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Purpose: Human amniotic fluid-derived stem cells (hAFSC) are multipotent stem cells sharing characteristics of both embryonic and adult stem cells. It has been already reported that hAFSC can differentiate toward cardiac lineage though the embryonic body (EB) formation, but the 3D structure and cellular heterogeneity of EB represent an important limitation. Aim of this study was to fully differentiate the hAFSC overcoming the EB limitations.Methods: hAFSC were obtained from normal amniocentesis. Cells cultured in monolayer were exposed sequentially to Ascorbic Acid, 5-Azacytidine, BMP4, ActivinA, VEGF up to 20 days. Differentiation was evaluated monitoring by immunofluorescent and cytometric analyses the expression of CD90, as mesenchymal stem cell marker, and of Nkx2.5, Gata4, sarcomeric α-actinin (αSA), α cardiac myosin heavy chain (αMHC), cardiac T-troponin (TnT)and Connexin43 as cardiac markers. An ImageStream analysis for a simultaneous quantitative and morphological evaluation was also performed.Results: During the differentiation cultures cells underwent a progressive decrease of CD90 accompanied by the induction cardiac markers. After 15 days we evidenced that almost the entire cell population was positive for αMHC, αSA cTnT and Connexin 43 expressions (Table I); moreover, even if the % of Gata4+ and Nkx2.5+ cells did not varied during the culture, a significant increase of Nkx2.5 nuclear translocation (9.1±0.9% vs 18.0±1.8% Nkx2.5 nuclear positive cells in hAFSC and differentiated cells respectively, p<.005, analysis by ImageStream) was detected. Some small beating foci (about 8-10% of the plate) were also observed.Conclusion. We demonstrate that hAFSC can fully differentiate into myocytes giving rise to a homogenous population with cardiac-specific molecular and functional properties.Table 1Cell Positivity (%) and Mean Fluorescence Intensity of hAFSC before and after differentiationhAFSCDifferentiated hAFSCCell Positivity (%)MFICell Positivity (%)MFICD9099.3±0.5141.6±45.24.5±2.5*3.2±2.8*GATA482.5±7.421.9±1.695.7±3.124.3±0.6Nkx2.584.5±6.514.2±4.798.7±0.326.7±6.6αMHC3.7±5.427.9±6.598.7±1.1*155.6±15.6*αSA0.3±1.25.9±9.289.5±5.4*236.0±10.0*cTnT0.1±0.10.8±0.495.4±3.1*66.1±3.5*Connexin 4343.5±8.14.9±1.595.5±4.2*134.4±15.8* [ABSTRACT FROM PUBLISHER]

Sleep quality (SQ) is a crucial aspect of overall health. Poor sleep quality may cause cognitive impairment, mood disturbances, and an increased risk of chronic diseases. Therefore, assessing sleep quality helps identify individuals at risk and develop effective interventions. SQ has been demonstrated to affect heart rate variability (HRV) and skin temperature even during wakefulness. In this perspective, using wearables and contactless technologies to continuously monitor HR and skin temperature is highly suited for assessing objective SQ. However, studies modeling the relationship linking HRV and skin temperature metrics evaluated during wakefulness to predict SQ are lacking. This study aims to develop machine learning models based on HRV and skin temperature that estimate SQ as assessed by the Pittsburgh Sleep Quality Index (PSQI). HRV was measured with a wearable sensor, and facial skin temperature was measured by infrared thermal imaging. Classification models based on unimodal and multimodal HRV and skin temperature were developed. A Support Vector Machine applied to multimodal HRV and skin temperature delivered the best classification accuracy, 83.4%. This study can pave the way for the employment of wearable and contactless technologies to monitor SQ for ergonomic applications. The proposed method significantly advances the field by achieving a higher classification accuracy than existing state-of-the-art methods. Our multimodal approach leverages the synergistic effects of HRV and skin temperature metrics, thus providing a more comprehensive assessment of SQ. Quantitative performance indicators, such as the 83.4% classification accuracy, underscore the robustness and potential of our method in accurately predicting sleep quality using non-intrusive measurements taken during wakefulness.

Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by the loss of midbrain dopaminergic neurons. Endocrine disrupting chemicals (EDCs) are active substances that interfere with hormonal signaling. Among EDCs, bisphenols (BPs) and perfluoroalkyls (PFs) are chemicals leached from plastics and other household products, and humans are unavoidably exposed to these xenobiotics. Data from animal studies suggest that EDCs exposure may play a role in PD, but data about the effect of BPs and PFs on human models of the nervous system are lacking. Previous studies demonstrated that machine learning (ML) applied to microscopy data can classify different cell phenotypes based on image features. In this study, the effect of BPs and PFs at different concentrations within the real-life exposure range (0.01, 0.1, 1, and 2 µM) on the phenotypic profile of human stem cell-derived midbrain dopaminergic neurons (mDANs) was analyzed. Cells exposed for 72 h to the xenobiotics were stained with neuronal markers and evaluated using high content microscopy yielding 126 different phenotypic features. Three different ML models (LDA, XGBoost and LightGBM) were trained to classify EDC-treated versus control mDANs. EDC treated mDANs were identified with high accuracies (0.88-0.96). Assessment of the phenotypic feature contribution to the classification showed that EDCs induced a significant increase of alpha-synuclein (αSyn) and tyrosine hydroxylase (TH) staining intensity within the neurons. Moreover, microtubule-associated protein 2 (MAP2) neurite length and branching were significantly diminished in treated neurons. Our study shows that human mDANs are adversely impacted by exposure to EDCs, causing their phenotype to shift and exhibit more characteristics of PD. Importantly, ML-supported high-content imaging can identify concrete but subtle subcellular phenotypic changes that can be easily overlooked by visual inspection alone and that define EDCs effects in mDANs, thus enabling further pathological characterization in the future., (© 2023. The Author(s).)

Bisphenols and Perfluoroalkyls are chemical compounds widely used in industry known to be endocrine disruptors (EDs). Once ingested through contaminated aliments, they mimic the activity of endogenous hormones leading to a broad spectrum of diseases. Due to the extensive use of plastic in human life, particular attention should be paid to antenatal exposure to Bisphenols and Perfluoroalkyls since they cross the placental barrier and accumulates in developing embryo. Here we investigated the effects of Bisphenol-A (BPA), Bisphenol-S (BPS), perfluorooctane-sulfonate (PFOS) and perfluorooctanoic-acid (PFOA), alone or combined, on human-induced pluripotent stem cells (hiPSCs) that share several biological features with the stem cells of blastocysts. Our data show that these EDs affect hiPSC inducing a great mitotoxicity and dramatic changes in genes involved in the maintenance of pluripotency, germline specification, and epigenetic regulation. We also evidenced that these chemicals, when combined, may have additive, synergistic but also negative effects. All these data suggest that antenatal exposure to these EDs may affect the integrity of stem cells in the developing embryos, interfering with critical stages of early human development that might be determinant for fertility. The observation that the effects of exposure to a combination of these chemicals are not easily foreseeable further highlights the need for wider awareness of the complexity of the EDs effects on human health and of the social and economic burden attributable to these compounds., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Angela Di Baldassarre reports financial support was provided by Government of Italy Ministry of Education University and Research. Giulia Gaggi reports financial support was provided by European Union., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The present study investigates the impact of two endocrine disruptors, namely Bisphenols (BPs) and Perfluoroalkyls (PFs), on human stem cells. These chemicals leach from plastic, and when ingested through contaminated food and water, they interfere with endogenous hormone signaling, causing various diseases. While the ability of BPs and PFs to cross the placental barrier and accumulate in fetal serum has been documented, the exact consequences for human development require further elucidation. The present research work explored the effects of combined exposure to BPs (BPA or BPS) and PFs (PFOS and PFOA) on human placenta (fetal membrane mesenchymal stromal cells, hFM-MSCs) and amniotic fluid (hAFSCs)-derived stem cells. The effects of the xenobiotics were assessed by analyzing cell proliferation, mitochondrial functionality, and the expression of genes involved in pluripotency and epigenetic regulation, which are crucial for early human development. Our findings demonstrate that antenatal exposure to BPs and/or PFs may alter the biological characteristics of perinatal stem cells and fetal epigenome, with potential implications for health outcomes at birth and in adulthood. Further research is necessary to comprehend the full extent of these effects and their long-term consequences.

Background: Dental implant is the principal treatment for edentulism and the healthiness of the peri-implant tissue has a pivotal role for its longterm success. In addition, it has been shown that also the topography of the healing abutment can influence the outcome of the restoration. The objective of this human clinical trial was to assess the impact of a novel laser-treated healing abutment on peri-implant connective tissue and extracellular matrix proteins compared to the conventional machined surface, which served as the control group., Methods: During second surgical stage a customized healing abutment were inserted on 30 single dental implants. Healing abutments were realized with two alternated different surface (two side laser-treated surfaces and two side machined surfaces) in order to be considered both as test and control on the same implant and reduce positioning bias. Following the soft tissue healing period (30 ± 7 days) a 5 mm circular biopsy was retrieved. Immuno-histochemical and quantitative real-time PCR (qPCR) analyses were performed on Collagen, Tenascin C, Fibrillin I, Metalloproteinases (MMPs) and their inhibitor (TIMPs). 15 were processed for qPCR, while the other 15 were processed for immunohistochemical analysis. Paired t-test between the two groups were performed. A value of p < 0.05 was considered statistically significant., Results: Results revealed that the connective tissue facing the laser-treated surface expressed statistically significant lower amount of MMPs (p < 0.05) and higher level of TIMPs 3 (p < 0.05), compared to the tissue surrounding the machined implant, which, in turn expressed also altered level of extracellular matrix protein (Tenascin C, Fibrillin I (p < 0.05)) and Collagen V, that are known to be altered also in peri-implantitis., Conclusions: In conclusion, the laser-treated surface holds promise in positively influencing wound healing of peri-implant connective tissue. Results demonstrated that topographic nature of the healing abutments can positively influence mucosal wound healing and molecular expression. Previous studies have been demonstrated how laser treatment can rightly influence integrity and functionality of the gingiva epithelium and cell adhesion. Regarding connective tissue different molecular expression demonstrated a different inflammatory pattern between laser treated or machined surfaces where laser treated showed better response. Targeted interventions and preventive measures on peri- implant topography could effectively minimize the risk of peri-implant diseases contributing to the long-term success and durability of restoration. However, new studies are mandatory to better understand this phenomenon and the role of this surface in the peri-implantitis process.  TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov Identifier: (Registration Number: NCT05754970 ). Registered 06/03/2023, retrospectively registered., (© 2023. The Author(s).)

Skeletal muscle atrophy is represented by a dramatic decrease in muscle mass, and it is related to a lower life expectancy. Among the different causes, chronic inflammation and cancer promote protein loss through the effect of inflammatory cytokines, leading to muscle shrinkage. Thus, the availability of safe methods to counteract inflammation-derived atrophy is of high interest. Betaine is a methyl derivate of glycine and it is an important methyl group donor in transmethylation. Recently, some studies found that betaine could promote muscle growth, and it is also involved in anti-inflammatory mechanisms. Our hypothesis was that betaine would be able to prevent tumor necrosis factor-α (TNF-α)-mediated muscle atrophy in vitro. We treated differentiated C2C12 myotubes for 72 hr with either TNF-α, betaine, or a combination of them. After the treatment, we analyzed total protein synthesis, gene expression, and myotube morphology. Betaine treatment blunted the decrease in muscle protein synthesis rate exerted by TNF-α, and upregulated Mhy1 gene expression in both control and myotube treated with TNF-α. In addition, morphological analysis revealed that myotubes treated with both betaine and TNF-α did not show morphological features of TNF-α-mediated atrophy. We demonstrated that in vitro betaine supplementation counteracts the muscle atrophy led by inflammatory cytokines.

Introduction: This paper examines the convergence of the opinions of European higher education institution (HEI) experts on possible implementation of dual career policies and provision areas at university level., Methods: An online 32-item questionnaire encompassing 26 dual career aspects collected the opinion of European HEI experts as the last phase of a Delphi method preceded by i) focus groups with student-athletes who aimed to identify needs for dual careers and ii) a workshop with 21 dual career experts to generate the statements to be included in the survey. Seventy-one HEI experts from 12 EU member states participated in the survey, rating each dual career aspect identified in previous phases., Results: The relative position of each aspect has been plotted based on relevance (x-axis) and feasibility (y-axis). The Quadrant IV of the resulting scatterplots identified the following nine aspects rated as highly relevant and highly feasible for implementation: tutorship/mentorship, psychological support, programmes based on integration of academic departments and sports services, and adaptable programmes to the needs of each student-athletes (assistance/tutorship area), individual study plans and distance learning (curricula requirements area), publicity for student-athletes and initiatives for increasing the awareness of student-athletes and knowledge of dual career issues (social support area), and access to educational facilities (logistic support area)., Discussion and Conclusions: The HEI experts' views represent a coherent and useful starting point to develop a deep understanding of the considered 26 aspects founded on a phenomenological lifeworld-led approach and emphasizes the need for a minimum standard for dual career policies and provisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Izzicupo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

High-sensitivity cardiac troponin assays have become the gold standard for diagnosing acute and chronic myocardial injury. The detection of troponin levels beyond the 99th percentile is included in the fourth universal definition of myocardial infarction, specifically recommending the use of sex-specific thresholds. Measurable concentrations below the proposed diagnostic thresholds have been shown to inform prognosis in different categories of inpatients and outpatients. However, clinical investigations from the last twenty years have yielded conflicting results regarding the incremental value of using different cut-offs for men and women. While advocates of a sex-specific approach claim it may help reduce gender bias in cardiovascular medicine, particularly in acute coronary syndromes, other groups question the alleged incremental diagnostic and prognostic value of sex-specific thresholds, ultimately asserting that less is more. In the present review, we aimed to synthesize our current understanding of sex-based differences in cardiac troponin levels and to reappraise the available evidence with regard to (i) the prognostic significance of sex-specific diagnostic thresholds of high-sensitivity cardiac troponin assays compared to common cut-offs in both men and women undergoing cardiovascular disease risk assessment, and (ii) the clinical utility of high-sensitivity cardiac troponin assays for cardiovascular disease prevention in women.

Human fetal membrane mesenchymal stromal cells (hFM-MSCs) are a cell population easily isolable from the amniochorionic membrane of term placentas, without ethical issues or safety limitations. We previously reported that hFM-MSCs share some epigenetic characteristics with pluripotent stem cells and can overcome the mesenchymal commitment. Here, we demonstrated that hFM-MSCs can give rise to spinal motor neurons by the sequential exposure to specific factors that induced a neuralization, caudalization and ventralization of undifferentiated cells, leading to a gradual gene and protein upregulation of early and late MN markers. Also, spontaneous electrical activity (spikes and bursts) was recorded. Finally, when co-cultured with myotubes, differentiated MNs were able to create functional neuromuscular junctions that induced robust skeletal muscle cell contractions. These data demonstrated the hFM-MSCs can generate a mature and functional MN population that may represent an alternative source for regenerative medicine, disease modeling or drug screening., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Introduction: Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB., Methods and Analysis: A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane's RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health's tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used., Ethics and Dissemination: No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance., Systematic Review Registration: CRD42021282874., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Increasing evidence supports the importance of the gut microbiota (GM) in regulating multiple functions related to host physical health and, more recently, through the gut-brain axis (GBA), mental health. Similarly, the literature on the impact of physical activity (PA), including exercise, on GM and GBA is growing. Therefore, this narrative review summarizes and critically appraises the existing literature that delves into the benefits or adverse effects produced by PA on physical and mental health status through modifications of the GM, highlighting differences and similarities between preclinical and human studies. The same exercise in animal models, whether performed voluntarily or forced, has different effects on the GM, just as, in humans, intense endurance exercise can have a negative influence. In humans and animals, only aerobic PA seems able to modify the composition of the GM, whereas cardiovascular fitness appears related to specific microbial taxa or metabolites that promote a state of physical health. The PA favors bacterial strains that can promote physical performance and that can induce beneficial changes in the brain. Currently, it seems useful to prioritize aerobic activities at a moderate and not prolonged intensity. There may be greater benefits if PA is undertaken from a young age and the effects on the GM seem to gradually disappear when the activity is stopped. The PA produces modifications in the GM that can mediate and induce mental health benefits., Competing Interests: The authors declare no conflict of interest.

Human amniotic fluids stem cells (hAFSCs) can be easily isolated from the amniotic fluid during routinely scheduled amniocentesis. Unlike hiPSCs or hESC, they are neither tumorigenic nor immunogenic and their use does not rise ethical or safety issues: for these reasons they may represent a good candidate for the regenerative medicine. hAFSCs are generally considered multipotent and committed towards the mesodermal lineages; however, they express many pluripotent markers and share some epigenetic features with hiPSCs. Hence, we hypothesized that hAFSCs may overcome their mesodermal commitment differentiating into to ectodermal lineages. Here we demonstrated that by the sequential exposure to specific factors, hAFSCs can give rise to spinal motor neurons (MNs), as evidenced by the gradual gene and protein upregulation of early and late MN markers (PAX6, ISL1, HB9, NF-L, vAChT). When co-cultured with myotubes, hAFSCs-derived MNs were able to create functional neuromuscular junctions that induced robust skeletal muscle contractions. These data demonstrated the hAFSCs are not restricted to mesodermal commitment and can generate functional MNs thus outlining an ethically acceptable strategy for the study and treatment of the neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gaggi, Di Credico, Guarnieri, Mariggiò, Di Baldassarre and Ghinassi.)

Heart rate variability (HRV) is a reliable tool for the evaluation of several physiological factors modulating the heart rate (HR). Importantly, variations of HRV parameters may be indicative of cardiac diseases and altered psychophysiological conditions. Recently, several studies focused on procedures for contactless HR measurements from facial videos. However, the performances of these methods decrease when illumination is poor. Infrared thermography (IRT) could be useful to overcome this limitation. In fact, IRT can measure the infrared radiations emitted by the skin, working properly even in no visible light illumination conditions. This study investigated the capability of facial IRT to estimate HRV parameters through a face tracking algorithm and a cross-validated machine learning approach, employing photoplethysmography (PPG) as the gold standard for the HR evaluation. The results demonstrated a good capability of facial IRT in estimating HRV parameters. Particularly, strong correlations between the estimated and measured HR ( r = 0.7), RR intervals ( r = 0.67), TINN ( r = 0.71), and pNN50 (%) ( r = 0.70) were found, whereas moderate correlations for RMSSD ( r = 0.58), SDNN ( r = 0.44), and LF/HF ( r = 0.48) were discovered. The proposed procedure allows for a contactless estimation of the HRV that could be beneficial for evaluating both cardiac and general health status in subjects or conditions where contact probe sensors cannot be used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Di Credico, Perpetuini, Izzicupo, Gaggi, Cardone, Filippini, Merla, Ghinassi and Di Baldassarre.)

Previous studies have found that student-athletes (S-As) have difficulties in achieving dual career (DC) success. However, no studies have analysed the opinion of the S-As on the functioning of DC with a qualitative methodology. The aim of the present work was to collect the opinions of elite university S-As in relation to DC policy adopted by their academic institutions in different European countries. In total, 77 athletes (F = 35, M = 42; age range: 20-25 years) participated in 15 national face-to-face focus groups in five different countries, to discuss aspects that higher education institutes should implement in relation to: 1) the athletes' needs; 2) assistance/tutorship: 2) curricula requirements; 3) financial support; 4) logistic support; 5) social support; and 6) dual career policies. Fifty of the athletes competed in individual sports and twenty-seven team sports. Of them, 57 was enrolled at undergraduate, 17 was enrolled in a master and 3 in a PhD. The athletes were presented with 13 open-ended questions one by one, and were ensured freedom to interact. All the discussions were recorded. After this, a general discussion took place in which the participants identified and agreed on a final list of statements from their focus group deemed to be relevant to DC athletes as university students. Then, at a consensus meeting, the findings were combined, repetitions were eliminated, and fragmented statements were condensed into broader ones. A final list of 31 statements, organized in six related content units, were identified in relation to the athletes' needs (n = 5), assistance/tutorship (n = 5), curricula requirements (n = 4), financial support (n = 4), logistic support (n = 4), social support (n = 6), and DC policies (n = 3), respectively. In conclusion, this cross-national qualitative research study synthesized the S-As views about their needs and the most relevant DC policies and provisions that higher education institutes should provide to ensure them with positive academic experiences towards the achievement of a degree., Competing Interests: The authors have declared that no competing interests exist.

Team handball is a highly dynamic sport where physical demands differ between categories and roles. Thus, physical characteristics are fundamental for the final performance. This study aims to (a) characterize a sample of young male and female elite team handball players with a non-athletic reference population; (b) to generate their 50%, 75%, and 95% percentiles of the bioelectrical variables. The study included 55 young elite team handball players (Males, n = 37, age = 17.0 ± 1.2 yrs, height = 185.8 ± 7.3 cm, weight = 82.0 ± 11.0 kg, body mass index (BMI) = 23.7 ± 2.5; Females, n = 18, age = 17.8 ± 0.9 yrs, height = 171.2 ± 6.4 cm, weight = 67.4 ± 7.2 kg, BMI = 23.0 ± 2.0). Height and bioelectrical variables were assessed in a state of euhydration and standard conditions. Bioelectrical impedance vector analysis (BIVA) was used to characterize the bioelectrical vector (BIA vector) distribution pattern for each group. Compared to the reference values, BIA vector showed statistically significant differences in males U17 ( n = 19, T 2 = 51.0, p < 0.0001), males U19 ( n = 18, T 2 = 82.0, p < 0.0001) and females U19 ( n = 18, T 2 = 85.8, p < 0.0001). Male groups were also bioelectrically different (T 2 = 13.7, p = 0.0036). BIVA showed specific bioelectrical characteristics in young male and female elite handball players. This study provides an original data set of bioelectrical impedance reference values of young male and female elite team handball players. Our result might help to interpret individual bioimpedance vectors and define target regions for young handball players.

Levetiracetam (LEV) is a broad-spectrum and widely used antiepileptic drug that also has neuroprotective effects in different neurological conditions. Given its complex interaction with neuronal physiology, a better comprehension of LEV effects on neurons activity is needed. Microelectrode arrays (MEAs) represent an advanced technology for the non-invasive study of electrophysiological activity of neuronal cell cultures. In this study, we exploited the Maestro Edge MEA system, a platform that allows a deep analysis of the electrical network behavior, to study the electrophysiological effect of LEV on a mixed population of human neurons (glutamatergic, GABAergic and dopaminergic neurons, and astrocytes). We found that LEV significantly affected different variables such as spiking, single-electrode bursting, and network bursting activity, with a pronounced effect after 15 min. Moreover, neuronal cell culture completely rescued its baseline activity after 24 h without LEV. In summary, MEA technology confirmed its high sensitivity in detecting drug-induced electrophysiological modifications. Moreover, our results allow one to extend the knowledge on the electrophysiological effects of LEV on the complex neuronal population that resembles the human cortex.

Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Here we present a novel epigenetic effect of the essential nutrient, NAD. We demonstrate that impairment of DNMT1 enzymatic activity by NAD-promoted ADP-ribosylation leads to demethylation and transcriptional activation of the CEBPA gene, suggesting the existence of an unknown NAD-controlled region within the locus. In addition to the molecular events, NAD- treated cells exhibit significant morphological and phenotypical changes that correspond to myeloid differentiation. Collectively, these results delineate a novel role for NAD in cell differentiation, and indicate novel nutri-epigenetic strategies to regulate and control gene expression in human cells.

Measuring exercise variables is one of the most important points to consider to maximize physiological adaptations. High-intensity interval training (HIIT) is a useful method to improve both cardiovascular and neuromuscular performance. The 30-15 IFT is a field test reflecting the effort elicited by HIIT, and the final velocity reached in the test is used to set the intensity of HIIT during the training session. In order to have a valid measure of the velocity during training, devices such as GPS can be used. However, in several situations (e.g., indoor setting), such devices do not provide reliable measures. The aim of the study was to predict exact running velocity during the 30-15 IFT using accelerometry-derived metrics (i.e., Player Load and Average Net Force) and heart rate (HR) through a machine learning (ML) approach (i.e., Support Vector Machine) with a leave-one-subject-out cross-validation. The SVM approach showed the highest performance to predict running velocity (r = 0.91) when compared to univariate approaches using PL (r = 0.62), AvNetForce (r = 0.73) and HR only (r = 0.87). In conclusion, the presented multivariate ML approach is able to predict running velocity better than univariate ones, and the model is generalizable across subjects.

Parkinson's disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD.

This study aimed to investigate the student-athletes' capability to face the academic, sport, and social challenges during the coronavirus disease 2019 (COVID-19) lockdown and to disclose novel aspects of dual careers. A 32-item online survey encompassing demographic characteristics, sport and university engagement, support and dual-career benefits, physical activity, sitting time, and the time deemed necessary to recover the previous level of performance was developed. Four hundred sixty-seven student-athletes (males: 57%, females: 43%) from 11 countries, competing in 49 different sports (individual: 63.4%, team: 36.6%) at regional (17.5%), national (43.3%), and international (39.2%) levels, and enrolled at high school (21.9%) and university (78.1%) levels completed the survey. During the lockdown, the respondents decreased the time dedicated to sport and academics, although they maintained an active lifestyle. Student-athletes from countries under severe contagion were more likely to train at home, dedicate to academics, and receive support from the coach but less likely receive support from their teachers. With respect to their team sport counterparts, athletes competing in individual sports trained more and were more likely to receive support from their coaches. International athletes showed the highest training time and support from their coaches and as student-athletes. High school students received more support from their coaches and teachers, whereas university students were more likely considering dual careers useful to cope with the COVID-19 pandemic. This study substantiates the relevant role of competitive sports participation in the maintenance of active lifestyles, with student-athletes considering home training and e-learning valuable resources during the lockdown. Furthermore, their sport and academic commitments helped student-athletes cope with the emergency of the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Izzicupo, Di Baldassarre, Abelkalns, Bisenieks, Sánchez-Pato, Cánovas-Alvarez, Doupona, Figueiredo, García-Roca, Ghinassi, Leiva-Arcas, Meroño, Paegle, Radu, Rus, Rusu, Sarmento, Stonis, Vaquero-Cristóbal, Vaz and Capranica.)

Childhood obesity is a major public health challenge. Summer camps for children with obesity represent an alternative setting to improve eating and physical activity habits. Here we evaluated if the participation in the camp improves objectively measured physical activity and sedentary behavior and whether there are differences between male and female participants. Twenty-eight children, 13 males and 15 females (body mass index >97° centile, weight excess >30%, Tanner stage I), agreed to participate in an 8-day camp. During the summer camp, children participated in sports-like games and outdoor activities for at least 3 h a day, and the school-camp staff also provided a theoretical nutritional learning plan. Accelerometry-derived physical activity was measured through the SenseWear Mini Armband during a week at home and during the camp experience. Before camping, the participants were far above the minimum daily values of moderate- to vigorous-intensity physical activity (MVPA) to be considered sufficiently active (≥60 min/day), but male participants were more active than females (MVPA: 186.2 ± 94.2, 111.0 ± 64.7; P = 0.020). Male participants increased their MVPA (234.3 ± 114.8, P = 0.020), whereas females not (111.9 ± 52.9, P = 0.020). No difference emerged for the sedentary behavior either before or during the camp. This study suggests that participation in a summer camp for obese children can determine different responses in physical activity levels, depending on the sex of young participants. Thus, summer camps for obese children should put particular attention on female participants, besides reducing sedentary behavior in both males and females., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Izzicupo, Di Blasio, Di Credico, Ghinassi, Capranica, Napolitano, Di Baldassarre, Modestini and Di Pietro.)

Background : Menopause is associated with negative cardiovascular adaptations related to estrogen depletion, which could be counteracted by physical exercise (PhE). However, the impact of total adherence-rate (TA) to PhE and sedentary time (SedT) on cardiometabolic profile in this population has not been elucidated. Methods: For 13-weeks, 43 women (57.1 ± 4.7 years) participated in a 4-days-a-week moderate-intensity walking training. They underwent laboratory, anthropometric and echocardiographic assessment, before and after training (T0-T1). Spontaneous physical activity (PhA) was assessed with a portable multisensory device. The sample was divided according to TA to PhE program: <70% ( n = 17) and ≥70% ( n = 26). Results: TA ≥ 70% group experienced a significant T1 improvement of relative wall thickness (RWT), diastolic function, VO2max, cortisol, cortisol/dehydroandrostenedione-sulphate ratio and serum glucose. After adjusting for SedT and 10-min bouts of spontaneous moderate-to-vigorous PhA, TA ≥ 70% showed the most significant absolute change of RWT and diastolic function, body mass index, weight and cortisol. TA ≥ 70% was major predictor of RWT and cortisol improvement. Conclusions: In a group of untrained, postmenopausal women, a high TA to a 13-weeks aerobic PhE program confers a better improvement in cardiometabolic profile, regardless of SedT and PhA levels.