Durvalumab and multiple sclerosis: a causal link or simple unmasking?

Non applicabile - Letter to the edito

Neuromyelitis optica spectrum disorders associated with systemic sclerosis: a case report and literature review

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system (CNS) afecting predominantly the spinal cord, brainstem, and optic nerves [1]. NMOSD may be associated with a variety of immunemediated disorders, such as systemic lupus erythematosus, Sjögren syndrome, and other organ-specifc autoimmune diseases [2], though accurate information about their prevalence is not available [3]. Systemic sclerosis (SSc) is characterized by vascular alterations, activation of the immune system, and tissue fbrosis [4]. Only a few cases of coexisting systemic sclerosis (SSc) and NMOSD are described [1, 5–9]. We report a case of an NMOSD AQP4-IgG antibodypositive patient associated with SSc and a review of the available evidence of the relationship between these autoimmune disease

Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide

Non applicale in quanto si tratta di di una Letter to the Edito

Predictors of unemployment status in people with relapsing multiple sclerosis: a single center experience

Background: Multiple sclerosis (MS) is the most common cause of nontraumatic chronic neurological disability affecting young adults during their crucial employment years. Objectives: To evaluate patients and disease related factors associated to unemployment in a cohort of relapsing–remitting (RR) MS patients. Methods: We included RRMS patients with a follow-up of at least 1 year. We collected data about years of school education and employment status. Patients underwent a neuropsychological evaluation using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Demographic and clinical predictors of unemployment were assessed through a multivariable stepwise logistic regression model. Results: We evaluated 260 consecutive RRMS patients. Employed patients were less frequently female (68.4% vs 83.3%, p = 0.006), less disabled (median Expanded Disability Status Scale (EDSS) score: 2.0 (0–7.0) vs 2.5 (0–7.5), p < 0.001), with more years of school education (mean ± standard deviation (SD), years: 13.74 ± 0.30 vs 10.86 ± 3.47, p < 0.001). Female sex and a higher EDSS score resulted associated with a greater risk of unemployment (OR 3.510, 95% CI 1.654–7.448, p = 0.001; OR 1.366, 95% CI 1.074–1.737, p = 0.011, respectively), whereas a greater number of years of schooling and current disease-modifying therapy exposure resulted protective factors (OR 0.788, 95% CI 0.723–0.858, p < 0,001; OR 0.414, 95% CI 0.217–0.790, p = 0.008, respectively). Conclusions: Understanding work is pervasively influenced by consequences of MS, we confirmed the impact of demographic, physical, and cognitive factors on employment status in RRMS patients

Electronic Structure of CeFeAsO1-xFx (x=0, 0.11/x=0.12) compounds

We report an extensive study on the intrinsic bulk electronic structure of the high-temperature superconductor CeFeAsO0.89F0.11 and its parent compound CeFeAsO by soft and hard x-ray photoemission, x-ray absorption and soft-x-ray emission spectroscopies. The complementary surface/bulk probing depth, and the elemental and chemical sensitivity of these techniques allows resolving the intrinsic electronic structure of each element and correlating it with the local structure, which has been probed by extended-x-ray absorption fine structure spectroscopy. The measurements indicate a predominant 4f1 (i.e. Ce3+) initial state configuration for Cerium and an effective valence-band-to-4f charge-transfer screening of the core hole. The spectra also reveal the presence of a small Ce f0 initial state configuration, which we assign to the occurrence of an intermediate valence state. The data reveal a reasonably good agreement with the partial density of states as obtained in standard density functional calculations over a large energy range. Implications for the electronic structure of these materials are discussed.Comment: Accepted for publication in Phys. Rev.

Longitudinal Evaluation of Serum MOG-IgG and AQP4-IgG Antibodies in NMOSD by a Semiquantitative Ratiometric Method

