Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation.

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.

Cross-neutralization of distant coronaviruses correlates with Spike S2-specific antibodies from immunocompetent and immunocompromised vaccinated SARS-CoV-2-infected patients.

As of May 2023, the public health emergency of COVID-19 was lifted across the globe. However, SARS-CoV-2 infections continue to be recorded worldwide. This situation has been attributed to the ability of the virus to evade host immune responses including neutralizing antibody-derived Immunity.

A Systematic Review of 207 Studies Describing Validation Aspects of the Dermatology Life Quality Index.

This study systematically analysed peer-reviewed publications describing validation aspects of the Dermatology Life Quality Index (DLQI) and used Naicker's Critically Appraising for Antiracism Tool to assess risk of racial bias. Seven online databases were searched from 1994 until 2022 for articles containing DLQI validation data. Methodology followed PRISMA guidelines, the protocol was registered in PROSPERO, and articles reviewed independently by two assessors.

Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance.

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded.

Emerging SARS-CoV-2 Resistance After Antiviral Treatment.

Importance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood.

Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound.

Design, Setting, And Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023.

Pedigree-based analysis of population structure and genetic diversity in high-milch Vrindavani crossbred cattle of India.

The present study aimed to elucidate the population structure and genetic diversity along with the estimation of genealogical parameters in Vrindavani cattle using pedigree data. The study was based on pedigree data on 12,718 animals, spread across multiple generations during a 52-year period (between 1971 and 2023). The pedigree data was used to estimate different population genealogical parameters including the generation interval; pedigree completeness; rate and level of inbreeding; effective population size; and parameters characterizing the probabilities of gene origin.

The Dermatology Life Quality Index (DLQI) used as the benchmark in validation of 101 quality-of-life instruments: A systematic review.

Background: The validation of psychometric measures requires use of other established and standardized validated measures. The Dermatology Life Quality Index (DLQI) is the most widely used tool to measure the burden of skin diseases and assess effectiveness of interventions based on patients' perspective.

Objectives: The objective of this study was to systematically analyse peer-reviewed publications describing use of the DLQI in validation of other patient-reported outcome (PRO) and quality-of-life (QoL) measures.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact on Quality of Life (QoL) of Persons with ME/CFS.

: We previously reported on the impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the QoL of persons with ME/CFS and their family members. Here, we present the findings of the impact on the QoL of individuals with ME/CFS whose family members did not participate in the survey. : A prospective multinational online survey was disseminated via patient charities, support groups and social media.

Determining the Failure Rate of Direct Restorations-Chart Review versus Electronic Health Record Reports.

Amalgam and composite restorations are used to treat minor dental issues. University of Michigan, School of Dentistry Electronic Health Record (EHR) reports show a 2.31% failure rate for amalgam and 1.

Phenazine-1 carboxylic acid of induces the expression of Tet38 MDR efflux pump and mediates resistance to phenazines and antibiotics.

In this study, we showed that phenazine-1 carboxylic acid (PCA) of induced the expression of Tet38 efflux pump triggering resistance to tetracycline and phenazines. Exposure of RN6390 to supernatants of PA14 and its pyocyanin (PYO)-deficient mutants showed that non-PYO phenazines could induce the expression of Tet38 efflux pump. Direct exposure of RN6390 to PCA compound at 0.

Genotoxicity of Formaldehyde: Effect of Whole-Body Exposure on Polychromatic Erythrocyte/Normochromatic Erythrocyte Ratio in Male and Female Rats.

Every day, millions of individuals are exposed to formaldehyde (FA) due to its extensive presence and versatile use. Many in vivoand in vitroexperiments revealed that the mechanism of genotoxicity induced by FA exposure is complex yet toxicity upon whole-body exposure (WBE) to FA is less. As teachers, students, and skilled assistants in the health care sectors are also extensively exposed to FA vapors, it might result in genotoxicity.

Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.

Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo.

Blocking HXA-mediated neutrophil elastase release during lung infection limits pulmonary epithelial barrier disruption and bacteremia.

(), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread.

Host innate immune systems gather intel on invading microbes via pathogen-derived extracellular vesicles.

Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect them. As carriers of nucleic acids, proteins, lipids, metabolites, and virulence factors, EVs act as delivery vehicles for intercellular communication and quorum sensing. Innate immune cells have the capacity to intercept, internalize, and interpret 'messages' contained within these EVs.

Is it time to reduce the length of postgraduate training for physician-scientists in internal medicine?

Physician-scientists play a crucial role in advancing medical knowledge and patient care, yet the long periods of time required to complete training may impede expansion of this workforce. We examined the relationship between postgraduate training and time to receipt of NIH or Veterans Affairs career development awards (CDAs) for physician-scientists in internal medicine. Data from NIH RePORTER were analyzed for internal medicine residency graduates who received specific CDAs (K08, K23, K99, or IK2) in 2022.

BTK inhibitor-induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α.

Inhibition of Bruton's tyrosine kinase (BTK) through covalent modifications of its active site (e.g., ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies.

Polymeric Molecular Envelope Technology for Improved Therapeutics Efficacy: A Review.

The review explores the enhancement of therapeutic efficacy through the innovative use of polymeric molecular envelope technology (MET). It delves into the diverse methods employed to achieve superior therapeutic outcomes, shedding light on strategies for improving drug delivery and bioavailability. MET is a promising approach to improve the solubility and bioavailability of poorly water-soluble drugs.

Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses.

Population genetics continues to identify genetic variants associated with diseases of the immune system and offers a unique opportunity to discover mechanisms of immune regulation. Multiple genetic variants linked to severe fungal infections and autoimmunity are associated with caspase recruitment domain-containing protein 9 (CARD9). We leverage the CARD9 R101C missense variant to uncover a biochemical mechanism of CARD9 activation essential for antifungal responses.

AbcA transporter enhances persister formation under β-lactam exposure.

We evaluated the role of AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased.

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( < 0.

Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING.

The host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown.