Symptoms Prior to Diagnosis of Multiple Sclerosis in Individuals Younger Than 18 Years.

Importance: A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS).

Objective: To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease-related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA).

Design, Setting, And Participants: This population-based, matched case-control study included children and adolescents (aged <18 years) in Germany with statutory health insurance from January 2010 to December 2020.

Adherence in Evidence-Based Neurotrauma Guidelines: A Worldwide Survey.

Background: Traumatic brain injury (TBI) management guidelines vary across regions and there is limited research on real-world adherence to these guidelines. We conducted a global survey to assess the adherence of neurosurgeons to TBI guidelines and evidence-based medicine (EBM).

Method: A 24-item survey was created using Google Forms, covering demographic information, neurotrauma training, basic knowledge of EBM, surgical and in-hospital management.

Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry.

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Synthesis and Application of Photocaged Isopropyl β-D-1-Thiogalactopyranoside for Light-Mediated Control of Bacterial Gene Expression.

Photocaged compounds are chemical conjugates that are designed to release an active molecule upon exposure to light of a specific wavelength. In recent years, photocaged inducer molecules such as caged isopropyl β-D-1-thiogalactopyranoside (cIPTG) have been increasingly used as a powerful tool for light-driven gene expression in bacteria, allowing researchers to precisely and noninvasively tune the expression of specific target genes. In this chapter, we present a guideline for the synthesis of 6-nitropiperonyl photocaged IPTG (NP-cIPTG) as well as its in vivo application as an optochemical on-switch of gene transcription in Escherichia coli and other bacteria.

Psychosocial work stressors and mental health in Ph.D. students in Germany-Evidence from two cross-sectional samples.

Background: Ph.D. students have been shown to report a lower mental health status compared to the general population.

TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

Bayesian Reanalyses of the Trials TOMAHAWK and COACT.

Background: The timing of coronary angiography in patients with successfully resuscitated out-of-hospital cardiac arrest and missing ST-segment elevations on the electrocardiogram has been investigated in 2 large randomized controlled trials, TOMAHAWK (Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation) and COACT (Coronary Angiography After Cardiac Arrest Trial). Both trials found neutral results for immediate vs delayed/selective coronary angiography on short-term all-cause mortality. The TOMAHAWK trial showed a tendency towards harm with immediate coronary angiography, though not statistically significant with traditional frequentist methods.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

An international expert survey on the worldwide digitalization in psychiatry: Global findings from the WPA survey.

Background: The World Psychiatric Association (WPA) Working Group on Digital Psychiatry aims to digitally supplement, support and improve mental health and care literacy, acceptance and accessibility across WPA member countries and National Psychiatric Associations (NPAs). To help with this goal, the present study was set to explore first the global status of digital mental health and care across NPAs METHODS: An international expert survey on the digitalization level across all 145 WPA NPAs was electronically distributed through Qualtrics. Descriptive statistics were carried out on the global dataset.

Effect of feeding in elevated side-lying and paced bottle feeding on swallow-breathe coordination in healthy preterm infants - First results.

Background: Preterm infants face challenges in their suck-swallow-breathe coordination leading to an increased risk of aspiration. Key components of the swallowing process are present around 34 to 35 weeks postmenstrual age (PMA), but preterm infants fatigue early affecting timing, quality and efficiency in swallowing and prolonging breathing pauses. Feeding strategies need to address these specific challenges in suck-swallow-breathe coordination.

Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies.

Background: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).

Methods: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation).

SLP2 and MIC13 synergistically coordinate MICOS assembly and crista junction formation.

The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging.

Physical activity and tobacco smoking in the German adult population.

Background: Physical inactivity and tobacco smoking remain the leading causes of morbidity and mortality worldwide. In Germany, smoking prevalence is high at around 30%, and only 45% achieve the WHO recommendation for physical activity (PA). Understanding how smoking and physical inactivity co-occur can inform interventions targeting these behaviours.

Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.

Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.

A multisite validation of brain white matter pathways of resilience to chronic back pain.

Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have pointed to brain characteristics as predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking.

Temporal dynamics in a red alga dominated geothermal feature in Yellowstone National Park.

Alga-dominated geothermal spring communities in Yellowstone National Park (YNP), USA, have been the focus of many studies, however, relatively little is known about the composition and community interactions which underpin these ecosystems. Our goal was to determine, in three neighboring yet distinct environments in Lemonade Creek, YNP, how cells cope with abiotic stressors over the diurnal cycle. All three environments are colonized by two photosynthetic lineages, and , both of which are extremophilic Cyanidiophyceae red algae.

Embracing native diversity to enhance the maximum quantum efficiency of photosystem II in maize.

The sustainability of maize cultivation would benefit tremendously from early sowing, but is hampered by low temperatures during early development in temperate climates. We show that allelic variation within the gene encoding subunit M of the NADH-dehydrogenase-like (NDH) complex (ndhm1) in a European maize landrace affects several quantitative traits that are relevant during early development in cold climates through NDH-mediated cyclic electron transport (CET) around photosystem I, a process crucial for photosynthesis and photoprotection. Beginning with a genome-wide association study for maximum potential quantum yield of photosystem II in dark-adapted leaves (Fv/Fm), we capitalized on the large phenotypic effects of a hAT transposon insertion in ndhm1 on multiple quantitative traits (early plant height, Fv/Fm, chlorophyll content, and cold tolerance) caused by the reduced protein levels of NDHM and associated NDH components.

Seasonal influenza vaccination coverage and the social determinants of influenza vaccination among people over 50 with diabetes in Europe: Analyzing population-based SHARE data for the 2019-2020 and 2021-2022 influenza seasons.

Background: Seasonal influenza vaccination coverage data for adults with chronic medical conditions are very scarce. We aimed to investigate the influenza vaccination rates and explore the common social determinants associated with vaccination in Europe across two influenza seasons.

Methods: This cross-sectional study used data from the European SHARE survey for the 2019-2020 and 2021-2022 influenza seasons.

Built-in selection or confounder bias? Dynamic Landmarking in matched propensity score analyses.

Background: Propensity score matching has become a popular method for estimating causal treatment effects in non-randomized studies. However, for time-to-event outcomes, the estimation of hazard ratios based on propensity scores can be challenging if omitted or unobserved covariates are present. Not accounting for such covariates could lead to treatment estimates, differing from the estimate of interest.

Cyto-, gene, and multireceptor architecture of the early postnatal mouse hippocampal complex.

Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative in vivo receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes.

Spatial separation of different drug substances in one microneedle array patch by combining inkjet printing and micromolding technology.

Transdermal drug delivery using microneedle array patches has been investigated using a wide range of drug substances. Inkjet printing and micromolding are established methods for the production of microneedle array patches and both were used to combine lisinopril embedded in povidone and ibuprofen in Eudragit® RS / RL in a single patch. Dissolution studies, visual inspection, mechanical strength and insertion into an artificial skin membrane model were investigated.