Age-related patterns of microbial dysbiosis in multiplex inflammatory bowel disease families.

Objective: IBD is characterised by dysbiosis, but it remains unclear to what extent dysbiosis develops in unaffected at-risk individuals. To address this, we investigated age-related patterns of faecal and serum markers of dysbiosis in high-risk multiplex IBD families (two or more affected first-degree relatives).

Design: Faecal and serum samples were collected from multiplex IBD and control families (95 IBD, 292 unaffected, 51 controls).

Sync fast and solve things-best practices for responsible digital health.

Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation.

Talking Ethics Early in Health Data Public Private Partnerships.

Data access and data sharing are vital to advance medicine. A growing number of public private partnerships are set up to facilitate data access and sharing, as private and public actors possess highly complementary health data sets and treatment development resources. However, the priorities and incentives of public and private organizations are frequently in conflict.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

Objective: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in ().

Design: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed.

Stuck in translation: Stakeholder perspectives on impediments to responsible digital health.

Spurred by recent advances in machine learning and electronic hardware, digital health promises to profoundly transform medicine. At the same time, however, it raises conspicuous ethical and regulatory issues. This has led to a growing number of calls for responsible digital health.

Beyond high hopes: A scoping review of the 2019-2021 scientific discourse on machine learning in medical imaging.

Machine learning has become a key driver of the digital health revolution. That comes with a fair share of high hopes and hype. We conducted a scoping review on machine learning in medical imaging, providing a comprehensive outlook of the field's potential, limitations, and future directions.

"Before I was like a Tarzan. But now, I take a pause": mixed methods feasibility study of the Naungan Kasih parenting program to prevent violence against children in Malaysia.

Background: Despite impressive strides in health, social protection, and education, children continue to experience high rates of child maltreatment in Malaysia. This mixed-methods study assessed the feasibility of a five-session, social learning-based parenting program delivered by government staff in a community setting to reduce violence against children.

Methods: Parents of children from birth to 17 years were recruited from two communities near Kuala Lumpur to participate in the government-run program called the Naungan Kasih Positive Parenting Program ("Protecting through Love" in Bahasa Melayu).

Crohn's disease in endoscopic remission, obesity, and cases of high genetic risk demonstrates overlapping shifts in the colonic mucosal-luminal interface microbiome.

Background: Crohn's disease (CD) patients demonstrate distinct intestinal microbial compositions and metabolic characteristics compared to unaffected controls. However, the impact of inflammation and underlying genetic risk on these microbial profiles and their relationship to disease phenotype are unclear. We used lavage sampling to characterize the colonic mucosal-luminal interface (MLI) microbiome of CD patients in endoscopic remission and unaffected controls relative to obesity, disease genetics, and phenotype.

Defining the Selectivity of Chemical Inhibitors Used for Cytochrome P450 Reaction Phenotyping: Overcoming Selectivity Limitations with a Six-Parameter Inhibition Curve-Fitting Approach.

The utility of chemical inhibitors in cytochrome P450 (CYP) reaction phenotyping is highly dependent on their selectivity and potency for their target CYP isoforms. In the present study, seventeen inhibitors of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 commonly used in reaction phenotyping were evaluated for their cross-enzyme selectivity in pooled human liver microsomes. The data were evaluated using a statistical desirability analysis to identify (1) inhibitors of superior selectivity for reaction phenotyping and (2) optimal concentrations for each.

An improved method for cytochrome p450 reaction phenotyping using a sequential qualitative-then-quantitative approach.

Cytochrome P450 reaction phenotyping to determine the fraction of metabolism values (f) for individual enzymes is a standard study in the evaluation of a new drug. However, there are technical challenges in these studies caused by shortcomings in the selectivity of P450 inhibitors and unreliable scaling procedures for recombinant P450 (rCYP) data. In this investigation, a two-step "qualitative-then-quantitative" approach to P450 reaction phenotyping is described.

Performance Characteristics of a Clinical Decision Support Tool for Disease Complications in Crohn's Disease.

Background: Patients with Crohn's disease (CD) are at risk of complications. Performance characteristics of a decision support tool assessing the risk of CD complications were evaluated.

Methods: CDPATH (formerly called the Personalized Risk and Outcome Prediction Tool [PROSPECT]) was calibrated and validated in 2 cohorts.

Digital Mental Health for Young People: A Scoping Review of Ethical Promises and Challenges.

Mental health disorders are complex disorders of the nervous system characterized by a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Mental illness is of particular concern for younger people. The WHO estimates that around 20% of the world's children and adolescents have a mental health condition, a rate that is almost double compared to the general population.

Preoperative Serum Vedolizumab Levels Do Not Impact Postoperative Outcomes in Inflammatory Bowel Disease.

Background: Vedolizumab has been proposed to lead to fewer postoperative complications because of its gut specificity. Studies, however, suggest an increased risk of surgical site infections, yet the data are conflicting.

Objective: This study aimed to assess the effect of vedolizumab drug levels on postoperative outcomes in patients undergoing major abdominal surgery for IBD.

How trauma related to sex trafficking challenges parenting: Insights from Mexican and Central American survivors in the US.

Sex trafficking, a form of human trafficking for the purpose of commercial sexual exploitation, with a global prevalence of 4.5 million, has pervasive effects in the mental and physical health of survivors. However, little is known about the experiences and needs of Latinx migrants (the majority of sex trafficking victims in the US) after trafficking, particularly regarding parenting.

Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML.

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells.

Ethical frameworks for quality improvement activities: an analysis of international practice.

Purpose: To examine international approaches to the ethical oversight and regulation of quality improvement and clinical audit in healthcare systems.

Data Sources: We searched grey literature including websites of national research and ethics regulatory bodies and health departments of selected countries.

Study Selection: National guidance documents were included from six countries: Ireland, England, Australia, New Zealand, the United States of America and Canada.

An International Perspective on Definitions and Terminology Used to Describe Serious Reportable Patient Safety Incidents: A Systematic Review.

Objectives: Patients are unintentionally, yet frequently, harmed in situations that are deemed preventable. Incident reporting systems help prevent harm, yet there is considerable variability in how patient safety incidents are reported. This may lead to inconsistent or unnecessary patterns of incident reporting and failures to identify serious patient safety incidents.

Characterization of a Dopamine Transporter and Its Splice Variant Reveals Novel Features of Dopaminergic Regulation in the Honey Bee.

Dopamine is an important neuromodulator involved in reward-processing, movement control, motivational responses, and other aspects of behavior in most animals. In honey bees (), the dopaminergic system has been implicated in an elaborate pheromonal communication network between individuals and in the differentiation of females into reproductive (queen) and sterile (worker) castes. Here we have identified and characterized a honey bee dopamine transporter (AmDAT) and a splice variant lacking exon 3 (AmDATΔex3).

Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine.

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema.

A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.

Loss of immune tolerance to self-antigens can promote chronic inflammation and disrupt the normal function of multiple organs, including the lungs. Degradation of elastin, a highly insoluble protein and a significant component of the lung structural matrix, generates proinflammatory molecules. Elastin fragments (EFs) have been detected in the serum of smokers with emphysema, and elastin-specific T cells have also been detected in the peripheral blood of smokers with emphysema.

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research.