Cryptosporidium life cycle small molecule probing implicates translational repression and an Apetala 2 transcription factor in macrogamont differentiation.

The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans, Cryptosporidium spp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate macrogamont differentiation and maturation. RNA-seq studies confirmed selective modulation of macrogamont differentiation for 10 identified compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompanies Cryptosporidium sexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in differentiation into macrogamonts. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for macrogamont formation.

Identifying the ideal weekly training load for in-game performance in an elite Brazilian soccer team.

Introduction: The purpose of this study was to investigate the ideal training load to be applied during periods of fixture congestion to ensure an adequate dose-response effect for performance maintenance. Methods: Match performance data and corresponding pre-match training load sessions (both N = 498 match performance cases and training-block session cases) were collected (with the catapult system, VECTOR7) from 36 male professional soccer players (23.5 ± 5.2 years; 178 ± 4 cm; 75.5 ± 6.0 kg) belonging to the Brazilian First Division team during the 2022 season. The following data were collected in match and training sessions: jump, acceleration, deceleration, and change of direction (COD); running distance producing metabolic power at different intensities (>20, >20-35, >35-45, >45-55, and >55 W kg-1), total distance (m), relative distance (m/min), running distance at different speeds (>20, >25, and >30 km/h), number of sprints (running >25 km/h), and maximum speed (km/h). Mixed linear model (MLM), decision tree regression (DTR), and cluster K means model (SPSS v.26) approach were performed to identify the most critical variables (and their respective load) in the training sessions that could explain the athlete's match performance. Results: MLM and DTR regression show that training load significantly affects game performance in a specific way. According to the present data, an interference phenomenon can occur when a high load of two different skills (running in a straight line vs COD, deceleration, and jumping) is applied in the same training block of the week. The cluster approach, followed by a chi-squared test, identified significant associations between training load and athlete match performance in a dose-dependent manner. Discussion: The high load values described here have a beneficial effect on match performance, despite the interference between stimuli discussed above. We present a positive training load from a congested season from the Brazilian First Division team. The study suggests that an interference effect occurs when high physical training loads are applied to different specific physical skills throughout the season.

Comparison of force variables and dynamic strength index between age groups in elite young Brazilian football goalkeepers.

Introduction: The application of muscle force is a determinant of football success as it is inherent to the motor control and sport. The aims of this study are: (1) to describe force variables Isometric Maximal Force (IMF), Concentric Peak Force (CPPF), and Dynamic Strength Index (DSI) in football goalkeepers from different age groups; (2) to compare these variables' behavior between those groups. Methods: The sample was formed by 19 youth players (15.97 ± 1.55 years old) from a first-division Brazilian football team. The CPPF and IMF variables were obtained through the Countermovement jump and isometric squat tests, respectively. For data collection, a force plate (Cefise, Brazil) was used with an acquisition frequency of 600 Hz and mono-axial. The DSI was calculated using the ratio between CPPF and IMF. For data analysis, the sample was separated into clusters by age. After the grouping, a descriptive analysis of the data and a comparison between the groups with p < 0.05. Results: The sample was grouped into three groups (GA, GB, and GC) and one of the individuals did not enter the group, totaling 18 individuals in the analyzed sample. The comparison between the ages of the groups showed a significant difference and small and moderate effect size (ES), validating the cluster strategy. The CPPF and IMF variables showed increased values according to chronological age. CPPF showed a significant difference between GA-GB, (ES = very large) GA-GC (ES = very large), and GB-GC (ES = moderate). The IMF variable had significant differences between GA-GB (ES = moderate) and GA-GC (ES = very large). However, DSI showed significant differences only between GA GB (ES = small) and GB-GC (ES = very large). Conclusions: The CPPF and IMF variables had constant increases and distinct values with an increase according to age, and this did not occur for DSI. The difference between CPPF and IMF compared to DSI bring to light the variability in dynamics and proportionality between muscular force in the concentric phase and maximal force in the isometric regime during the developmental process over chronological age in soccer goalkeepers.

The Effectiveness of Pilates Training Interventions on Older Adults' Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Pilates training intervention programs have gained attention as a potential approach to enhancing balance in older adults, thereby reducing the risk of falls. In light of these considerations, this systematic review and meta-analysis aimed to critically evaluate the existing evidence and determine the effect of Pilates training intervention programs on older adults' balance. MATERIALS AND METHODS: The literature was searched through the PubMed, Web of Science, and Scopus databases from inception until July 2023. The primary keywords used for the literature search included "elderly" or "older adults" and "pilates training" and "balance". RESULTS: The systematic review through qualitative analysis showed robust evidence about the efficacy of Pilates intervention programs in improving older adults' balance. The pooled meta-analysis of static and dynamic balance showed that eight (53%) out of a total fifteen analyzed interventions presented a significant effect of Pilates in improving the participants' balance, without between-study heterogeneity. In addition, the meta-analysis regarding dynamic balance showed that six (67%) out of nine analyzed interventions presented a significant effect of Pilates in improving the participants' balance, without heterogeneity between studies. Similarly, the meta-analysis regarding static balance showed that four (50%) out of eight analyzed studies presented significant effects on the older adults' balance, where moderate between-study heterogeneity was found. Sensitivity analysis showed that three studies reduced the between-study heterogeneity (19, 17.6, and 17%), regressing from moderate to low heterogeneity, p < 0.05. CONCLUSIONS: This systematic review and meta-analysis underscores the potential of Pilates training as a valuable intervention to enhance balance in the elderly population.

Effects of applying a multivariate training program on physical fitness and tactical performance in a team sport taught during physical education classes.

Introduction: A multivariate training program could be a pedagogical choice to improve physical and tactical performance in a team sport taught during physical education classes at different levels of education. Thus, the aim of this study was to verify the effects of applying a multivariate training program on physical fitness and tactical performance during the teaching of a basketball didactic unit in basic and secondary education. Methods: Seventy-five students from a Portuguese school, with an average age of 15.02 ± 1.31 years, included forty-two students from basic school and thirty-three students from secondary school. The FITescola® test battery was used to assess physical fitness (i.e., sit-ups, push-ups, horizontal impulse, shuttle test, 40 m sprint, agility 4 × 10 m). The Game Performance Assessment Instrument (GPAI) was used to assess students' tactical performance for each player's game performance during a 20-minute 3 vs. 3 match. The GPAI variables were decision making index (DMI), skill execution index (SEI), support actions index (SI), and adaptability index (AI). During a basketball didactic unit teaching, the students were randomly divided into two groups, a control group that will not carry out the training program and an experimental group that will carry out a strength training program, high intensity explosive exercises and activities based on small-sided games (SSG) for 6 weeks. The two groups were evaluated in two moments: before the application of the training program and after the application of the training program regarding changes in physical fitness and tactical performance. The independent samples t-test (samples from two groups) and paired sample Test (for the same group) were applied for pre and post-assessment comparisons. Results: All indexes present significant differences between basic and secondary students in the pre- and post-assessment tests with small effects (t = -6.54 to -4.82, Δ = -27.57 to -0.16, p<0.05-p< 0.001, d = 0.78-1.05). Discussion: The results allow to conclude that in a school environment, a well-structured multivariate training program can effectively improve students' tactical skills, increasing their physical conditioning levels.

Perspectives on Player Performance during FIFA World Cup Qatar 2022: A Brief Report.

Changing the date of the FIFA World Cup Qatar 2022 may represent a factor to consider for the expected performance of participating players. This was due to fixture congestion at the start of the season and expected weather conditions during the competition. Thus, the main purpose of this brief report was to critically analyze the potential impact of changing the competition date and weather conditions on players' performance. In addition, a brief description about the performance during the World Cup is also provided. For the research, the Web of Science, PubMed and SPORTDiscus databases were accessed using the primary keywords FIFA World Cup and World Soccer Cup associated with the secondary keywords match running performance, fixture congestion, fatigue and weather conditions. After applying inclusion and exclusion criteria, 52 articles were considered for analysis. The results seem to indicate that although changes were expected due to the modifications made (i.e., the competition date and scheduling congestion), the performance of the players seems not to have been affected in terms of the analyzed indicators. Furthermore, it seems possible to identify some patterns in the behavior of the teams that reached the most advanced stages of the competition.

Concentric Isokinetic Strengthening Program's Impact on Knee Biomechanical Parameters, Physical Performance and Quality of Life in Overweight/Obese Women with Chronic Meniscal Lesions.

Meniscal injuries are one of the most common intra-articular knee injuries. Different treatments are presented depending on the symptoms and duration of meniscus tears, such as arthroscopic partial meniscectomy, physiotherapy, or even pharmacological treatment. The purpose was to investigate the effect of a concentric isokinetic knee muscle strengthening program on strength, joint range of motion, physical performance, quality of life and pain tolerance in overweight/obese women with chronic meniscal lesions. Twenty-four overweight/obese women were randomized into two groups. A control group (CG) performed a usual rehabilitation program plus isokinetic muscle strengthening (IMS) in the continuous passive motion mode and measured with an isokinetic dynamometer. An experimental group (EG) performed the same program in combination with IMS in the isokinetic active mode. The peak torque of the knee extensors (PTE) and flexors (PTF), sit-to-stand test, stair climb test, joint amplitude, heel-to-buttock distance, Thessaly test, KOOS questionnaire of pain and quality of life were measured pre- and post-protocol. After the intervention, the sit-stand number for both groups was significantly higher (p < 0.001) and the time to climb stairs was significantly reduced for the EG (p < 0.001). A significant improvement in joint range of motion, life quality (p < 0.001), relief in knee pain (p < 0.001) and in the post-program evaluation at the EG (p < 0.05) was noted. There was no significant difference in PTE and PTF between groups at 60°/s and 180°/s. The IMS in the active mode could be an effective therapeutic modality in managing middle-aged patients suffering from a degenerative meniscal tear.

Structure-Activity Relationship Studies of the Aryl Acetamide Triazolopyridazines against Cryptosporidium Reveals Remarkable Role of Fluorine.

Our previous work identified compound 1 (SLU-2633) as a potent lead compound toward the identification of a novel treatment for cryptosporidiosis, caused by the parasite Cryptosporidium (EC50 = 0.17 µM). While this compound is potent and orally efficacious, the mechanism of action and biological target(s) of this series are currently unknown. In this study, we synthesized 70 compounds to develop phenotypic structure-activity relationships around the aryl "tail" group. In this process, we found that 2-substituted compounds are inactive, confirmed that electron withdrawing groups are preferred over electron donating groups, and that fluorine plays a remarkable role in the potency of these compounds. The most potent compound resulting from this work is SLU-10482 (52, EC50 = 0.07 µΜ), which was found to be orally efficacious with an ED90 < 5 mg/kg BID in a Cryptosporidium-infection mouse model, superior to SLU-2633.

Prevalence of Type 2 Diabetes, Impaired Fasting Glucose, and Diabetes Risk in an Adult and Older North-Eastern Portuguese Population.

The aims of this study were (1) to evaluate the prevalence of type 2 diabetes (T2D) in a middle-aged north-eastern Portuguese population, (2) to analyze the prevalence of impaired fasting glucose (IFG), and (3) to assess the risk of T2D in this community-based sample. An exploratory, retrospective, and cross-sectional study was conducted from a total of 6570 individuals aged 18-102 years, among which 3865 were women (57.4 ± 18.1 years) and 2705 were men (60.0 ± 16.8 years). T2D diagnosis, IFG, and the diabetes risk score (low to very high risk) were assessed. The prevalence of T2D in this adult and an older north-eastern Portuguese population was 17.4%. A higher prevalence of T2D was reported in men (22.2%) than in women (14.0%); however, this was without significant differences (p = 0.086). Otherwise, the prevalence of T2D was significantly different among the age groups and increased with age (p < 0.001). Regarding IFG, a higher percentage of cases was observed in men (14.1%) than in women (8.4%) (p < 0.001). The risk of developing T2D in the next 10 years showed an association with sex and age group (p < 0.001) with a small-to-moderate effect (V = 0.1-0.3). Men and the elderly had the highest percentage of cases in the moderate-to-very high-risk bands. The current research confirmed a higher prevalence of T2D, IFG, and diabetes risk than previous Portuguese epidemiological reports. The results also suggest potential prediabetes cases, which should be carefully monitored. The current research adds evidence to the worldwide trend of the increasing prevalence of T2D and intermediate hyperglycemia (i.e., prediabetes).

Structure-Activity relationships of replacements for the triazolopyridazine of Anti-Cryptosporidium lead SLU-2633.

Cryptosporidiosis is a diarrheal disease particularly harmful to children and immunocompromised people. Infection is caused by the parasite Cryptosporidium and leads to dehydration, malnutrition, and death in severe cases. Nitazoxanide is the only FDA approved drug but is only modestly effective in children and ineffective in immunocompromised patients. To address this unmet medical need, we previously identified triazolopyridazine SLU-2633 as potent against Cryptosporidium parvum, with an EC50 of 0.17 µM. In the present study, we develop structure-activity relationships (SAR) for the replacement of the triazolopyridazine head group by exploring different heteroaryl groups with the aim of maintaining potency while reducing affinity for the hERG channel. 64 new analogs of SLU-2633 were synthesized and assayed for potency versus C. parvum. The most potent compound, 7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine 17a, was found to have a Cp EC50 of 1.2 µM, 7-fold less potent than SLU-2633 but has an improved lipophilic efficiency (LipE) score. 17a was found to decrease inhibition in an hERG patch-clamp assay by about two-fold relative to SLU-2633 at 10 µM despite having similar inhibition in a [3H]-dofetilide competitive binding assay. While most other heterocycles were significantly less potent than the lead, some analogs such as azabenzothiazole 31b, have promising potency in the low micromolar range, similar to the drug nitazoxanide, and represent potential new leads for optimization. Overall, this work highlights the important role of the terminal heterocyclic head group and represents a significant extension of the understanding of the SAR for this class of anti-Cryptosporidium compounds.

The Reliability of the Timed Up and Go Test among Portuguese Elderly.

Assessment of dynamic balance is typically completed through functional tests, such as the Timed Up and Go (TUG) test, which measures the time it takes for an individual to stand up from a chair, walk a set distance, turn around, and sit back down. This test has been validated in several countries. However, in the Portuguese population there is a gap on testing the reliability of this functional test in a sample of the elderly both living in the community or in nursing homes. Thus, this study aimed at examining the reliability of the TUG in a sample of Portuguese elderly. An Intraclass Correlation Coefficient (ICC) analysis was performed between the first time (T1) and the time score after 16 weeks (T2) in TUG test by 38 males and 79 females aged between 60 and 92 years. The results showed acceptable scores of ICC in community-dwelling and nursing home resident elderly in both moments. In addition, significant differences were found between these groups of older adults, showing that community-dwelling elderly show greater agility and balance capacity compared to those living in nursing homes. Thus, the TUG test can be applied in the Portuguese elderly in both community-dwelling and nursing home resident elderly.

Associations between Coronavirus and Immune Response, Cardiorespiratory Fitness Rehabilitation and Physical Activity: A Brief Report.

COVID-19 has serious effects on cardiorespiratory capacity. In this sense, physical activity has been identified as beneficial in the treatment of cardiorespiratory diseases due to its anti-inflammatory and immunosuppressive benefits. To date, no study has been found on cardiorespiratory capacity and rehabilitation in patients cured after COVID-19. Thus, this brief report aims to relate the benefits of physical activity to cardiorespiratory function after COVID-19. It is important to know how different levels of physical activity can be related to the different symptoms of COVID-19. In view of this, the objectives of this brief report were to: (1) explore the theoretical associations between COVID-19 symptoms and physical activity; (2) compare the cardiorespiratory function of non-COVID-19 participants and post-COVID-19 patients; and (3) propose a physical activity program to improve the cardiorespiratory fitness of post-COVID-19 patients. Thus, we note that moderate-intensity physical activity (i.e., walking) has a greater beneficial effect on immune function, whereas vigorous activity (i.e., marathon running) tends to temporarily reduce immune function through an imbalance of cytokine types I and II in the hours and days after exercise. However, there is no consensus in the literature in this regard, since other investigations suggest that high-intensity training can also be beneficial, not causing clinically relevant immunosuppression. Physical activity has been shown to be beneficial in improving the clinical conditions most frequently associated with severe COVID-19. Thus, it is possible to infer that physically active individuals seem to be less exposed to the dangers of severe COVID-19 compared to non-active individuals through the benefits of physical activity in strengthening the immune system and fighting infections. The current study demonstrates that physical activity appears to be beneficial in improving the clinical conditions most often associated with severe COVID-19.

Exercise Biomechanics for Health: Evaluating Lifelong Activities for Well-Being.

Biomechanics is a multidisciplinary study of the mechanical laws and principles that govern human movement and the functioning of biological systems [...].

Weekly Training Load across a Standard Microcycle in a Sub-Elite Youth Football Academy: A Comparison between Starters and Non-Starters.

Compensatory training sessions have been highlighted as useful strategies to solve the differential weekly training load between the players' starting status. However, the influence of the players' starting status is still understudied in sub-elite youth football. Thus, the aim of this study was to compare the weekly training load on a standard microcycle in starters and non-starters of a sub-elite youth football academy. The weekly training load of 60 young sub-elite football players was monitored during a 6-week period using an 18 Hz global positioning system (GPS), 1 Hz telemetry heart rate, rating of perceived exertion (RPE), and total quality recovery (TQR). The total distance (TD) covered presented a significant difference between starters and non-starters with a moderate effect (t = -2.38, Δ = -428.03 m, p = 0.018, d = 0.26). Training volume was higher in non-starters than in starter players (TDStarters = 5105.53 ± 1684.22 vs. TDNon-starters = 5533.56 ± 1549.26 m). Significant interactive effects were found between a player's starting status, playing time, and session duration in overall training load variables for within (F = 140.46; η2 = 0.85; p < 0.001) and between-subjects (F = 11.63 to 160.70; η2 = 0.05 to 0.76; p < 0.001). The player's starting status seems to only influence the training volume in sub-elite youth football, unless one considers the covariance of the playing time and session duration. Consequently, coaches should prioritize complementary training to equalize training volume and emphasize similar practice opportunities for non-starters. Future studies should evaluate the gap between training and match load, measuring the impact of recovery and compensatory sessions.

Effect of Blood Flow Restriction Technique on Delayed Onset Muscle Soreness: A Systematic Review.

Background and Objectives: The effect of the blood flow restriction technique (BFR) on delayed onset muscular soreness (DOMS) symptoms remains unclear. Since there is no consensus in the literature, the aim of the present study is to systematically identify and appraise the available evidence on the effects of the BFR technique on DOMS, in healthy subjects. Materials and Methods: Computerized literature search in the databases Pubmed, Google Scholar, EBSCO, Cochrane and PEDro to identify randomized controlled trials that assessed the effects of blood flow restriction on delayed onset muscular soreness symptoms. Results: Eight trials met the eligibility criteria and were included in this review, presenting the results of 118 participants, with a mean methodological rating of 6/10 on the PEDro scale. Conclusions: So far, there is not enough evidence to confirm or refute the influence of BFR on DOMS, and more studies with a good methodological basis are needed, in larger samples, to establish protocols and parameters of exercise and intervention. Data analysis suggests a tendency toward the proinflammatory effect of BFR during high restrictive pressures combined with eccentric exercises, while postconditioning BFR seems to have a protective effect on DOMS. Prospero ID record: 345457, title registration: "Effect of Blood Flow Restriction Technique on the Prevention of Delayed Onset Muscle Soreness: A Systematic Review".

Modeling the Major Influencing Factor on Match Running Performance during the In-Season Phase in a Portuguese Professional Football Team.

The aim of this study was two-fold: (1) to analyze the influence of season phase (i.e., the start of the in-season and mid-in-season) on match running performance in a Portuguese professional football team; (2) to determine and model the main factor influencing match running performance during the in-season in this specific football team. Eighteen matches were collected by an 18 Hz global positioning system (GPS) from a professional Portuguese football team during the start of the in-season and mid-in-season. The match running performance was analyzed according to season phases, presenting significant differences in total distance (TD) (tlowerbound = 4.71, p < 0.001; tupperbound = −2.22, p = 0.002), average speed (AvS) (tlowerbound = 359.45, p < 0.001; tupperbound = −359.87, p < 0.001), and relative high speed running (rHSR) (tlowerbound = 13.10, p < 0.001; tupperbound = −10.21, p < 0.001). The logistic regression showed TD (ß = −1.59, z = −2.84, p = 0.005) and AvS (ß = 2.68, z = −2.84, p = 0.007) as the major factors influencing match running performance during seasonal variation. Sprints and accelerations showed no significance for predicting match running performance during the season phases (ß = −0.05 to 1.07, z = −0.95 to 1.07, p = 0.29 to 0.72). Current research confirms that lower and upper bounds should be used to quantify seasonal differences on match running performance. TD and AvS were described as the main factors influencing match running performance during the in-season phase. Thus, it is important to highlight the pace and volume of the game to maximize match running performance.

Multivariate Training Programs during Physical Education Classes in School Context: Theoretical Considerations and Future Perspectives.

Physical Education plays a fundamental role in promoting healthy habits and lifestyles, as well as in the development of individual and cognitive skills. To date, several investigations have reported positive effects on indicators of physical fitness, motor proficiency, and creativity as a result of specific training programs during Physical Education classes. However, the effects of multivariate training programs on the improvement of the aforementioned skills remain unclear in the literature. Through this brief review, the benefit of applying multivariate training programs during Physical Education classes on indicators of physical fitness, motor proficiency and creativity was critically analyzed. A narrative approach was applied to summarize the availed research as following: (i) theoretical background; (ii) research gaps/issues; (iii) subject explanation about multivariate training programs in Physical Education; and (iv) practical application and further research. The evidence reported in this regard may be useful for the development of multivariate training programs that simultaneously enable the improvement of indicators of physical fitness, motor proficiency and creativity. However, there is still no consensus in the literature on the best strategies (i.e., type of program, duration, intensity) to enhance motor proficiency and creativity in the context of Physical Education classes using multivariate training programs.

The Effects of 32 Weeks of Multicomponent Training with Different Exercises Order in Elderly Women's Functional Fitness and Body Composition.

Background and objectives: Starting the multicomponent training sessions with aerobic-based exercises or resistance-based exercises may have different effects on functional fitness and body composition. Thus, the aim of this study was to assess the effects of the order of exercises in elderly women's physical fitness and body composition by multicomponent training. Materials and Methods: A sample of 91 elderly females, aged between 60 and 81, were randomly divided into three groups (A, B, C). Each group performed the following order of exercises: Group A consisted of warm-up followed by aerobic training, strength training, stretching and cool down; Group B consisted of warm-up followed by strength training, aerobic training, stretching and cool down; while the control group (C) did not perform any exercise. Functional fitness and body composition were assessed at 3 moments of the 32 weeks (baseline and after each 16-week) intervention. One-way ANOVA for comparison between groups, ANOVA for repeated measures and multiple linear regression were used for statistical analysis. Results: The results showed that the functional fitness and body composition varied over the 32 weeks of multicomponent training. However, group A seems to show higher improvements in more variables. Conclusion: In the current study, group A obtained better results in most of the evaluated parameters. Thus, to improve functional fitness, warm-up, followed by aerobic training, strength training and relaxation may be the most suitable training for elderly women.