Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis.

The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity.

Dimerisation of the Yeast K Translocation Protein Trk1 Depends on the K Concentration.

In baker's yeast (), Trk1, a member of the superfamily of K-transporters (SKT), is the main K uptake system under conditions when its concentration in the environment is low. Structurally, Trk1 is made up of four domains, each similar and homologous to a K-channel α subunit. Because most K-channels are proteins containing four channel-building α subunits, Trk1 could be functional as a monomer.

Trial of Prasinezumab in Early-Stage Parkinson's Disease.

Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease.

Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks.

Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS.

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease.

Education in Palliative and End-of-Life Care-Pediatrics: Curriculum Use and Dissemination.

Context: The majority of seriously ill children do not have access to specialist pediatric palliative care (PPC) services nor to clinicians trained in primary PPC. The Education in Palliative and End-of-Life Care (EPEC)-Pediatrics curriculum and dissemination project was created in 2011 in response to this widespread education and training need. Since its implementation, EPEC-Pediatrics has evolved and has been disseminated worldwide.

Spinal Cord Atrophy Predicts Progressive Disease in Relapsing Multiple Sclerosis.

Objective: A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).

Methods: From a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated.

Phenylalanine Effects on Brain Function in Adult Phenylketonuria.

Objective: To evaluate the relationship between circulating phenylalanine and brain function as well as neuropsychiatric symptoms in adults with phenylketonuria.

Methods: In this prospective cross-sectional study, early-treated patients with phenylketonuria older than 30 years and age- and sex-matched controls were included. Extensive neurologic evaluation, neuropsychological and behavioral testing, sensory and motor evoked potentials, and MRI were performed.

Ofatumumab versus Teriflunomide in Multiple Sclerosis.

Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown.

Depiction of the Superior Petrosal Vein Complex by 3D Contrast-Enhanced MR Angiography.

Background And Purpose: Intraoperative obliteration of the superior petrosal vein complex has a relevant risk of postoperative complications. A large venous diameter and the absence of anastomoses have been previously suggested as possible risk factors. 3D contrast-enhanced MRA was evaluated for the identification of superior petrosal vein anatomy.

KCNJ11 variants and their effect on the association between serum potassium and diabetes risk in the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts.

Background: In the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts, serum potassium (K) is an independent predictor of diabetes risk, particularly among African-American participants. Experimental studies show that serum K levels affects insulin secretion. The KCNJ11 gene encodes for a K channel that regulates insulin secretion and whose function is affected by serum K levels.

Somatic instability of the expanded GAA repeats in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is a genetic neurodegenerative disorder caused by transcriptional silencing of the frataxin gene (FXN) due to expansions of GAA repeats in intron 1. FRDA manifests with multiple symptoms, which may include ataxia, cardiomyopathy and diabetes mellitus. Expanded GAA tracts are genetically unstable, exhibiting both expansions and contractions.

SNPs in Aβ clearance proteins: Lower CSF Aβ levels and earlier onset of dementia in PD.

Objective: To evaluate whether genetic variants in β-amyloid (Aβ) clearance proteins are associated with CSF levels of Aβ on a biological level and the onset of dementia on a clinical level in Parkinson disease (PD).

Methods: We analyzed genetic variants known to be involved in Aβ clearance in a PD group comprising 456 patients, 103 of them with dementia. Single nucleotide polymorphisms in the genes , cystatin C (), and membrane metalloendopeptidase () were evaluated in relation to demographic variables, clinical phenotypes, and CSF Aβ levels using a cross-sectional approach.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α.

Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.

Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.

A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men.

Background: Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD).

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

Background: Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence.

Methods: Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array.

Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine.

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

Introduction: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders.

Purpose: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU).

Methods: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization.

Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union.

Context: Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability.

Objective: The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU).

Design: A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism.

Measurement of splitting scales in → events at [Formula: see text] with the ATLAS detector.

A measurement of splitting scales, as defined by the clustering algorithm, is presented for final states containing a boson produced in proton-proton collisions at a centre-of-mass energy of 7 TeV. The measurement is based on the full 2010 data sample corresponding to an integrated luminosity of 36 pb which was collected using the ATLAS detector at the CERN Large Hadron Collider. Cluster splitting scales are measured in events containing bosons decaying to electrons or muons.

A cluster within the continuum of biopsychosocial distress can be labeled "fibromyalgia syndrome"--evidence from a representative German population survey.

Objective: We tested the hypothesis that "fibromyalgia syndrome" is a biopsychosocial continuum disorder.

Methods: A cross-sectional survey of a representative sample of the German general population with persons >or= 14 years of age was conducted based on face-to-face contacts. Physical distress was measured by the regional pain scale (RPS) and the Patient Health Questionnaire 15 (PHQ-15), psychological distress by the PHQ-9, and social distress by the Oslo Social Support Scale.

The universal stress protein UspC scaffolds the KdpD/KdpE signaling cascade of Escherichia coli under salt stress.

The sensor kinase KdpD and the response regulator KdpE control induction of the kdpFABC operon encoding the high-affinity K(+)-transport system KdpFABC in response to K(+) limitation or salt stress. Under K(+) limiting conditions the Kdp system restores the intracellular K(+) concentration, while in response to salt stress K(+) is accumulated far above the normal content. The kinase activity of KdpD is inhibited at high concentrations of K(+), so it has been puzzling how the sensor can be activated in response to salt stress.