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BackgroundChronic sympathetic stimulation drives desensitization and downregulation of β1 adrenergic receptor (β1AR) in heart failure. We aim to explore the differential downregulation subcellular pools of β1AR signaling in the heart.Methods and resultsWe applied chronic infusion of isoproterenol to induced cardiomyopathy in male C57BL/6J mice. We applied confocal and proximity ligation assay to examine β1AR association with L-type calcium channel, ryanodine receptor 2, and SERCA2a ((Sarco)endoplasmic reticulum calcium ATPase 2a) and Förster resonance energy transfer-based biosensors to probe subcellular β1AR-PKA (protein kinase A) signaling in ventricular myocytes. Chronic infusion of isoproterenol led to reduced β1AR protein levels, receptor association with L-type calcium channel and ryanodine receptor 2 measured by proximity ligation (puncta/cell, 29.65 saline versus 14.17 isoproterenol, P

Autism spectrum disorders and developmental coordination disorders are both associated with sensorimotor impairments, yet their nature and specificity remain unknown. In order to clearly distinguish the specificity between the two disorders, children with autism spectrum disorder or developmental coordination disorder presenting the same degree of motor impairment, thus homogeneous profiles, were examined in a reach-to-displace paradigm, which allows the integrity of two main aspects of motor control (anticipation/feedforward control and movement correction/feedback control) to be separately interrogated. We manipulated children's previous knowledge of the weight of the object they were to displace: when known, participants could anticipate the consequences of the weight when reaching for the object, prior to contact with it, thus allowing for feedforward control. Conversely, when unknown prior to contact, participants had to cope with the object weight in the displacing phase of the movement, and use feedback control. Results revealed a preserved feedforward control, but an impaired movement execution (atypical slowness) in children with developmental coordination disorder, while children with autism spectrum disorder displayed the opposite pattern with an impaired feedforward control, but a preserved feedback one. These findings shed light on how specific motor impairments might differently characterize developmental disorders and call for motor rehabilitation programmes adapted to each population.

Abstract Background In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer’s disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future. Methods The ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50–85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ([18F]FDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1–40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram. Discussion This paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions. Trial registration ClinicalTrials.gov NCT03834402. Registered on February 8, 2019

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS: A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS: SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.

Background Chronic sympathetic stimulation drives desensitization and downregulation of β1 adrenergic receptor (β1AR) in heart failure. We aim to explore the differential downregulation subcellular pools of β1AR signaling in the heart. Methods and Results We applied chronic infusion of isoproterenol to induced cardiomyopathy in male C57BL/6J mice. We applied confocal and proximity ligation assay to examine β1AR association with L‐type calcium channel, ryanodine receptor 2, and SERCA2a ((Sarco)endoplasmic reticulum calcium ATPase 2a) and Förster resonance energy transfer‐based biosensors to probe subcellular β1AR‐PKA (protein kinase A) signaling in ventricular myocytes. Chronic infusion of isoproterenol led to reduced β1AR protein levels, receptor association with L‐type calcium channel and ryanodine receptor 2 measured by proximity ligation (puncta/cell, 29.65 saline versus 14.17 isoproterenol, P

Severe tricuspid regurgitation (TR) is a pathological condition associated with worse cardiovascular outcomes. In the vicious cycle of right ventricular compensation and maladaptation to TR, the development of right ventricle (RV) dysfunction has significant prognostic implications, especially in patients undergoing surgical or percutaneous treatments. Indeed, RV dysfunction is associated with increased operative morbidity and mortality in both surgical and percutaneously treated patients. In this context, the identification of clinical or subtle right ventricle dysfunction plays a critical role inpatient selection and timing of surgical or percutaneous tricuspid valve intervention. However, in the presence of severe TR, evaluation of RV function is challenging, given the increase in preload that may lead to an overestimation of systolic function for the Frank–Starling law, reduced reliability of pulmonary artery pressure estimation, the sensitivity of RV to afterload that may result in afterload mismatch after treatment. Consequently, conventional echocardiographic indices have some limitations, and the use of speckle tracking for right ventricular free wall longitudinal strain (RV-FWLS) analysis and the use of 3D echocardiography for RV volumes and ejection fraction estimation are showing promising data. Cardiac magnetic resonance (CMR) represents the gold standards for volumes and ejection fraction evaluation and may add further prognostic information. Finally, cardiac computer tomography (CCT) provides measurements of RV and annulus dimensions that are particularly useful in the transcatheter field. Identification of subtle RV dysfunction may need, therefore, more than one imaging technique, which will lead to tip the balance between medical therapy and early intervention towards the latter before disease progression. Therefore, the aim of this review is to describe the main imaging techniques, providing a comprehensive assessment of their role in RV function evaluation in the presence of severe TR. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Health Education, Sport & Inclusive Didactics is the property of Edizioni Universitarie Romane and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nuova Rivista Storica is the property of Societa Editrice Dante Alighieri s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Autism spectrum disorders and developmental coordination disorders are both associated with sensorimotor impairments, yet their nature and specificity remain unknown. In order to clearly distinguish the specificity between the two disorders, children with autism spectrum disorder or developmental coordination disorder presenting the same degree of motor impairment, thus homogeneous profiles, were examined in a reach-to-displace paradigm, which allows the integrity of two main aspects of motor control (anticipation/feedforward control and movement correction/feedback control) to be separately interrogated. We manipulated children's previous knowledge of the weight of the object they were to displace: when known, participants could anticipate the consequences of the weight when reaching for the object, prior to contact with it, thus allowing for feedforward control. Conversely, when unknown prior to contact, participants had to cope with the object weight in the displacing phase of the movement, and use feedback control. Results revealed a preserved feedforward control, but an impaired movement execution (atypical slowness) in children with developmental coordination disorder, while children with autism spectrum disorder displayed the opposite pattern with an impaired feedforward control, but a preserved feedback one. These findings shed light on how specific motor impairments might differently characterize developmental disorders and call for motor rehabilitation programmes adapted to each population. A vast majority of individuals with autism spectrum disorder experience impairments in motor skills. Those are often labelled as additional developmental coordination disorder despite the lack of studies comparing both disorders. Consequently, motor skills rehabilitation programmes in autism are often not specific but rather consist in standard programmes for developmental coordination disorder. Here, we compared motor performance in three groups of children: a control group, an autism spectrum disorder group and a developmental coordination disorder group. Despite similar level of motor skills evaluated by the standard movement assessment battery for children, in a Reach-to-Displace Task, children with autism spectrum disorder and developmental coordination disorder showed specific motor control deficits. Children with autism spectrum disorder failed to anticipate the object properties, but could correct their movement as well as typically developing children. In contrast, children with developmental coordination disorder were atypically slow, but showed a spared anticipation. Our study has important clinical implications as motor skills rehabilitations are crucial to both populations. Specifically, our findings suggest that individuals with autism spectrum disorder would benefit from therapies aiming at improving their anticipation, maybe through the support of their preserved representations and use of sensory information. Conversely, individuals with developmental coordination disorder would benefit from a focus on the use of sensory information in a timely fashion. [ABSTRACT FROM AUTHOR]

In the context of recent educational reforms, the resolution CNE/CP 02/2019 was promulgated, defining the National Curricular Guidelines for Teacher Education, replacing the old Guidelines (Resolution CNE/CP 02/2015), and requiring Higher Education Institutions to reformulate the pedagogical projects of undergraduate courses. The present paper seeks to trace a comparative analysis between the two guidelines, understanding the social, economic and political contexts of their implementation, exposing their similarities and differences, as well as the possible consequences of the modification in the training profile of new teachers. The study carried out here points out that, in general, the current guidelines are more prescriptive and standardizing in relation to their predecessors, besides not bringing elements about continuing education and not talking much about the issue of professional development of teachers. Considering such characteristics and the undemocratic context of its implementation, the current resolution can be seen as a step backwards in Brazilian public educational policies. [ABSTRACT FROM AUTHOR]

The article discusses the use of indirect immunofluorescence (IIF) for diagnosing bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) in patients. The study compares the sensitivity and specificity of human salt-split skin sections (hSSS) and monkey salt-split skin sections (mSSS) in detecting autoantibodies from BP and MMP patients. The results show that hSSS is more sensitive in detecting BP reactivity to the epidermal side, while mSSS is more sensitive in detecting reactivity to the dermal side in both BP and MMP patients. The study suggests carefully choosing the most suitable substrate to improve the diagnostic performance of IIF. [Extracted from the article]