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.

Diagnosis and treatment of a biliary fistula to walled-off pancreatic necrosis.

Video 1Visualization and treatment of a biliary fistula into a walled-off pancreatic necrosis collection.

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice.

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated by the stomach hormone, ghrelin.

Bi-directional signaling between the intestinal epithelium and type-3 innate lymphoid cells regulates secretory dynamics and interleukin-22.

Type-3 innate lymphoid cells (ILC3) respond to localized environmental cues to regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator and downstream target of ILC3 signaling, however, the complexity of mucosal tissues can hinder efforts to define specific interactions between these two compartments. Here, we employ a reductionist co-culture system of murine epithelial small intestinal organoids (SIO) with ILC3 to uncover bi-directional signaling mechanisms that underlie intestinal homeostasis.

Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3.

Innate lymphoid cells (ILCs) are tissue-resident effector cells with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) are classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type 3 effector modules that exhibit significant ontological, transcriptional, phenotypic, and functional heterogeneity.

Trainee autonomy and surgical outcomes after emergency gastrointestinal surgery.

Background: Operative meaningful trainee autonomy is an essential component of surgical training. Reduced trainee autonomy is frequently attributed to patient safety concerns, but this has not been examined within Kenya. We aimed to assess whether meaningful trainee autonomy was associated with a change in patient outcomes.

The importance of SNOMED CT concept specificity in healthcare analytics.

Background: Healthcare data frequently lack the specificity level needed to achieve clinical and operational objectives such as optimising bed management. Pneumonia is a disease of importance as it accounts for more bed days than any other lung disease and has a varied aetiology. The condition has a range of SNOMED CT concepts with different levels of specificity.

Data quality and autism: Issues and potential impacts.

Introduction: Large healthcare datasets can provide insight that has the potential to improve outcomes for patients. However, it is important to understand the strengths and limitations of such datasets so that the insights they provide are accurate and useful. The aim of this study was to identify data inconsistencies within the Hospital Episodes Statistics (HES) dataset for autistic patients and assess potential biases introduced through these inconsistencies and their impact on patient outcomes.

Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.

Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration.

Comorbidities Matter as Distressed Communities Index Fails to Predict Mortality in Necrotizing Soft Tissue Infection.

Necrotizing soft tissue infections (NSTIs) are life-threatening infections requiring prompt intervention. The Distressed Communities Index (DCI) is a comprehensive ranking of socioeconomic well-being based on zip code. We sought to identify the role of DCI in predicting mortality in NSTI, because it remains unknown.

Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease.

The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson's disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival.

Organoids capture tissue-specific innate lymphoid cell development in mice and humans.

Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, murine intestinal and pulmonary organoids are harnessed to demonstrate that the epithelial niche is sufficient to drive tissue-specific maturation of all innate lymphoid cell (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex human induced pluripotent stem cell (hiPSC)-based gut and lung organoid models are used to demonstrate that human epithelial cells recapitulate maturation of ILC from a stringent systemic human ILCP population, but only when the organoid-associated stromal cells are depleted.

Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis.

Objective: Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium-glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies.

Research Design And Methods: Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.

Helper-Like Type-1 Innate Lymphoid Cells in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic condition characterized by chronic relapsing inflammation in the intestine. While the precise etiology of IBD remains unknown, genetics, the gut microbiome, environmental factors, and the immune system have all been shown to contribute to the disease pathophysiology. In recent years, attention has shifted towards the role that innate lymphoid cells (ILCs) may play in the dysregulation of intestinal immunity observed in IBD.

Differential Regulation of Allergic Airway Inflammation by Acetylcholine.

Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus , and immune responses in the airways and lung tissues were analyzed.

Cyclin-dependent Kinase 9 as a Potential Target for Anti-TNF-resistant Inflammatory Bowel Disease.

Background & Aims: Resistance to single cytokine blockade, namely anti-tumor necrosis factor (TNF) therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines interferon (IFN)-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically.

Safety and effectiveness of appropriately and inappropriately dosed rivaroxaban or apixaban versus warfarin in patients with atrial fibrillation: a cohort study with nested case-control analyses from UK primary care.

Objectives: To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF).

Design: Cohort study with nested case-control analyses using primary care electronic health records (IQVIA Medical Research Data UK database).

Setting: UK primary care.

Acute pain assessments and records: a pilot study of digital transformation.

Background: Pain is a leading cause of disability worldwide. Pain assessments are an essential part of evidence-based care and management. Among comparable care providers, there is variation in how nurses document assessments as well as the content in them, and there is a notable associated administrative burden.

Heartbreakers or Healers? Innate Lymphoid Cells in Cardiovascular Disease and Obesity.

Cardiovascular diseases (CVDs) are responsible for most pre-mature deaths worldwide, contributing significantly to the global burden of disease and its associated costs to individuals and healthcare systems. Obesity and associated metabolic inflammation underlie development of several major health conditions which act as direct risk factors for development of CVDs. Immune system responses contribute greatly to CVD development and progression, as well as disease resolution.