HUMAN SKELETAL MUSCLE MITOCHONDRIA: CHANGES WITH AGING AND ROLE IN SARCOPENIA

Sarcopenia, the age-related progressive loss of muscle mass, strength and physical function, is a well-established risk factor for several negative health-related conditions. While cellular, systemic and lifestyle factors have shown to be associated with the onset and development of sarcopenia, the primary mechanisms contributing to this process are still uncertain, especially in humans. Among the cellular factors hypothesized to play a role on muscle aging is mitochondrial function. Several questions, however, remain. The purpose of study 1 of this dissertation was to investigate the association between mitochondrial capacity and chronological aging. Percutaneous biopsies of the vastus lateralis were obtained from 68 healthy men and women with a wide range of age (20-88yrs), body mass index (BMI, 19-47kg/m2) and cardiorespiratory fitness (VO2max: 1.08-5.04L/min). Mitochondrial capacity was evaluated through mitochondrial respiration in permeabilized myofibers and expression of proteins that mediate mitochondrial fusion, fission and autophagy. Mitochondrial respiration and expression of mitochondrial quality control proteins were elevated in young physically active individuals, but were similar among sedentary young, middle-aged and older subjects. The findings of this study suggest that mitochondrial capacity is not influenced by chronological age per se, but is closely related to BMI and cardiorespiratory fitness. Study 2 was performed to investigate the association between mitochondrial function and sarcopenia in very old adults. Specifically, the association between mitochondrial respiration and myofiber cross-sectional area, intramyocellular lipid content, and physical function were evaluated. Percutaneous biopsies from vastus lateralis were collected from 41 very old men and women (85-95yrs). Myofiber cross-sectional area and intramyocellular lipid content were evaluated histologically. Grip strength was tested by a handheld dynamometer, and knee extension torque was evaluated by an isokinetic dynamometer. Physical function was evaluated by physical performance tests including the multiple chair stand, standing balance, and gait speed. Mitochondrial respiration explained a significant amount of variation in grip strength and knee extension peak torque, and was associated with preferred gait speed. The findings of this study suggest that mitochondrial capacity plays a role in sarcopenia among the very old, but that other factors secondary to aging, including decreased physical activity and higher adiposity may influence this association

Liver injury, SARS-COV-2 infection and COVID-19: What physicians should really know?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre-existing liver disease in COVID-19 affected patients

Craniocervical posture in dysphonic women

OBJETIVO: Analisar a postura e a função da região crânio-cervical em sujeitos disfônicos. MÉTODOS: Participaram do estudo 28 mulheres (31,25±8,14 anos), divididas em dois grupos: experimental (N=16 portadoras de disfonia) e controle (N=12 clinicamente normais). As voluntárias foram submetidas à avaliação do Índice de Disfunção Crânio-Cervical (IDCC) e fotogrametria, sendo determinado o ângulo anterior formado entre a sétima vértebra cervical e o tragus, o qual corresponde à posição da cabeça no plano sagital. A análise das fotos foi realizada por três examinadores, duas vezes cada um, com intervalo de uma semana entre elas. A análise dos dados constou do teste de Shapiro-Wilk, seguido do teste t de Student, (p<0,05). RESULTADOS: Em relação à fotogrametria, não houve diferença (p=0,2565) entre os valores médios do ângulo anterior do grupo controle (50,92±5,18 graus) e do grupo experimental (49,63±5,46 graus). O IDCC mostrou que o grupo experimental apresentou disfunção crânio-cervical, sendo 37,5 % leve, 37,5% moderada e 25% severa. Já no grupo controle 100% das voluntárias apresentaram disfunção crânio-cervical leve. CONCLUSÃO: Não houve diferença na posição da cabeça entre os grupos avaliados. Porém, as mulheres disfônicas apresentaram disfunção crânio-cervical mais acentuada que as do grupo controle.Purpose: To analyze the posture and the function of the craniocervical region in women with dysphonia. METHODS: Twenty eight women participated in the study (31.25±8.14 years), divided into two groups: experimental (N=16, patients with dyphonia) and control (N=12, clinically normal). The volunteers were submitted to evaluation of the Craniocervical Dysfunction Index (CDI) and photogrammetry, determining the anterior angle formed between the seventh cervical vertebra and the tragus, which corresponds to the head position in the sagittal plane. The analysis of the photos was carried out by three examiners, twice each, with an interval of one week between them. Data analysis used the Shapiro-Wilk test, followed by the Student's t-test, (p<0,05). RESULTS: No difference was found between the mean values of the anterior angle of the control (50.92±5.18 degrees) and the experimental (49.63±5.46 degrees) groups in the photogrammetry (p=0.2565). The CDI showed that the experimental group had craniocervical dysfunction, which was mild in 37.5% of the cases, moderate, in 37.5%, and severe in 25%. In the control group, 100% of the volunteers had presented mild craniocervical dysfunction. CONCLUSION: There was no difference between the evaluated groups regarding head position. However, dysphonic women presented more severe craniocervical dysfunction than the group control

Impact of sleep disorders on behavioral issues in preschoolers with autism spectrum disorder

BackgroundSleep disorders are one of the most common problems in children with Autism Spectrum Disorder (ASD). However, they often tend to be underdiagnosed and incorrectly treated in clinical practice. This study aims to identify sleep disorders in preschool children with ASD and to explore their relationship with the core symptoms of autism, the child's developmental and cognitive level as well as the psychiatric comorbidities. MethodsWe recruited 163 preschool children with a diagnosis of ASD. The Children's Sleep Habits Questionnaire (CSHQ) assessed sleep conditions. Multiple standardized tests were used to evaluate intellectual abilities, the presence of repetitive behaviors (through the Repetitive Behavior Scale-Revised), as well as the emotional-behavioral problems and the psychiatric comorbidities (through the Child Behavior Checklist -CBCL 1(1/2)-5). ResultsThe results showed that poor disorders had consistently higher scores in all areas assessed by the CSHQ and on the CBCL across all domains. The correlational analysis showed that severe sleep disorders were associated with higher scores in internalizing, externalizing, and total problems at the CBCL syndromic scales, and in all DSM-oriented CBCL subscales. Moreover, we found that the association between sleep disorders and restricted and repetitive behaviors (RRBs) is explained by the anxiety-related symptoms. ConclusionBased on these findings, the study recommends that screening for sleep problems followed by early intervention should constitute a routine part of clinical practice for children with ASD

Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle. © 2013 Distefano et al

OltreMare - Un progetto per il futuro della Biodiversità del Mediterraneo

Osservatorio e comunicazione. Questo progetto narra dello sguardo degli artisti dell’Accademia di Belle Arti di Palermo sul lavoro di ricerca portato avanti dall’IAS - CNR (ex IAMC) riguardo all’osservazione e alla tutela della Biodiversità e costituisce uno strumento eccellente di comunicazione per un pubblico quanto mai ampio. La divulgazione della scienza è un’attività complessa e sicuramente necessita di competenze e attitudini multidisciplinari oltreché di motivazione ed entusiasmo. La comunicazione delle tematiche scientifiche, di per sè ostiche nella traduzione al grande pubblico, grazie alla forza e all’immediatezza tipica dell’espressione artistica diventa prodigioso spunto di riflessione e di osservazione, sia per i giovani che per la comunità intera. Grazie al progetto Osservatorio della Biodiversità Siciliana, sono state realizzate da partners con competenze istituzionali complementari , quali l’Accademia di Belle Arti di Palermo e l’IAS - CNR di Capo Granitola, delle azioni didattiche e creative di valore scientifico espresse con straordinaria forza e bellezza. La sinergia creata, nata da un rapporto consolidato ormai da tempo, ha portato ad uno scambio tra ricercatori e professori che si sono messi in gioco in uno sforzo congiunto per avvicinare le proprie competenze. In seguito ad un’intensa attività di coordinamento e pianificazione dei lavori, si è riusciti a portare avanti un progetto ambizioso e imponente, coinvolgendo moltissimi ambiti scientifici e altrettante cattedre, sensibilizzando così gli artisti ai temi della Biodiversità. Le opere prodotte, accompagnate da schede scientifiche, hanno dunque acquisito un valore, oltreché artistico, didattico, e restano come testimonianze oggettive, nel percorso culturale, per i visitatori dell’Osservatorio. Questa collaborazione conferma l’importanza e l’opportunità di unire arte e scienza per esaltare la percezione della ricerca scientifica da parte della comunità e ,ancora una volta, si conferma come, per fare “cose straordinarie”, siano più importanti i rapporti umani piuttosto che le competenze tecniche. A tal proposito, un ringraziamento sentito al Prof. Calogero Piro che, con passione e dedizione, ha reso possibile questa esperienza, e al gruppo di Comunicazione EDU Lab dell’IAS - CNR, che è stato, per me, un supporto indispensabile per la realizzazione di questo complesso progetto

Architecture and performance of the KM3NeT front-end firmware

The KM3NeT infrastructure consists of two deep-sea neutrino telescopes being deployed in the Mediterranean Sea. The telescopes will detect extraterrestrial and atmospheric neutrinos by means of the incident photons induced by the passage of relativistic charged particles through the seawater as a consequence of a neutrino interaction. The telescopes are configured in a three-dimensional grid of digital optical modules, each hosting 31 photomultipliers. The photomultiplier signals produced by the incident Cherenkov photons are converted into digital information consisting of the integrated pulse duration and the time at which it surpasses a chosen threshold. The digitization is done by means of time to digital converters (TDCs) embedded in the field programmable gate array of the central logic board. Subsequently, a state machine formats the acquired data for its transmission to shore. We present the architecture and performance of the front-end firmware consisting of the TDCs and the state machine

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches