Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.

The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.

spp. in neonatal sepsis: an urgent global threat.

Neonatal sepsis causes substantial morbidity and mortality, the burden of which is carried by low-income countries (LICs). The emergence of multidrug-resistant pathogens in vulnerable neonatal populations poses an urgent threat to infant survival. spp.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment.

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics.

Treatment options for Achilles tendinopathy: a scoping review of preclinical studies.

Background: Achilles tendinopathy (AT) management can be difficult, given the paucity of effective treatment options and the degenerative nature of the condition. Innovative therapies for Achilles tendinopathy are therefore direly needed. New therapeutic developments predominantly begin with preclinical animal and in vitro studies to understand the effects at the molecular level and to evaluate toxicity.

E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.

The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.

Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple P. falciparum isolates.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

A qualitative exploration of the enablers of and barriers to conformance with antibiotic withdrawal periods on smallholding, peri-urban pig farms in Kiambu County, Kenya.

Non-conformance with antibiotic withdrawal period guidelines represents a food safety concern, with potential for antibiotic toxicities and allergic reactions as well as selecting for antibiotic resistance. In the Kenyan domestic pig market, conformance with antibiotic withdrawal periods is not a requirement of government legislation and evidence suggests that antibiotic residues may frequently be above recommended limits. In this study, we sought to explore enablers of and barriers to conformance with antibiotic withdrawal periods for pig farms supplying a local independent abattoir in peri-urban Nairobi.

Exosome-Mediated Lectin Pathway and Resistin-MIF-AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody-mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high-throughput data, except for the belated emergence of autoreactive antibodies.

Prognostic value of tumor-infiltrating lymphocyte subtypes and microorganisms in triple-negative breast cancer.

Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results.

The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT.

Complete genome sequence of B273 and its epidermicin NI01 biosynthesis plasmid.

The human skin commensal produces diverse, therapeutically relevant bacteriocins. We report the complete whole-genome sequence of the nasal isolate B273, which contains a plasmid with the biosynthetic gene cluster for epidermicin NI01, a broad-spectrum type II antimicrobial peptide.

Microbe Profile: Typhimurium: the master of the art of adaptation.

Typhimurium is a major serovar that is found globally. It is responsible for outbreaks of self-limiting gastroenteritis that are broadly linked to the industrialization of food production. .

Changes in pressure distribution of the solar surface after a single trimming event are associated with external hoof measurements in the equine fore foot.

Background: Trimming is critical for a functioning equine hoof. Pressure distribution provides information on loading; however, information on the effects of trimming on pressure distribution is lacking.

Objectives: To describe the pressure changes of equine fore feet following trimming.

Predicting the effect of landscape structure on epidemic invasion using an analytical estimate for infection rate.

The influence of landscape structure on epidemic invasion of agricultural crops is often underestimated in the construction and analysis of epidemiological models. Computer simulations of individual-based models (IBMs) are widely used to characterize disease spread under different management scenarios but can be slow in exploring large numbers of different landscape configurations. Here, we address the problem of finding an analytical measure of the impact of the spatial structure of a crop landscape on the invasion and spread of plant pathogens.

Impact of normocapnia vs. mild hypercapnia on prognosis after cardiac arrest: A systematic review and meta-analysis.

Objective: To explore the impact of mild hypercapnia or normocapnia on the prognosis of patients after the return of spontaneous circulation (ROSC) following cardiac arrest (CA).

Methods: This systematic review and meta-analysis followed the guidelines in the PROSPERO report. Information was retrieved in PubMed, Cochrane Library, Embase, and Web of Science to collect all publications in English from January 1, 2000, to March 1, 2024, involving post-CA with mild hypercapnia.

Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK.

Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes.

Inflammation and response to bacterial infection as potential drivers of equine odontoclastic tooth resorption and hypercementosis: A proteomics insight.

Background: Equine dental diseases significantly impact a horse's overall health, performance and quality of life. They can result in secondary infections and digestive disturbances, potentially leading to colic. A recently described disease affecting the incisors of horses is equine odontoclastic tooth resorption and hypercementosis (EOTRH).

Identification and characterisation of temporal abundance of microRNAs in synovial fluid from an experimental equine model of osteoarthritis.

Background: MicroRNAs, a class of small noncoding RNAs, serve as post-transcriptional regulators of gene expression and are present in a stable and quantifiable form in biological fluids. MicroRNAs may influence intra-articular responses and the course of disease, but very little is known about their temporal changes in osteoarthritis.

Objectives: To identify miRNAs and characterise the temporal changes in their abundance in SF from horses with experimentally induced osteoarthritis.

Phlorotannin-Rich Seaweed Extract Inhibits Influenza Infection.

Seaweed-derived compounds are a renewable resource utilised in the manufacturing and food industry. This study focuses on an enriched seaweed extract (ESE) isolated from The ESE was screened for antiviral activity by plaque reduction assays against influenza A/Puerto Rico/8/1934 H1N1 (PR8), A/X-31 H3N2 (X31) and A/England/195/2009 H1N1 (Eng195), resulting in the complete inhibition of infection. Time of addition assays and FACS analysis were used to help determine the modes of action.

Assessment of Favipiravir and Remdesivir in Combination for SARS-CoV-2 Infection in Syrian Golden Hamsters.

Favipiravir (FVP) and remdesivir (RDV) have demonstrable antiviral activity against SARS-CoV-2. Here, the efficacy of FVP, RDV, and FVP with RDV (FVP + RDV) in combination was assessed in Syrian golden hamsters challenged with SARS-CoV- 2 (B.1.

Respiratory Flora Intervention: A New Strategy for the Prevention and Treatment of Occupationally Related Respiratory Allergy in Healthcare Workers.

Occupational allergic respiratory disease in healthcare workers due to occupational exposure has received widespread attention. At the same time, evidence of altered respiratory flora associated with the development of allergy has been found in relevant epidemiologic studies. It is of concern that the composition of nasopharyngeal flora in healthcare workers differs significantly from that of non-healthcare workers due to occupational factors, with a particularly high prevalence of carriage of pathogenic and drug-resistant bacteria.

Separating Infectious Proctitis from Inflammatory Bowel Disease-A Common Clinical Conundrum.

Proctitis refers to inflammation in the rectum and may result in rectal bleeding, discharge, urgency, tenesmus, and lower abdominal pain. It is a common presentation, particularly in genitourinary medicine and gastroenterology, as the two most common causes are sexually transmitted infections and inflammatory bowel disease. The incidence of infective proctitis is rising, particularly amongst high-risk groups, including men who have sex with men, those with HIV seropositive status, and those participating in high-risk sexual behaviours.