Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). We identified five immunodominant loops from the FadL orthologs TP0856, TP0858 and TP0865 by immunoblotting and ELISA.

Potassium bicarbonate, not sodium bicarbonate, maintains acidosis-mediated bone dissolution.

Treatments for metabolic acidosis are not well studied; however, one treatment that is commonly used is sodium bicarbonate administration. Sodium bicarbonate has been shown to help reduce symptoms of metabolic acidosis, but its benefits for bone health remain uncertain. Potassium bicarbonate has become a potential new treatment due to its reduction in bone resorption markers, unlike sodium bicarbonate.

Allostatic Load, Educational Attainment, and Risk of Cancer Mortality Among US Men.

Importance: Health disparities among racial and ethnic minoritized populations, particularly for cancer mortality rates, remain a major public health concern. Men from underrepresented backgrounds (Black and Hispanic men, specifically) face the pervasive effects of discrimination in their daily lives, which also contribute to the complex associations among allostatic load (a marker of chronic stress), educational opportunities, and elevated risks of cancer mortality.

Objective: To elucidate the associations among educational attainment, allostatic load, and cancer mortality risk among men.

Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects.

Lysine deacetylases (KDACs or HDACs) are metal-dependent enzymes that regulate lysine acetylation, a post-translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off-target binding, but the biological consequences of off-target binding were not evaluated.

Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure.

It is well established that humoral immunity targeting hepatitis B virus surface antigen (HBsAg) plays a critical role in viral clearance and clinical cure. However, the functional changes in HBsAg-specific B cells before and after achieving functional cure remain poorly understood. In this study, we characterized circulating HBsAg-specific B cells and identified functional shifts and B-cell epitopes directly associated with HBsAg loss.

Impact of Hepatitis B Virus Point-of-care DNA Viral Load Testing Compared With Laboratory-based Standard-of-care Approaches on Uptake of HBV Viral Load Testing, Treatment, and Turnaround Times: A Systematic Review and Meta-analysis.

Background: Point-of-care (PoC) hepatitis B virus (HBV) DNA viral load (VL) assays represent an alternative to laboratory-based standard-of-care (SoC) VL assays to accelerate diagnosis and treatment. We evaluated the impact of using PoC versus SoC approaches on the uptake of VL testing, treatment, and turnaround times from testing to treatment across the HBV care cascade.

Methods: We searched 5 databases, 6 conference websites, and contacted manufacturers for unpublished reports, for articles with or without a comparator (SoC VL testing), and had data on the uptake of VL testing, treatment, or turnaround times between hepatitis B surface antigen (HBsAg) testing, VL testing, and treatment in the cascade.

Testing Outlier Detection Algorithms for Identifying Early Stage Solute Clusters in Atom Probe Tomography.

Atom probe tomography (APT) is commonly used to study solute clustering and precipitation in materials. However, standard techniques used to identify and characterize clusters within atom probe data, such as the density-based spatial clustering applications with noise (DBSCAN), often underperform with respect to small clusters. This is a limitation of density-based cluster identification algorithms, due to their dependence on the parameter Nmin, an arbitrary lower limit placed on detectable cluster sizes.

Immunodominant extracellular loops of FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against (), we used thioredoxin (Trx) to display extracellular loops (ECLs) from three outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant.

Autoimmune Thyroid Disease: An Unusual Cause or Confounder of Vertigo.

Over the last decade, the published literature investigating the association between thyroid function and recurrent or persistent vertigo has become more robust. We present an interesting case of persistent vertigo in a healthy 31-year-old active duty Navy pilot who was restricted from operating single-pilot rotary aircraft because of the severity of her symptoms. During her work-up, she was newly diagnosed with autoimmune thyroid disease and started on thyroid hormone supplementation.

Pseudoephedrine for ejaculatory dysfunction after retroperitoneal lymph node dissection in testicular cancer.

Objective: To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment.

Patients And Methods: In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken.

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

Background: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations.

Atom Probe Tomography Investigation of Clustering in Model P2O5-Doped Borosilicate Glasses for Nuclear Waste Vitrification.

Atom probe tomography (APT) has been utilized to investigate the microstructure of two model borosilicate glasses designed to understand the solubility limits of phosphorous pentoxide (P2O5). This component is found in certain high-level radioactive defence wastes destined for vitrification, where phase separation can potentially lead to a number of issues relating to the processing of the glass and its long-term chemical and structural stability. The development of suitable focused ion beam (FIB)-preparation routes and APT analysis conditions were initially determined for the model glasses, before examining their detailed microstructures.

Associations between vicarious discrimination and mental health among young adult college students: Findings from the 2020-2021 Healthy Minds Study.

Background: Poor mental health among young adults in higher education is a growing concern. In recent years, the visibility of racism has sharply risen. Vicarious discrimination is defined as the secondhand witnessing of racism, and given society's increased accessibility to social media and the Internet, addressing indirect violence is urgently needed to inform anti-racism and mental health efforts.

Clinical Presentation of Early Syphilis and Genomic Sequences of Treponema pallidum Strains in Patient Specimens and Isolates Obtained by Rabbit Inoculation.

Background: The global resurgence of syphilis necessitates vaccine development.

Methods: We collected ulcer exudates and blood from 17 participants with primary syphilis (PS) and skin biopsies and blood from 51 patients with secondary syphilis (SS) in Guangzhou, China, for Treponema pallidum subsp pallidum (TPA) quantitative polymerase chain reaction, whole genome sequencing (WGS), and isolation of TPA in rabbits.

Results: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens.

Predictors of substance use disorder treatment and mutual support group participation among Black women across the criminal legal spectrum: A latent class approach.

Background: The purpose of this study includes: 1) identifying classes of substance-related needs among Black women, and 2) examining the effect of substance-related need classes and culturally-relevant factors on Black women's use of substance use disorder (SUD) treatment and mutual support groups.

Methods: As part of a longitudinal cohort study, Black women were recruited in prison nearing release, on probation, and in the community without involvement in the criminal legal system (CLS, n=565) and followed-up at 18-months. We conducted a baseline latent class analysis of substance-related needs among Black women.

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens.

Diverse and rapidly mutating viruses pose challenges to immunogen and vaccine design. In this study, we evaluated the ability of memory B-cells obtained from two independent NHP trials to cross-react with individual HIV-1 vaccine components of two different multivalent immunization strategies. We demonstrated that while an HIV-1 Env multiclade, multivalent immunization regimen resulted in a dominant memory B-cell response that converged toward shared epitopes, in a sequential immunization with clonally-related non-stabilized gp140 HIV-1 Envs followed by SOSIP-stabilized gp140 trimers, the change in immunogen format resulted in repriming of the B-cell response.

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer, who were germline BRCA1 and BRCA2 wild type. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery.

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.

Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing.

Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses.

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.

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation.

Physiochemical effects of acid exposure on bone composition and function.

Bone is primarily composed of collagen and apatite, two materials which exhibit a high sensitivity to pH dysregulation. As a result, acid exposure of bone, both clinically and in the laboratory is expected to cause compositional and mechanical changes to the tissue. Clinically, Metabolic acidosis (MA), a condition characterized by a reduced physiological pH, has been shown to have negative implications on bone health, including a decrease in bone mineral density and volume as well as increased fracture risk.