Association of obesity with disease outcome in multiple sclerosis.

Background: Obesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation.

Methods: This nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were compared at baseline and at years 2, 4 and 6 between obese (body mass index, BMI ≥30 kg/m) and non-obese (BMI <30 kg/m) patients and correlated with individual BMI values.

Early spinal cord pseudoatrophy in interferon-beta-treated multiple sclerosis.

Background And Purpose: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain.

Framework and baseline examination of the German National Cohort (NAKO).

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany.

Presurgical diffusion metrics of the thalamus and thalamic nuclei in postoperative delirium: A prospective two-centre cohort study in older patients.

Background: The thalamus seems to be important in the development of postoperative delirium (POD) as previously revealed by volumetric and diffusion magnetic resonance imaging. In this observational cohort study, we aimed to further investigate the impact of the microstructural integrity of the thalamus and thalamic nuclei on the incidence of POD by applying diffusion kurtosis imaging (DKI).

Methods: Older patients without dementia (≥65 years) who were scheduled for major elective surgery received preoperative DKI at two study centres.

Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses.

Anticancer T cells acquire a dysfunctional state characterized by poor effector function and expression of inhibitory receptors, such as PD-1. Blockade of PD-1 leads to T cell reinvigoration and is increasingly applied as an effective anticancer treatment. Recent work challenged the commonly held view that the phosphatase PTPN11 (known as SHP-2) is essential for PD-1 signaling in T cells, suggesting functional redundancy with the homologous phosphatase PTPN6 (SHP-1).

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease.

Walking parameters of older adults from a lower back inertial measurement unit, a 6-year longitudinal observational study.

Gait changes during aging and differs between sexes. Inertial measurement units (IMUs) enable accurate quantitative evaluations of gait in ambulatory environments and in large populations. This study aims to provide IMU-based gait parameters' values derived from a large longitudinal cohort study in older adults.

Acute kidney injury biomarkers in the single-cell transcriptomic era.

Acute kidney injury (AKI) affects many hospitalized patients and is associated with increased morbidity and mortality even at milder and reversible stages. The current clinical definition relies on serum creatinine increases or decreased urinary output. However, both parameters are of limited use because of poor sensitivity, specificity, and timeliness.

Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.

Background: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.

Methods: We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria).

Fragmentation, circadian amplitude, and fractal pattern of daily-living physical activity in people with multiple sclerosis: Is there relevant information beyond the total amount of physical activity?

Background: Physical activity is lower in people with multiple sclerosis (pwMS) compared to healthy controls. Previous work focused on studying activity levels or activity volume, but studies of daily-living rest-activity fragmentation patterns, circadian rhythms, and fractal regulation in pwMS are limited. Based on findings in other cohorts, one could suggest that these aspects of daily-living physical activity will provide additional information about the health and well-being of pwMS.

Stroke-Heart Syndrome: Recent Advances and Challenges.

After ischemic stroke, there is a significant burden of cardiovascular complications, both in the acute and chronic phase. Severe adverse cardiac events occur in 10% to 20% of patients within the first few days after stroke and comprise a continuum of cardiac changes ranging from acute myocardial injury and coronary syndromes to heart failure or arrhythmia. Recently, the term was introduced to provide an integrated conceptual framework that summarizes neurocardiogenic mechanisms that lead to these cardiac events after stroke.

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort.

Background: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data.

The Role of Optical Coherence Tomography Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis.

Background And Objectives: Recent studies have suggested that intereye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell + inner plexiform (GCIPL) thickness by spectral domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history.

Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations.

Background: The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear.

Methods: We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression.

Results: During a median follow-up of 9.

Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.

Aims: Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies of DCM, the molecular mechanisms underlying the pathogenesis of familial DCM remain unknown, translating to a lack of disease-specific therapies. The discovery of novel targets for the treatment of DCM was sought using phenotypic sceening assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate the disease phenotypes in vitro.

Overnight unilateral withdrawal of thalamic deep brain stimulation to identify reversibility of gait disturbances.

Background: Gait disturbances are frequent side effects related to chronic thalamic deep brain stimulation (DBS) that may persist beyond cessation of stimulation.

Objective: We investigate the temporal dynamics and clinical effects of an overnight unilateral withdrawal of DBS on gait disturbances.

Methods: 10 essential tremor (ET) patients with gait disturbances following thalamic DBS underwent clinical and kinematic gait assessment ON DBS, after instant and after an overnight unilateral withdrawal of DBS of the hemisphere corresponding to the non-dominant hand.

Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis.

Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation.

Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort.

SMER28 Attenuates PI3K/mTOR Signaling by Direct Inhibition of PI3K p110 Delta.

SMER28 (Small molecule enhancer of Rapamycin 28) is an autophagy-inducing compound functioning by a hitherto unknown mechanism. Here, we confirm its autophagy-inducing effect by assessing classical autophagy-related parameters. Interestingly, we also discovered several additional effects of SMER28, including growth retardation and reduced G1 to S phase progression.

Associations of ultra-processed food intake with maternal weight change and cardiometabolic health and infant growth.

Background: Excessive intake of ultra-processed foods, formulated from substances extracted from foods or derived from food constituents, may be a modifiable behavioral risk factor for adverse maternal and infant health outcomes. Prior work has predominately examined health correlates of maternal ultra-processed food intake in populations with substantially lower ultra-processed food intake compared to the US population. This longitudinal study investigated relations of ultra-processed food intake with maternal weight change and cardiometabolic health and infant growth in a US cohort.

HDHL-INTIMIC: A European Knowledge Platform on Food, Diet, Intestinal Microbiomics, and Human Health.

Studies indicate that the intestinal microbiota influences general metabolic processes in humans, thereby modulating the risk of chronic diseases such as type 2 diabetes, allergy, cardiovascular disease, and colorectal cancer (CRC). Dietary factors are also directly related to chronic disease risk, and they affect the composition and function of the gut microbiota. Still, detailed knowledge on the relation between diet, the microbiota, and chronic disease risk is limited.