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The aim of this study was to examine the relationship between perceived mother- and father-initiated motivational climates and players' fear of failure in youth male team sports. A sample of 336 youth male players from five team sports (basketball, football, handball, volleyball, and water polo) completed the Parent-Initiated Motivational Climate Questionnaire-2 and the Performance Failure Appraisal Inventory. The results showed that perceived mother- and father-initiated motivational climates were related to fear of failure predispositions. While a mastery orientation (perceived learning-enjoyment climate) had a low association with fear of failure, an ego orientation (perceived worry-conducive and success-without-effort climates) was highly related to fear of failure. Father-initiated climates had stronger associations with fear of failure than mother-initiated ones, revealing that mothers and fathers may have different influences when considering the developmental origins of fear of failure. The relationships between mother- and father-initiated motivational climates and fear of failure varied according to the type of sport, with basketball, football, and volleyball presenting stronger associations. The dimensions "Fear of important others losing interest" and "Fear of upsetting important others" presented the highest explained variance in all sports when predicted by the father-initiated motivational climate. The findings can inform important evidence-based guidelines and recommendations for parents, coaches, and organizations, enabling them to create supportive environments that aid athletes in developing the necessary psychological skills for long-term success and well-being.

Summary: Bariatric surgery is increasingly being accepted as a viable treatment for managing the growing obesity epidemic. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures. Perforated duodenal ulcer following RYGB is a rare condition with a low incidence. We report a case of a patient with a perforated duodenal ulcer post RYGB, and the surgical approach. A 66-year-old man with hypertension and a history of laparoscopic RYGB for class III obesity was admitted to the emergency department with severe epigastric pain radiating to the right side of his abdomen and right shoulder, associated with nausea and vomiting. Computed tomography (CT) showed intraperitoneal free fluid, a thickened wall of the duodenum and free air, duodenal perforation was suspected. The patient underwent exploratory laparoscopy that revealed a perforated duodenal ulcer that was closed with an absorbable barbed suture and omental patch. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis, and clinicians should be aware of and have a low threshold for diagnostic laparoscopy., Learning Points: Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in bariatric surgery. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis. The pathophysiology of this perforation is not clear, but several mechanisms have been proposed. Helicobacter pylori has been implicated. Clinicians should be aware and have a low threshold for diagnostic laparoscopy for a patient who has acute abdominal pain after RYGB, despite negative diagnostic measures.

Purpose: The aim of this study was to assess the reliability and validity of the My Jump 2 ® app in measuring jump height, flight time, and peak power among elite women beach volleyball players on sand surfaces., Methods: Eleven elite female beach volleyball players (aged 23.6 ± 6.2 years; weight 66.3 ± 5.8 kg; height 174.4 ± 5.8 cm; with 8.4 ± 4.8 years of professional experience) participated in this study. Each player performed six countermovement jumps in a wooden box filled with sand on a force platform while simultaneously recording a video for subsequent analysis using the My Jump 2 ® app., Results: We found excellent agreement for flight time, jump height and peak power between observers (ICC = 0.92, 0.91 and 0.97, respectively). No significant differences between force platform and My Jump 2 ® app were detected in the values obtained for the three variables ( P > 0.05). For the force platform and the My Jump 2 ® app, we found a good agreement measuring jump height and flight time (ICC = 0.85 and 0.85, respectively). However, we only found a moderate agreement for peak power (ICC = 0.64). The difference in jump height showed a limit of agreement between -4.10 and 4.74 cm in Bland-Altman, indicating a high level of agreement between the two measurement tools., Conclusion: Based on our findings, the My Jump 2 ® app reveals a valid tool for measuring jump height and flight time of CMJ on sand surfaces. However, more caution is needed when measuring peak power., Competing Interests: Victor Coswig and Alexandre Igor Araripe Medeiros are an Academic Editor for PeerJ., (© 2024 Medeiros et al.)

Aim: Patients with a lymphoma diagnosis undergo non-gated chest computed tomography (CT) scans as part of cancer diagnosis or staging. Although coronary artery calcification (CAC) is traditionally evaluated on dedicated cardiac CT, CAC can also be detected on standard chest CT. This exploratory study aimed to determine the prognostic value of CAC detected on non-gated chest CT and to report its use on clinical practice., Method: Consecutive patients with a lymphoma diagnosis who performed non-contrasted non-gated chest CT for cancer diagnosis or staging were included and retrospectively evaluated. Coronary artery calcification was evaluated by quantitative (Agatston score) and qualitative (visual) assessment., Results: Fifty-seven patients were included in this study (mean age 61±15 years; 58% male). Coronary artery calcification was identified in 22 patients (39%), most of them with multi-vessel involvement. Coronary artery calcification was qualitatively classified as mild, moderate and severe in 11%, 19% and 9% patients, respectively. This study suggested that moderate or severe CAC was an independent predictor of all-cause mortality (odds ratio 3, 95% confidence interval 2-11; p=0.04) after adjusting for cardiovascular risk factors and lymphoma staging. Regarding quantitative evaluation, a higher CAC score was also associated with higher mortality. While significant CAC was identified in 22 patients, it was only reported in four patients., Conclusions: The preliminary findings of this hypothesis-generating study support the investigation of CAC identified by chest CT for diagnosis/staging of cancer as a risk modifier in the global risk assessment of patients with lymphoma. The unrecognition and underreporting of this finding may represent a wasted opportunity to detect subclinical coronary atherosclerosis in these patients and may help in guiding preventive cardiology care., Competing Interests: Declarations of Interest None., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Dietary polyphenol consumption is associated with a wide range of neuroprotective effects by improving mitochondrial function and signaling. Consequently, the use of polyphenol supplementation has been investigated as an approach to prevent neurodevelopmental diseases during gestation; however, the data obtained are still very inconclusive, mostly because of the difficulty of choosing the correct doses and period of administration to properly prevent neurodegenerative diseases without undermining normal brain development. Thus, we aimed to evaluate the effect of naringin supplementation during the third week of gestation on mitochondrial health and signaling in the cerebellum of 21-day-old offspring. The offspring born to naringin-supplemented dams displayed higher mitochondrial mass, membrane potential, and superoxide content in the cerebellum without protein oxidative damage. Such alterations were associated with dynamin-related protein 1 (DRP1) and phosphorylated AKT (p-AKT) downregulation, whereas the sirtuin 3 (SIRT3) levels were strongly upregulated. Our findings suggest that high dietary polyphenol supplementation during gestation may reduce mitochondrial fission and affect mitochondrial dynamics even 3 weeks after delivery via SIRT3 and p-AKT. Although the offspring born to naringin dams did not present neurobehavioral defects, the mitochondrial alterations elicited by naringin may potentially interfere during neurodevelopment and need to be further investigated., (© 2024 International Society for Developmental Neuroscience.)

