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This review aimed to identify risk factors for soccer injuries and provide researchers the needed elements to build a soccer-player's injury risk profile. An umbrella review was conducted following the PRIOR criteria (OSF registration link: https://osf.io/jr7xe/). A literature search was run to identify studies investigating soccer-related injury risk factors. We included systematic reviews published between 2013 and 2023 related to soccer and analysed the identified risk factors to classify these in intrinsic and extrinsic, group in categories and identify relationships between risk factors and injury location. Among 240 risk factors, 181 (75.4%) were classified as intrinsic and 59 (24.6%) as extrinsic. We grouped risk factors in 14 categories. Finally, we found relationships between risk factors and injury locations for 159 factors, with the knee representing the body area most affected by risk factors ( N  = 101), followed by the ankle ( N  = 65) and the thigh ( N  = 65).

Objectives: This study introduces EMPATIC (Electro-Modulation of PAncreaTic Islet Cells), a miniaturized intraneural device designed for transversal insertion into small nerves with a mean diameter of 400 μm. EMPATIC aims to modulate glucose tolerance through intraneural vagus nerve stimulation (VNS) in rats., Materials and Methods: EMPATIC design was optimized to fit into the cervical vagus nerve of rats and was developd through thin film microtechnologies. We evaluated the efficacy of the stimulation protocol (200 μA for 10 μs at 1 Hz) on glucose tolerance after intraperitoneal injection of glucose in three rat groups: control (no implant), sham (EMPATIC implant, no stimulation), and VNS (EMPATIC implant with stimulation)., Results: EMPATIC treatment in the VNS group significantly affected glucose tolerance tests compared with control and sham groups. The glucose tolerance test's area under the curve was 17,652 ± 913 mg∗min/dL in the control group, 16,929 ± 765 mg∗min/dL in the sham group, and reduced to 12,749 ± 1,075 mg∗min/dL in the stimulated group with statistical significance (p < 0.05 stimulated vs sham group, p < 0.05 stimulated vs control group). Blood glucose and insulin levels were measured, also under fasting conditions, for control and VNS groups, producing no statistically significant difference., Conclusions: EMPATIC treatment is effective in hyperglycemic conditions after glucose intake. No significant effects were observed when VNS was applied under fasting conditions. This study indicated the suitability of applying thin-film intrafascicular electrodes for transversal insertion into small nerves (mean diameter of 400 μm), which, to the best of our knowledge, represents an advancement over the state of the art. It also establishes the feasibility of investigating neural pathways related to glucose homeostasis using invasive intraneural electrodes in the right cervical vagus nerve of rats., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In alfalfa (Medicago sativa), the coexistence of interfertile subspecies (i.e. sativa, falcata and coerulea) characterized by different ploidy levels (diploidy and tetraploidy) and the occurrence of meiotic mutants capable of producing unreduced (2n) gametes, have been efficiently combined for the establishment of new polyploids. The wealth of agronomic data concerning forage quality and yield provides a thorough insight into the practical benefits of polyploidization. However, many of the underlying molecular mechanisms regarding gene expression and regulation remained completely unexplored. In this study, we aimed to address this gap by examining the transcriptome profiles of leaves and reproductive tissues, corresponding to anthers and pistils, sampled at different time points from diploid and tetraploid Medicago sativa individuals belonging to progenies produced by bilateral sexual polyploidization (dBSP and tBSP, respectively) and tetraploid individuals stemmed from unilateral sexual polyploidization (tUSP)., Results: Considering the crucial role played by anthers and pistils in the reduced and unreduced gametes formation, we firstly analyzed the transcriptional profiles of the reproductive tissues at different stages, regardless of the ploidy level and the origin of the samples. By using and combining three different analytical methodologies, namely weighted-gene co-expression network analysis (WGCNA), tau (τ) analysis, and differentially expressed genes (DEGs) analysis, we identified a robust set of genes and transcription factors potentially involved in both male sporogenesis and gametogenesis processes, particularly in crossing-over, callose synthesis, and exine formation. Subsequently, we assessed at the same floral stage, the differences attributable to the ploidy level (tBSP vs. dBSP) or the origin (tBSP vs. tUSP) of the samples, leading to the identification of ploidy and parent-specific genes. In this way, we identified, for example, genes that are specifically upregulated and downregulated in flower buds in the comparison between tBSP and dBSP, which could explain the reduced fertility of the former compared to the latter materials., Conclusions: While this study primarily functions as an extensive investigation at the transcriptomic level, the data provided could represent not only a valuable original asset for the scientific community but also a fully exploitable genomic resource for functional analyses in alfalfa., (© 2024. The Author(s).)

Fixed-Dose antiretroviral Combinations (FDCs) are the most used drug regimes in adult patients with human-immunodeficiency virus 1 infection, since they increase adherence to antiretroviral therapy and enable good quality of life. The European AIDS Clinical Society guidelines recommend the use of FDCs in paediatrics. However, the use of FDCs in paediatric population is restricted since studies in children and adolescents are mostly conducted in small sample sizes and are heterogeneous in settings and design. This systematic review aims to summarize the current knowledge about the use of FDCs in paediatric population, highlighting the relevant outcomes regarding efficacy and effectiveness, adherence, safety, and adverse events of these regimens.

Apolipoprotein E (ApoE) is a lipid carrier in both the peripheral and the central nervous systems (CNSs). Lipid-loaded ApoE lipoprotein particles bind to several cell surface receptors to support membrane homeostasis and brain injury repair. In the brain, ApoE is produced predominantly by astrocytes, but it is also abundantly expressed in most neurons of the CNS. In this study, we addressed the role of ApoE in the hippocampus in mice, focusing on its role in response to radiation injury. To this aim, 8-week-old, wild-type, and ApoE-deficient (ApoE -/- ) female mice were acutely whole-body irradiated with 3 Gy of X-rays (0.89 Gy/min), then sacrificed 150 days post-irradiation. In addition, age-matching ApoE -/- females were chronically whole-body irradiated (20 mGy/d, cumulative dose of 3 Gy) for 150 days at the low dose-rate facility at the Institute of Environmental Sciences (IES), Rokkasho, Japan. To seek for ApoE-dependent modification during lineage progression from neural stem cells to neurons, we have evaluated the cellular composition of the dentate gyrus in unexposed and irradiated mice using stage-specific markers of adult neurogenesis. Our findings indicate that ApoE genetic inactivation markedly perturbs adult hippocampal neurogenesis in unexposed and irradiated mice. The effect of ApoE inactivation on the expression of a panel of miRNAs with an established role in hippocampal neurogenesis, as well as its transcriptional consequences in their target genes regulating neurogenic program, have also been analyzed. Our data show that the absence of ApoE -/- also influences synaptic functionality and integration by interfering with the regulation of mir-34a, mir-29b, and mir-128b, leading to the downregulation of synaptic markers PSD95 and synaptophysin mRNA. Finally, compared to acute irradiation, chronic exposure of ApoE null mice yields fewer consequences except for the increased microglia-mediated neuroinflammation. Exploring the function of ApoE in the hippocampus could have implications for developing therapeutic approaches to alleviate radiation-induced brain injury.

Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE -/- ) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE -/- mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology., Competing Interests: The authors declare no conflict of interest.

Integrase strand transfer inhibitors (INSTIs), including raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB), are increasingly used, given excellent data on their efficacy, effectiveness, and tolerability profile in adults, while data in children are accumulating. To review the most recent evidence on the efficacy, effectiveness, safety, and resistance of INSTIs in children, a quick narrative review of the available literature data was performed using the MEDLINE/PubMed and Scopus databases, including only English-language studies, published between 2009 and 2022. Six studies (259 children) on RAL use, 17 studies (3,448 children) on DTG, 2 studies (73 children) on EVG, and 1 study (102 children) on BIC were retrieved. Results on efficacy and effectiveness were close to those reported in adult studies, suggesting similarities between children and adult population. Resistance to RAL was detected in four studies, ranging between 5.0% to 35.3% of participants. In four studies resistance to DTG occurred in 12.4% to 22% of children. Adverse events to RAL have been uncommon reported. In studies on EVG, 8% to 74% of children developed uveitis, nausea, or abdominal pain. In DTG studies, the proportion of weight gain ranged from 10% to 87%, and neuropsychiatric effects ranged 1% to 16% of participants. One BIC study reported adverse events >10% of participants. The evidence supports high efficacy and low toxicity of INSTIs in pediatric and adolescent populations.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Lolium multiflorum Lam., commonly known as Italian ryegrass, is a forage grass mostly valued for its high palatability and digestibility, along with its high productivity. However, Italian ryegrass has an outbreeding nature and therefore has high genetic heterogeneity within each variety. Consequently, the exclusive use of morphological descriptors in the existing varietal identification and registration process based on the Distinctness, Uniformity, and Stability (DUS) test results in an inadequately precise assessment. The primary objective of this work was to effectively test whether the uniformity observed at the phenological level within each population of Italian ryegrass was confirmed at the genetic level through an SSR marker analysis. In this research, using 12 polymorphic SSR loci, we analyzed 672 samples belonging to 14 different Italian ryegrass commercial varieties to determine the pairwise genetic similarity (GS), verified the distribution of genetic diversity within and among varieties, and investigated the population structure. Although the fourteen commercial varieties did not show elevated genetic differentiation, with only 13% of the total variation attributable to among-cultivar genetic variation, when analyzed as a core, each variety constitutes a genetic cluster on its own, resulting in distinct characteristics from the others, except for two varieties. In this way, by combining a genetic tool with the traditional morphological approach, we were able to limit biases linked to the environmental effect of field trials, assessing the real source of diversity among varieties and concretely answering the key requisites of the Plant Variety Protection (PVP) system.