Effect of COVID-19 on Key Performance Indicators of Spanish Professional Soccer League.

The unprecedented COVID-19 health crisis severely disrupted global sports in 2020, prompting lengthy suspensions followed by resumed competitions under abnormal behind-closed-doors conditions without fans. These disruptions necessitated tactical adaptations by coaches and teams, attempting to still achieve successful outcomes. This study investigates the pandemic's impacts on performance metrics and indicators within Spanish professional soccer. Utilizing systematic notational analysis, 760 match cases from the 2019-2020 La Liga season were examined, comprising 27 matchdays from the pre-COVID context and 11 after resumption. Multivariate tests identified significant pre/post differences and interactions for various technical indicators including shots, cards, corners, and offside calls. The pandemic was associated with a reduction from 12 to just 5 identifiable playing styles, suggestive of increased conservatism featuring more passive play, limited attacking depth, and horizontal ball movement. Such tactical changes appear provoked by condensed fixture scheduling post-lockdown, the lack of supportive crowds, and compromised player fitness/recovery. By quantifying these COVID-precipitated changes, the analysis provides tangible evidence for coaches to make informed adjustments in training and preparation for functioning effectively in disrupted environments. The findings emphasize that versatility and flexibility will be vital to optimize performance during times of unprecedented uncertainty.

A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.

Mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. We investigated how G protein-coupled receptors (GPCRs) and G proteins control mitochondrial dynamics and trafficking. The activation of Gαq inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCß pathway. Mitoproteome analysis revealed that Gαq interacted with the Eutherian-specific mitochondrial protein armadillo repeat-containing X-linked protein 3 (Alex3) and the Miro1/Trak2 complex, which acts as an adaptor for motor proteins involved in mitochondrial trafficking along dendrites and axons. By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of Gαq on mitochondrial trafficking and dendritic growth in neurons. Alex3-deficient mice had altered amounts of ER stress response proteins, increased neuronal death, motor neuron loss, and severe motor deficits. These data revealed a mammalian-specific Alex3/Gαq mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs.

Spanish mental health residents' perspectives about residency education on the genetics of psychiatric disorders: A cross-sectional survey.

Despite compelling evidence that some patients with a psychiatric diagnosis could benefit from genetic assessment, genetic testing for psychiatric patients is underutilized. Few studies have reported psychiatric genetics training for mental health specialists, and such research is especially lacking in Spain. We aimed to gather the opinions of Spanish mental health residents, including resident intern nurses (RINs), doctors (RIDs) and psychologists (RIPs). A short survey was prepared by an expert team and distributed to all mental health residency centers in Spain during the first semester of 2021. Of the 2028 residents, 18% responded. Participants were mainly females (71%), in their first year of residency (37%) and within the 27-31-year age range. While participants received little theoretical (13.4%) and practical (4.6%) training on average, RIDs had the most affirmative responses. Notably, RINs and RIDs were interested in genetics during residency (>40%) and strongly believed (85.0%) that genetics training using both theoretical and practical methodologies should be incorporated into residency training. However, RIPs were less interested (20%), and only 60% believed that genetics training should be incorporated. Spanish mental health residents, although interested in genetics in psychiatry, receive little training on this topic. They strongly believe that genetics training using theoretical and practical methodologies should be incorporated.

Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes.

Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, as a protein that potently inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock-out mouse embryonic fibroblasts to investigate its endocytic function. We found that kazrin depletion delays juxtanuclear enrichment of internalized material, indicating a role in endocytic traffic from early to recycling endosomes. Consistently, we found that the C-terminal domain of kazrin C, predicted to be an intrinsically disordered region, directly interacts with several early endosome (EE) components, and that kazrin depletion impairs retrograde motility of these organelles. Further, we noticed that the N-terminus of kazrin C shares homology with dynein/dynactin adaptors and that it directly interacts with the dynactin complex and the dynein light intermediate chain 1. Altogether, the data indicate that one of the primary kazrin functions is to facilitate endocytic recycling by promoting dynein/dynactin-dependent transport of EEs or EE-derived transport intermediates to the recycling endosomes.

Assessment of genotoxicity induced by subchronic exposure to graphene in HaCaT human skin cell line.

The applications of graphene-based materials (GBMs) and their processing involve prolonged contact with cellular barriers such as human skin. Even though the potential cytotoxicity of graphene has been studied in recent years, the impact of long-term graphene exposure has rarely been explored. We tested in the HaCaT epithelial cells, in vitro, the effect of subchronic treatments with sublethal doses of four different, well-characterized GBMs, two commercial graphene oxides (GO) and two few-layer graphenes (FLG). Cells were exposed weekly to low doses of the GBMs for 14 days, 30 days, 3 months, and 6 months. GBMs-cells uptake was assessed by confocal microscopy. Cell death and cell cycle were determined by fluorescence microscopy and cytometry. DNA damage was measured by comet assay and γ-H2AX staining, followed by the determination of p-p53 and p-ATR by immunolabeling. Subchronic exposure to different GBMs at noncytotoxic doses has potential genotoxic effects on HaCaT epithelial cells that can be recovered depending on the GBM and exposure time. Specifically, GO-induced genotoxicity can be detected after 14 and 30 days from treatment. At this time, FLG appears less genotoxic than GO, and cells can recover more quickly when genotoxic pressure disappears after some days of removal of the GBM. Long-term exposure, 3 and 6 months, to different GBMs induces permanent, nonreversible, genotoxic damage comparable to the exerted by arsenite. This should be considered for the production and future applications of GBMs in scenarios where low concentrations of the material interact chronically with epithelial barriers.

Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation.

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer's disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI-MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.

Influence of Menstrual Cycle on Internal and External Load in Professional Women Basketball Players.

The menstrual cycle can be seen as a potential determinant of performance. This study aims to analyze the influence of the menstrual cycle in women on sports performance, more specifically on the internal and external load of professional women basketball players. The sample consisted of 16 women players and 14 training sessions were recorded. A descriptive analysis of the mean and standard deviation of the variables according to the different phases of the menstrual cycle was performed, as well as an ANCOVA, partial Eta2 effect size criteria, and Bonferroni's Post Hoc test to identify differences among phases. The results establish that ovulation is the phase in which higher values of external load are recorded and, therefore, the late follicular phase is the time of the cycle where a greater intensity in explosive distance, accelerations and decelerations are recorded. Considering women's hormonal cycles, understanding their function and the individual characteristics of each athlete is essential since it allows for the development of specific training, the prevention of injuries and therefore positively affects the performance of women players. To this end, individual training profiles should be created in specific contexts, not following general rules. In addition, psychological factors and the specific position of the athletes should be monitored.

Easy and Versatile Synthesis of Bulk Quantities of Highly Enriched 13C-Graphene Materials for Biological and Safety Applications.

The preparation of bulk quantities of 13C-labeled graphene materials is relevant for basic investigations and for practical applications. In addition, 13C-labeled graphene materials can be very useful in biological and environmental studies, as they may allow the detection of graphene or its derivatives in cells or organs. In this paper, we describe the synthesis of 13C-labeled graphene materials (few-layer graphene, FLG, and graphene oxide, GO) on a tens of mg scale, starting from 13C-labeled methane to afford carbon fibers, followed by liquid-phase exfoliation (FLG) or oxidation (GO). The materials have been characterized by several analytical and microscopic techniques, including Raman and nuclear magnetic resonance spectroscopies, thermogravimetric analysis, X-ray photoelectron spectroscopy, and X-ray powder diffraction. As a proof of concept, the distribution of the title compounds in cells has been investigated. In fact, the analysis of the 13C/12C ratio with isotope ratio mass spectrometry (IRMS) allows the detection and quantification of very small amounts of material in cells or biological compartments with high selectivity, even when the material has been degraded. During the treatment of 13C-labeled FLG with HepG2 cells, 4.1% of the applied dose was found in the mitochondrial fraction, while 4.9% ended up in the nuclear fraction. The rest of the dose did not enter into the cell and remained in the plasma membrane or in the culture media.

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation.

PURPOSE: Most monotherapies available against glioblastoma multiforme (GBM) target individual hallmarks of this aggressive brain tumor with minimal success. In this article, we propose a therapeutic strategy using coenzyme Q10 (CoQ10) as a pleiotropic factor that crosses the blood-brain barrier and accumulates in cell membranes acting as an antioxidant, and in mitochondrial membranes as a regulator of cell bioenergetics and gene expression. METHODS: Xenografts of U251 cells in nu/nu mice were used to assay tumor growth, hypoxia, angiogenesis, and inflammation. An orthotopic model was used to explore microglial infiltration, tumor growth, and invasion into the brain parenchyma. Cell proliferation, migration, invasion, proteome remodeling, and secretome were assayed in vitro. Conditioned media were used to assay angiogenesis, monocyte chemoattraction, and differentiation into macrophages in vitro. RESULTS: CoQ10 treatment decreased tumor volume in xenografts and orthotopic models, although its effect on tumor cell proliferation was not direct. Tumors from mice treated with CoQ10 were less hypoxic and vascularized, having less infiltration from inflammatory cells. Treatment-induced downregulation of HIF-1α and NF-kB led to a complete remodeling of the tumor cells proteome and secretome, impacting angiogenesis, monocyte infiltration, and their differentiation into macrophages. Besides, tumor cell migration and invasion were drastically restricted by mechanisms involving modulation of the actin cytoskeleton and downregulation of matrix metalloproteases (MMPs). CONCLUSIONS: CoQ10 has a pleiotropic effect on GBM growth, targeting several hallmarks simultaneously. Thus, its integration into current treatments of this fatal disease should be considered.

New insights in the Spanish gene pool of olive (Olea europaea L.) preserved ex situ and in situ based on high-throughput molecular markers.

In Spain, several local studies have highlighted the likely presence of unknown olive cultivars distinct from the approximately 260 ones previously described in the literature. Furthermore, recent advancements in identification techniques have significantly enhanced in terms of efficacy and precision. This scenario motivated a new nationwide prospecting effort aimed at recovering and characterizing new cultivated germplasm using high-throughput molecular markers. In the present study, the use of 96 EST-SNP markers allowed the identification of a considerable amount of new material (173 new genotypes) coming from areas with low intensification of production in different regions of Spain. As a result, the number of distinct national genotypes documented in the World Olive Germplasm Bank of IFAPA, Córdoba (WOGBC-ESP046) increased to 427. Likewise, 65 and 24 new synonymy and homonymy cases were identified, respectively. This rise in the number of different national cultivars allowed to deepen the knowledge about the underlying genetic structure. The great genetic variability of Spanish germplasm was confirmed, and a new hot spot of diversity was identified in the northern regions of La Rioja and Aragon. Analysis of the genetic structure showed a clear separation between the germplasm of southern and northern-northeastern Spain and indicated a significantly higher level of admixture in the latter. Given the expansion of modern olive cultivation with only a few cultivars, this cryptic germplasm is in great danger of disappearing. This underlines the fact that maintaining as many cultivars as possible will increase the genetic variability of the olive gene pool to meet the future challenges of olive cultivation.

Daily and weekly external loads in the microcycle: Characterization and comparison between playing positions on amateur soccer.

Ensuring adequate levels of training and recovery to maximize player performance is critical; however, there are methodological challenges in designing a periodized training program for soccer teams. This study aims to describe and characterize the daily and weekly external load in an amateur soccer team and based on the weighting factors determined by the match reference, compare the external loads between playing positions. Twenty-four amateur soccer players (22.3 ± 1.7 years) were monitored using a global positioning system. Data collected comprises 19 competitive microcycles with a standard structure composed of 3 training sessions (matchday-5, matchday-3, and matchday-2) and one match. Match-reference values were calculated as the mean of the five best values recorded during official matches. The results show, on matchday-5 session, the existence of significant differences between playing positions to relative total distance covered (p = 0.050), relative sprint distance (p = 0.001), relative moderate-intensity accelerations (p < 0.001), relative high-intensity accelerations (p = 0.003), relative moderate-intensity decelerations (p < 0.001), and relative high-intensity decelerations (p = 0.017). On matchday-3 session, there are significant differences to relative very high-speed running distance (p = 0.017) and relative moderate-intensity decelerations (p = 0.014). On matchday-2 session, there are significant differences to relative high-speed running distance (p = 0.025), relative very high-speed running distance (p = 0.008), and relative moderate-intensity decelerations (p < 0.001). Weekly significant differences are observed between the playing positions to relative moderate-intensity accelerations (p = 0.002), relative high-intensity accelerations (p < 0.001), and relative moderate-intensity decelerations (p < 0.001). The weekly load is characterized by a greater weighting on accelerations and decelerations, compared to distances at very-high speed and sprint. The training loads must respect a standard training model that contemplates the individualization of the physical demands of the match, for each playing position, as for each individual.

From Junior to Elite in Soccer: Exploring the Relative Age Effect and Talent Selection in Spanish Youth National Teams.

The implications of relative age grouping in sport are known as the Relative Age Effect (RAE). This study has the twofold purpose of analyzing RAE in Spanish youth national soccer teams and examining the prediction value of being selected for national youth teams to be a professional. The sample was composed of 548 players divided into five groups. A descriptive analysis of distribution and participation, frequencies, mean and standard deviation, crosstabs, Sankey charts, coefficient correlation and Cohen's effect size criteria and two regression analyses were performed. Results established that the RAE is present in U'17 to U'21 Spanish youth national teams. Talent detection and selection programs are more reliable the closer they are to adulthood, reaching a success rate of almost 100% at the U'21 stage. The selection of players for such programs should be delayed as much as possible, thus, preventing younger players from dropping out and those selected from thinking they have already reached their goal. To this end, they should focus on long-term improvement, not short-term performance. In addition, factors such as the RAE or the maturity level of the athletes should be monitored.

Antifibrotics and lung transplantation: A Spanish multicentre case-controlled study.

BACKGROUND AND OBJECTIVE: Antifibrotic drugs are the standard treatments for patients with idiopathic pulmonary fibrosis (IPF). This study aims to assess the safety of antifibrotic treatment in IPF patients undergoing lung transplantation. METHODS: Patients with a diagnosis of IPF who received a lung transplant between January 2015 and June 2019 at four Spanish hospitals specialized in lung transplantation were retrospectively recruited. Cases were defined as patients receiving antifibrotic treatments at time of transplant. Each case was matched with a control who did not receive antifibrotic treatment. RESULTS: A total of 164 patients were included in the study cohort (103 cases and 61 controls). There were no statistically significant differences between the cases and controls in any of the items studied related to transplantation except the time until the appearance of chest wall dehiscence: although there were no differences in the incidence of wall dehiscence in either group (12.3% vs. 13.7%; p = 0.318), the patients on antifibrotic drugs experienced it earlier (21 days [IQR = 12.5-41.5] vs. 63 days [IQR = 46.75-152.25]; p = 0.012). There were no differences in overall post-transplant survival between the two groups (p = 0.698) or in conditional survival at 30 days, 90 days, 3 years or 5 years. However, 1 year survival was significantly greater among controls (80.6% vs. 93.3%; p = 0.028). CONCLUSION: There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.

ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-ß plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-ß load, tau pathology, autophagy, and cell-cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.

Subchronic Graphene Exposure Reshapes Skin Cell Metabolism.

In recent years, the toxicity of graphene-related materials (GRMs) has been evaluated in diverse models to guarantee their safety. In most applications, sublethal doses of GRMs contact human barriers such as skin in a subchronic way. Herein, the subchronic effect (30 day exposure) of three GRMs (GO 1, GO 2, and FLG) with different oxidation degrees and sizes was studied. The effects of these materials on human skin cells, HaCaTs, were assayed through high-throughput metabolic-based readout and other cell-based assays. A differential effect was found between the different GRMs. GO 2 induced a metabolic remodeling in epithelial cells, increasing the level of tricarboxylic acid components, mirrored by increased cell proliferation and changes in cell phenotype. The oxidation degree, size, and method of manufacture of GRMs dictated harmful effects on cell metabolism and behavior generated by nontoxic exposures. Therefore, a "safe by design" procedure is necessary when working with these nanomaterials.

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells.

Graphene and its derivative materials are manufactured by numerous companies and research laboratories, during which processes they can come into contact with their handlers' physiological barriers-for instance, their respiratory system. Despite their potential toxicity, these materials have even been used in face masks to prevent COVID-19 transmission. The increasingly widespread use of these materials requires the design and implementation of appropriate, versatile, and accurate toxicological screening methods to guarantee their safety. Murine models are adequate, though limited when exploring different doses and lengths of exposure-as this increases the number of animals required, contrary to the Three R's principle in animal experimentation. This article proposes an in vitro model using primary, non-transformed normal human bronchial epithelial (NHBE) cells as an alternative to the most widely used model to date, the human lung tumor cell line A549. The model has been tested with three graphene derivatives-graphene oxide (GO), few-layer graphene (FLG), and small FLG (sFLG). We observed a cytotoxic effect (necrosis and apoptosis) at early (6- and 24-h) exposures, which intensified after seven days of contact between cells and the graphene-related materials (GRMs)-with cell death reaching 90% after a 5 µg/mL dose. A549 cells are more resistant to necrosis and apoptosis, yielding values less than half of NHBE cells at low concentrations of GRMs (between 0.05 and 5 µg/mL). Indeed, GRM-induced cell death in NHBE cells is comparable to that induced by toxic compounds such as diesel exhaust particles on the same cell line. We propose NHBE as a suitable model to test GRM-induced toxicity, allowing refinement of the dose concentrations and exposure timings for better-designed in vivo mouse assays.