Evaluation of intestinal biopsy tissue preservation methods to facilitate large-scale mucosal microbiota research.

Background: Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility.

Global deletion of the immune cell transcription factor, T-bet, alters gut microbiota and insulin sensitivity in mice.

The gut microbiota plays a role in energy homeostasis: its composition differs in lean and obese mice and may impact insulin sensitivity. The immune system has co-evolved with the gut microbiota, but direct regulation of microbial communities by the immune system and its metabolic impact is unclear. Mice lacking the immune cell specific transcription factor T-bet (Tbx21) are insulin sensitive.

The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade.

Functional analysis of G6PD variants associated with low G6PD activity in the All of Us Research Program.

The glucose-6-phosphate dehydrogenase (G6PD) enzyme protects red blood cells against oxidative damage. Individuals with G6PD-impairing polymorphisms are at risk of hemolytic anemia from oxidative stressors. Prevention of G6PD deficiency-related hemolytic anemia is achievable by identifying affected individuals through G6PD genetic testing.

CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner.

The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors, particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease and immune checkpoint colitis.

Evaluating protocols for reproducible targeted metabolomics by NMR.

Metabolomics aims to study the downstream effects of variables like diet, environment, or disease on a given biological system. However, inconsistencies in sample preparation, data acquisition/processing protocols lead to reproducibility and accuracy concerns. A systematic study was conducted to assess how sample preparation methods and data analysis platforms affect metabolite susceptibility.

A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19.

Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK.

Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic.

Factors influencing implementation and adoption of direct oral penicillin challenge for allergy delabelling: a qualitative evaluation.

Background: Over 95% of penicillin allergy labels are inaccurate and may be addressed in low-risk patients using direct oral penicillin challenge (DPC). This study explored the behaviour, attitudes and acceptability of patients, healthcare professionals (HCPs) and managers of using DPC in low-risk patients.

Methods: Mixed-method, investigation involving patient interviews and staff focus groups at three NHS acute hospitals.

A metabolic constraint in the kynurenine pathway drives mucosal inflammation in IBD.

Inflammatory bowel disease (IBD) is associated with perturbed metabolism of the essential amino acid tryptophan (Trp). Whether increased degradation of Trp directly fuels mucosal inflammation or acts as a compensatory attempt to restore cellular energy levels via nicotinamide adenine dinucleotide (NAD ) synthesis is not understood. Employing a systems medicine approach on longitudinal IBD therapy intervention cohorts and targeted screening in preclinical IBD models, we discover that steady increases in Trp levels upon therapy success coincide with a rewiring of metabolic processes within the kynurenine pathway (KP).

Investigating cocaine- and abstinence-induced effects on astrocyte gene expression in the nucleus accumbens.

In recent years, astrocytes have been increasingly implicated in cellular mechanisms of substance use disorders (SUD). Astrocytes are structurally altered following exposure to drugs of abuse; specifically, astrocytes within the nucleus accumbens (NAc) exhibit significantly decreased surface area, volume, and synaptic colocalization after operant self-administration of cocaine and extinction or protracted abstinence (45 days). However, the mechanisms that elicit these morphological modifications are unknown.

Co-creating community wellbeing initiatives: what is the evidence and how do they work?

Background: Addressing wellbeing at the community level, using a public health approach may build wellbeing and protective factors for all. A collaborative, community-owned approach can bring together experience, networks, local knowledge, and other resources to form a locally-driven, place-based initiative that can address complex issues effectively. Research on community empowerment, coalition functioning, health interventions and the use of local data provide evidence about what can be achieved in communities.

Activation of the interleukin-23/Th17 axis in major depression: a systematic review and meta-analysis.

The interleukin-23/Th17 axis is a promising modifiable target for depression. However, its association with depression has not been systematically evaluated. We systematically searched four databases (EMBASE, Web of Science, Pubmed and PsycINFO) for studies comparing patients with major depression and healthy controls for plasma/serum levels of Th17 cells and their canonical cytokines (interleukin-17A [IL-17A], IL-22, granulocyte macrophage colony stimulating factor [GM-CSF]).

CDC Prioritizes HIV Prevention and Treatment to Reduce HIV Disparities Among Cis-Gender Black Women.

To succeed in ending the HIV epidemic in the United States, the Centers for Disease Control and Prevention (CDC) focuses on delivering combinations of scientifically proven, cost-effective, and scalable interventions to priority populations. Systemic factors continue to contribute to persistent health disparities and disproportionately higher rates of HIV diagnosis in some communities. The National HIV/AIDS Strategy has designated cis-gender Black women (CgBW) as a priority population to address the racial and ethnic inequities in HIV.

The appropriateness of penicillin allergy de-labelling by non-allergist clinical ward teams.

Objectives: We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin.

Methods: Opportunistic, prospective observational study of usual clinical care, between 16 May 2023 and 14 August 2023, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history.

Cultivating a Meaningful Application of IMFs through Backward Laboratory Course Design.

This paper describes the development of a first- and second-year inquiry-based laboratory course focused on the development of a meaningful application of intermolecular forces (IMFs). Instead of broad expository coverage of topics, we used backward design: the techniques and concepts for the course were structured around what students are expected to be able to do at the end-individually isolate caffeine from a consumer product as a culminating lab practical, using IMFs to justify solvent choices and determining procedural details. We have found that instructors can select a challenging multilevel experiment that incorporates the application of IMFs in multiple ways and backward design the course so that students are able to complete this experiment individually and autonomously at the end of the semester.

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension.

Background: Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen () messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases transcription.

Developmental maturation of millimeter-scale functional networks across brain areas.

Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others.

Eliciting the barriers and enablers towards anaesthetists giving penicillin-based antibiotic prophylaxis to low-risk patients who have had their penicillin allergy label removed as part of a preoperative delabelling process.

Background: Some penicillin allergy labels can be removed by non-allergy specialists by direct oral challenge, but there is reluctance amongst anaesthetists to give penicillin to these patients. We aimed to assess anaesthetist beliefs about giving penicillin to patients delabelled by direct oral challenge.

Methods: A survey, developed using the Theoretical Domains Framework, was circulated to anaesthetists within a regional research network in England.

Functional Analysis of G6PD Variants Associated With Low G6PD Activity in the All of Us Research Program.

Glucose-6-phosphate dehydrogenase (G6PD) protects red blood cells against oxidative damage through regeneration of NADPH. Individuals with polymorphisms (variants) that produce an impaired G6PD enzyme are usually asymptomatic, but at risk of hemolytic anemia from oxidative stressors, including certain drugs and foods. Prevention of G6PD deficiency-related hemolytic anemia is achievable through genetic testing or whole-genome sequencing (WGS) to identify affected individuals who should avoid hemolytic triggers.

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

Introduction: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%.