Characterization of children with early onset pediatric multiple sclerosis.

Background: Early onset pediatric multiple sclerosis (EOPMS) provides an early window of opportunity to understand the mechanisms leading to MS.

Objective: To investigate clinical, laboratory and imaging differences between children with early onset pediatric MS (<11 years, EOPMS) and late onset pediatric MS (≥11 years, LOPMS).

Methods: Mostly prospectively collected data of children with MS including clinical presentation, MRI at onset, time to second relapse, relapse rate, treatment history, and CSF markers were eligible.

Evaluation of stabilizing additives to protect activities of cytochrome P450 enzymes for in vitro drug testing and pharmacogenetic studies: Focus on CYP2D6.

In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell models and organoids, offer promising alternatives but may not fully replicate physiological processes, especially for Cytochrome P450 (CYP) families involved in extrahepatic metabolism.

Aspirin Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis Among Patients With Post-Thrombotic Syndrome: The Multicenter, Multinational, Randomized, Open-label ARIVA Trial.

Background: In patients with post-thrombotic syndrome (PTS), stent recanalization of iliofemoral veins or the inferior vena cava can restore venous patency and improve functional outcomes. The risk of stent thrombosis is particularly increased during the first 6 months after intervention. The ARIVA trial tested whether daily aspirin 100 mg plus rivaroxaban 20 mg is superior to rivaroxaban 20 mg alone to prevent stent thrombosis within 6 months after stent placement for PTS.

First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors.

Background: Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.

Metabolic Activity in Human Intermuscular Adipose Tissue Directs the Response of Resident PPARγ Macrophages to Fatty Acids.

: Peroxisome proliferator-activated receptor gamma (PPARγ) is a fatty acid-binding transcription activator of the adipokine chemerin. The key role of PPARγ in adipogenesis was established by reports on adipose tissue-resident macrophages that express PPARγ. The present study examined PPARγ macrophages in human skeletal muscle tissues, their response to fatty acid (FA) species, and their correlations with age, obesity, adipokine expression, and an abundance of other macrophage phenotypes.

Autoradiography of Intracerebral Tumours in the Chick Embryo Model: A Feasibility Study Using Different PET Tracers.

Purpose: In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has yet to be demonstrated.

Procedures: Human U87 glioblastoma cells and U87-IDH1 mutant glioma cells were implanted into the brains of chick embryos at developmental day 5.

Expanding the Scope of Microvascular Inflammation: Unveiling Its Presence Beyond Antibody-Mediated Rejection Into T-Cell Mediated Contexts.

Microvascular inflammation (MVI) in kidney transplant biopsies is mainly associated with antibody-mediated rejection (AMR), sparking debate within the Banff Classification of Renal Allograft Pathology regarding its exclusivity. This study reviewed the literature on MVI in T cell-mediated rejection (TCMR) and analyzed MVI in our transplant population. We searched English publications in MEDLINE, Embase, Web of Science, Cochrane, and Google Scholar until June 2024, focusing on glomerulitis (g), peritubular capillaritis (ptc), or MVI in kidney transplant biopsies classified as TCMR.

Revolutionizing liver fibrosis research: the promise of 3D organoid models in understanding and treating chronic liver disease.

Introduction: Liver fibrosis, marked by excessive extracellular matrix deposition, is a significant consequence of chronic liver injuries from various conditions. It can progress to end-stage liver disease, with liver transplantation often being the only treatment option. Recent advancements in 3D-organoid technology have transformed liver disease research by providing models that mimic the human liver's physiological environment, offering insights into mechanisms of fibrosis and potential therapies.

Linking altered neuronal and synaptic properties to nicotinic receptor Alpha5 subunit gene dysfunction: a translational investigation in rat mPFC and human cortical layer 6.

Genetic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit of mice results in behavioral deficits linked to the prefrontal cortex (PFC). rs16969968 is the primary Single Nucleotide Polymorphism (SNP) in CHRNA5 strongly associated with nicotine dependence and schizophrenia in humans. We performed single cell-electrophysiology combined with morphological reconstructions on layer 6 (L6) excitatory neurons in the medial PFC (mPFC) of wild type (WT) rats, rats carrying the human coding polymorphism rs16969968 in Chrna5 and α5 knockout (KO) rats.

Enhancing Hemocompatibility in ECMO Systems With a Fibrinolytic Interactive Coating: in Vitro Evaluation of Blood Clot Lysis Using a 3D Microfluidic Model.

Blood-contacting medical devices, especially extracorporeal membrane oxygenators (ECMOs), are highly susceptible to surface-induced coagulation because of their extensive surface area. This can compromise device functionality and lead to life-threatening complications. High doses of anticoagulants, combined with anti-thrombogenic surface coatings, are typically employed to mitigate this risk, but such treatment can lead to hemorrhagic complications.

