Repeated Sprints, High-Intensity Interval Training, Small-Sided Games: Theory and Application to Field Sports

Due to the broad spectrum of physical characteristics necessary for success in field sports, numerous training modalities have been used develop physical preparedness. Sports like rugby, basketball, lacrosse, and others require athletes to be not only strong and powerful but also aerobically fit and able to recover from high-intensity intermittent exercise. This provides coaches and sport scientists with a complex range of variables to consider when developing training programs. This can often lead to confusion and the misuse of training modalities, particularly in the development of aerobic and anaerobic conditioning. This review outlines the benefits and general adaptations to 3 commonly used and effective conditioning methods: high-intensity interval training, repeated-sprint training, and small-sided games. The goals and outcomes of these training methods are discussed, and practical implementations strategies for coaches and sport scientists are provided

Repeated Sprints, High-Intensity Interval Training, Small-Sided Games: Theory and Application to Field Sports

Due to the broad spectrum of physical characteristics necessary for success in field sports, numerous training modalities have been used develop physical preparedness. Sports like rugby, basketball, lacrosse, and others require athletes to be not only strong and powerful but also aerobically fit and able to recover from high-intensity intermittent exercise. This provides coaches and sport scientists with a complex range of variables to consider when developing training programs. This can often lead to confusion and the misuse of training modalities, particularly in the development of aerobic and anaerobic conditioning. This review outlines the benefits and general adaptations to 3 commonly used and effective conditioning methods: high-intensity interval training, repeated-sprint training, and small-sided games. The goals and outcomes of these training methods are discussed, and practical implementations strategies for coaches and sport scientists are provided

Does sex hormone-binding globulin cause insulin resistance during pubertal growth?

Abstract Background: The directional influences between serum sex hormone-binding globulin (SHBG), adiposity and insulin resistance during pubertal growth remain unclear. The aim of this study was to investigate bidirectional associations between SHBG and insulin resistance (HOMA-IR) and adiposity from childhood to early adulthood. Methods: Participants were 396 healthy girls measured at baseline (age 11.2 years) and at 1, 2, 4 and 7.5 years. Serum concentrations of estradiol, testosterone and SHBG were determined by ELISA, glucose and insulin by enzymatic photometry, insulin-like growth factor 1 (IGF-1) by time-resolved fluoroimmunoassays, whole-body fat mass by dual-energy X-ray absorptiometry and HOMA-IR were determined by homeostatic model assessment. The associations were examined using cross-lagged path models. Results: In a cross-lagged path model, SHBG predicted HOMA-IR before menarche β = −0.320 (95% CI: −0.552 to −0.089), P = 0.007, independent of adiposity and IGF-1. After menarche, no directional effect was found between SHBG and insulin resistance or adiposity. Conclusions: Our results suggest that in early puberty, decline in SHBG predicts development of insulin resistance, independent of adiposity. However, after menarche, no directional influences between SHBG, adiposity and insulin resistance were found, suggesting that observational associations between SHBG, adiposity and insulin resistance in pubertal children may be subject to confounding. Further research is needed to understand the underlying mechanisms of the associations between SHBG and cardiometabolic risk markers in peripubertal children

Protease specificity determination by using cellular libraries of peptide substrates (CLiPS)

We report a general combinatorial approach to identify optimal substrates of a given protease by using quantitative kinetic screening of cellular libraries of peptide substrates (CLiPS). A whole-cell protease activity assay was developed by displaying fluorescent reporter substrates on the surface of Escherichia coli as N-terminal fusions. This approach enabled generation of substrate libraries of arbitrary amino acid composition and length that are self-renewing. Substrate hydrolysis by a target protease was measured quantitatively via changes in whole-cell fluorescence by using FACS. FACS enabled efficient screening to identify optimal substrates for a given protease and characterize their cleavage kinetics. The utility of CLiPS was demonstrated by determining the substrate specificity of two unrelated proteases, caspase-3 and enteropeptidase (or enterokinase). CLiPS unambiguously identified the caspase-3 consensus cleavage sequence DXVDG. Enteropeptidase was unexpectedly promiscuous, but exhibited a preference for substrates with the motif (D)/(E)RM, which were cleaved substantially faster than the canonical DDDDK recognition sequence, widely used for protein purification. CLiPS provides a straightforward and versatile approach to determine protease specificity and discover optimal substrates on the basis of cleavage kinetics

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

Background & Aims: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog. Methods: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq). Results: Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies (p = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of CDKN2A, SMAD4, NRG1, TP53. Sequencing also identified worse survival in patients with tumors containing tetraploid genomes. Conclusions: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients. Lay summary: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients