(1) Background: Training load monitoring has become a relevant research-practice gap to control training and match demands in team sports. However, there are no systematic reviews about accumulated training and match load in football. (2) Methods: Following the preferred reporting item for systematic reviews and meta-analyses (PRISMA), a systematic search of relevant English-language articles was performed from earliest record to March 2020. The search included descriptors relevant to football, training load, and periodization. (3) Results: The literature search returned 7972 articles (WoS = 1204; Pub-Med = 869, SCOPUS = 5083, and SportDiscus = 816). After screening, 36 full-text articles met the inclusion criteria and were reviewed. Eleven of the included articles analyzed weekly training load distribution; fourteen, the weekly training load and match load distribution; and eleven were about internal and external load relationships during training. The reviewed articles were based on short-telemetry systems (n = 12), global positioning tracking systems (n = 25), local position measurement systems (n = 3), and multiple-camera systems (n = 3). External load measures were quantified with distance and covered distance in different speed zones (n = 27), acceleration and deceleration (n = 13) thresholds, accelerometer metrics (n = 11), metabolic power output (n = 4), and ratios/scores (n = 6). Additionally, the internal load measures were reported with perceived exertion (n = 16); heart-rate-based measures were reported in twelve studies (n = 12). (4) Conclusions: The weekly microcycle presented a high loading variation and a limited variation across a competitive season. The magnitude of loading variation seems to be influenced by the type of week, player’s starting status, playing positions, age group, training mode and contextual variables. The literature has focused mainly on professional men; future research should be on the youth and female accumulated training/match load monitoring.

Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies, in vitro toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against Cryptosporidium parvum Iowa and field isolates was comparable to that against Cryptosporidium hominis. Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.

Cryptosporidiosis is a leading cause of life-threatening diarrhea in children, and the only currently approved drug is ineffective in malnourished children and immunocompromised people. Large-scale phenotypic screens are ongoing to identify anticryptosporidial compounds, but optimal approaches to prioritize inhibitors and establish a mechanistically diverse drug development pipeline are unknown. Here, we present a panel of medium-throughput mode of action assays that enable testing of compounds in several stages of the Cryptosporidium life cycle. Phenotypic profiles are given for thirty-nine anticryptosporidials. Using a clustering algorithm, the compounds sort by phenotypic profile into distinct groups of inhibitors that are either chemical analogs (i.e. same molecular mechanism of action (MMOA)) or known to have similar MMOA. Furthermore, compounds belonging to multiple phenotypic clusters are efficacious in a chronic mouse model of cryptosporidiosis. This suite of phenotypic assays should ensure a drug development pipeline with diverse MMOA without the need to identify underlying mechanisms.

Monitoring the training load in football is an important strategy to improve athletic performance and an effective training periodization. The aim of this study was two-fold: (1) to quantify the weekly training load and recovery status variations performed by under-15, under-17 and under-19 sub-elite young football players; and (2) to analyze the influence of age, training day, weekly microcycle, training and playing position on the training load and recovery status. Twenty under-15, twenty under-17 and twenty under-19 players were monitored over a 2-week period during the first month of the 2019–2020 competitive season. Global positioning system technology (GPS) was used to collect external training loads: total distance covered, average speed, maximal running speed, relative high-speed running distance, high metabolic load distance, sprinting distance, dynamic stress load, accelerations and decelerations. Internal training load was monitored using ratings of perceived exertion (RPE) and session rating of perceived exertion (sRPE). Recovery status was obtained using the total quality recovery (TQR) scale. The results show an age-related influence for external training load (p ≤ 0.001; d = 0.29–0.86; moderate to strong effect), internal training load (p ≤ 0.001, d = 0.12–0.69; minimum to strong effect) and recovery status (p ≤ 0.001, d = 0.59; strong effect). The external training load presented differences between training days (p < 0.05, d = 0.26–0.95; moderate to strong effect). The playing position had a minimum effect on the weekly training load (p < 0.05; d = 0.06–0.18). The weekly microcycle had a moderate effect in the TD (p < 0.05, d = 0.39), RPE (p < 0.05; d = 0.35) and sRPE (p < 0.05, d = 0.35). Interaction effects were found between the four factors analyzed for deceleration (F = 2.819, p = 0.017) and between inter-day, inter-week and age for total covered distance (F = 8.342, p = 0.008). This study provided specific insights about sub-elite youth football training load and recovery status to monitor training environments and load variations. Future research should include a longer monitoring period to assess training load and recovery variations across different season phases.