Application and interpretation of core elements of the 2015 NMOSD diagnostic criteria in routine clinical practice.

Background: We evaluated comprehension and application of the 2015 neuromyelitis optica spectrum disorder (NMOSD) criteria core elements by neurologists in Latin America (LATAM) who routinely diagnose and care for NMOSD patients by (i) identifying typical/suggestive NMOSD syndromes, (ii) detecting typical MRI NMOSD lesions and meeting MRI dissemination in space (DIS) criteria, and (iii) evaluating historical symptoms suggestive of NMOSD.

Methods: We conducted an anonymous, voluntary, self-administered web- and case-based survey cross-sectional study from October 2023 to January 2024 of neurologists identified through the LACTRIMS database. Questions were presented first through iterative clinical cases or imaging, followed by questions directly evaluating comprehension of definitions.

The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits H-ATPases in Target Pathogens.

Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H-ATPases. This protein includes an ancestral structural motif (i.e.

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis.

Background: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data.

Integrated transcriptomic analysis reveals immune signatures distinguishing persistent versus resolving outcomes in MRSA bacteremia.

Introduction: bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs.

Tensor modeling of MRSA bacteremia cytokine and transcriptional patterns reveals coordinated, outcome-associated immunological programs.

Methicillin-resistant (MRSA) bacteremia is a common and life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy determined by minimum inhibitory concentration breakpoints, antibiotics often fail to resolve these infections in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified.

Anti-aquaporin-4 immune complex stimulates complement-dependent Th17 cytokine release in neuromyelitis optica spectrum disorders.

Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear.

The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.

Background: Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates.

Methods: Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

Background And Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD.

Use of Transcriptional Signatures to Differentiate Pathogen-Specific and Treatment-Specific Host Responses in Patients With Bacterial Bloodstream Infections.

Background: Clinical outcomes in bacterial bloodstream infections (BSIs) are influenced by bacterial species, host immunity, and antibiotic therapy. The mechanisms by which such factors influence outcomes are poorly understood. We aimed to identify bacterial- and antibiotic-specific host transcriptional signatures in patients with bacterial BSI.

Diflunisal and Analogue Pharmacophores Mediating Suppression of Virulence Phenotypes in .

Invasive methicillin-resistant (MRSA) infections are leading causes of morbidity and mortality that are complicated by increasing resistance to conventional antibiotics. Thus, minimizing virulence and enhancing antibiotic efficacy against MRSA is a public health imperative. We originally demonstrated that diflunisal (DIF; [2-hydroxy-5-(2,4-difluorophenyl) benzoic acid]) inhibits virulence factor expression.

Diflunisal Attenuates Virulence Factor Gene Regulation and Phenotypes in .

Virulence factor expression is integral to pathogenicity of . We previously demonstrated that aspirin, through its major metabolite, salicylic acid (SAL), modulates virulence phenotypes in vitro and in vivo. We compared salicylate metabolites and a structural analogue for their ability to modulate virulence factor expression and phenotypes: (i) acetylsalicylic acid (ASA, aspirin); (ii) ASA metabolites, salicylic acid (SAL), gentisic acid (GTA) and salicyluric acid (SUA); or (iii) diflunisal (DIF), a SAL structural analogue.

Longitudinal analysis of SARS-CoV-2 infection and vaccination in the LA-SPARTA cohort reveals increased risk of infection in vaccinated Hispanic participants.

Introduction: SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19). Questions remain regarding correlates of risk and immune protection against COVID-19.

Methods: We prospectively enrolled 200 participants with a high risk of SARS-CoV-2 occupational exposure at a U.

Tensor-based insights into systems immunity and infectious disease.

Profiling immune responses across several dimensions, including time, patients, molecular features, and tissue sites, can deepen our understanding of immunity as an integrated system. These studies require new analytical approaches to realize their full potential. We highlight recent applications of tensor methods and discuss several future opportunities.

adaptive evolution: Recent insights on how immune evasion, immunometabolic subversion and host genetics impact vaccine development.

Despite meritorious attempts, a vaccine that prevents infection or mitigates severity has not yet achieved efficacy endpoints in prospective, randomized clinical trials. This experience underscores the complexity of host- interactions, which appear to be greater than many other bacterial pathogens against which successful vaccines have been developed. It is increasingly evident that employs strategic countermeasures to evade or exploit human immune responses.