Actuation and Control of a Steerable Catheter for Mitral Valve Repair

In the field of Structural Heart Diseases, Mitral Regurgitation's incidence is rising because of an aging population worldwide, and it has reached an annual mortality rate near 34%. The procedures of Structural Intervention Cardiology have enlarged the number of treated patients, since their minimally invasive and trans-catheter approach. To provide a forward step-change in this procedure, the aim of this work is to improve the use of the commercially available MitraClip system®, suggesting an innovative robot-assisted platform with autonomous control for the aforementioned system. The presented methodology is constituted of two phases: in the first one, we design, in the Solidworks® environment, 3D print and integrate the mechanical support with electrical motors and micro-controller devoted to catheter's steering. In the second phase, we develop the closed-loop position control to improve the accuracy in the autonomous positioning of the catheter. The described approach was tested to demonstrate its feasibility and dexterity: a position accuracy of 1.1±0.54 mm in following a given optimal trajectory was obtained

Ocrelizumab reduces cortical and deep grey matter loss compared to the S1P-receptor modulator in multiple sclerosis

Introduction: Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. Aim: To compare the effect of OCR and FGL on clinical and MRI endpoints. Methods: 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36 months underwent a 3-Tesla MRI at baseline and after 24 months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. Results: OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. Conclusions: When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss

Immune Response after COVID-19 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs

The impact of disease-modifying therapies (DMTs) on the immune response to coronavirus disease-2019 (COVID-19) vaccines in persons with multiple sclerosis (pwMS) needs further elucidation. We investigated BNT162b2 mRNA COVID-19 vaccine effects concerning antibody seroconversion, inflammatory mediators' level and immunophenotype assessment in pwMS treated with cladribine (c-pwMS, n = 29), fingolimod (f-pwMS, n = 15) and ocrelizumab (o-pwMS, n = 54). Anti-spike immunoglobulin (Ig)-G detection was performed by an enzyme immunoassay; molecular mediators (GrB, IFN-gamma and TNF-alpha) were quantified using the ELLA platform, and immunophenotype was assessed by flow cytometry. ANCOVA, Student's t-test and Pearson correlation analyses were applied. Only one o-pwMS showed a mild COVID-19 infection despite most o-pwMS lacking seroconversion and showing lower anti-spike IgG titers than c-pwMS and f-pwMS. No significant difference in cytokine production and lymphocyte count was observed in c-pwMS and f-pwMS. In contrast, in o-pwMS, a significant increase in GrB levels was detected after vaccination. Considering non-seroconverted o-pwMS, a significant increase in GrB serum levels and CD4+ T lymphocyte count was found after vaccination, and a negative correlation was observed between anti-spike IgG production and CD4+ T cells count. Differences in inflammatory mediators' production after BNT162b2 vaccination in o-pwMS, specifically in those lacking anti-spike IgG, suggest a protective cellular immune response

Defining neurotrauma in administrative data using the International Classification of Diseases Tenth Revision

Abstract Background It is essential to use a definition that is precise and accurate for the surveillance of traumatic brain injuries (TBI) and spinal cord injuries (SCI). This paper reviews the International Classification of Diseases 10th revision (ICD-10) definitions used internationally to inform the definition for neurotrauma surveillance using administrative data in Ontario, Canada. Methods PubMed, Web of Science, Medline and the grey literature were searched for keywords "spinal cord injuries" or "brain injuries" and "international classification of diseases". All papers and reports that used an ICD-10 definition were included. To determine the ICD-10 codes for inclusion consensus across papers and additional evidence were sought to look at the correlation between the condition and brain or spinal injuries. Results Twenty-four articles and reports were identified; 15 unique definitions for TBI and 7 for SCI were found. The definitions recommended for use in Ontario by this paper are F07.2, S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S06, S07.1, T90.2, and T90.5 for traumatic brain injuries and S14.0, S14.1, S24.0, S24.1, S34.1, S34.0, S34.3, T06.0, T06.1 and T91.3 for spinal cord injuries. Conclusions Internationally, inconsistent definitions are used to define brain and spinal cord injuries. An abstraction study of data would be an asset in understanding the effects of inclusion and exclusion of codes in the definition. This paper offers a definition of neurotrauma for surveillance in Ontario, but the definition could be applied to other countries that have mandated administrative data collection

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones