Behavioral Threshold Predictions From Auditory Brainstem Response Measures in Infants.

Purpose: Auditory brainstem response (ABR) thresholds are corrected to estimate behavioral thresholds in infants. Corrections were validated, and a comparison of behavioral threshold estimates between systems was conducted to inform equipment transition and protocols in Ontario, Canada.

Method: In Study 1, a retrospective file review was conducted.

Advancing Health Equity: A Collaborative Framework to Address HIV Disparities in Georgia and Louisiana through Data, Education, and Policy Initiatives.

The United States grapples with over 30,000 new HIV infections annually, a challenge exacerbated by delayed diagnosis and treatment. HIV stigma hinders data collection and contributes to health disparities. High-quality data and a community-driven approach are critical to reducing these disparities.

High level of genomic divergence in orf-I p12 and hbz genes of HTLV-1 subtype-C in Central Australia.

Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection remains a largely neglected public health problem, particularly in resource-poor areas with high burden of communicable and non-communicable diseases, such as some remote populations in Central Australia where an estimated 37% of adults are infected with HTLV-1. Most of our understanding of HTLV-1 infection comes from studies of the globally spread subtype-A (HTLV-1a), with few molecular studies reported with the Austral-Melanesian subtype-C (HTLV-1c) predominant in the Indo-Pacific and Oceania regions.

Results: Using a primer walking strategy and direct sequencing, we constructed HTLV-1c genomic consensus sequences from 22 First Nations participants living with HTLV-1c in Central Australia.

Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia.

Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26-32 Y) and older children (12-14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages.

CRISPR-Cas13b-mediated suppression of HBV replication and protein expression.

Background & Aims: New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression.

A mobile app providing individually-tailored psychoeducation about sleep for older adults with chronic health conditions and low health literacy.

Objective: This paper reports on a study of a mobile app that provides tailored information about sleep to individuals aged 40 and older who have chronic health conditions and low health literacy.

Methods: The sleep module was a part of a multitopic app focused on chronic disease self-management. Participants were randomly assigned to receive sleep psychoeducation at reading levels equivalent to 3, 6 or 8 grade.

Validation of 3- and 5-point severity scales to assess ARIA-E.

Introduction: Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) offer the promise of disease modification and are emerging treatment options in Alzheimer's disease. Anti-Aβ mAbs require brain magnetic resonance imaging (MRI) examinations to detect anti-amyloid-induced amyloid-related imaging abnormalities (ARIA), important adverse drug reactions associated with some anti-Aβ mAbs currently available in the United States and in clinical development. We present a simple rating system for ARIA-edema (ARIA-E) that can assess severity on a 3- or 5-point scale based upon a single linear measurement of the largest area of lesion, and dissemination in space, termed the 3-point Severity Scale of ARIA-E (SSAE-3) and the 5-point Severity Scale of ARIA-E (SSAE-5), respectively.

Use of Resonant Acoustic Mixing Technology for Ultra-Low-Dose Blending in a Single-Step Mixing Process.

Purpose: To evaluate the use of resonant acoustic mixing (RAM) technology for homogenous blending of a morphologically challenging model API in low-dose concentrations (<0.1% w/w), and assess the potential for blend uniformity (BU) optimization.

Methods: Caffeine (CAF) mixing was carried out using a LabRAM I benchtop mixer.

Validation of an integrated pressure level measured earmold wideband real-ear-to-coupler difference measurement.

Objective: To validate measurement of predicted earmold wideband real-ear-to-coupler difference (wRECD) using an integrated pressure level (IPL) calibrated transducer and the incorporation of an acoustically measured tubing length correction.

Design: Unilateral earmold SPL wRECD using varied hearing aid tubing length and the proposed predicted earmold IPL wRECD measurement procedure were completed on all participants and compared.

Study Sample: 22 normal hearing adults with normal middle ear status were recruited.

SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates.

The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-β signaling.

Woman-to-woman: Feasibility of a lay health advisor program for cervical cancer education in Grenada, W.I.

Objective: The aim of this study was to evaluate the impact of Woman- to-Woman, a lay health advisor (LHA)-led educational intervention on cervical cancer and human papillomavirus (HPV) knowledge in a cohort of at-risk Grenadian women.

Methods: LHAs from high-risk parishes were trained in the administration of the intervention and administered the program to 78 local women. Participants completed a pre- and post-knowledge test and a session evaluation.

e-Health Literacy Scale, Patient Attitudes, Medication Adherence, and Internal Locus of Control.

Background: Health literacy is related to a variety of health outcomes, including disease control, health-related quality of life, and risk for death. Few studies have investigated the relation of electronic health literacy (e-health literacy) to outcomes or the mechanism by which they may be related.

Methods: Secondary data were drawn from participants in a larger study on chronic disease self-management who were age 40 years and older, had at least one chronic health condition and a health literacy score of 8th grade or below on the validated short form of the Rapid Estimate of Adult Literacy in Medicine.

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.

Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines.

Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain.

Validity and reliability of integrated pressure level real-ear-to-coupler difference measurements.

Objectives: (1) To validate the measurement of foam-tip real-ear-to-coupler differences (wRECD) using an integrated pressure level (IPL) method and (2) to compare the reliability of this method to SPL-based measurement of the wRECD.

Design: SPL-based wRECD and the proposed IPL wRECD measurement were completed bilaterally. Test-retest reliability of IPL wRECD was determined with full re-insertion into the ear canal and compared to published SPL wRECD test-retest data.