Fibroma of tendon sheath located within the ankle joint capsule

We report a very rare case of fibroma of the tendon sheath arising from the anteromedial ankle joint capsule, with no apparent connection to any tendon in the area, found in a 58-year-old patient complaining of progressive local swelling. This uncommon tumor has its usual localization in tendon sheaths, is extremely rare in joint capsules, and has never been described in this location previously. MRI showed nonuniform low signal intensity in T1- and T2-weighted images and high intensity in STIR images. The mass was completely excised by open surgery. Histopathological analysis later confirmed the diagnosis of a fibroma of the tendon sheath

The Italian open data meteorological portal: MISTRAL

AbstractAt the national level, in Italy, observational and forecast data are collected by various public bodies and are often kept in various small, heterogeneous and non‐interoperable repositories, released under different licenses, thus limiting the usability for external users. In this context, MISTRAL (the Meteo Italian SupercompuTing PoRtAL) was launched as the first Italian meteorological open data portal, with the aim of promoting the reuse of meteorological data sets available at national level coverage. The MISTRAL portal provides (and archives) meteorological data from various observation networks, both public and private, and forecast data that are generated and post‐processed within the Consortium for Small‐scale Modeling‐Limited Area Model Italia (COSMO‐LAMI) agreement using high performance computing (HPC) facilities. Also incorporated is the Italy Flash Flood use case, implemented with the collaboration of European Centre for Medium‐Range Weather Forecasts (ECMWF), which exploits cutting edge advances in HPC‐based post‐processing of ensemble precipitation forecasts, for different model resolutions, and applies those to deliver novel blended‐resolution forecasts specifically for Italy. Finally, in addition to providing architectures for the acquisition and display of observational data, MISTRAL also delivers an interactive system for visualizing forecast data of different resolutions as superimposed multi‐layer maps

Endothelial and Smooth Muscle Cells from Abdominal Aortic Aneurysm Have Increased Oxidative Stress and Telomere Attrition

Background: Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. Methods: TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG). Results and Conclusions: Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed. © 2012 Cafueri et al

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers

Introduction: Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk.Methods: Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated.Results: Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed.Conclusion: NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation

Physical and sedimentological characterisation of dredged sediments.

Port dredging operations inevitably create a turbid plume around the dredge and it is necessary to follow the movement of this to impede its diffusion into the surrounding environment and reduce any negative impacts. To characterise the extension and concentration of the plume induced by dredging it is necessary to study the physical properties of the water, the residence time of the sediments in the water column and the diffusion velocity of the water and sediments. It is also essential to characterise the area and determine the specifics of the port environment under so-called normal maritime-traffic conditions. During the initial stage of such a study it is necessary to obtain measurements under diverse wind-wave conditions to characterise the physical features of the water column of the port area, the turbidity, the quantity and dimension of the suspended particulate matter and the current dynamics. In this article we present a series of physico-sedimentological operations to characterise a zone to be dredged based upon our experience during pre-dredging work in the Port of Genoa (Italy)