Background and purpose: Immunoadsorption (IA) is an antibody-depleting therapy used to treat neuromyelitis optica spectrum disorder (NMOSD) associated to antiaquaporin 4 (anti-AQP4-IgG) and antimyelin oligodendrocyte glycoprotein (anti-MOG-IgG) serum autoantibodies. Our aim was to evaluate longitudinal changes of serum MOG-IgG and AQP4-IgG antibody titer and to correlate it with the clinical status. Methods: Autoantibody titer and clinical features of two MOG-IgG+/AQP4-IgG– and two AQP4-IgG+/MOG-IgG– patients with NMOSD were collected at baseline (T0), after 6 IA courses (T1), and then 2 weeks (T2) and 6 months after treatment (T3). A fluorescent ratiometric assay was used for a quantitative detection of MOG and AQP4 antibodies, based on HEK-293 cells transfected with the full-length hMOG fused to GFP or h-AQP4-M23 isoform fused to m-cherry, respectively. We defined the antibody titer as MOG quantitative ratio (MOGqr) and AQP4 quantitative ratio (AQP4qr). Results: In Case 1, the MOGqr dropped from 0.98 at T0 to 0.14 at T3, and in Case 2, it decreased from 0.96 at T0 to undetectable at T3. In Case3, the AQP4qr remained high: 0.90 at T0 and 0.92 at T3. In Case 4, the AQP4qr decreased from 0.50 at T0 to undetectable at T3. Complete recovery was found in Cases 1, 2, and 4. Conclusions: Semiquantitative ratiometric method accurately detects even slight variation of MOG-IgG and AQP4-IgG titer, suggesting it may be useful to monitor the antibody titer during the disease course and maintenance immunotherapy

Ag/mgo nanoparticles via gas aggregation nanocluster source for perovskite solar cell engineering

Nanocluster aggregation sources based on magnetron-sputtering represent precise and versatile means to deposit a controlled quantity of metal nanoparticles at selected interfaces. In this work, we exploit this methodology to produce Ag/MgO nanoparticles (NPs) and deposit them on a glass/FTO/TiO2 substrate, which constitutes the mesoscopic front electrode of a monolithic perovskite-based solar cell (PSC). Herein, the Ag NP growth through magnetron sputtering and gas aggregation, subsequently covered with MgO ultrathin layers, is fully characterized in terms of structural and morphological properties while thermal stability and endurance against air-induced oxidation are demonstrated in accordance with PSC manufacturing processes. Finally, once the NP coverage is optimized, the Ag/MgO engineered PSCs demonstrate an overall increase of 5% in terms of device power conversion efficiencies (up to 17.8%)

Ballistic nanofriction

Sliding parts in nanosystems such as Nano ElectroMechanical Systems (NEMS) and nanomotors, increasingly involve large speeds, and rotations as well as translations of the moving surfaces; yet, the physics of high speed nanoscale friction is so far unexplored. Here, by simulating the motion of drifting and of kicked Au clusters on graphite - a workhorse system of experimental relevance -- we demonstrate and characterize a novel "ballistic" friction regime at high speed, separate from drift at low speed. The temperature dependence of the cluster slip distance and time, measuring friction, is opposite in these two regimes, consistent with theory. Crucial to both regimes is the interplay of rotations and translations, shown to be correlated in slow drift but anticorrelated in fast sliding. Despite these differences, we find the velocity dependence of ballistic friction to be, like drift, viscous

Analyses of circRNA expression throughout the light-dark cycle reveal a strong regulation of (Cdr1as), associated with light entrainment in the SCN

Circular RNAs (circRNAs) are a large class of relatively stable RNA molecules that are highly expressed in animal brains. Many circRNAs have been associated with CNS disorders accompanied by an aberrant wake-sleep cycle. However, the regulation of circRNAs in brain homeostasis over daily light-dark (LD) cycles has not been characterized. Here, we aim to quantify the daily expression changes of circRNAs in physiological conditions in healthy adult animals. Using newly generated and public RNA-Seq data, we monitored circRNA expression throughout the 12:12 h LD cycle in various mouse brain regions. We identified that (Cdr1as), a conserved circRNA that regulates synaptic transmission, is highly expressed in the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Despite its high stability, (Cdr1as) has a very dynamic expression in the SCN throughout the LD cycle, as well as a significant regulation in the hippocampus following the entry into the dark phase. Computational integration of different public datasets predicted that (Cdr1as) is important for regulating light entrainment in the SCN. We hypothesize that the expression changes of (Cdr1as) in the SCN, particularly during the dark phase, are associated with light-induced phase shifts. Importantly, our work revises the current beliefs about natural circRNA stability and suggests that the time component must be considered when studying circRNA regulation

Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia.

Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75 <sup>NTR</sup> ) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO