3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser.

Estimating the potential risk of transmission of arboviruses in the Americas and Europe: a modelling study.

Background: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available.

Methods: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records.

Antithrombotic prophylaxis following total hip arthroplasty: a level I Bayesian network meta-analysis.

Background: Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA).

Evaluating the Reliability of YouTube as a Source of Information for Meniscal Ramp Lesions.

Background: Videos uploaded to YouTube do not go through a review process, and therefore, videos related to medial meniscal ramp lesions may have little educational value.

Purpose: To assess the educational quality of YouTube videos regarding ramp lesions of the meniscus.

Study Design: Cross-sectional study.

Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy.

Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA).

Methods: People aged between 18 and 60 were recruited as being DRA carriers.

Storage and Learning Phase Transitions in the Random-Features Hopfield Model.

The Hopfield model is a paradigmatic model of neural networks that has been analyzed for many decades in the statistical physics, neuroscience, and machine learning communities. Inspired by the manifold hypothesis in machine learning, we propose and investigate a generalization of the standard setting that we name random-features Hopfield model. Here, P binary patterns of length N are generated by applying to Gaussian vectors sampled in a latent space of dimension D a random projection followed by a nonlinearity.

Length Scale of Molecular Motions Governing Glass Equilibration in Hyperquenched and Slow-Cooled Polystyrene.

Polymer glasses attain thermodynamic equilibrium owing to structural relaxation at various length scales. Herein, calorimetry experiments were conducted to trace the macroscopic relaxation of slow-cooled (SC) and hyperquenched (HQ) polystyrene (PS) glasses and based on detailed comparisons with molecular dynamics probed by dye reorientation, we discussed the possible molecular process governing the equilibration of PS glasses near the glass transition temperatures (). Both SC and HQ glasses equilibrate owing to the cooperative segment motion above a characteristic temperature () slightly lower than the .

Association between air pollution and emergency room admission for eye diseases in Rome, Italy: A time-series analysis.

Eye diseases impose a significant burden on health services due to high case numbers. However, exposure to outdoor air pollution is seldom mentioned as potential harmful factor. We conducted a time-series analysis in Rome, Italy, to estimate the association between daily mean concentration of NO, PM and PM and daily number of emergency room (ER) admissions for a selected cluster of eye diseases from 2006 to 2016.

Surgical Treatment of Complex Craniofacial Fractures.

Objective: Severe craniofacial fractures may present different needs in treating intracranial lesions over facial injuries. This paper examines the results of our strategy, consisting of a single-stage combined neurosurgical-maxillofacial treatment.

Methods: A retrospective review was conducted of 33 consecutive patients with complex fractures of the anterior cranial fossa and facial skeleton, who required elective surgery for craniofacial reconstruction.

Exploring the infiltrative and degradative ability of Fusarium oxysporum on polyethylene terephthalate (PET) using correlative microscopy and deep learning.

Managing the worldwide steady increase in the production of plastic while mitigating the Earth's global pollution is one of the greatest challenges nowadays. Fungi are often involved in biodegradation processes thanks to their ability to penetrate into substrates and release powerful catabolic exoenzymes. However, studying the interaction between fungi and plastic substrates is challenging due to the deep hyphal penetration, which hinders visualisation and evaluation of fungal activity.

Level I of evidence does not support manual lymphatic drainage for total knee arthroplasty: a meta-analysis.

It is unclear whether manual lymphatic drainage (MLD) following primary total knee arthroplasty (TKA) is effective in reducing pain and swelling and improving knee function. The present study investigated the efficacy of MLD after TKA. The outcomes of interest are the range of motion (ROM), pain (visual analogue scale, VAS), and circumference of the lower leg.

Membrane-permeable tenofovir-di- and monophosphate analogues.

The development of new antiviral agents such as nucleoside analogues or acyclic nucleotide analogues (ANPs) and prodrugs thereof is an ongoing task. We report on the synthesis of three types of lipophilic triphosphate analogues of (R)-PMPA and dialkylated diphosphate analogues of (R)-PMPA. A highly selective release of the different nucleotide analogues ((R)-PMPA-DP, (R)-PMPA-MP, and (R)-PMPA) from these compounds was achieved.

Promoting mental health and preventing mental health problems in child and adolescent refugees and asylum seekers: A systematic review on psychosocial interventions.

Background: According to the United Nations Commissioner for Refugees (UNHCR), children and adolescents represent 41% of all forcibly displaced individuals. They have to deal with conflicts, violence, and the many difficulties of flight and resettlement during a critical stage of their emotional, social, cognitive, and physical development. They are more likely to experience mental health problems during migration.

Bimodal Feature Analysis with Deep Learning for Autism Spectrum Disorder Detection.

Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder which affects a significant proportion of the population, with estimates suggesting that about 1 in 100 children worldwide are affected by ASD. This study introduces a new Deep Neural Network for identifying ASD in children through gait analysis, using features extracted from frames composing video recordings of their walking patterns. The innovative method presented herein is based on imagery and combines gait analysis and deep learning, offering a noninvasive and objective assessment of neurodevelopmental disorders while delivering high accuracy in ASD detection.

Can lifelong endurance exercise improve ageing through beneficial effects on circadian timing function, muscular performance and health status in men? Protocol for a comparative cross-sectional study.

A well-synchronized circadian system is a manifestation of an individual's health. A gradual weakening of the circadian timing function characterizes aging. Regular exercise has been suggested as a modality to improve many detrimental changes associated with aging.

Effects of cannabis smoking on the respiratory system: A state-of-the-art review.

The diminished perception of the health risks associated with the consumption of cannabis (marijuana) lead to a progressive increase in its inhalational use in many countries. Cannabis can be smoked through the use of joints, spliffs and blunts, and it can be vaporised with the use of hookah or e-cigarettes. Delta-9 tetrahydrocannabinol (THC) is the main psychoactive component of cannabis smoke but contains numerous other substances.

Periodic health evaluation in athletes competing in Tokyo 2020: from SARS-CoV-2 to Olympic medals.

Background: The Tokyo Olympic games were the only games postponed for a year in peacetime, which will be remembered as the COVID-19 Olympics. No data are currently available on the effect on athlete's performance.

Aim: To examine the Italian Olympic athletes who have undergone the return to play (RTP) protocol after COVID-19 and their Olympic results.

Impact of adenomyosis on in vitro fertilization outcomes in women undergoing donor oocyte transfers: a prospective observational study.

Objective: To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes.

Design: A prospective observational cohort study.

Setting: University-affiliated in vitro fertilization center.