A novel LMNA mutation (R189W) in familial dilated cardiomyopathy: evidence for a 'hot spot' region at exon 3: a case report

We describe a case of a patient with idiopathic dilated cardiomyopathy and cardiac conduction abnormalities who presented a strong family history of sudden cardiac death. Genetic screening of lamin A/C gene revealed in proband the presence of a novel missense mutation (R189W), near the most prevalent lamin A/C mutation (R190W), suggesting a "hot spot" region at exon 3

Becoming adults: Exploring the late ontogeny of the human talus

Introduction: The talus plays an important role in receiving and dissipating the forces and linking the leg and the foot. As such, it is of paramount importance to analyze how its morphology, internal and external, changes during late ontogeny and through adolescence. Method: To explore both the external shape and the internal architecture of the talus, Geometric Morphometrics and trabecular analysis have been applied to a sample of 35 tali from modern human juveniles aged between 5 and 15 years old (Middle Neolithic (4800-4500 BCE) to mid-20th century). Results: Results show that, as the overall size of the talus increases, the shape and orientation of talar facets also change. The youngest individuals exhibit a functional talus that is still characterized by a relatively immature shape (e.g., subtly expressed margins of articular surfaces) with articular facets only minimally rotated towards an adult configuration. In adolescents, talar shape has achieved adult form after the age of 11, with all the articular facets and posterior processes well-developed. Considering internal morphology, trabecular bone varies between age classes. While Bone Volume Fraction shifts during the age 5-15 range, Degree of Anisotropy is relatively more stable over the developmental period examined in the study since it exhibits smaller variations between age classes. Discussion: This study examined the late ontogeny of the human talus by considering both internal and external morphology. Results suggest that, although the locomotion has already assumed an adult-like pattern, the exploration of late talar growth may help understand how the talus adapts to changes in locomotor activity and how it responds to the increase in weight. Present results can be used to a better understanding of talar plasticity, improving interpretations of adult human talar form

Document Delivery and Resource Sharing: Global Perspectives

This publication is intended to provide librarians, library practitioners, as well as teachers, researchers, and students of universities and research organizations and other interested parties, a foundation in resource sharing principles, practices and management. This publication provides an overview of where things stand today with resource sharing, including key trends, challenges, opportunities, and priorities. The publication seeks to address international resource sharing, exploring the current state of European and international resource sharing systems and the governing laws and regulations and includes case studies and best practices from various countries

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Knowledge and attitudes towards clinical trials among women with ovarian cancer: results of the ACTO study

Background Despite several initiatives by research groups, regulatory authorities, and scientific associations to engage citizens/patients in clinical research, there are still obstacles to participation. Among the main discouraging aspects are incomplete understanding of the concepts related to a clinical trial, and the scant, sometimes confused, explanations given. This observational, cross-sectional multicenter study investigated knowledge, attitudes and trust in clinical research. We conducted a survey among women with ovarian cancer at their first follow-up visit or first therapy session, treated in centers belonging to the Mario Negri Gynecologic Oncology (MaNGO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups. A questionnaire on knowledge, attitudes and experience was assembled ad hoc after a literature review and a validation process involving patients of the Alliance against Ovarian Cancer (ACTO). Results From 25 centers 348 questionnaire were collected; 73.5% of responders were 56 years or older, 54.8% had a high level of education, more than 80% had no experience of trial participation. Among participants 59% knew what clinical trials were and 71% what informed consent was. However, more than half did not know the meaning of the term randomization. More than half (56%) were in favor of participating in a clinical trial, but 35% were not certain. Almost all responders acknowledged the doctor's importance in decision-making. Patients' associations were recognized as having a powerful role in the design and planning of clinical trials. Conclusions This study helps depict the knowledge and attitudes of women with ovarian cancer in relation to clinical trials, suggesting measures aimed at improving trial "culture", literacy and compliance, and fresh ways of communication between doctors and patients

Roadmap on thermoelectricity

The increasing energy demand and the ever more pressing need for clean technologies of energy conversion pose one of the most urgent and complicated issues of our age. Thermoelectricity, namely the direct conversion of waste heat into electricity, is a promising technique based on a long-standing physical phenomenon, which still has not fully developed its potential, mainly due to the low efficiency of the process. In order to improve the thermoelectric performance, a huge effort is being made by physicists, materials scientists and engineers, with the primary aims of better understanding the fundamental issues ruling the improvement of the thermoelectric figure of merit, and finally building the most efficient thermoelectric devices. In this Roadmap an overview is given about the most recent experimental and computational results obtained within the Italian research community on the optimization of composition and morphology of some thermoelectric materials, as well as on the design of thermoelectric and hybrid thermoelectric/photovoltaic devices

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Hemorrhagic transformation in acute ischemic stroke patients and atrial fibrillation: time to initiation of anticoagulants and outcome

Background: In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results: HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions: In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients