Source of dietary protein alters the abundance of proteases, intestinal epithelial and immune proteins both directly and via interactions with the gut microbiota.

Dietary protein has been shown to impact long-term health outcomes differentially depending on its amount and source. It has been suggested that interactions of the gut microbiota with dietary proteins mediate some of the effects of dietary protein on health outcomes. However, it remains unclear what specific host responses drive the health effects of dietary proteins from different plant and animal sources.

EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents.

Introduction: The identification of type 1 diabetes at an early presymptomatic stage has clinical benefits. These include a reduced risk of diabetic ketoacidosis (DKA) at the clinical manifestation of the disease and a significant reduction in clinical symptoms. The European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception (EDENT1FI) represents a pioneering effort to advance early detection of type 1 diabetes through public health screening.

Prompt Initiation of Maternal Antiretroviral Therapy After HIV Seroconversion in Pregnancy Effectively Prevents Vertical Transmission and Other Adverse Infant Outcomes.

From January 2008 to December 2018, 1348 HIV-exposed infants were born in Porto Alegre, Brazil; 18.8% had adverse infant outcomes (AIO) including vertical transmission (1.9%), stillbirth/neonatal death (4.

ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta Cell Function in Children and Adolescents with Type 1 Diabetes.

Introduction This guideline serves as an update to the 2022 International Society for Pediatric and Adolescent Diabetes (ISPAD) consensus guideline on staging for Type 1 Diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta cell function in those with Stage 3 T1D is included.

[Prioritization of research questions in health crises-presentation of a concept developed during the COVID-19 pandemic].

In acute crises such as the COVID-19 pandemic, scientific questions need to be addressed quickly in order to protect the health of the population and to maintain the function of the healthcare system. The prevailing urgency and the large number of issues to be addressed, combined with the limitation of time, personnel, or monetary resources make prioritization indispensable. In the COVID-19 Evidence Ecosystem (CEOsys) project initiated by the University Medicine Network (NUM), a procedure for the rapid prioritization of questions was used specifically for evidence syntheses and clinical guideline recommendations, which was further developed in the follow-up project PREparedness and Pandemic Response in Germany (PREPARED).

Discovery and functional analysis of a novel ALPK1 variant in ROSAH syndrome.

Retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and migraine headache (ROSAH) syndrome is an autosomal dominant disorder and to date is known to be caused by either the Thr237Met or Tyr254Cys variant in the protein kinase ALPK1. Here, we identify a family in which ROSAH syndrome is caused by a novel variant in which Ser277 is changed to Phe. All six patients examined display ocular inflammation and optic nerve elevation, four have retinal degeneration and four are registered blind.

Identification of Biochemical Determinants for Diagnosis and Prediction of Severity in 5q Spinal Muscular Atrophy Using H-Nuclear Magnetic Resonance Metabolic Profiling in Patient-Derived Biofluids.

This study explores the potential of H-NMR spectroscopy-based metabolic profiling in various biofluids as a diagnostic and predictive modality to assess disease severity in individuals with 5q spinal muscular atrophy. A total of 213 biosamples (urine, plasma, and CSF) from 153 treatment-naïve patients with SMA across five German centers were analyzed using H-NMR spectroscopy. Prediction models were developed using machine learning algorithms which enabled the patients with SMA to be grouped according to disease severity.

Early-life sodium restriction programs autonomic dysfunction and salt sensitivity in male C57BL/6J mice.

Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period [postnatal day (PD)21-PD42] programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity.

Rapid determination of sphingosine 1-phosphate association with carrier molecules by flow-induced dispersion analysis to predict sepsis outcome.

Flow-induced dispersion analysis (FIDA) was used to investigate the association of fluorescein isothiocyanate-labeled signaling lipid sphingosine 1-phosphate (S1P) with its carrier molecules human serum albumin (HSA) and high-density lipoprotein (HDL). Associations were measured in plasma samples of patients after surgery, with sepsis or septic shock. All patients demonstrated a significant shift between the carrier binding: decrease of S1P bound to HSA with a concomitant increase of S1P bound to HDL.

Looking back at the TEDDY study: lessons and future directions.

The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed.

Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.

Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study.

Universal newborn screening using genome sequencing: early experience from the GUARDIAN study.

For more than 20 years there has been speculation about a future in which newborns are routinely screened at birth for genetic disorders using genome sequencing, but prospective large-scale studies assessing this vision have only recently begun. Genome sequencing may provide a means of expanding the scope of conditions included in newborn screening programs and improving the positive predictive value of traditional newborn screening. However, the use of genome sequencing for newborn screening has also raised concerns including acceptability, equity, and scalability.

Emerging Concepts and Success Stories in Type 1 Diabetes Research: A Road Map for a Bright Future.

Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration approval of teplizumab to delay disease development.

Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study.

Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH).

Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region.

Gene expression profiles in placenta and their association with anesthesia, delivery mode and maternal diabetes.

Introduction: Fetal development is dependent on placenta and affected by multiple factors including maternal diabetes. Here we aimed to identify maternal diabetes-associated changes in placentas and analyzed placental gene expression to understand its modulation by maternal diabetes and birth mode.

Methods: Placental RNAseq transcriptome analyses were performed on maternally-derived decidua and fetal-derived villous tissue from pregnancies of mothers with type 1 diabetes (n = 14), gestational diabetes (n = 6) and without diabetes (n = 14).

Discrimination and precision of Continuous Glucose Monitoring in staging children with presymptomatic type 1 diabetes.

Context: Staging and monitoring of pre-symptomatic type 1 diabetes includes the assessment for dysglycemia.

Objective: To assess the ability of Continuous Glucose Monitoring (CGM) to differentiate between islet autoantibody-negative controls and early-stage type 1 diabetes and explore whether CGM classifiers predict progression to clinical diabetes.

Research Design And Methods: Children and adolescents participating in public health screening for islet autoantibodies in Bavaria, Germany were invited to undergo CGM with Dexcom G6.

How to make cardiology clinical trials more inclusive.

Cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution. Here we describe strategies to foster trial representativeness, with proposed actions at the levels of trial funding, design, conduct and dissemination. In particular, trial representativeness may be increased through broad recruitment strategies and site selection criteria that reflect the diversity of patients in the catchment area, as well as limiting unjustified exclusion criteria and using pragmatic designs that minimize research burden on patients (including embedded and decentralized trials).