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4 + T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4 + Th1 and CD8 + T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80 + CD11b + CD11c + macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies., (© 2023 John Wiley & Sons Ltd.)

Leishmania infection of macrophages results in altered Ras isoforms expression and Toll-like receptor-2 (TLR2) expression and functions. Therefore, we examined whether TLR2 would selectively alter Ras isoforms' expression in macrophages. We observed that TLR2 ligands- Pam3CSK4, peptidoglycan (PGN), and FSL- selectively modulated the expression of Ras isoforms in BALB/c-derived elicited macrophages. Lentivirally-expressed TLR1-shRNA significantly reversed this Ras isoforms expression profile. TLR2-deficient L. major-infected macrophages and the lymph node cells from the L. major-infected mice showed similarly reversed Ras isoforms expression. Transfection of the macrophages with the siRNAs for the adaptors- Myeloid Differentiation factor 88 (MyD88) and Toll-Interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP)- or Interleukin-1 Receptor-Associated Kinases (IRAKs)- IRAK1 and IRAK4- significantly inhibited the L. major-induced down-regulation of K-Ras, and up-regulation of N-Ras and H-Ras, expression. The TLR1/TLR2-ligand Pam3CSK4 increased IL-10 and TGF-β expression in macrophages. Pam3CSK4 upregulated N-Ras and H-Ras, but down-regulated K-Ras, expression in C57BL/6 wild-type, but not in IL-10-deficient, macrophages. IL-10 or TGF-β signaling inhibition selectively regulated Ras isoforms expression. These observations indicate the specificity of the TLR2 regulation of Ras isoforms and their selective modulation by MyD88, TIRAP, and IRAKs, but not IL-10 or TGF-β, signaling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This article presents a discussion of research in Physical Education and Sport Didactics in Portugal. It starts by situating it from an historical perspective, placing the 1980s as the beginning era, mainly based on the studies provided by the two first Physical Education higher education institutes of the country. The initial research, first based on master and doctoral dissertations, progressed to ongoing projects that have been disseminated in international and national journals and books. This development is also reported from the theoretical, conceptual, and methodological perspectives, showing how it has informed the quality of Physical Education and teacher education as the two main research strands to be described, however, acknowledging that a strand on sports coaching and coach education exists. On teaching Physical Education, the article discusses the elements relative to the teacher and to the student, focusing from the immediate and short-term to the distant and long-term events that lead into young adulthood's active lifestyles. In this analysis, research on curriculum and assessment are also reported. On physical education teacher education, the article shows the prevalence of the post-primary Physical Education to argue for the need for more research on primary-level education, and discusses the diverse foci from initial teacher education to in-service education practises. In line with current trends in research, we suggest a set of four features for the future research agenda: (1) addressing short to long-term outcomes of Physical Education; (2) adopting multifactorial and multi-layered perspectives of analysis; (3) embracing inter- and multidisciplinary designs; and (4) taking comparative perspectives within and between European countries, and between Europe and other continents. We conclude that these features need to focus on four levels of integration and cooperation: (a) integration between the research initiatives and the needs of the professional field; (b) integration between research on teaching and learning, teacher education and the curriculum; (c) cooperation between the different national higher education and professional institutions; and (d) integration in the international research agenda by leading and participating in project partnerships which are needed to fully and effectively implement such agenda., 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., (© 2023 Onofre, Costa, Martins, Quitério, Farias and Mesquita.)

Leishmania donovani infection of macrophages drives profound changes in the metabolism of both the host macrophage and the parasite, which undergoes different phases of development culminating in replication and propagation. However, the dynamics of this parasite-macrophage cometabolome are poorly understood. In this study, a multiplatform metabolomics pipeline combining untargeted, high-resolution CE-TOF/MS and LC-QTOF/MS with targeted LC-QqQ/MS was followed to characterize the metabolome alterations induced in L. donovani -infected human monocyte-derived macrophages from different donors at 12, 36, and 72 h post-infection. The set of alterations known to occur during Leishmania infection of macrophages, substantially expanded in this investigation, characterized the dynamics of the glycerophospholipid, sphingolipid, purine, pentose phosphate, glycolytic, TCA, and amino acid metabolism. Our results showed that only citrulline, arginine, and glutamine exhibited constant trends across all studied infection time points, while most metabolite alterations underwent a partial recovery during amastigote maturation. We determined a major metabolite response pointing to an early induction of sphingomyelinase and phospholipase activities and correlated with amino acid depletion. These data represent a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages that contributes to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.

This study characterised the sport participation patterns of 546 male youth team sport players. A retrospective questionnaire was used to identify the sport starting age (general sports and main sport) and the quantity and type of sports undertaken during the early years of development. A mixed-ANOVA and Chi-square tests were implemented. All participants started involvement in sports at the same age (~5 years) and participated in the same number of sports during their early years (1 to 2 sports). However, football players started participating mainly in team games (football, futsal) and water polo players in CGS sports (swimming). Participants reported different ages for initial participation in: (i) main sport (football players started participating earlier, around 5-6 years), (ii) onset of specialisation (football players specialised earlier, around 7 or 8 years), (iii) types of sports engaged in (football players were involved in more team games and water polo in more CGS sports), and (iv) variations in weekly training hours (water polo reported more hours of training). This study provided empirical evidence for understanding the effects of different sporting pathways on long-term athlete development. Some key incongruities between contemporary knowledge and practice are acknowledged. Further investigations should be developed by examining the trajectories in different sports, countries, genders, and cultural contexts.

While skin is a site of active immune surveillance, primary melanomas often escape detection. Here, we have developed an in silico model to determine the local cross-talk between melanomas and Langerhans cells (LCs), the primary antigen-presenting cells at the site of melanoma development. The model predicts that melanomas fail to activate LC migration to lymph nodes until tumors reach a critical size, which is determined by a positive TNF-α feedback loop within melanomas, in line with our observations of murine tumors. In silico drug screening, supported by subsequent experimental testing, shows that treatment of primary tumors with MAPK pathway inhibitors may further prevent LC migration. In addition, our in silico model predicts treatment combinations that bypass LC dysfunction. In conclusion, our combined approach of in silico and in vivo studies suggests a molecular mechanism that explains how early melanomas develop under the radar of immune surveillance by LC.

Purpose : Although emerging research has explored the development of coach education curricula, coach learning and how a deep learning approach can be made accessible to aspiring coaches, the study of coach educators' scaffolding of micro-pedagogies in action remains a missing link in the field. Therefore, the purpose of this study was to explore scaffolding strategies adopted by an experienced coach educator to encourage aspiring coaches to adopt an active approach to learning. Method : A case-study was conducted for a full semester of twelve practical lessons in the unit "Sports Methodology I-Volleyball" of a renowned sport sciences coach education program. Multiple data collection sources included participant observation, video and audio recordings, individual interviews with the coach educator and focus group interviews with the aspiring coaches. A thematic analysis was performed, and trustworthiness criteria included data triangulation, crosschecking, and collaborative interpretational analysis. Results : The strategies adopted by the coach educator progressively unfolded throughout three main stages: (i) laying the foundations of a learner-oriented approach; (ii) enhancing personally meaningful learning experiences; and (iii) mediating peer-coaching activities. An intricate interplay was unraveled between the nature and reduction of the support given and the increased responsibility transferred to the aspiring coaches for their active participation in learning experiences. Conclusions : The learner-oriented scaffolding processes employed by the coach educator sought to promote enhanced understanding of game-play problem-solving and the aspiring coaches' development of a deeper sense of what is required to become a coach through engagement in coaching technical activities and peer-coaching interventions.

Background: Persistent headache/facial/neck pain attributed to past cervicocephalic arterial dissection is under-documented in literature. Our main goal was to evaluate clinical characteristics and contributors to this persistence., Methods: A retrospective cohort study which included patients with a radiologically confirmed cervicocephalic arterial dissection (2015-2020) in a Portuguese tertiary hospital. Headache persistence was identified through clinical records. A questionnaire aimed to characterize headache in three moments: previous, persistent, and headache at the time of the interview (on average 2.5 years post-event)., Results: Ninety-two patients were identified; 24 (26.1%) had headache persistence ≥3 months, and 20 (22.2%) on average after 2.5 years post-event. There were no differences regarding demographics and vascular risk factors among patients with (n = 22) and without (n = 68) headache persistence. The first group had higher previous headache history (68.2% vs 4.4%, p < 0.001), delay in diagnosis (3.6 vs 1.9 days, p < 0.001), and headache/cervicalgia as the first symptom (81.8% vs 41.2%, p < 0.001). At the time of the interview, 20% still reported daily headache. A logistic regression model depicted headache history (OR = 59.8, p < 0.001), acute headache/cervicalgia (odds ratio, OR = 25.4, p = 0.005), posterior circulation dissection (OR = 7.6, p < 0.001), and less than 4 points by National Institutes of Health Stroke Scale score (OR = 5.0, p = 0.025) as contributors to headache persistence., Conclusion: Headache persistence post-cervicocephalic arterial dissection is common, and frequently affects patients daily. As it potentially affects functional outcomes and quality of life, the contributors identified in this study may help clinicians manage patients after the acute event.

According to the Quality Education and Gender Equality ambitions established at the 2030 Agenda for Sustainable Development Goals, we aimed to test the feasibility of a flexible planning and assessment process, using ongoing, bidirectional feedback between planning and assessment. Eighteen players (11.5 ± 0.5 years of age) from a U13 female volleyball team were randomized into an experimental group (in which the plan could be changed daily) or a contrast group (pre-defined planning, adjusted monthly). The pedagogical intervention lasted three months. Besides ongoing daily assessments from the training practices, the Game Performance Assessment Instrument was adopted as a starting point for the weekly assessments in 4 vs. 4 game-forms (i.e., the instrument was modified monthly based on feedback from the training process). Information from daily and weekly formal assessment was used in the planning of the experimental group, and monthly in the contrast group. Data suggested that pre-established and strict planning (even updated monthly) failed to fit current learner needs. Over 12 weeks, the pre-established planning suffered regular modifications in the experimental group, and the assessment tool changed monthly. In conclusion, both planning and assessment should be open and flexible to exchange information mutually, and support the design of tailor-made learning environments., Competing Interests: The authors declare no conflicts of interest.

Quality in education is one of the 17 goals in the United Nations' sustainable agenda for 2030, presupposing careful planning and assessment of learning. Traditional planning in sports education (either in training or school settings) largely adopts pre-determined learning sequences and temporal milestones that, in theory, enhance the learning process. However, learning is a context-dependent, non-linear process with considerable intra- and interindividual variability, whereby planning and assessment should also be non-linear. In this narrative review, the main findings suggest that the specific teaching or training contents and their relative (i.e., ordering or sequencing) and absolute timing (i.e., the specific time point where certain learning or adaptations are expected) should vary depending on the learners and the context. In a process-oriented perspective, this requires flexible planning and the establishment of ongoing bidirectional links between planning and assessment. In this framework, assessment should be a flexible, evolving, and daily pedagogical tool instead of a set of formal checkpoints. We further explored how planning and assessment could be linked to provide an ongoing feedback loop that respects the individuality of each learner and its context, and therefore hope this review helps bring about a change in current planning and assessment paradigms in sports education.

Postural control mechanisms have a determinant role in reaching tasks and are typically impaired in post-stroke patients. Functional electrical stimulation (FES) has been demonstrated to be a promising therapy for improving upper limb (UL) function. However, according to our knowledge, no study has evaluated FES influence on postural control. This study aims to evaluate the influence of FES UL assistance, during turning on the light task, in the related postural control mechanisms. An observational study involving ten post-stroke subjects with UL dysfunction was performed. Early and anticipatory postural adjustments (EPAs and APAs, respectively), the weight shift, the center of pressure and the center of mass (CoM) displacement were analyzed during the turning on the light task with and without the FES assistance. FES parameters were adjusted to improve UL function according to a consensus between physiotherapists' and patients' perspectives. The ANOVA repeated measures, Paired sample t and McNemar tests were used to compare postural control between the assisted and non-assisted conditions. When the task was assisted by FES, the number of participants that presented APAs increased (p = 0.031). UL FES assistance during turning on the light task can improve postural control in neurological patients with UL impairments., (© 2022. The Author(s).)

Stroke leads to significant impairment in upper limb (UL) function. The goal of rehabilitation is the reestablishment of pre-stroke motor stroke skills by stimulating neuroplasticity. Among several rehabilitation approaches, functional electrical stimulation (FES) is highlighted in stroke rehabilitation guidelines as a supplementary therapy alongside the standard care modalities. The aim of this study is to present a comprehensive review regarding the usability of FES in post-stroke UL rehabilitation. Specifically, the factors related to UL rehabilitation that should be considered in FES usability, as well a critical review of the outcomes used to assess FES usability, are presented. This review reinforces the FES as a promising tool to induce neuroplastic modifications in post-stroke rehabilitation by enabling the possibility of delivering intensive periods of treatment with comparatively less demand on human resources. However, the lack of studies evaluating FES usability through motor control outcomes, specifically movement quality indicators, combined with user satisfaction limits the definition of FES optimal therapeutical window for different UL functional tasks. FES systems capable of integrating postural control muscles involving other anatomic regions, such as the trunk, during reaching tasks are required to improve UL function in post-stroke patients.

Combining Constraint-led (ecological) and Step-Game (constructivist) approaches through an Action-Research (AR) design conducted throughout a competitive volleyball season, this study aimed to: (i) analyse the impact of increased tactical complexity on lateral and longitudinal collective Synchronisation Tendencies (ST) during defensive and offensive counterattack-subphases, and (ii) examine how opposition attacking contexts (i.e. playing in full -system or in -system) might influence ST throughout each counterattack-subphase. Performance of a youth team, comprised of 15 players, was studied across three AR-cycles. The team's competitive performance was analysed through three competitive matches (one per cycle). Team ST were evaluated using the cluster-phase method and a 3 (matches) × 2 (counterattack-subphases) × 2 (opposition attacking contexts) × 2 (court directions) repeated-measures ANOVA were used to calculate the differences in cluster-amplitude mean values. Results showed that increments in tactical complexity (second AR-cycle) were followed by decreases in collective ST, which were (re)achieved during the third AR-cycle, possibly due to the ecological-constructivist coaching intervention. Our findings imply that coaches could design representative and specific-didactical learning environments, predicated on a team's tactical needs and strategical ideas from a game-plan, framing player intentionality. Results also support the use of questioning strategies to narrow players' attentional focus, stimulating perceptual attunement to relevant constraints emerging in performance. Finally, the insider AR-design provided valuable contextualised insights on coaching interventions for developing collective coordinative structures.

Purpose : Using an action-research design, this study examined the impact of combining concepts from two contemporary pedagogical approaches, the Constraints-led Approach (CLA) and Step-Game Approach (SGA), on the development of youth volleyballers' tactical knowledge, as expressed in performance, throughout a full competitive season. Method : Fifteen players and one coach participated in this study, which involved three action-research cycles, each including the processes of planning, acting and monitoring, reflecting, and fact-finding. The first author, who had the role of coach-researcher, collected data using a reflexive diary and field notes between September 2017 and June 2018, as well as eight semi-structured focus-group interviews. Data were analyzed using thematic analysis, in which inductive procedures deepened understanding of the development of the participants' tactical knowledge. Results : Findings suggested that combining CLA with SGA improved tactical knowledge in specific ways. Players progressed from a starting point where they were only able to describe game scenarios, and act without tactical criteria or considering contextual game constraints, to a point where their intentions during tactical actions were shaped by their ability to think strategically and guide their attention to recognize and interpret different constraints. Conclusions : Results suggested that the development of players' tactical knowledge benefited from a mutual integration of different, yet complementary, pedagogical approaches. By integrating SGA and CLA it was possible to enhance players' adaptable thinking using learning tasks involving the manipulation of meaningful constraints that afforded variable repetition and the resolution of tactical problems.

Leishmania, a protozoan parasite inflicting the complex of diseases called Leishmaniases, resides and replicates as amastigotes within mammalian macrophages. As macrophages are metabolically highly active and can generate free radicals that can destroy this parasite, Leishmania also devise strategies to modulate the host cell metabolism. However, the metabolic changes can also be influenced by the anti-leishmanial immune response mediated by cytokines. This bidirectional, dynamic and complex metabolic coupling established between Leishmania and its host is the result of a long co-evolutionary process. Due to the continuous alterations imposed by the host microenvironment, such metabolic coupling continues to be dynamically regulated. The constant pursuit and competition for nutrients in the host-Leishmania duet alter the host metabolic pathways with major consequences for its nutritional reserves, eventually affecting the phenotype and functionality of the host cell. Altered phenotype and functions of macrophages are particularly relevant to immune cells, as perturbed metabolic fluxes can crucially affect the activation, differentiation, and functions of host immune cells. All these changes can deterministically direct the outcome of an infection. Cytokines and metabolic fluxes can bidirectionally influence each other through molecular sensors and regulators to dictate the final infection outcome. Our studies along with those from others have now identified the metabolic nodes that can be targeted for therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Phthalate esters are synthetic chemicals used in the plastic industry as plasticizers and consumable products. According to United Nations, about 400 million tons of plastic are produced every year. In parallel with increased production, the concerns about its effects on human health have increased because phthalates are endocrine-disrupting compounds. Humans are continuously exposed to phthalates through different routes of exposure. Experimental data have associated the phthalates exposure to adverse effects on development and reproduction in women (e.g., earlier puberty, primary ovarian insufficiency, endometriosis, preterm birth, or in vitro fertilization) and men (e.g., anogenital distance, cryptorchidism, hypospadias, and changes in adult reproductive function) although there is no consensus. Therefore, one question arises: could the increase in infertility be related to phthalates exposure? To answer this question, we aimed to assess the disrupting-effects of phthalates on the human reproductive system. For this, we reviewed the current literature based on epidemiological and experimental data and experimental studies in humans. The phthalate effects were discussed in a separate mode for female and male reproductive systems. In summary, phthalates induce toxicity in the reproductive system and human development. The increased plastic production may be related to the increase in human infertility., (© 2021 Wiley Periodicals LLC.)

The purpose of this study was to understand the perceptions of highly skilled and less skilled volleyball players about the influences that parents, coaches, and peers had on their sport development and performance achievement. Highly skilled ( n = 30) and less skilled ( n = 30) volleyball players participated in semi-structured retrospective interviews to explain how parents, coaches and peers may have influenced their sport participation. Data was analyzed through a process of content analysis. Results indicated that parents, coaches, and peers had an important influence in player's sport development but differing according to players' expertise level. Concerning to parental influences, tangible support during the early years of development was mentioned by all players. However, parents' level of involvement and parenting styles revealed interesting differences between highly skilled and less skilled players. Highly skilled players perceived a moderate parental involvement and an autonomy-supportive parenting style, while less skilled players referred a excessive parental involvement in players' sport participation. Coaches influences showed to have some similarities in the early years with all players mentioning coaches as caring and recognizing their value as an athlete. However, highly skilled players described a different training environment characterized by a demanding coach, individualized instruction, and specific goal setting. Regarding peers' influence, all players recognized that friends were not only one of the main reasons to start playing volleyball, but also an important source of support to remain engaged and staying motivated to do sport. Highly skilled players, however, mentioned the importance of teammates' positive push and critiques during practice for enhancing their motivation, team cohesion and friendship. They also highlighted the importance of friends outside of sport in the later years of their career by acting as an escape from all the pressure that emerged from volleyball training and competition demands. Overall, these findings highlight different social influences according to the players' expertise level suggesting the need to examine more extensively the nature of significant others' support on athlete and talent development., 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 Coutinho, Ribeiro, da Silva, Fonseca and Mesquita.)

The aim of the research was to know the perception of high-level volleyball players of the changes produced (in relation to the previous season) in the efficiency of the training process, after a match analysis intervention program based on the Constraint-led Approach (CLA). The sample consisted of 11 players from a women's volleyball team. The protocol of the intervention program consisted of providing objective, contextualised and systematic information to the coach (adapted to his needs) that would allow understanding the different real game contexts. We used semi-structured interviews to assess players' perceptions. The athletes perceived changes in training, both in their preparation and development, specifically in greater involvement and organisation in preparing the training; in an increase in the specificity and suitability of training tasks according to individual needs; in the representativeness of the restrictions of the game; in a more tactical approach; in the variability of task and in the accountability to achieve the objective proposed. In addition, in the preparation and development for competition, the players detected more game planning; a deeper analysis of the opponents; an objective selection of the most relevant data, an increase in the depth of match analysis and the inclusion of the weekly meeting with the use of video compared to the previous season. These results expose the benefits of coaches incorporate programmes to obtain objective information about the game in their training process., 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 Fernández-Echeverría, Mesquita, González-Silva and Moreno.)

Obesity is an emerging health problem and its incidence has been increasing throughout the workforce. In industrial workstations, vertical handling tasks (VHT), including lifting and lowering, are very common and can cause a significant muscular overload for the involved workers. During these tasks, muscular activity may be considerably affected by workers' body conditions. This study aims to analyze and compare the muscular activity in subjects with different obesity levels, using surface electromyography (EMG), during predefined VHT. Six different VHT (combining 5, 10 and 15-kg loads with two task styles) were performed. EMG data normalization was based on the percentage of maximum contraction during each task (MCT%). The results show that obesity influences the MCT%, which in turn increases the muscular effort during VHT. The current investigation demonstrates that obesity is a relevant musculoskeletal risk factor regarding VHT. The engineering analysis and design implications of this work can thus be perceived.

This systematic review aimed to examine the main findings concerning to the investigations focused on compare, within Physical Education context, the influence of Sport Education (SE) and Traditional Teaching (TT) on students' learning outcomes. A literature search was conducted on nine electronic databases (PubMed, Google Scholar, Web of Science, SCOPUS, Academic Search Ultimate, ERIC, Education Source, APA PsycINFO and APA PsycARTICLES). Inclusion criteria were defined before the selection process. Accordingly, were only included articles that (i) were published in peer-reviewed international journals indexed in Journal Citation Reports or Scientific Journal Rankings; (ii) were available in full-text; (iii) were published in English, Portuguese or Spanish; (iv) were performed within Physical Education context; and (v) provided specifically a comparison between the effects of SE and TT on students' learning outcomes. Globally, twenty-eight studies met the inclusion criteria. The manuscripts' methodological quality was assessed through Downs and Black checklist, with all studies displaying moderate quality. Results showed that comparisons among SE and TT tend to analyze team sports activities sampling high-school students via quasi-experimental designs, with more than half of them were published over the past five years. Also, these investigations typically focused on the differences between both models on the development of personal and social skills, as well as its impact on the motor and cognitive domains. In this respect, although the results tend to point out increases in both SE and TT, superior values are achieved when SE is implemented. The analysis of the teaching-learning process using alternative research methods and designs (i.e., experimental studies, qualitative data, longitudinal analysis, action-research and case studies), longer units with appropriate planning, and the report of model's fidelity so that robust findings can endorse the teachers' praxis, must be a concern in future studies., (© Journal of Sports Science and Medicine.)

An Action-Research (AR) design was implemented throughout a competitive season in which Constraint-led and Step-Game approaches were combined. This intervention study investigated the impact of increased performance complexity on emergence of counterattacking synchronisation tendencies in team players (laterally and longitudinally on court) at different set moments. Fifteen youth volleyball team players were studied across three action-research cycles, with performance in one competitive match analysed per cycle. Team synchronisation tendencies were assessed using the cluster phase method, with a 3 (matches) x 2 (set moments) x 2 (court direction) repeated-measures ANOVA statistical procedure to calculate differences in cluster amplitude mean values. Results revealed a reduction in team synchrony levels when tactical complexity of counterattacking play increased (second AR-cycle). Nevertheless, similar levels of team synchrony emerged between the first and third AR-cycles. Results also revealed the final moments of a set as a significant environmental constraint that shaped synchronisation tendencies. Evidence suggested that the (re)achievement of functional synchrony was realised through integration of Constraint-led and Step-Game approaches during practices designed to enhance tactical awareness in players. Finally, an insider action-research design provided relevant contextualised insights on the development of a team's synchronisation tendencies.

Purpose: Previously, inflammation has been found to be associated with the development of lung cancer. Despite their well-characterized pro-inflammatory functions, the putative roles of interleukin-17 (IL-17) cytokine family members in tumorigenesis have remained controversial. While IL-17A exhibits both pro- and anti-tumor effects, IL-17F has been suggested to serve as a candidate for cancer therapy. Thus, we aimed at clarifying the involvement of IL-17A/F in lung cancer., Methods: IL-17 receptor expression in human and murine lung cancer cells was assessed using immunofluorescence. The effect of IL-17A/F stimulation on lung cancer cell viability (SRB assay) and metabolism (glucose consumption and lactate production) was evaluated under normoxic and hypoxic conditions. Characterization of IL-17A/F-stimulated macrophages was performed by flow cytometry and ELISA. The effect of conditioned media (CM) from IL-17A/F-stimulated macrophages was evaluated on lung cancer cell migration. The effect of CM-stimulated macrophages on lung tumor growth, proliferation and angiogenesis was evaluated in vivo using a chicken chorioallantoic membrane (CAM) assay., Results: No alterations in lung cancer cell viability or metabolism were observed upon direct stimulation with IL-17A/F. We found, however, that CM from IL-17A/F-stimulated macrophages promoted both murine and human lung cancer cell progression through an increased migration capacity in vitro and enhanced in vivo tumor growth, proliferation and angiogenesis. These findings were supported by an increased polarization of human macrophages towards a M2-like phenotype., Conclusions: Our data indicate that IL-17A/F act through immune cell orchestration, i.e., of macrophages, to promote lung cancer cell growth and progression. In addition, our data provide a link between IL-17A/F activity and lung cancer cell-macrophage crosstalk.

Purpose : This longitudinal study provided a retrospective examination of the impact of student participation in a year-long Sport Education curricular experience on physical literacy development. A focus was placed on students' reported motivation, attitudes and disposition to participate in physical education (PE) and sport, and their re-actualizations of a healthy sport culture in the years following the Sport Education experience. Methods : Three years following the Sport Education experience, a cohort of 24 tenth-grade students (nine girls and 15 boys) were traced back and invited to share their recollected memories and accounts of their PE experience and subsequent attributes of physical literacy. The data collection protocol included augmented memory retrieval techniques and a retrospective survey, which informed semi-structured individual and focus groups interviews. A thematic analysis of data was performed and trustworthiness criteria included data triangulation, crosschecking, and collaborative interpretational analysis. Results : Prolonged participation in a year-long Sport Education curriculum promoted a transformation in students' physical literacy dispositions, both within and outside the school context. Physical literacy attributes included empathetic attitudes toward others, resilience against discriminatory learning activities and a commitment of the participants to actively pursue equitable and meaningful participation in PE and sport. Embodied interpersonal, managerial, and peer-teaching skills sustained the participants' sport culture activism against impoverished instructional practices in PE. Conclusions : Prolonged participation in Sport Education, and consequential development of enthusiasm, competency, and literacy can positively contribute to individuals' lifelong physical literacy journey.

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.

Background: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown., Methods: We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry., Findings: We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response., Conclusions: Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in infected HIF-1α -/- macrophages. L. donovani-infected HIF-1α-deficient mice develop hypertriglyceridemia and lipid accumulation in splenic and hepatic myeloid cells. Most importantly, our data demonstrate that manipulating FASN or SREBP-1c using pharmacological inhibitors significantly reduced parasite burden. As such, genetic deficiency of HIF-1α is associated with increased lipid accumulation, which results in impaired host-protective anti-leishmanial functions of myeloid cells., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to conduct a review of the research on the Sport Education (SE) studies that have examined the development of students' personal and social skills. Research articles selected were found through Web of Science, SCOPUS, Academic Search Complete, ERIC, SPORTDiscus with Full Text, Education Source, PsycINFO and PsycARTICLES databases. The keywords "Sport Education" and "physical education" were used in different combinations. The articles were included for analysis if the following criteria were met: (i) were published in peer-reviewed international journals indexed in JCR (Journal Citation Reports) or SJR (Scientific Journal Rankings); (ii) were available in full-text; (iii) examined personal and social variables included or measured as main outcomes within the SE model. The quality of the selected studies was scored using a quality assessment list. Fifty-one studies were included. Results showed that, considering the development of social and personal competencies, the majority of SE research took place in Spain and USA in a co-educational PE context (high school). Enjoyment/satisfaction, enthusiasm and engagement were the predominant outcome measures, using a non-experimental design and multiple qualitative tools in more than half of the studies. Few studies established the fidelity of the model implementation. There is a need for future research to consider other samples, contexts, cultures and types of sports seeking to reinforce the positive impact of SE on the personal and social competencies. Longer units with a good planning, mixed and quantitative methodological designs and the report of the model fidelity would be also particularly important for future investigations., (© Journal of Sports Science and Medicine.)

Perovskite solar cells (PSC) have emerged as a promising substitute for conventional silicon panels, showing the fastest power conversion efficiency evolution within the photovoltaic field, going from 3.8 % to 23.7 % in a few years. However, PSC thermal stability is still an obstacle to their commercialization. In this study, the temperature effect on mesoporous triple-cation perovskite solar cells with two different hole extraction materials-2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD) and poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA)-is assessed. The cells are exposed to thermal stress between -5 °C and 80 °C and their photovoltaic performance is monitored in situ to reproduce real operating conditions. At low temperatures, the devices present very stable values (average loss <5 %), but as the temperature increases significant decreases in the open circuit potential and short-circuit current are observed. X-ray diffraction shows no change in the perovskite crystal structure with temperature. However, electron scanning microscopy and X-ray photoelectron spectroscopy indicate that temperature has a great impact on the hole extraction layer. The cell performance loss is attributed to the evaporation of additives added to the hole extraction layer to enhance its conductivity. Although the decrease in power conversion efficiency at 80 °C is slightly higher for PTAA cells, spiro-OMeTAD cells present a higher irreversible loss of (21.6±2.3) % after thermal stress tests, whereas PTAA devices showed only a loss of (8.2±1.6) %., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sulfate administration (pMT-10). We addressed the role of IL-10 during the initial stages of L. donovani infection by analyzing the parasite burden in the spleen and liver of the infected pMT-10 and WT mice as well as the histopathological alterations upon IL-10 induction. Furthermore, the profile of cytokines expressed by T cells was assessed. Our results demonstrate that an increase in IL-10 production has an impact early but not later after infection. This specific temporal role for IL-10-mediated susceptibility to VL is of interest., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Objective: 5-Alpha reductase type 2 deficiency (5-ARD) is a rare disorder of sex development. The lack of 5-alpha reductase, an enzyme that converts testosterone into dihydrotestosterone, results in external genitalia that may appear female, or predominantly male, albeit undervirilized, or, more often, ambiguous., Methods: This study describes a series of patients with 5-ARD raised as female, focusing on aspects related to gender identity. Following a retrospective chart review, patients with 5-ARD were invited to return to the clinic to enable their gender identity to be assessed using an 11-item structured in-house questionnaire. The Golombok-Rust Inventory of Sexual Satisfaction was applied to patients who had initiated their sexual life., Results: Six patients aged >15 years with 5-ARD and raised as female were included. Most patients were diagnosed late: two before and four after puberty. The mean length of the phallus was 2.8 cm (0.5-5.0). Reasons for seeing a doctor included genital appearance (n = 3), amenorrhea/absence of breast development (n = 2), and changes in gender role attitudes (n = 1). According to the gender identity assessment, 4 patients identified as female, 1 as male, and 1 as both genders. Only the patient identified as male requested gender re-assignment. Of the two patients who had initiated their sexual life, sexual satisfaction was found to be good in one and poor in the other due to vaginal discomfort during intercourse., Conclusion: In the present series, the majority of undervirilized patients with a diagnosis of 5-ARD raised as female were in complete conformation with being female and described themselves as heterosexual. The more virilized patients were those least in conformity with their female-assigned gender., (Copyright © 2018. Published by Elsevier Ltd.)

Social Network Analysis establishes a network system and provides information about the relationships (edges) between system components (nodes). Although nodes usually correspond to actors within the network (e.g., the players), it is possible to stipulate game actions as nodes, thus creating a network of the flow of game actions. In this study, Eigenvector Centrality (a form of weighted centrality that considers n-order connections) was used to identify differences in the centrality of distinct game actions within each of the six game complexes of volleyball. Thirteen matches (46 sets, 2,049 rallies) of the final round of the 2015 FIVB's World Grand Prix (Women) were analyzed. Results showed that analyzing actions as actors (i.e., nodes) offers a clear and comprehensive understanding of game flow and poses an interesting alternative to mainstream research where players are considered nodes. Functional differences between the six game complexes were highlighted, denoting the validity of such division. Out-of-system playing (i.e., having to set the attack under non-ideal conditions, e.g., in KI, KII, KIII and KIV), emerged as a regularity of the game and should be translated into the training process., Competing Interests: The authors have declared that no competing interests exist.

The teaching and learning of games and sport-based activities has historically been the dominant form of the physical education curricula. With an interest in providing to students meaningful and culturally situated sporting experiences, Sport Education is probably the most implemented and researched pedagogical model worldwide. However, although there is considerable evidence that the model as a curriculum approach can benefit the development of social goals and healthy sport behaviors, not a single study as to date examined students' game-play development beyond participation in single and isolated teaching units. Therefore, the purpose of this study was to examine students' development of Game Performance and Game Involvement during participation in three consecutive Sport Education seasons of invasion games. The participants were an experienced physical education teacher and one seventh-grade class totaling 26 students (10 girls and 16 boys). Using the Game Performance Assessment Instrument (Oslin et al., 1998), pre-test to post-tests measures of students' Game Performance and Game Involvement were collected during their participation in basketball (20 lessons), handball (16 lessons), and football (18 lessons) units. Inter-group differences and pre-test to post-test improvements within each season were analyzed through 2 (time) x group (sport) repeated measures ANOVA tests. There were found significant pre-test to post-test improvements in Game Performance and Game Involvement in the second (handball) and third (football) seasons, but not in the first season (basketball). Students' Game Performance and Involvement scores of handball and football were significantly higher than their scores while playing basketball. The opportunity for an extended engagement in game-play activities and prolonged membership of students in the same teams throughout three consecutive seasons of Sport Education were key to the outcomes found. The specific configurations of the game forms played by students either inhibited or enabled their game-play development.

Purpose: The purpose of this study was to provide an integrated analysis of a teacher's peer-teaching mediation strategies, the student-coaches' instruction, and the students' gameplay development across 3 consecutive seasons of sport education., Method: Twenty-six 7th-grade students participated in 3 consecutive sport education seasons of invasion games (basketball, handball, and soccer). The research involved 3 action research cycles, 1 per season, and each cycle included the processes of planning, acting and monitoring, reflecting, and fact finding. Data collection consisted of videotape and audiotape records of all 47 lessons, a reflective field diary kept by the first author in the role of teacher-researcher, and a total of 24 semistructured focus-group interviews. Trustworthiness criteria for assuring the quality of qualitative research included extensive data triangulation, stakeholders' crosschecking, and collaborative interpretational analysis., Results: Through the application of systematic preparation strategies, student-coaches were able to successfully conduct team instruction that resulted in students' tactical development and improved performance. Aspects such as the study of predominant configurations of players' gameplay and similar tactical principles across games within the same category prevented a setback in the complexity of the learning content addressed at the beginning of each season. Players also showed an increasing ability to adapt gameplay to game conditions., Conclusions: While sport education has the capacity to develop competent players, different levels of teacher guidance and learners' instructional responsibility are necessary when teaching tactics.

Contextual influences on talent development (e.g., birthplace effects) have become a topic of interest for sport scientists. Birthplace effects occur when being born in a certain city size leads to participation or performance advantages, typically for those born in smaller or mid-sized cities. The purpose of this study was to investigate birthplace effects in Portuguese volleyball players by analysing city size, as well as population density - an important but infrequently used variable. Participants included 4062 volleyball players (M age  = 33), 53.2% of whom were men. Using Portuguese national census data from 1981, we compared participants (within each sex) across five population categories. In addition, we used ANOVAs to study expertise and population density. Results indicated that men and women athletes born in districts of 200,000-399,999 were 2.4 times more likely to attain elite volleyball status, while all other districts decreased the odds of expert development. For men, being born in high-density areas resulted in less chance of achieving expertise, whereas there were no differences for women. The results suggest that athletes' infrastructure and social structure play an important role in talent development, and that these structures are influenced by total population and population density, respectively.

Metabolism is highly coordinated component of the cellular activity that involves sequential chemical transformations, within a so-called metabolic network. Through these coordinated actions, living organisms acquire energy and biosynthetic precursors to maintain cellular homeostasis and function. Metabolism relies on the breaking down of macromolecules to produce energy [catabolism] and/or intermediary metabolites that are then used to construct essential building blocks for macromolecule production [anabolism]. Overall, these metabolic processes are controlled by cellular energy status: when the energy released from catabolic processes exceeds the cellular demands the storage of metabolites in the form of lipids and glycogen takes place. These phenomena have been vastly associated with the genesis of metabolic disorders, such as obesity. In recent years, we have assisted to a rediscovery of metabolism through the identification of metabolic intermediaries that act as key players on differentiation, proliferation, and function of immune cells. This recent acknowledgement of the impact of metabolism in the overall immune response originated the ground-breaking field of immunometabolism. Here, we will provide a holistic view of metabolism highlighting the biochemical principles underlying its regulation.

The cofactors nicotinamide adenine dinucleotide (NAD + ) and its phosphate form, NADP + , are crucial molecules present in all living cells. The delicate balance between the oxidized and reduced forms of these molecules is tightly regulated by intracellular metabolism assuring the maintenance of homeostatic conditions, which are essential for cell survival and proliferation. A recent cluster of data has highlighted the importance of the intracellular NAD + /NADH and NADP + /NADPH ratios during host-pathogen interactions, as fluctuations in the levels of these cofactors and in precursors' bioavailability may condition host response and, therefore, pathogen persistence or elimination. Furthermore, an increasing interest has been given towards how pathogens are capable of hijacking host cell proteins in their own advantage and, consequently, alter cellular redox states and immune function. Here, we review the basic principles behind biosynthesis and subcellular compartmentalization of NAD + and NADP + , as well as the importance of these cofactors during infection, with a special emphasis on pathogen-driven modulation of host NAD + /NADP + levels and contribution to the associated immune response.

Viruses are intracellular parasites that rely on host machinery to replicate and achieve a successful infection. Viruses have evolved to retain a broad range of strategies to manipulate host cell metabolism and metabolic resources, channeling them toward the production of virion components leading to viral production. Although several viruses share similar strategies for manipulating host cell metabolism, these processes depend on several factors, namely, the viral life cycle and the metabolic and energetic status of the infected cell. Based on this knowledge, the development of new therapeutic approaches that circumvent viral spread through the target of altered metabolic pathways is an opportunity to tackle the infection. However, finding effective broad-spectrum strategies that aim at restoring to homeostasis the metabolic alterations induced upon virus infection is still a Holy Grail quest for antiviral therapies. Here, we review the strategies by which viruses manipulate host metabolism for their own benefit, with a particular emphasis on carbohydrate, glutamine, and lipid metabolism.

Variability analysis has been used to understand how competitive constraints shape different behaviours in team sports. In this study, we analysed and compared variability of tactical performance indices in players within complex I at two different competitive levels in volleyball. We also examined whether variability was influenced by set type and period. Eight matches from the 2012 Olympics competition and from the Portuguese national league in the 2014-2015 season were analysed (1496 rallies). Variability of setting conditions, attack zone, attack tempo and block opposition was assessed using Shannon entropy measures. Magnitude-based inferences were used to analyse the practical significance of compared values of selected variables. Results showed differences between elite and national teams for all variables, which were co-adapted to the competitive constraints of set type and set periods. Elite teams exploited system stability in setting conditions and block opposition, but greater unpredictability in zone and tempo of attack. These findings suggest that uncertainty in attacking actions was a key factor that could only be achieved with greater performance stability in other game actions. Data suggested how coaches could help setters develop the capacity to play at faster tempos, diversifying attack zones, especially at critical moments in competition.

Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7.1 (3.6-11.8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10.4%; cg2=20.8%; cg3=68.8%). Moderate microvascular inflammation was present in 56.3% (g+ptc≥2), and almost half of recipients (51.1%) were C4d positive in immunofluorescence. Female gender (P=.001), age (P=.043), renal dysfunction (P=.002), acute rejection episodes (P=.026), and anti-HLA class II antibodies (P=.004) were associated with kidney allograft failure. Treatment of transplant glomerulopathy was performed in 67.6% of patients. The histologic and laboratory features that led to a therapeutic intervention were score ptc (P=.021), C4d (P=.03), and the presence of anti-HLA antibodies (P=.029), whereas score ah (P=.005) was associated with conservative measure. The overall cumulative kidney allograft survival at 10 years was 75%. Treatment of transplant glomerulopathy was ineffective to improve long-term kidney allograft survival., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodization is a core concept in training. Recently, systematic reviews and meta-analyses have attempted to provide a comprehensive overview of the topic, but theoretical criticisms have arisen with regard to how such research has been conducted. The purpose of the study was to review comprehensively the conceptual and methodological issues surrounding empirical research on periodization in training with human subjects. A search was conducted late in February 2016 on Academic Search Complete, CINAHL Plus, MedicLatina, MEDLINE, PsycINFO, PubMed, Scielo, Scopus, SPORTDiscus and Web of Science. Forty-two randomized or randomized controlled trials were retrieved. Problems emerged in three domains: (a) Conceptually, periodization and variation were applied differently in research, while no empirical research tested predictions concerning direction, timing or magnitude of the adaptations; (b) Study design: More than 95% of papers investigated the 'physical' factor (mainly strength). Research on long-term effects was absent (no study lasted more than nine months). Controlling for confounding factors such as nutrition, supplementation and medication was largely ignored; (c) Data analysis was biased as dispersion in responsiveness was ignored when discussing the findings. Overall, research on periodization fails to analyze the conceptual premises proposed by these approaches.