Plasma levels of glial fibrillary acidic protein and neurofilament light chain in patients with chronic migraine: a multicenter case-control study.

Objective: Plasma glial fibrillary acidic protein (pGFAP) and plasma neurofilament light chain (pNfL) levels reflect astrocyte activation and neuronal damage, respectively. Whether these phenomena play a role in migraine is unknown. This study aimed to compare pGFAP and pNfL levels in patients with chronic migraine (CM) and age-matched controls and to analyze their relation with clinical features.

Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.

Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.

Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential.

We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response.

Comprehensive benchmarking of computational tools for predicting toxicokinetic and physicochemical properties of chemicals.

Ensuring the safety of chemicals for environmental and human health involves assessing physicochemical (PC) and toxicokinetic (TK) properties, which are crucial for absorption, distribution, metabolism, excretion, and toxicity (ADMET). Computational methods play a vital role in predicting these properties, given the current trends in reducing experimental approaches, especially those that involve animal experimentation. In the present manuscript, twelve software tools implementing Quantitative Structure-Activity Relationship (QSAR) models were selected for the prediction of 17 relevant PC and TK properties.

Assessing chronic stress in cats: measuring hair cortisol using an ELISA.

Evaluating stress in shelter and institutionally owned cats is important to help guide improvements in their welfare. Welfare assessments often focus on behavior metrics and physiologic measurements, such as systemic cortisol levels. The gold standard for measuring acute stress is serum cortisol; measuring cortisol in feces and urine gives reliable time-integrated assessments of acute stress.

Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter.

Background: the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain.

Results: through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.

Bempedoic Acid, the First-in-Class Oral ATP Citrate Lyase Inhibitor with Hypocholesterolemic Activity: Clinical Pharmacology and Drug-Drug Interactions.

Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug-drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg.

Solid-State Nanopores for Spatially Resolved Chemical Neuromodulation.

Most neural prosthetic devices are based on electrical stimulation, although the modulation of neuronal activity by a localized chemical delivery would better mimic physiological synaptic machinery. In the past decade, various drug delivery approaches attempted to emulate synaptic transmission, although they were hampered by poor retention of their cargo while reaching the target destination, low spatial resolution, and poor biocompatibility and stability of the materials involved. Here, we propose a planar solid-state device for multisite neurotransmitter translocation at the nanoscale consisting of a nanopatterned ceramic membrane connected to a reservoir designed to store neurotransmitters.

Intensive 2-days training on perfused human placenta for microvascular anastomoses.

Background And Purpose: We report on an intensive two-day training program on microanastomoses performed on perfused human placenta models. A specific scoring system was elaborated to evaluate the participants' microsurgical skills and report the participants' results.

Materials And Methods: Trainees who attended the Zurich Microsurgery Courses in 2023 were included in the study.

Correlation between nova volume flow rate and TOF signal intensity ratio: value in unilateral internal carotid artery occlusion.

Background And Purposes: Non-invasive optimal vessel analysis quantitative magnetic resonance angiography (NOVA-QMRA) has emerged as a valuable tool to characterize cerebral hemodynamics in intracranial atherosclerotic disease (ICAD). Our aim was to explore the eventual correlation between volume flow rate (VFR) measured via NOVA-QMRA and signal intensity ratio (SIR) of time-of-flight (TOF) MRA in M1- and P2-segments bilaterally in patients with unilateral internal carotid artery (ICA) occlusion.

Materials And Methods: Patients with acute, subacute or chronic unilaterall ICA occlusion receiving NOVA-QMRA between June 2019 and June 2021 were retrospectively included.

Reliable change indices for the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.

Background: . The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson's disease (PD) patients.

Methods: N = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.

Clinical usefulness of the Verbal Fluency Index (VFI) in amyotrophic lateral sclerosis.

Background: This study aimed at assessing the clinical utility of the Verbal Fluency Index (VFI) over a classical phonemic verbal fluency test in Italian-speaking amyotrophic lateral sclerosis (ALS) patients.

Methods: N = 343 non-demented ALS patients and N = 226 healthy controls (HCs) were administered the Verbal fluency - S task from the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The associations between the number of words produced (NoW), the time to read words aloud (TRW) and the VFI (computed as [(60"-TRW)/NoW]) on one hand and both bulbar/respiratory scores from the ALS Functional Rating Scale - Revised (ALSFRS-R) and the ECAS-Executive on the other were tested.

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

Background: This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients.

Methods: A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs).

Weight of Evidence: Criteria and Applications.

Toxicologists and authorities evaluate substances that in the traditional way refer to data and knowledge on the toxic mechanism. Non-testing methods (NTMs) proved to be a valuable resource for risk assessment of chemical substances. Indeed, they can be particularly useful when the information provided by different sources is integrated to increase confidence in the result.

Is tumour sequencing effective for the identification of germline pathogenic variant carriers?

Introduction: Tumour /2 sequencing has progressively increased along with the expanding indications for poly(ADP-ribose) polymerase inhibitors. In our study, we investigated the feasibility and outcomes of a workflow for the identification of germline carriers based on tumour sequencing results.

Methods: Between April 2020 and December 2022, tumour testing results from 2020 patients were reviewed.

Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke.

Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion.

Further insights into anti-IgLON5 disease: a case with complex clinical presentation.

Background: Anti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy.

Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets.

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment.

Transcranial static magnetic stimulation for amyotrophic lateral sclerosis: a bicentric, randomised, double-blind placebo-controlled phase 2 trial.

Background: Enhanced glutamatergic transmission leading to motor neuron death is considered the major pathophysiological mechanism of amyotrophic lateral sclerosis (ALS). Motor cortex excitability can be suppressed by transcranial static magnetic stimulation (tSMS), thus tSMS can be evaluated as a potential treatment for ALS. The aim of present study was to investigate the efficacy and safety of tSMS in ALS.

Microstates of Accelerating and Supersymmetric AdS_{4} Black Holes from the Spindle Index.

We provide a first principles derivation of the microscopic entropy of a very general class of supersymmetric, rotating, and accelerating black holes in AdS_{4}. This is achieved by analyzing the large-N limit of the spindle index and completes the construction of the first example of a holographic duality involving supersymmetric field theories defined on orbifolds with conical singularities.

Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.

Introduction: Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028.