Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Characterization of Human CD8αβ Interaction With Classical and Unconventional MHC Molecules.

The CD8 co-receptor exists as both an αα homodimer, expressed on subsets of specialized lymphoid cells, and as an αβ heterodimer, which is the canonical co-receptor on cytotoxic T-cells, tuning TCR thymic selection and antigen-reactivity in the periphery. However, the biophysical parameters governing human CD8αβ interactions with classical MHC class I (MHCI) and unconventional MHC-like molecules have not been determined. Using hetero-dimerized Fc-fusions to generate soluble human CD8αβ, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8αα.

Maintenance oral steroids are not required in severe asthma.

https://bit.ly/4cgrJEL.

IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease.

Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33, IL-33 and IL-33/sST2 complexes in samples from patients hospitalised with COVID-19.

Urine and serum-based ELISA using a recombinant protein and synthetic peptide for the diagnosis of tegumentary leishmaniasis.

The diagnosis of tegumentary leishmaniasis (TL) presents problems by the variable sensitivity and specificity of the tests, and the biological samples used are also invasive. Here, ELISA experiments were performed using paired TL patient urine and serum samples in reaction against the recombinant LiHyS protein, a predicted B cell epitope and parasite antigenic extract (SLA). Two hundred and five paired samples were used, which were provided by TL patients, healthy controls and patients with Chagas disease, leprosy, malaria or HIV-infected.

Zoonotic and other veterinary chlamydiae - an update, the role of the plasmid and plasmid-mediated transformation.

The obligate intracellular bacterial genus Chlamydia harbours species with zoonotic potential, particularly C. psittaci, causative agent of psittacosis, and C. abortus, which may lead to miscarriage in pregnant women.

Uplift of genetic diagnosis of rare respiratory disease using airway epithelium transcriptome analysis.

Rare genetic respiratory disease has an incidence rate of more than 1:2500 live births in Northern Europe and carries significant disease burden. Early diagnosis improves outcomes, but many individuals remain without a confident genetic diagnosis. Improved and expanded molecular testing methods are required to improve genetic diagnosis rates and thereby improve clinical outcomes.

Recent advances in the influenza virus vaccine landscape: a comprehensive overview of technologies and trials.

SUMMARYIn the United Kingdom (UK) in 2022/23, influenza virus infections returned to the levels recorded before the COVID-19 pandemic, exerting a substantial burden on an already stretched National Health Service (NHS) through increased primary and emergency care visits and subsequent hospitalizations. Population groups ≤4 years and ≥65 years of age, and those with underlying health conditions, are at the greatest risk of influenza-related hospitalization. Recent advances in influenza virus vaccine technologies may help to mitigate this burden.

Real-world performance of a single-use, analyser-free, molecular point-of-care test for COVID-19 used in the emergency department: Results of a prospective trial (ED-POC).

Background: A novel single-use, analyser-free, molecular point-of-care test for SARS-CoV-2 (Veros COVID-19 test, Sherlock Biosciences) could reduce time to results and improve patient care and flow in the emergency department (ED), but its performance in this setting is unknown.

Methods: Adults aged ≥18 years presenting to Southampton General Hospital (UK) with suspected COVID-19 were tested with the Veros COVID-19 test in addition to standard of care near-patient PCR. Measures of diagnostic accuracy were calculated for the Veros COVID-19 test stratified by Ct value.

Antimicrobial activity of compounds identified by artificial intelligence discovery engine targeting enzymes involved in Neisseria gonorrhoeae peptidoglycan metabolism.

Background: Neisseria gonorrhoeae (Ng) causes the sexually transmitted disease gonorrhoea. There are no vaccines and infections are treated principally with antibiotics. However, gonococci rapidly develop resistance to every antibiotic class used and there is a need for developing new antimicrobial treatments.

Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products.

NK Cells in the Lymph Nodes and Their Role in Anti-Tumour Immunity.

The lymph nodes are vital to enable adaptive immune responses to infection. Natural killer (NK) cells are cytotoxic lymphocytes that directly kill cancer cells and modulate the activation of other immune cells during anti-tumour immune response. NK cells in the lymph nodes are involved in the regulation of T-cell and B-cell populations and the clearance of viral infections.

The nuclear export protein XPO1 provides a peptide ligand for natural killer cells.

XPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells.

Microbiome alterations are associated with apolipoprotein E mutation in and humans with Alzheimer's disease.

Gut microbiome dysbiosis is linked to many neurological disorders including Alzheimer's disease (AD). A major risk factor for AD is polymorphism in the apolipoprotein E () gene, which affects gut microbiome composition. To explore the gut-brain axis in AD, long-lived animal models of naturally developing AD-like pathologies are needed.

Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.

Post-tuberculosis (post-TB) lung disease is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to post-TB lung disease are not well understood, thus limiting the development of therapeutic interventions to improve long-term outcomes after TB. This report summarizes the work of the Pathogenesis and Risk Factors Committee for the Second International Post-Tuberculosis Symposium, which took place in Stellenbosch, South Africa, in April 2023.

Qualitative evaluation of a molecular point-of-care testing study for influenza in UK primary care.

Background: Influenza contributes to the surge in winter infections and the consequent winter pressures on the health service. Molecular point-of-care testing (POCT) for influenza may improve patient management by providing rapid and accurate clinical diagnosis to inform the timely initiation of antiviral therapy and reduce unnecessary admissions and antibiotics use.

Aim: To explore factors that influence the adoption or non-adoption of POCT in English general practices and provide insights to enable its integration into routine practice workflows.

Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans.

To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4 and CD8 T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients.

Standards for the care of people with cystic fibrosis (CF); Planning for a longer life.

This is the final of four papers updating standards for the care of people with CF. That this paper "Planning a longer life" was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy.

Clearing the air: Assessing healthcare professionals' awareness of air pollution's health consequences.

Air pollution (AP) significantly jeopardises health, with the Royal College of Physicians accepting the adverse effects of AP are not being sufficiently communicated to patients by healthcare professionals (HCP). To explore HCPs' understanding and attitudes toward AP and its health impacts, we conducted a service evaluation survey in a group of hospital doctors. A questionnaire comprising 20 questions about AP and its health associations was completed by 133 hospital doctors working at University Hospital Southampton NHS Foundation Trust, UK.

B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles.

B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease.