Effects of a 12% carbohydrate beverage on tackling technique and running performance during rugby league activity: a randomised, placebo-controlled trial

The purpose of this study was to investigate the effects of a 12% carbohydrate (CHO) beverage on tackling technique and running performance during rugby league activity. Using a double-blind, placebo-controlled, randomised, crossover design, 15 academy rugby league players ingested a 250 ml bolus of a 12% CHO solution (30 g maltodextrin and 30 g sucrose in 500 ml) 15 minutes before two bouts of rugby activity. The rugby league match simulation for interchange players was used to standardise the movement patterns of activity and provide reliable outcome measures, whilst also reflecting the duration of a typical field-based conditioning session. Measures of tackling technique, external responses (e.g., fatigue index from sprint data) and rating of perceived exertion (RPE) were recorded throughout. Gut discomfort was measured before each bout. The interaction effect was largely compatible with the hypothesis for relative distance (P<0.001, η2 = 0.217) and fairly compatible for tackling technique (P = 0.068, η2 = 0.0640). The time effect for tackling technique, relative and high-intensity distance, sprint, and sprint to contact velocity, time at high metabolic power, PlayerLoad™, and RPE (all P<0.05; η2 = 0.131–0.701) was compatible with the hypothesis. Data for tackling technique, relative and high-intensity distance, sprint, and sprint to contact velocity, sprint, and sprint to contact fatigue index (all P<0.05; η2 = 0.189–0.612) was compatible with a supplement effect overall despite few differences in the pattern of change (interaction). Minimal gut discomfort was reported for the CHO (bout 1 = 27 ± 17; bout 2 = 23 ± 17 AU) and placebo (bout 1 = 23 ± 18 AU; bout 2 = 24 ± 13) trials. This study shows that a 12% CHO beverage before two bouts of standardised rugby activity is a practical and effective strategy for retaining tackling technique, increasing external responses, and reducing RPE without compromising gut comfort

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis