The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.

This study combines two innovative mouse models in a major gene discovery project to assess the influence of host genetics on asbestos related disease (ARD). Conventional genetics studies provided evidence that some susceptibility to mesothelioma is genetic. However, the identification of host modifier genes, the roles they may play, and whether they contribute to disease susceptibility remain unknown.

Endothelial NOX5 Obliterates the Reno-Protective Effect of Nox4 Deletion by Promoting Renal Fibrosis via Activation of EMT and ROS-Sensitive Pathways in Diabetes.

Chronic hyperglycemia induces intrarenal oxidative stress due to the excessive production of reactive oxygen species (ROS), leading to a cascade of events that contribute to the development and progression of diabetic kidney disease (DKD). NOX5, a pro-oxidant NADPH oxidase isoform, has been identified as a significant contributor to renal ROS in humans. Elevated levels of renal ROS contribute to endothelial cell dysfunction and associated inflammation, causing increased endothelial permeability, which can disrupt the renal ecosystem, leading to progressive albuminuria and renal fibrosis in DKD.

Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans.

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat.

Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening.

Background: Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results.

Methods: Initiated as part of the COACH multicenter observational study, outpatients aged 12 to 21 years participating in the National Pediatric Rheumatological Database (NPRD) were prospectively screened for mental health using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder Scale-7 (GAD-7).

Imaging Markers Derived From MRI-Based Automated Kidney Segmentation—an Analysis of Data From the German National Cohort (NAKO Gesundheitsstudie).

Background: Population-wide research on potential new imaging biomarkers of the kidney depends on accurate automated segmentation of the kidney and its compartments (cortex, medulla, and sinus).

Methods: We developed a robust deep-learning framework for kidney (sub-)segmentation based on a hierarchical, three-dimensional convolutional neural network (CNN) that was optimized for multiscale problems of combined localization and segmentation. We applied the CNN to abdominal magnetic resonance images from the population-based German National Cohort (NAKO) study.

Management of pasireotide-induced hyperglycemia in patients with acromegaly: An experts' consensus statement.

Pasireotide is a somatostatin analogue for the treatment of acromegaly, a chronic condition caused by excess growth hormone. Despite the therapeutic benefits of pasireotide as a second-line treatment for inadequately controlled acromegaly, a major concern is its hyperglycemic side-effect. Here, we provide guidance on how to select appropriate patients with acromegaly for treatment with pasireotide.

Childhood maltreatment and sleep apnea: Findings from a cross-sectional general population study.

Objective: Cumulative evidence indicates that childhood maltreatment (CM) is associated with sleep disturbances possibly suggesting sleep apnea. However, the relation between CM and objective measures of sleep apnea as determined by polysomnography (PSG) has not yet been assessed.

Methods: Using a cross-sectional design and based on PSG measurements from N = 962 subjects from the SHIP-Trend general population study, we used linear regression models to investigate the relationship between apnea-hypopnea (AHI) and oxygen desaturation index (ODI) and Epworth sleepiness scale (ESS) metrics and the Childhood Trauma Questionnaire (CTQ).

Diabetes and gender incongruence: frequent mental health issues but comparable metabolic control - a DPV registry study.

Context: The condition when a person's gender identity does not match the sex assigned at birth is called gender incongruence (GI). Numbers of GI people seeking medical care increased tremendously over the last decade. Diabetes mellitus is a severe and lifelong disease.

Demographic, Clinical, Management, and Outcome Characteristics of 8,004 Young Children With Type 1 Diabetes.

Objective: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes age <6 years across three international registries: Diabetes Prospective Follow-Up Registry (DPV; Europe), T1D Exchange Quality Improvement Network (T1DX-QI; U.S.), and Australasian Diabetes Data Network (ADDN; Australasia).

Regulation of multiple signaling pathways promotes the consistent expansion of human pancreatic progenitors in defined conditions.

The unlimited expansion of human progenitor cells in vitro could unlock many prospects for regenerative medicine. However, it remains an important challenge as it requires the decoupling of the mechanisms supporting progenitor self-renewal and expansion from those mechanisms promoting their differentiation. This study focuses on the expansion of human pluripotent stem (hPS) cell-derived pancreatic progenitors (PP) to advance novel therapies for diabetes.

Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.

Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls.

Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.

Objectives: Osteoarthritis (OA) is a joint disease with a heritable component. Genetic loci identified via genome-wide association studies (GWAS) account for an estimated 26.3% of the disease trait variance in humans.

Diet in the management of type 2 diabetes: umbrella review of systematic reviews with meta-analyses of randomised controlled trials.

Objective: To systematically summarise and evaluate the existing evidence on the effect of diet on the management of type 2 diabetes and prevention of complications.

Design: Umbrella review of systematic reviews with meta-analyses of randomised controlled trials.

Data Sources: PubMed, Embase, Epistemonikos, and Cochrane, from inception up to 5 June 2022.

Family structures and parents' occupational models: its impact on children's diabetes.

Aims: This study examines how family-related factors influence the management of children and adolescents with type 1 diabetes (T1DM). We investigate the relationship between family patterns, parental work schedules and metabolic control.

Materials And Methods: We analysed data from a nationwide diabetes survey (DPV) focusing on HbA1c, severe hypoglycaemia, diabetic ketoacidosis, hospital admissions and inpatient treatment duration.

Eating out intensity, ultra-processed foods and BMI among Albanian youth.

Objective: Ultra-processed foods (UPF) and eating out of home (OH) are changing nutrition, particularly among youth in constrained settings. We aimed to assess the role of eating OH intensity on the associations of UPF and unprocessed or minimally processed foods (UMPF) with BMI among Albanian youth.

Design: Cross-sectional.

S-methyl cysteine sulfoxide and its potential role in human health: a scoping review.

Higher intakes of cruciferous and allium vegetables are associated with a lower risk of cardiometabolic-related outcomes in observational studies. Whilst acknowledging the many healthy compounds within these vegetables, animal studies indicate that some of these beneficial effects may be partially mediated by S-methyl cysteine sulfoxide (SMCSO), a sulfur-rich, non-protein, amino acid found almost exclusively within cruciferous and alliums. This scoping review explores evidence for SMCSO, its potential roles in human health and possible mechanistic action.

Rationale and design of a randomised phase III registration trial investigating finerenone in participants with type 1 diabetes and chronic kidney disease: The FINE-ONE trial.

Aims: Despite guideline-recommended treatments, including renin angiotensin system inhibition, up to 40 % of individuals with type 1 diabetes develop chronic kidney disease (CKD) putting them at risk of kidney failure. Finerenone is approved to reduce the risk of kidney failure in individuals with type 2 diabetes. We postulate that finerenone will demonstrate benefits on kidney outcomes in people with type 1 diabetes.

Leveraging genetic diversity to identify small molecules that reverse mouse skeletal muscle insulin resistance.

Systems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations. 'Diversity Outbred in Australia (DOz)' is a population of genetically unique mice with profound metabolic heterogeneity. We leveraged this variance to explore skeletal muscle's contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice.

Glyoxal in hyperglycaemic ischemic stroke - a cohort study.

Background: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke.

Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts.

Background: Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways.

Methods: We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites.