Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Oltre il Segno/OltreMare

La realizzazione di un volume contenente le incisioni scelte all’interno della Scuola di Grafica d’Arte dell’Accademia di Belle Arti di Palermo, coordinata dai Proff. Giovanni D’Alessandro e Riccardo Mazzarino rappresenta motivo di orgoglio e di soddisfazione per la nostra Istituzione che costruisce i percorsi didattici dei propri corsi a partire dall’esperienza laboratoriale. L’incisione grafica è tra le tecniche artistiche più antiche ma nel contempo più contemporanee. La gestualità intrinseca al segno, che si manifesta nella carta, svela universi della visione inaspettati.(Mario Zito - Direttore dell’Accademia di Belle Arti di Palermo) Il segno è il risultato di un gesto a volte deciso, a volte contorto, a volte leggero, i cui risultati spesso sono inattesi e sorprendenti. Il volume contiene esemplari di incisioni fortemente caratterizzanti della scuola di Grafica d’Arte che vanta all’interno del proprio corso di studi docenti-artisti che consapevoli della ricchezza del loro bagaglio esperienziale offrono agli studenti gli strumenti necessari per far sì che l’arte del saper fare artigianale, si trasformi in mera poetica artistica

Postural Stability Induced by Supervised Physical Training may improve also Oxygen Cost of Exercise and Walking Capacity in Post-Menopause, Obese Women

We utilized the training impulses method to numerically quantify the volume of physical exercise to be prescribed to postmenopausal obese women in such a way of obtain the best possible improvement of their health-related quality of life. Nine women (57±4 years, 89±2 kg, 157±9 cm) carried out 3-months of exercise training (3 session/week each lasting 80 min) under the supervision of skilled operators which indirectly calculated the volume of physical exercise by assessing heart rate values while patient exercised and making sure that the workload corresponded to 50-60% of their maximum oxygen uptake. Before and after training anthropometric, functional and biomechanical variables were assessed. After training patients shoved statistically signifi cant (P<0.05) reduction in body mass (-2%) and body mass index (-4%), waist circumference (-4%), total (-6%) and LDL (-26%) serum cholesterol and glycaemia (-8%), diastolic arterial blood pressure (-14%), and oxygen cost (-14%) at the maximum workload during incremental cardiopulmonary test, the sway area from unipedal stance (right leg) of 20 s on a pressure platform (-49%), while increased both free fat body mass percentage (+3%) and space covered during the six minute walk test (+11%). It was concluded that, when an exercise protocol is carried out by postmenopausal obese women and the volume of exercise is instrumentally controlled by experienced operators, it could result in an effective benefi t on the quality of life of these patients since they ameliorate some critical anthropometric and functional parameters

Switching-on fluorescence by copper (II) and basic anions: A case study with a pyrene-functionalized squaramide

The new symmetric acyclic N,N’-bis(1-pyrenyl) squaramide (H2L) functionalized with the pyrene moiety as a fluorogenic fragment has been designed and its ability to selectively detect specific anions and metals investigated. H2L selectively binds Cl− both in solution (DMSO 0.5% H2O and MeCN) and in the solid state, and allows to selectively detect Cu2+ in MeCN with the formation of a 2:1 metal-receptor complex, with a green intense emission appreciable by naked eye under the UV lamp. The H2L copper complex preserves its emission properties in the presence of Cl−. The addition of basic anions (OH−, CN−, and F−) up to 10 equivalents caused the deprotonation of the squaramide NHs and a dramatic change of the emission properties of the H2L copper complex

Coordination Chemistry and Sensing Properties Towards Anions and Metal Ions of a Simple Fluorescent Urea

The coordination and sensing properties towards anions and transition metal ions of the simple novel fluorescent urea 1-(2-aminophenyl)-3-(naphthalen-1)-yl)urea (L) were investigated in solution, and in the solid state. An electron donating amine group in the molecular skeleton of L decreased the acidity of the urea NHs that are usually deprotonated by basic anions and allowed for a good degree of affinity towards fluoride in DMSO-d6-0.5 %H2O. Moreover, the amine moiety acted as a further binding group for metal ions. Indeed, L was able to bind Zn2+ both in solution and in the solid state, and to respond to the presence of this metal ion in MeCN with an enhancement of the fluorescence emission. Although solution studies evidenced the formation of a 1 : 1 complex of L with Zn2+, complexes with a 2 : 1 ligand-to-metal stoichiometry were isolated in the solid state. DFT calculations helped to clarify the stability reasons behind these results.</p

Comparison of Two Therapeutic Approaches of Cerebellar Transcranial Direct Current Stimulation in a Sardinian Family Affected by Spinocerebellar Ataxia 38: a Clinical and Computerized 3D Gait Analysis Study

Spinocerebellar ataxia 38 (SCA 38) is a very rare autosomal dominant inherited disorder caused by a mutation in ELOV5 gene, specifically expressed in cerebellar Purkinje cells, encoding an enzyme involved in the synthesis of fatty acids. Seven symptomatic SCA 38 patients of a Sardinian family were administered 15 sessions of cerebellar anodal transcranial direct current stimulation (tDCS) in a cross-over study, employing deltoid cerebellar-only (C-tDCS) and cerebello-spinal (CS-tDCS) cathodal montage. Clinical evaluation was performed at baseline (T0), after 15 sessions of tDCS (T1) and after 1 month of follow-up (T2). Modified International Cooperative Ataxia Rating Scale (MICARS) and the Robertson dysarthria profile were used to rate ataxic and dysarthric symptoms, respectively. Alertness and split attention tests from Zimmermann test battery for attentional performance were employed to rate attentive functions. Moreover, 3D computerized gait analysis was employed to obtain a quantitative measure of efficacy of tDCS on motor symptoms. While clinical data showed that both CS and C-tDCS improved motor, dysarthric, and cognitive scores, the quantitative analysis of gait revealed significant improvement in spatio-temporal parameters only for C-tDCS treatment. Present findings, yet preliminary and limited by the small size of the tested sample, confirm the therapeutic potential of cerebellar tDCS in improving motor and cognitive symptoms in spinocerebellar ataxias and underline the need to obtain quantitative and objective measures to monitor the efficacy of a therapeutic treatment and to design tailored rehabilitative interventions. ClinicalTrials.gov identifier: NCT05951010

History, geography and population structure influence the distribution and heritability of blood and anthropometric quantitative traits in nine Sardinian genetic isolates

Isolated founder populations which exhibit great genetic and environmental homogeneity provide an attractive setting for the study of quantitative traits (QTs). Geneticists have repeatedly turned to population isolates and the past successes have prompted increased interest among medical researchers. We studied nine small isolated villages of a secluded area of Sardinia (Ogliastra), all of them characterized by a few founders, high endogamy rates, slow population expansion and a distinct genetic makeup. Anthropometric and blood parameters, 43 QTs in all, were analysed in about 9000 voluntary subjects for whom extended genealogical information was available. We explored the distribution and examined mean differences of each trait among villages by analysis of variance (ANOVA). A heritability analysis with the variance component (VC) method was performed. Results show significant differences in the distribution of most traits between groups of villages located in two distinct geographical areas already identified by a previous population structure analysis, thus supporting the existence of differentiation among sub-populations in the same region. Heritability estimates range between 30 and 89%, demonstrating that genetic effects substantially contribute to phenotypic variation of all investigated traits and that this population provides excellent research conditions for gene-mapping projects. Results suggest that history, geographic location and population structure may have influenced the genetic and phenotypic features of these isolates. Our findings may be useful for the ongoing linkage and association studies in these isolates and suggest that a thorough characterization of population is valuable to better identify genes or variants that may be rare in the population at large and peculiar to single villages

Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or &gt;= 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care