De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease.

Cardiovascular disease (CVD) is a major complication of chronic kidney disease (CKD), despite improvements in patient care. Vascular inflammation is a crucial process in the pathogenesis of CVD and a critical factor in the cardiovascular complications in CKD patients. CKD promotes a pro-inflammatory environment that impacts the vascular wall, leading to endothelial dysfunction, increased oxidative stress, and vascular remodeling.

Targeting Oxidative Stress and Inflammation in the Eye: Insights from a New Model of Experimental Autoimmune Uveitis.

Autoimmune uveitis is a relapsing blind-causing ocular condition with complex pathogenesis that is not completely understood. There is a high demand for accurate animal models of experimental autoimmune uveitis (EAU) suitable for elucidating the molecular mechanisms of the disease and testing new therapeutic approaches. Here, we demonstrated that photoreceptor Ca/Zn-sensor protein recoverin is a uveoretinal antigen in albino rabbits provoking typical autoimmune chorioretinitis 2-4 weeks after immunization.

Genetic Downregulation of GABA Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord.

GABAergic signaling and GABA receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic downregulation of GABA receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord.

Lack of Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer in Real Life, with the Emergence of Immunotherapy.

Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy.

Vestibular epilepsy: clinical and electroencephalographic characteristics with the proposed diagnostic criteria.

Background: Focal seizures may encompass vestibular sensations in their symptomatology. When these manifestations occur in isolation or constitute the predominant symptom, they prompt consideration for diagnosing recurrent paroxysmal vertigo. However, the characterization of "vestibular epilepsy" remains debated and underexplored.

The VGCC auxiliary subunit α2δ1 is an extracellular GluA1 interactor and regulates LTP, spatial memory, and seizure susceptibility.

Activity-dependent synaptic accumulation of AMPA receptors (AMPARs) and subsequent long-term synaptic strengthening underlie different forms of learning and memory. The AMPAR subunit GluA1 amino-terminal domain is essential for synaptic docking of AMPAR during LTP, but the precise mechanisms involved are not fully understood. Using unbiased proteomics, we identified the epilepsy and intellectual disability-associated VGCC auxiliary subunit α2δ1 as a candidate extracellular AMPAR slot.

Change in standing acetabular orientation 2 years postoperatively after surgical correction of adult spinal deformity.

Introduction: Although sagittal alignment is known to influence pelvic position, few studies accurately identify the relationship between sagittal alignment and acetabular orientation. We hypothesized that postoperative PT should be correlated with acetabular change in native hips after surgical correction of adult spinal deformity. The objective of this study was therefore to describe the correlation between the change in pelvic tilt and the change in acetabular orientation two years after surgical correction of adult spinal deformity.

PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.

Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions.

[University hospital nurse: the challenges of this new status].

Combining hospital and university activities encourages the professionals involved in these missions to innovate, to overcome divisions and energize career paths for the benefit of all: patients, students, teachers, researchers, caregivers and supervisors.

Neuropsychological profile of French adults with early-treated phenylketonuria: a multicenter study.

Background And Objective: Adult patients with early-treated phenylketonuria (AwET-PKU) may present some subtle neurocognitive deficits. The aim of the study was to investigate 1) neurocognitive functions in a large group of AwET-PKU 2) the influence of plasma phenylalanine (Phe).

Methods: Participants: 187 AwET-PKU (classic PKU [cPKU] 81%, mild PKU [mPKU] 14%, and mild persistent hyperphenylalaninemia [MPH] 5%).

Candida krusei (Pichia kudriavzevii) multilocus sequence typing and antifungal susceptibility profile in Cameroon.

Among the Candida species commonly involved in superficial and more significant life-threatening infections, C. krusei exhibits the most worrisome resistance profile to antifungals. This study aimed to analyse the population structure using multilocus sequence typing (MLST), and to evaluate the antifungal susceptibility profile of C.

Associations between weight-control methods and depression among Korean adolescents: a study based on a national dataset.

Background/objectives: The increasing prevalence of overweight and obesity has become a significant global burden, with more than 40% of the global adult population attempting to lose weight. Previous studies on the impact of weight-control methods on mental health, especially among adolescents, are limited. Thus, this study aimed to investigate the association between various weight-control methods and depression among adolescents, with the goal of informing healthier weight management decisions and promoting effective methods.

[Platypnea-orthodeoxia syndrome in a patient with heart failure: A case report].

Introduction: The platypnea orthodeoxia syndrome is a rare clinical entity combining positional dyspnea and arterial oxygen desaturation during the transition to orthostatism, reversible on return to decubitus. The most frequent etiology of this syndrome is the presence of a patent foramen ovale (PFO) responsible for a right-to-left intracardiac shunt, the severity of which results in significant functional disability and a risk of death from hypoxia.

Case Report: We report the case of a 93-year old patient on long-term oxygen, initially hospitalized for acute heart failure following a community-acquired urinary tract infection.

Secondary cleft lip rhinoplasty. Our experience of two decades.

Patients who underwent cleft lip surgery in childhood may develop nasal malformation later in life. Various procedures have been described to correct these malformations. This study aims to describe our surgical approach and assess the morphometric outcomes of secondary cleft-lip rhinoplasty performed at the plastic surgery department in Marseille between 2002 and 2022.

Understanding paralogous epilepsy-associated GABA receptor variants: Clinical implications, mechanisms, and potential pitfalls.

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in , , and Seven mutations (α1, α1, β2, β3, β3, γ2, and γ2) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations.

TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system, where immune dysregulation plays a critical role. We sought to explore the modulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFɑ) and TNF-like weak inducer of apoptosis (TWEAK), along with their respective autoantibodies, TNAb and TWAb, and to decipher potential associations between these and clinical characteristics which could assist personalized therapy in MS. We also assessed the complementarity to leading candidate biomarkers in MS patient monitoring, namely, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL).

Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease.

The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of changes may differ is these changes correspond to full-length species or proteolytic fragments. Here, we determined that full-length ACE2 decreased in the plasma of uninfected Crohn's disease (CD) patients before treatment onset compared to controls.

Sportsman's Hernia repair using Nesovic procedure, a 13-year single-center experience.

Sportsman's hernia is very frequent in some sports, particularly in football. This painful syndrome is reported by high-level athletes as well as amateurs. There is no consensus about the management of sportsman's hernia, because of the heterogeneity in anatomoclinic forms.