Zinc Deficiency Exacerbates Lead-Induced Interleukin-2 Suppression by Regulating CREM Expression.

Lead, a prevalent heavy metal, impairs the immune system by affecting T cell function. Similarly, zinc deficiency adversely affects T cells, with zinc deficiency and lead exposure being linked to reduced interleukin-2 (IL-2) production. Zinc deficiency has been associated with increased expression of the transcription factor CREM 100 kDa, which downregulates IL-2.

Distribution and Maturity of Medial Collagen Fibers in Thoracoabdominal Post-Dissection Aortic Aneurysms: A Comparative Study of Marfan and Non-Marfan Patients.

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome.

Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis.

Background: Ageing often affects biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin <4.

Segmentation of the iliac crest from CT-data for virtual surgical planning of facial reconstruction surgery using deep learning.

Background And Objectives: For the planning of surgical procedures involving the bony reconstruction of the mandible, the autologous iliac crest graft, along with the fibula graft, has become established as a preferred donor region. While computer-assisted planning methods are increasingly gaining importance, the necessary preparation of geometric data based on CT imaging remains largely a manual process. The aim of this work was to develop and test a method for the automated segmentation of the iliac crest for subsequent reconstruction planning.

Reconstruction of Abdominal Defects After Open Abdomen Treatment Using Propeller Flaps of the Superior and Deep Inferior Epigastric Artery System: Report of Two Cases.

Open abdomen treatment (OAT) is associated with significant morbidity and mortality. In cases where primary or delayed fascial closure cannot be achieved, vacuum-assisted wound closure and mesh-mediated fascial traction are indicated, which often result in a planned ventral hernia. If secondary skin closure is not feasible, common treatment of granulated abdominal defects involves split-thickness skin-grafting or healing by secondary intention leading to significant scarring and sometimes mutilating defects.

A study of long-term GABA and high-energy phosphate alterations in the primary motor cortex using anodal tDCS and H/P MR spectroscopy.

Introduction: Anodal transcranial direct current stimulation (tDCS) has been reported to modulate gamma-aminobutyric acid levels and cerebral energy consumption in the brain. This study aims to investigate long-term GABA and cerebral energy modulation following anodal tDCS over the primary motor cortex.

Method: To assess GABA and energy level changes, proton and phosphorus magnetic resonance spectroscopy data were acquired before and after anodal or sham tDCS.

A hepatocellular carcinoma model with and without parenchymal liver damage that integrates technical and pathophysiological advantages for therapy testing.

Hepatocellular Carcinoma (HCC) is the most common form of primary liver cancer, with cirrhosis being its strongest risk factor. Interestingly, an increasing number of HCC cases is also observed without cirrhosis. We developed an HCC model via intrasplenic injection of highly tumorigenic HCC cells, which, due to cellular tropism, invade the liver and allow for a controllable disease progression.

Bronchoscopic biopsies - a novel source for primary airway epithelial cells in respiratory research.

Background: Using primary airway epithelial cells (AEC) is essential to mimic more closely different types and stages of lung disease in humans while reducing or even replacing animal experiments. Access to lung tissue remains limited because these samples are generally obtained from patients who undergo lung transplantation for end-stage lung disease or thoracic surgery for (mostly) lung cancer. We investigated whether forceps or cryo biopsies are a viable alternative source of AEC compared to the conventional technique.

Remission induction therapies and long-term outcomes in granulomatosis with polyangiitis and microscopic polyangiitis: real-world data from a European cohort.

To explore disease characteristics, renal involvement and induction treatment strategies over the last decades and evaluate relapse rates and renal outcomes in ANCA-associated vasculitides (AAV). We retrospectively analyzed remission, relapse rates and the occurrence of the composite endpoint (comprising death and renal failure) in newly diagnosed AAV cases in four tertial referral centers in Germany and Switzerland diagnosed between 1999 and 2022. Hazard ratios were computed by Cox proportional hazard and Kaplan-Meier curves were plotted to compare therapeutic strategies after propensity-matching.

Assessing hand motor function in chronic immune-mediated neuropathies: a proof-of-concept study using a data glove.

Background: Chronic immune-mediated neuropathies are clinically heterogeneous and require regular, objective, and multidimensional monitoring to individualize treatment. However, established outcome measures are insufficient regarding measurement quality criteria (e.g.

Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, non-malignant hematologic disease characterized by complement-mediated hemolysis (with or without hemoglobinuria), fatigue, increased susceptibility to thrombosis, and bone marrow dysfunction. The development of complement inhibitors has transformed outcomes for patients with PNH, but patients may still experience pharmacodynamic breakthrough hemolysis (BTH), which can be caused by exposure to a complement amplifying condition (CAC), such as vaccination, infection, or surgery.

Materials And Methods: A 13-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on how to classify pharmacodynamic BTH in patients with complement-inhibitor treated PNH.