Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.

Dysregulation of FURIN and Other Proprotein Convertase Genes in the Progression from HPV Infection to Cancer.

Productive infections of oncogenic human papillomaviruses (HPVs) are closely linked to the differentiation of host epithelial cells, a process that the virus manipulates to create conditions favorable to produce virion progeny. This viral interference involves altering the expression of numerous host genes. Among these, proprotein convertases (PCs) have emerged as potential oncogenes due to their central role in cellular functions.

Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility.

Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. Recent studies investigating antimicrobial susceptibility in mammalian cell culture media, a more host-mimicking environment, demonstrate that exposure to host factors significantly alters susceptibility profiles.

Antimicrobial Resistance in Curable Sexually Transmitted Infections.

Purpose Of Review: Antimicrobial resistance in sexually transmitted infections (STIs) has become an urgent global public health threat, raising the specter of untreatable infections. This review summarizes the determinants of resistance among the five most common curable STIs Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Treponema pallidum, and Trichomonas vaginalis, as well as strategies to mitigate the spread of resistance.

Recent Findings: Genetic mutations are key drivers of resistance for N.

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine.

Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.

Estimation and Characterization of Dengue Serotypes in Patients Presenting with Dengue Fever at Makkah Hospitals.

Dengue fever is caused by four common serotypes of the dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4). Patients infected with one serotype may develop lifelong serotype-specific protective immunity. However, they remain susceptible to reinfection with the other serotypes, often increasing the risk of severe forms of dengue.

Machine learning for antimicrobial peptide identification and design.

Artificial intelligence (AI) and machine learning (ML) models are being deployed in many domains of society and have recently reached the field of drug discovery. Given the increasing prevalence of antimicrobial resistance, as well as the challenges intrinsic to antibiotic development, there is an urgent need to accelerate the design of new antimicrobial therapies. Antimicrobial peptides (AMPs) are therapeutic agents for treating bacterial infections, but their translation into the clinic has been slow owing to toxicity, poor stability, limited cellular penetration and high cost, among other issues.

Comparison of immune responses to respiratory syncytial virus in infancy, childhood, and adulthood using an in vitro model of human respiratory infection.

Respiratory syncytial virus (RSV) is a major contributor to morbidity and mortality in infants. We developed an in vitro model of human respiratory infection to study cellular immune responses to RSV in infants, children, and adults. The model includes human lung epithelial A549 cells or human fetal lung fibroblasts infected with a clinical strain of RSV at a multiplicity of infection of 0.

Surveillance for variants escaping detection with the Aptima Combo 2 assay in Canada from 2019 to 2021.

Unlabelled: Nucleic acid amplification tests (NAATs) are the method of choice for diagnosis, but these strategies are susceptible to target site mutations. variants escaping detection with the Aptima Combo 2 (AC2) assay on the Hologic Panther instrument from 23S rRNA mutations have been reported in Nordic countries, England, Japan, and the United States. Given the potential for false negative results, this study investigated whether strains of with AC2 target site mutations were present in Canada.

Protective or limited? Maternal antibodies and RSV-associated lower respiratory tract infection in hospitalized infants aged 28-90 days.

Background: Respiratory syncytial virus (RSV) is a major cause of severe health problems in newborns and young children. The protective role and limitations of serum maternal RSV antibodies in infants under 3 months remain controversial.

Methods: A two-center prospective study from 2020 to 2023 recruited infants (n=286) admitted to the respiratory departments of two children's hospitals in southwestern and southeastern China during RSV epidemic.

Burden of pertussis in infants in the Eastern Mediterranean Region and the impact of maternal vaccination: a systematic review.

Background: Despite vaccine availability, Pertussis remains a global public health challenge, especially among infants. The Eastern Mediterranean Region (EMR) presents a diverse epidemiological landscape with varying vaccination coverages and healthcare infrastructures. This systematic review aimed to assess the burden of pertussis in infants < 1 year of age in the EMR and evaluate the use and impact of pertussis vaccination during pregnancy.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates.

Small and Versatile Cyclotides as Anti-infective Agents.

Plants provide an abundant source of potential therapeutic agents, including a diverse array of compounds, such as cyclotides, which are peptides known for their antimicrobial activity. Cyclotides are multifaceted molecules with a wide range of biological activities. Their unique topology forms a head-to-tail cyclic structure reinforced by a cysteine knot, which confers chemical and thermal stability.

Epigenetic and epitranscriptomic regulation during oncogenic -herpesvirus infection.

Oncogenic gamma herpesviruses, including Epstein-Barr Virus (EBV) and Kaposi's Sarcoma-associated Herpesvirus (KSHV), are opportunistic cancer-causing viruses and induces oncogenesis through complex mechanisms, which involves manipulation of cellular physiology as well as epigenetic and epitranscriptomic reprogramming. In this review, we describe the intricate processes by which these viruses interact with the epigenetic machinery, leading to alterations in DNA methylation, histone modifications, and the involvement of non-coding RNAs. The key viral proteins such as EBNA1 and LMP1 encoded by EBV; LANA and vGPCR encoded by KSHV; play pivotal roles in these modifications by interacting with host factors, and dysregulating signaling pathways.

Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.

Background: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.

Methods: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring©; 7.

Prospective Trial of a Passive Diversion Device to Reduce Blood Culture Contamination.

Background: Blood culture contaminants can lead to inappropriate antibiotic use, prolonged length of stay, and additional hospital costs. Several devices have been developed to reduce the risk of blood culture contamination by diverting a portion of the initial blood sample from the blood culture bottle. We assessed the effectiveness of 1 blood diversion device (BDD) in a prospective trial performed at the 2 separate emergency departments (EDs) of an academic medical center.

Increasing incidence of is driven by people living with HIV and PrEP users.

Background: (MG) is responsible for non-gonococcal urethritis. Our aim is to describe MG positivity rate and incidence in specific populations.

Methods: Retrospective, surveillance study included all samples collected from 2018 to 2022.

Exploring the effect of hsa-miR-19b-3p on IL-1R1 expression and serum levels in alopecia areata.

Alopecia areata (AA) is an autoimmune condition marked by hair loss, linked to inflammatory processes involving the interleukin-1 receptor type 1 (IL-1R1) pathway. This study aims to explore the relationship between IL-1R1 gene expression, serum IL-1R1 levels, and hsa-miR-19b-3p in relation to AA severity. Using a case-control design, we assessed 100 AA patients and 100 healthy controls, measuring serum IL-1R1 through enzyme-linked immunosorbent assay (ELISA) and analyzing IL-1R1 gene and hsa-miR-19b-3p expression levels via quantitative real-time PCR (qRT-PCR).

Toll-like receptor 2/6-stimulated HMC-1 mast cells promote keratinocyte migration in wound healing.

Mast cells, immune sentinels that respond to various stimuli in barrier organs, provide defense by expressing pattern recognition receptors, such as Toll-like receptors (TLRs). They may affect inflammatory responses and wound healing. Here, we investigated the effect of TLR2/6-stimulated mast cells on wound healing in keratinocytes.

Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis.

Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea.

Brain RNA profiling highlights multiple disease pathways in persons with HAND: uncovering determinants of biotype diversity.

Objective: To discover microRNA (miRNA)-RNA transcript interactions dysregulated in brains from persons with HIV-associated neurocognitive disorder (HAND), we investigated RNA expression using machine learning tools.

Design: Brain-derived host RNA transcript and miRNA expression was examined from persons with or without HAND using bioinformatics platforms.

Methods: By combining next generation sequencing, droplet digital (dd)PCR quantitation of HIV-1 genomes, with bioinformatics and statistical tools, we investigated differential RNA expression in frontal cortex from persons without HIV (HIV[-]), with HIV without brain disease (HIV[+]), with HIV-associated neurocognitive disorder (HAND), or HAND with encephalitis (HIVE).

Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation.

Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid.