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Cahill, MJ, Oliver, JL, Cronin, JB, Clark, K, Cross, MR, Lloyd, RS, and Lee, JE. Influence of resisted sled-pull training on the sprint force-velocity profile of male high-school athletes. J Strength Cond Res 34(10): 2751-2759, 2020-Although resisted sled towing is a commonly used method of sprint-specific training, little uniformity exists around training guidelines for practitioners. The aim of this study was to assess the effectiveness of unresisted and resisted sled-pull training across multiple loads. Fifty-three male high-school athletes were assigned to an unresisted (n = 12) or 1 of 3 resisted groups: light (n = 15), moderate (n = 14), and heavy (n = 12) corresponding to loads of 44 ± 4 %BM, 89 ± 8 %BM, and 133 ± 12 %BM that caused a 25, 50, and 75% velocity decrement in maximum sprint speed, respectively. All subjects performed 2 sled-pull training sessions twice weekly for 8 weeks. Split times of 5, 10, and 20 m improved across all resisted groups (d = 0.40-1.04, p < 0.01) but did not improve with unresisted sprinting. However, the magnitude of the gains increased most within the heavy group, with the greatest improvement observed over the first 10 m (d ≥ 1.04). Changes in preintervention to postintervention force-velocity profiles were specific to the loading prescribed during training. Specifically, F0 increased most in moderate to heavy groups (d = 1.08-1.19); Vmax significantly decreased in the heavy group but increased in the unresisted group (d = 012-0.44); whereas, Pmax increased across all resisted groups (d = 0.39-1.03). The results of this study suggest that the greatest gains in short distance sprint performance, especially initial acceleration, are achieved using much heavier sled loads than previously studied in young athletes.

Background: The triple hop for distance test commonly uses a limb symmetry index (LSI) 'pass' threshold of >90% for total hop distance following anterior cruciate ligament reconstruction (ACLR). However, understanding the manner in which athletes generate and dissipate forces during consecutive hops within the test may provide greater insight into residual limb deficits. The aim of the study was to examine reactive strength ratios (RSR) of individual hops during a triple hop test in a cohort of ACLR patients at discharge prior to return-to-sport., Methods: Twenty male athletes (24.6 ± 4.2 years; height 175.3 ± 10.2 cm; mass 73.6 ± 14.5 kg) completed the test on both non-operated and operated limbs. Total distance hopped, contact times, flight times and RSR were collected for each hop using a floor-level optical measurement system., Results: Significant, small to moderate between-limb differences (p < 0.05; d = 0.45-0.72) were shown for triple hop distance, flight time and RSR for each hop, with lower performance consistently displayed in the operated limb. Large, significant differences in RSR were evident between hops one and two on the operated limb (p < 0.05; d = 0.97). Despite 80% of participants achieving >90% LSI for total hop distance, less than 50% of participants reached the >90% LSI threshold for RSR., Conclusions: Standardised LSI 'pass' thresholds (>90% LSI) for triple hop distance may mask residual deficits in reactive strength performance of operated limbs; therefore, more detailed analyses of individual hop performance may be warranted to enhance return to sport criteria following ACLR., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Examine growth and maturation trends in dynamic balance using the anterior reach Y-Balance test, and its utility as an injury risk screening tool., Design: Cross sectional and prospective cohort., Setting: Elite male youth soccer players., Participants: 346 players grouped as pre, circa or post peak height velocity (PHV)., Main Outcome Measures: Pre-season anterior reach absolute and relative Y-Balance test scores and seasonal prospective lower extremity injury monitoring., Results: Absolute reach distances were greatest post-PHV (p < 0.05). Relative to leg length, pre-PHV achieved the highest scores and increased between-limb differences. Significant associations between injury and anterior reach scores were present in pre (OR: 0.94, CI: 0.91-0.98, p < 0.05) and circa-PHV (OR: 1.05, 95% CI: 1.05-1.10, p < 0.05). Increased age (OR: 1.49, 95% CI: 1.04-2.13, p < 0.05) and height (OR: 1.06, 95% CI: 0.99-1.13, p = 0.82) were risk factors post-PHV. No differences in injury occurrence were shown between players with absolute reach difference >4 cm in any group., Conclusions: Anterior reach scores increased injury risk, but associations were small and inconsistent. The Y-Balance should be used with caution as a screening tool in this cohort., Competing Interests: Declaration of competing interest Paul J. Read, Jon L. Oliver, Gregory D. Myer, PhD, Abdulaziz Farooq, Mark De Ste Croix, and Rhodri S. Lloyd confirm there are no conflicts of interest associated with any aspects or content of this manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Moeskops, S, Oliver, JL, Read, PJ, Cronin, JB, Myer, GD, Haff, GG, and Lloyd, RS. The influence of biological maturity and competitive level on isometric force-time curve variables and vaulting performance in young female gymnasts. J Strength Cond Res 34(8): 2136-2145, 2020-This cross-sectional study investigated isometric force-time curve variables and vaulting performance in young female gymnasts of varying maturity and competitive levels. One hundred twenty gymnasts aged 5-14 years were subdivided into maturity groupings and also according to their competitive level. Subjects performed isometric midthigh pulls (IMTP) before completing straight jump vaults that were recorded using two-dimensional video. All significance values were accepted at p < 0.05. Absolute peak force (PF abs) and force at various time epochs were significantly greater in more mature gymnasts, although no significant differences were observed in relative peak force (PF rel). When grouped by competitive level, elite gymnasts produced a significantly greater absolute rate of force development (RFD abs) at 0-150, 0-200, and 0-250 ms as well as relative RFD (RFD rel) at 0-200 and 0-250 ms than recreational gymnasts. Based upon regression analyses, force at 50 ms during the IMTP test explained 15% of vertical takeoff velocity during vaulting. Biological maturation seems to impact isometric force-time curve characteristics in young female gymnasts, and higher-level gymnasts produce greater RFD than those competing at a lower level. Vaulting vertical takeoff velocity seems to be largely independent of isometric force-time characteristics with only a small amount of variance explained by force at 50 ms.

Examining association between serial participation in youth organized sports (OS) and concurrent cardiometabolic risk factors, with long-term health status, will aid understanding the role of OS participation. Combining data from a prospective study and a follow-up survey, we aimed to determine association between youth OS participation and cardiometabolic risk factors with health and physical activity (PA) in young adulthood. Cardiometabolic risk factors were monitored yearly, and OS involvement through middle school, high school, and college, together with current status was recorded 12 years after the initial study began; 462 participants completed follow-up. Cardiometabolic risk factors included: body mass index (BMI), waist circumference, blood pressure, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides, fasting glucose and insulin. Participants continuing OS participation from middle to high school and/or college had significantly lower BMI/BMI z-scores [24.7 vs 27.4 (p < 0.05) and 0.51 vs 0.82 (p < 0.05), respectively] and significantly higher HDL [48.7 vs 45.4 (p ≤ 0.05)] than those without OS participation after middle school. Waist circumference of females was significantly smaller in those who participated in OS from middle to high school and/or college (84.9 cm) compared to those who had no OS (92.1 cm), (p < 0.05). Participants continuing OS from middle to high school and/or college reported significantly higher follow-up PA levels than those who had no OS after middle school (p < 0.001). This study provides novel data showing serial participation in OS from middle to high school and/or college was associated with a superior cardiometabolic health profile in school and increased PA levels at 12-year follow-up., Competing Interests: 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., (© 2020 Published by Elsevier Inc.)

Purpose: To determine the differences in muscle architecture of the lower limb in pre-peak height velocity (PHV), circa-PHV, and post-PHV boys., Method: Muscle architecture variables from both the gastrocnemius medialis (GM) and vastus lateralis (VL) were derived from ultrasonographic images in 126 school-aged boys. One-way analysis of variance using Bonferroni post hoc comparisons was employed to determine between-group differences, and effect sizes were calculated to establish the magnitude of these differences., Results: All muscle architecture variables showed significant small to large increases from pre-PHV to post-PHV, excluding GM fascicle length (d = 0.59-1.39; P < .05). More discrete between-group differences were evident as GM and VL muscle thickness, and physiological thickness significantly increased between pre-PHV and circa-PHV (d > 0.57; P < .05); however, only the VL muscle thickness and physiological thickness increased from circa-PHV to post-PHV (d = 0.68; P < .05). The post-PHV group also showed larger GM pennation angles than the circa-PHV group (d = 0.59; P < .05)., Conclusion: The combined results showed that maturation is associated with changes in muscle morphology. These data quantify that the maturity-related changes in muscle architecture variables provide a reference to differentiate between training-induced adaptations versus changes associated with normal growth and maturation.

The gene encoding the tumor suppressor, phosphatase and tensin homolog (PTEN), located on chromosome 10, is frequently expressed at low levels in various tumors, resulting in the stimulation of cell proliferation and migration. However, the role of exosomal PTEN in cell-cell communication during the progress of benzene-induced carcinogenesis remains unclear. The goal of this study was to explore whether exosomes derived from normal human bronchial epithelial cells (16HBE) could transmit PTEN to hydroquinone-transformed malignant recipient cells (16HBE-t) and its possible effects on cell proliferation and migration. Consistent with PTEN expression being down-regulated in transformed cells, we found that its expression was significantly decreased in 16HBE-t relative to 16HBE cells and that purified exosomes secreted by 16HBE, up-regulated PTEN levels in recipient 16HBE-t cells. Thus, down-regulating their proliferation and migration. Further, when exosomes derived from 16HBE cells that had been treated with the PTEN inhibitor SF1670, were incubated with recipient 16HBE-t cells, they exhibited decreased PTEN levels, with a corresponding increase in their proliferation and migration. In conclusion, our study demonstrates that exosomes derived from 16HBE cells can down-regulate proliferation and migration of recipient 16HBE-t cells via transferring PTEN., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Dobbs, IJ, Oliver, JL, Wong, MA, Moore, IS, and Lloyd, RS. Effects of a 12-week training program on isometric and dynamic force-time characteristics in pre- and post-peak height velocity male athletes. J Strength Cond Res 34(3): 653-662, 2020-Literature shows that training children and adolescents can enhance strength and power irrespective of their stage of development; however, the development of the kinetic variables that underpin strength and power performance are typically unreported in youth training studies. Twenty-four pre- and 14 post-peak height velocity (PHV) male athletes were divided into maturity-specific experimental (EXP) and control groups (CON), with the EXP groups completing a twice-weekly, 12-week training program. Force-time characteristics during the isometric midthigh pull (IMTP), countermovement jump, and squat jump tests were quantified at both baseline and after the completion of the 12-week program. Alpha level was set at p < 0.05. No changes in total score for back-squat assessment were observed in any group (p > 0.05). Analysis of IMTP data revealed that only the post-PHV EXP group significantly increased absolute isometric peak force (PFabs) and peak rate of force development within the IMTP after training. Both EXP groups displayed significant increases in isometric PF at time epochs 0-90, 0-150, 0-200, and 0-250 ms. Data from the dynamic tests indicated that the pre-PHV EXP cohort improved concentric qualities as reflected by increased squat jump height and countermovement jump concentric power. There were no significant changes for any variables across all tests within either CON group (p > 0.05). Maturity-related differences in response to short-term training affects the kinetic variables associated with strength and power performance, but not movement competency in young male athletes.

Objective: Determine how lower limb neuromuscular control changes over the course of a competitive soccer season., Design: Repeated measures., Setting: Academy soccer club., Participants: 43 male youth soccer players (age 13.1 ± 2.2 yr; height 160.1 ± 15.7 cm; body mass 49.4 ± 14.3 kg; maturity offset 0.2 ± 1.9 yr)., Main Outcome Measures: Pre-, mid- and end of season assessments of peak landing forces during single leg 75% horizontal hop and stick (75%HOP) and a single leg countermovement jump (SLCMJ), single leg hop for distance (SLHD), knee valgus during the tuck jump assessment (TJA) and inter-limb symmetries., Results: Hop distance increased significantly. Absolute peak landing forces in the left leg during the SLCMJ and 75%HOP increased significantly, with significant increases also present in the same leg for SLCMJ relative peak landing force. TJA knee valgus score was reduced in the right leg, but remained at a 'moderate' level in the left knee., Conclusion: Neuromuscular control, as evidenced by increased absolute and relative peak landing forces, appears to reduce over the course of a competitive season. Young soccer players should engage in neuromuscular training throughout the season to offset any decrements in neuromuscular control and to facilitate appropriate landing strategies., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

miR-221, an oncogenic microRNA, can promote cell proliferation and is highly expressed in various types of tumors. However, the role of exosomal miR-221 in benzene-caused carcinogenesis remains elusive. Our study was designed to investigate whether exosomes secreted by the hydroquinone (HQ; an active metabolite of benzene)-transformed malignant cells can transmit miR-221 to normal recipient cells and its possible effects on cell viability. Our investigation revealed that expression levels of miR-221 were significantly increased in HQ-transformed malignant cells relative to normal controls. Furthermore, exposure of control cells to exosomes that were derived from HQ-transformed malignant cells increased miR-221 levels and promoted their proliferation. Analyses of the biological potency of exosomes derived from HQ-transformed malignant cells in which miR-221 levels were decreased using an inhibitor, showed that both miR-221 levels and proliferation of recipient cells were decreased, but still were higher than those of normal 16HBE cells. Our study indicates that exosomal miR-221 derived from HQ-transformed malignant human bronchial epithelial cells is involved in the proliferation of recipient cells., (© 2019 John Wiley & Sons, Ltd.)

OGG1-deficient (Ogg1-/-) animals display increased propensity to age-induced and diet-induced metabolic diseases, including insulin resistance and fatty liver. Since the intestinal microbiome is increasingly understood to play a role in modulating host metabolic responses, we examined gut microbial composition in Ogg1-/- mice subjected to different nutritional challenges. Interestingly, Ogg1-/- mice had a markedly altered intestinal microbiome under both control-fed and hypercaloric diet conditions. Several microbial species that were increased in Ogg1-/- animals were associated with increased energy harvest, consistent with their propensity to high-fat diet induced weight gain. In addition, several pro-inflammatory microbes were increased in Ogg1-/- mice. Consistent with this observation, Ogg1-/- mice were significantly more sensitive to intestinal inflammation induced by acute exposure to dextran sulfate sodium. Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice., Competing Interests: The authors have declared that no competing interests exist.

Pre-mRNA encoding human NEIL1 undergoes editing by adenosine deaminase ADAR1 that converts a single adenosine to inosine, and this conversion results in an amino acid change of lysine 242 to arginine. Previous investigations of the catalytic efficiencies of the two forms of the enzyme revealed differential release of thymine glycol (ThyGly) from synthetic oligodeoxynucleotides, with the unedited form, NEIL1 K242 being ≈30-fold more efficient than the edited NEIL1 K242R. In contrast, when these enzymes were reacted with oligodeoxynucleotides containing guanidinohydantoin or spiroiminohydantoin, the edited K242R form was ≈3-fold more efficient than the unedited NEIL1. However, no prior studies have investigated the efficiencies of these two forms of NEIL1 on either high-molecular weight DNA containing multiple oxidatively-induced base damages, or oligodeoxynucleotides containing a bulky alkylated formamidopyrimidine. To understand the extent of changes in substrate recognition, γ-irradiated calf thymus DNA was treated with either edited or unedited NEIL1 and the released DNA base lesions analyzed by gas chromatography-tandem mass spectrometry. Of all the measured DNA lesions, imidazole ring-opened 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) were preferentially released by both NEIL1 enzymes with K242R being ≈1.3 and 1.2-fold more efficient than K242 on excision of FapyAde and FapyGua, respectively. Consistent with the prior literature, large differences (≈7.5 to 12-fold) were measured in the excision of ThyGly from genomic DNA by the unedited versus edited NEIL1. In contrast, the edited NEIL1 was more efficient (≈3 to 5-fold) on release of 5-hydroxycytosine. Excision kinetics on DNA containing a site-specific aflatoxin B 1 -FapyGua adduct revealed an ≈1.4-fold higher rate by the unedited NEIL1. Molecular modeling provides insight into these differential substrate specificities. The results of this study and in particular, the comparison of substrate specificities of unedited and edited NEIL1 using biologically and clinically important base lesions, are critical for defining its role in preservation of genomic integrity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pichardo, AW, Oliver, JL, Harrison, CB, Maulder, PS, Lloyd, RS, and Kandoi, R. Effects of combined resistance training and weightlifting on motor skill performance of adolescent male athletes. J Strength Cond Res 33(12): 3226-3235, 2019-Resistance training and weightlifting are regarded as safe and effective training methods for youth. However, no studies have examined the effects of a year-long resistance training program using weightlifting movements on strength, speed, or power. Therefore, the purpose of this study was to determine the long-term effects of combined resistance training (traditional strength training + plyometrics) with or without weightlifting movements on motor skill performance of adolescent males. Fifty-nine males aged 12-14 years were matched by maturity and allocated to a combined resistance training or a combined resistance training with weightlifting group. Each group completed 28 total weeks of training over an academic year. Pre-, mid- (14 weeks of training), and post-training (28 weeks of training) tests included the resistance training skills battery quotient (RTSQ), absolute isometric midthigh pull peak force (IMTPABS) and ratio-scaled isometric midthigh pull peak force (IMTPREL), countermovement jump, horizontal jump, and 10-, 20-, and 30-m sprint. Repeated-measure analysis of variance revealed that there were no significant between-group responses, but all variables improved significantly within-group. Both groups made small-moderate improvements in RTSQ, IMTPABS, and IMTPREL after the first 14 training weeks (d = 0.45-0.86), whereas small-moderate improvements in lower body power, upper body power, and speed were made after the second 14 training weeks (d = 0.30-0.95). Both groups made small-moderate improvements in all performance variables after 28 weeks of training. These findings highlight the importance of establishing movement competency and strength as a foundation for the subsequent development of power. Furthermore, these findings may help practitioners understand the time course of certain adaptations following a long-term periodized plan for adolescent males.

Context: Despite the popularity of jump-landing tasks being used to identify injury risk factors, minimal data currently exist examining differences in knee kinematics during commonly used bilateral jumping tasks. This is especially the case for rebounding-based protocols involving young athletes., Objective: To compare the frontal plane projection angles (FPPAs) during the drop vertical jump (DVJ) and tuck jump assessment (TJA) in a cohort of elite male youth soccer players of varying maturity status., Methods: A total of 57 male youth soccer players from an English championship soccer club participated in this study. Participants performed 3 trials of the DVJ and TJA, during which movement was recorded with 2-dimensional video cameras. FPPA for both right (FPPA-r) and left (FPPA-l) legs, with values <180° indicative of medial knee displacement., Results: On a whole-group level, FPPA-r (172.7° [7.4°] vs 177.2° [11.7°]; P < .05; effect size [ES] = 0.46) and FPPA-l (173.4° [7.3°] vs 179.2° [11.0°]; P < .05; ES = 0.62) were significantly greater for both limbs in the TJA compared with the DVJ; however, these differences were less consistent when grouped by maturity status. FPPA-r during the TJA was significantly and moderately greater in the circa-peak height velocity (PHV) group compared with the post-PHV cohorts (169.4° [6.4°] vs 175.3° [7.8°]; P < .05; ES = 0.49). Whole-group data showed moderate relationships for FPPA-r and FPPA-l between the TJA and DVJ; however, stronger relationships were shown in circa- and post-PHV players compared with the pre-PHV cohort., Conclusions: Considering that the TJA exposed players to a larger FPPA and was sensitive to between-group differences in FPPA-r, the TJA could be viewed as a more suitable screen for identifying FPPA in young male soccer players.

Cellular damage produced by conditions generating oxidative stress have far-reaching implications in human disease that encompass, but are not restricted to aging, cardiovascular disease, type 2 diabetes, airway inflammation/asthma, cancer, and metabolic syndrome including visceral obesity, insulin resistance, fatty liver disease, and dyslipidemia. Although there are numerous sources and cellular targets of oxidative stress, this review will highlight literature that has investigated downstream consequences of oxidatively-induced DNA damage in both nuclear and mitochondrial genomes. The presence of such damage can in turn, directly and indirectly modulate cellular transcriptional and repair responses to such stressors. As such, the persistence of base damage can serve as a key regulator in coordinated gene-response cascades. Conversely, repair of these DNA lesions serves as both a suppressor of mutagenesis and by inference carcinogenesis, and as a signal for the cessation of ongoing oxidative stress. A key enzyme in all these processes is 8-oxoguanine DNA glycosylase (OGG1), which, via non-catalytic binding to oxidatively-induced DNA damage in promoter regions, serves as a nucleation site around which changes in large-scale regulation of inflammation-associated gene expression can occur. Further, the catalytic function of OGG1 can alter the three-dimensional structure of specialized DNA sequences, leading to changes in transcriptional profiles. This review will concentrate on adverse deleterious health effects that are associated with both the diminution of OGG1 activity via population-specific polymorphic variants and the complete loss of OGG1 in murine models. This mouse model displays diet- and age-related induction of metabolic syndrome, highlighting a key role for OGG1 in protecting against these phenotypes. Conversely, recent investigations using murine models having enhanced global expression of a mitochondrial-targeted OGG1 demonstrate that they are highly resistant to diet-induced disease. These data suggest strategies through which therapeutic interventions could be designed for reducing or limiting adverse human health consequences to these ubiquitous stressors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to examine the extent to which maturity offset, strength, and movement competency influences motor skill performance in adolescent boys. One hundred and eight secondary school boys completed anthropometric and physical testing on two non-consecutive days for the following variables: Maturity offset, isometric mid-thigh pull absolute (IMTP ABS ) and relative (IMTP REL ) peak force, resistance training skills quotient, 10-, 20-, and 30-m sprint time, countermovement jump height, horizontal jump distance, anaerobic endurance performance, and seated medicine ball throw (SMBT). The IMTP REL displayed significant small to large correlations with all performance variables ( r = 0.27-0.61), whereas maturity offset was significantly correlated with IMTP ABS ( r = 0.69), sprint ( r = 0.29-0.33), jump ( r = 0.23-0.34), and SMBT ( r = 0.32). Absolute and relative strength were the strongest predictors of all performance variables and combined with maturity to explain 21%-76% of the variance. Low and average relative strength boys were nearly eight times (odds ratio: 7.80, confidence interval: 1.48-41.12, p < 0.05) and nearly four times (odds ratio: 3.86, confidence interval: 0.95-15.59, p < 0.05) more likely to be classified as lower competency compared to high relative strength boys. Relative strength has more influence on motor skill performance than maturity when compared with movement competency.

Meyers, RW, Moeskops, S, Oliver, JL, Hughes, MG, Cronin, JB, and Lloyd, RS. Lower-limb stiffness and maximal sprint speed in 11-16-year-old boys. J Strength Cond Res 33(7): 1987-1995, 2019-The purpose of the study was to examine the relationship between vertical stiffness, leg stiffness, and maximal sprint speed in a large cohort of 11-16-year-old boys. Three-hundred thirty-six boys undertook a 30-m sprint test using a floor-level optical measurement system, positioned in the final 15-m section. Measures of speed, step length, step frequency, contact time, and flight time were directly measured while force, displacement, vertical stiffness, and leg stiffness, were modeled from contact and flight times, from the 2 fastest consecutive steps for each participant over 2 trials. All force, displacement, and stiffness variables were significantly correlated with maximal sprint speed (p ≤ 0.05). Relative vertical stiffness had a very large (r > 0.7) relationship with sprint speed, whereas vertical center of mass displacement, absolute vertical stiffness, relative peak force, and maximal leg spring displacement had large (r > 0.5) relationships. Relative vertical stiffness and relative peak force did not significantly change with advancing age (p > 0.05), but together with maximal leg spring displacement accounted for 96% of the variance in maximal speed. It seems that relative vertical stiffness and relative peak force are important determinants of sprint speed in boys aged 11-16 years, but are qualities that may need to be trained because of no apparent increases from natural development. Practitioners may wish to use training modalities such as plyometrics and resistance training to enable adaptation to these qualities because of their importance as predictors of speed in youth.

The combination of chronic dietary exposure to the fungal toxin, aflatoxin B 1 (AFB 1 ), and hepatitis B viral (HBV) infection is associated with an increased risk for early onset hepatocellular carcinomas (HCCs). An in-depth knowledge of the mechanisms driving carcinogenesis is critical for the identification of genetic risk factors affecting the susceptibility of individuals who are HBV infected and AFB 1 exposed. AFB 1 -induced mutagenesis is characterized by G to T transversions. Hence, the DNA repair pathways that function on AFB 1 -induced DNA adducts or base damage from HBV-induced inflammation are anticipated to have a strong role in limiting carcinogenesis. These pathways define the mutagenic burden in the target tissues and ultimately limit cellular progression to cancer. Murine data have demonstrated that NEIL1 in the DNA base excision repair pathway was significantly more important than nucleotide excision repair relative to elevated risk for induction of HCCs. These data suggest that deficiencies in NEIL1 could contribute to the initiation of HCCs in humans. To investigate this hypothesis, publicly-available data on variant alleles of NEIL1 were analyzed and compared with genome sequencing data from HCC tissues derived from individuals residing in Qidong County (China). Three variant alleles were identified and the corresponding A51V, P68H, and G245R enzymes were characterized for glycosylase activity on genomic DNA containing a spectrum of oxidatively-induced base damage and an oligodeoxynucleotide containing a site-specific AFB 1 -formamidopyrimidine guanine adduct. Although the efficiency of the P68H variant was modestly decreased, the A51V and G245R variants showed nearly wild-type activities. Consistent with biochemical findings, molecular modeling of these variants demonstrated only slight local structural alterations. However, A51V was highly temperature sensitive suggesting that its biological activity would be greatly reduced. Overall, these studies have direct human health relevance pertaining to genetic risk factors and biochemical pathways previously not recognized as germane to induction of HCCs., (Copyright © 2019. Published by Elsevier B.V.)

The purpose of this study was to examine the usefulness of individual load-velocity profiles and the between-athlete variation using the decrement in maximal velocity (Vdec) approach to prescribe training loads in resisted sled pulling in young athletes. Seventy high school, team sport, male athletes (age 16.7 ± 0.8 years) were recruited for the study. All participants performed one un-resisted and four resisted sled-pull sprints with incremental resistance of 20% BM. Maximal velocity was measured with a radar gun during each sprint and the load-velocity relationship established for each participant. A subset of 15 participants was used to examine the reliability of sled pulling on three separate occasions. For all individual participants, the load-velocity relationship was highly linear ( r > 0.95). The slope of the load-velocity relationship was found to be reliable (coefficient of variation (CV) = 3.1%), with the loads that caused a decrement in velocity of 10, 25, 50, and 75% also found to be reliable (CVs = <5%). However, there was a large between-participant variation (95% confidence intervals (CIs)) in the load that caused a given Vdec, with loads of 14-21% body mass (% BM) causing a Vdec of 10%, 36-53% BM causing a Vdec of 25%, 71-107% BM causing a Vdec of 50%, and 107-160% BM causing a Vdec of 75%. The Vdec method can be reliably used to prescribe sled-pulling loads in young athletes, but practitioners should be aware that the load required to cause a given Vdec is highly individualized.

Chronic dietary exposure to aflatoxin B 1 (AFB 1 ), concomitant with hepatitis B infection is associated with a significant increased risk for hepatocellular carcinomas (HCCs) in people living in Southeast Asia and sub-Saharan Africa. Human exposures to AFB 1 occur through the consumption of foods that are contaminated with pervasive molds, including Aspergillus flavus. Even though dietary exposures to aflatoxins constitute the second largest global environmental risk factor for cancer development, there are still significant questions concerning the molecular mechanisms driving carcinogenesis and what factors may modulate an individual's risk for HCC. The objective of this review is to summarize key discoveries that established the association of chronic inflammation (most commonly associated with hepatitis B viral (HBV) infection) and environmental exposures to aflatoxin with increased HCC risk. Special emphasis will be given to recent investigations that have: 1) refined the aflatoxin-associated mutagenic signature, 2) expanded the DNA repair mechanisms that limit mutagenesis via adduct removal prior to replication-induced mutagenesis, 3) implicated a specific DNA polymerase in the error-prone bypass and resulting mutagenesis, and 4) identified human polymorphic variants that may modulate individual susceptibility to aflatoxin-induced cancers. Collectively, these investigations revealed that specific sequence contexts are differentially resistant against, or prone to, aflatoxin-induced mutagenesis and that these associations are remarkably similar between in vitro and in vivo analyses. These recent investigations also established DNA polymerase ζ as the major polymerase that confers the G to T transversion signature. Additionally, although the nucleotide excision repair (NER) pathway has been previously shown to repair aflatoxin-induced DNA adducts, recent murine data demonstrated that NEIL1-initiated base excision repair was significantly more important than NER relative to the removal of the highly mutagenic AFB 1 -Fapy-dG adducts. These data suggest that inactivating polymorphic variants of NEIL1 could be a potential driver of HCCs in aflatoxin-exposed populations., (Copyright © 2019. Published by Elsevier B.V.)

Dietary exposure to aflatoxin B 1 (AFB 1 ) is a significant contributor to the incidence of hepatocellular carcinomas globally. AFB 1 exposure leads to the formation of AFB 1 -N 7 -guanine (AFB 1 -N 7 -Gua) and two diastereomers of the imidazole ring-opened 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B 1 (AFB 1 -FapyGua) in DNA. These adducts lead to G → T transversion mutations with the ring-opened adduct being more mutagenic than the cationic species. Accurate measurement of these three adducts as biomarkers in DNA and urine will help identify dietary exposure to AFB 1 as a risk factor in the development of hepatocellular carcinoma worldwide. Herein, we report an improved methodology for the measurement of AFB 1 -N 7 -Gua and the two diastereomers of AFB 1 -FapyGua using liquid chromatography-tandem mass spectrometry with isotope dilution. We measured the levels of these compounds in liver DNA of six control mice and six AFB 1 -treated mice. Levels varying from 1.5 to 45 lesions/10 6 DNA bases in AFB 1 -treated mice were detected depending on the compound and animal. No background levels of these adducts were detected in control mice. We also tested whether the AFB 1 treatment caused oxidatively induced DNA base damage using gas chromatography-tandem mass spectrometry with isotope dilution. Although background levels of several pyrimidine- and purine-derived lesions were detected, no increases in these levels were found upon AFB 1 treatment of mice. On the other hand, significantly increased levels of (5' R)- and (5' S)-8,5'-cyclo-2'-deoxyadenosines were observed in liver DNA of AFB 1 -treated mice. The impact of this work is expected to achieve the accurate measurement of three AFB 1 -DNA adducts and oxidatively induced DNA lesions as biomarkers of AFB 1 exposure as germane to investigations designed for the prevention of aflatoxin-related hepatocellular carcinomas and for determining the effects of genetic deficiencies in human populations.

Read, PJ, Oliver, JL, Croix, MS, Myer, GD, and Lloyd, RS. A review of field-based assessments of neuromuscular control and their utility in male youth soccer players. J Strength Cond Res 33(1): 283-299, 2019-Lower-extremity injuries in male youth soccer are common and equate to a substantial time loss from training and competitions during the course of a season. Extended periods of absence will impact player involvement in skill and physical development activities, as well as participation in competitive match play. Neuromuscular risk factors for lower-extremity injury in male youth soccer players can be categorized into quadriceps dominance, leg dominance, ligament dominance, trunk dominance, and reduced dynamic stability. Valid screening methods to identify risk factors that are practically viable are needed for youth athletes who may be at a greater risk of injury in soccer. Although field-based tests of neuromuscular control provide a reliable option for the assessment of injury risk in adults and females, less data are available in male youth soccer players, and further research is required to examine their ability to predict injury risk. This article provides a review of the current literature pertaining to field-based screening tests and critically appraises their suitability for use with male youth soccer players. Currently, the only method that has been validated in male youth soccer players is the landing error scoring system. Asymmetrical anterior reach measured during the Y-Balance test may also be considered because of its strong predictive ability in male youth basketball players; however, further research is required to fully support its use with soccer players.

Jeffreys, MA, De Ste Croix, MBA, Lloyd, RS, Oliver, JL, and Hughes, JD. The effect of varying plyometric volume on stretch-shortening cycle capability in collegiate male rugby players. J Strength Cond Res 33(1): 139-145, 2019-The purpose of this study was to identify the effectiveness of low and high volume plyometric loads on developing stretch-shortening cycle capability in collegiate rugby players. A between-group repeated measures design was used. Thirty-six subjects (age 20.3 ± 1.6 years, mass 91.63 ± 10.36 kg, stature 182.03 ± 5.24 cm) were randomly assigned to one of 3 groups: a control group (CG), a low volume plyometric group (LPG), or a high volume plyometric group (HPG). Data were collected from a force plate, and measures of reactive strength index (RSI) and leg stiffness were calculated from jump height, contact time, and flight time. A significant between-group × time (F = 4.01, p ≤ 0.05) interaction effect for RSI was observed. Bonferroni post hoc analysis indicated that both the LPG training group (p = 0.002) and HPG training group (p = 0.009) were significantly higher than the control group. No significant interaction effect between time × group was observed for leg stiffness (F = 1.39, p = 0.25). This study has demonstrated that it is possible to improve reactive strength capabilities through the use of a low volume plyometric program. The low volume program elicited the same performance improvement in RSI as a high volume program while undertaking a lower dose. This suggests that strength and conditioning coaches may be able to benefit from the ability to develop more time-efficient and effective plyometric programs.

A variety of agents cause DNA base alkylation damage, including the known hepatocarcinogen aflatoxin B 1 (AFB 1 ) and chemotherapeutic drugs derived from nitrogen mustard (NM). The N7 site of guanine is the primary site of alkylation, with some N7-deoxyguanosine adducts undergoing imidazole ring-opening to stable mutagenic N 5 -alkyl formamidopyrimidine (Fapy-dG) adducts. These adducts exist as a mixture of canonical β- and unnatural α-anomeric forms. The β species are predominant in double-stranded (ds) DNA. Recently, we have demonstrated that the DNA glycosylase NEIL1 can initiate repair of AFB 1 -Fapy-dG adducts both in vitro and in vivo, with Neil1 -/- mice showing an increased susceptibility to AFB 1 -induced hepatocellular carcinoma. Here, we hypothesized that NEIL1 could excise NM-Fapy-dG and that NEIL3, a closely related DNA glycosylase, could excise both NM-Fapy-dG and AFB 1 -Fapy-dG. Product formation from the reaction of human NEIL1 with ds oligodeoxynucleotides containing a unique NM-Fapy-dG followed a bi-component exponential function under single turnover conditions. Thus, two adduct conformations were differentially recognized by hNEIL1. The excision rate of the major form (∼13.0 min -1 ), presumed to be the β-anomer, was significantly higher than that previously reported for 5-hydroxycytosine, 5-hydroxyuracil, thymine glycol (Tg), and AFB 1 -Fapy-dG. Product generation from the minor form was much slower (∼0.4 min -1 ), likely reflecting the rate of conversion of the α anomer into the β anomer. Mus musculus NEIL3 (MmuNEIL3Δ324) excised NM-Fapy-dG from single-stranded (ss) DNA (turnover rate of ∼0.4 min -1 ), but not from ds DNA. Product formation from ss substrate was incomplete, presumably because of a substantial presence of the α anomer. MmuNEIL3Δ324 could not initiate repair of AFB 1 -Fapy-dG in either ds or ss DNA. Overall, the data suggest that both NEIL1 and NEIL3 may protect cells against cytotoxic and mutagenic effects of NM-Fapy-dG, but NEIL1 may have a unique role in initiation of base excision repair of AFB 1 -Fapy-dG., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study examined individual responses in leg stiffness, reactive strength index (RSI), movement proficiency (deep overhead squat and in-line lunge), and trunk muscular endurance (flexor and extensor tests) in young female gymnasts following an 8-week neuromuscular training intervention. Thirty-four pre-peak height velocity (PHV) female gymnasts were divided into either an experimental group (EXP n = 17) or control group (CON n = 17). The EXP replaced their normal gymnastics physical preparation with a neuromuscular training program, while the CON continued with their habitual gymnastics program. Chi square analysis showed that the EXP resulted in significantly more positive responders compared to CON for measures of leg stiffness (41% versus 12% responded positively), extensor muscular endurance, (76% versus 29%), and competency in the deep overhead squat, (76% versus 29%) and in-line lunge (left lead leg) (65% versus 18%). Conversely, the number of positive responders for RSI (53% versus 61%), the flexor endurance test (88% versus 53%), and the right in-line lunge (47% versus 35%) were not significantly different between groups. These findings suggest that most young gymnasts responded positively to neuromuscular training from the perspective of improving movement proficiency and trunk endurance; however, changes in leg stiffness and RSI were more variable and may require higher intensities to realise further adaptations.

Obesity and related metabolic pathologies represent a significant public health concern. Obesity is associated with increased oxidative stress that damages genomic and mitochondrial DNA. Oxidatively-induced lesions in both DNA pools are repaired via the base-excision repair pathway, initiated by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). Global deletion of OGG1 and common OGG1 polymorphisms render mice and humans susceptible to metabolic disease. However, the relative contribution of mitochondrial OGG1 to this metabolic phenotype is unknown. Here, we demonstrate that transgenic targeting of OGG1 to mitochondria confers significant protection from diet-induced obesity, insulin resistance, and adipose tissue inflammation. These favorable metabolic phenotypes are mediated by an increase in whole body energy expenditure driven by specific metabolic adaptations, including increased mitochondrial respiration in white adipose tissue of OGG1 transgenic (Ogg1 Tg ) animals. These data demonstrate a critical role for a DNA repair protein in modulating mitochondrial energetics and whole-body energy balance.

Objectives: Examine the effects of maturation on single leg jumping performance in elite male youth soccer players., Design: Cross sectional., Setting: Academy soccer clubs., Participants: 347 male youth players classified as either pre, circa or post-peak height velocity (PHV)., Main Outcome Measures: Single leg countermovement jump (SLCMJ) height, peak vertical landing forces (pVGRF), knee valgus and trunk side flexion., Results: Vertical jump height and absolute pVGRF increased with each stage of maturation (p < 0.001; d = 0.85-2.35). Relative to body weight, significantly higher landing forces were recorded on the left leg in circa versus post-PHV players (p < 0.05; d = -0.40). Knee valgus reduced with maturation but the only notable between-group differences were shown in post-PHV players (p < 0.05; d = 0.67); however, greater ipsilateral lateral trunk flexion angles was also present and these differences were significantly increased relative to circa-PHV players (p < 0.05; d = 0.85)., Conclusion: Periods of rapid growth are associated with landing kinetics which may heighten injury risk. While reductions in knee valgus were displayed with maturation; a compensatory strategy of greater trunk lateral flexion was evident in post-PHV players and this may increase the risk of injury., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Moeskops, S, Oliver, JL, Read, PJ, Cronin, JB, Myer, GD, Haff, GG, and Lloyd, RS. Within- and between-session reliability of the isometric midthigh pull in young female athletes. J Strength Cond Res 32(7): 1892-1901, 2018-To investigate the within- and between-session reliability of the isometric midthigh pull (IMTP) in pre- and post-peak height velocity (PHV) female athletes. Nineteen pre- and 19 post-PHV athletes performed bilateral IMTPs using a custom-designed isometric testing system. Participants attended 3 separate testing sessions and performed 3 trials within each session. Peak force, relative peak force, force at 30, 50, 90, 100, 150, 200, and 250 ms, rate of force development (RFD) within time-specific bands, time to peak force (TPF), and time to peak RFD were obtained for analysis. Within- and between-session reliability for each variable was calculated from repeated-measures analysis of variance, intraclass correlation coefficients (ICCs), and coefficients of variation (CV) with 95% confidence intervals. Within- and between-session measures of absolute and relative peak force were found to be reliable for both pre-PHV (CV ≤ 9.4%, ICC ≥ 0.87) and post-PHV (CV ≤ 7.3%, ICC ≥ 0.92), but systematic bias was evident between sessions in the pre-PHV group, from session 1 to 2. Analyses of force at the specific time points revealed CVs between 19-37% and 5-24% for pre-PHV and post-PHV athletes, respectively. Greater variability was evident in TPF, and all RFD-related variables for pre-PHV (CV ≥ 38%) and post-PHV (CV ≥ 27%) athletes, respectively. The IMTP appears a reliable and safe method for evaluating peak force in young female athletes. Overall, post-PHV athletes were more reliable than pre-PHV athletes, with pre-PHV athletes needing additional familiarization to minimize the influence of systematic bias.

Regulations now state that professional academies in the United Kingdom are required to substantially increase the volume of soccer training. This study assessed the current injury occurrence, providing an update to reports published prior to the introduction of the Elite Player Performance Plan (EPPP). 608 soccer players aged 11-18 years from six professional soccer clubs were prospectively monitored, recording injuries during the 2014-2015 season. An injury rate of 1.32 injuries per player/season was indicated with a mean time loss of 21.9 days per injury. The greatest time loss per injury was in the U14s-U15s, and the highest rate of severe injuries in the U15s. Strains and sprains were the most common injury type, with the knee and ankle the most frequently injured anatomical sites. Seasonal variation indicated two peaks in injury incidence, occurring in September and January. In comparison to a published audit prior to the inception of the EPPP, this study indicates that academy soccer players are three-times more likely to experience an injury. Given that time loss and injury severity also increased during periods that typically follow rapid growth, these players should be considered an important group for training load monitoring and injury prevention strategies.

Forty-one practitioners inclusive of physiotherapists, sports scientists and strength and conditioning coaches from the academies of elite soccer clubs in the United Kingdom completed an on-line questionnaire which examined their: (1) background information; (2) perceptions of injury occurrence and risk factors; (3) screening and return to play; and (4) approach to designing and delivering injury prevention programmes with a response rate of 55% (41/75). Contact injuries were the most common mechanism reported and players between 13-16 years of age were perceived to be at the greatest risk. Pertinent risk factors included: reduced lower limb and eccentric hamstring strength, proprioception, muscle imbalances, and under developed foundational movement skills. Joint range of motion, jump tests, the functional movement screen, overhead and single leg squats were the most utilised screening methods. Training modalities rated in order of importance included: resistance training, flexibility development, agility, plyometrics and balance training. Training frequency was most commonly once or twice per week, during warm-ups, independent sessions or a combination of both. Injury prevention strategies in this cohort appear to be logical; however, the classification of injury occurrence and application of screening tools to identify "at risk" players do not align with existing research. The frequency and type of training used may also be insufficient to elicit an appropriate stimulus to address pertinent risk factors based on current recommendations.

Context:   Despite the high frequency of knee injuries in athletes, few researchers have studied the effects of chronologic age and stage of maturation on knee-joint kinematics in male youth soccer players., Objective:   To use a coach-friendly screening tool to examine knee-valgus scores for players of different ages and at different stages of maturation., Design:   Cross-sectional study., Setting:   Academy soccer clubs., Patients or Other Participants:   A total of 400 elite male youth soccer players aged 10 to 18 years categorized by chronologic age and stage of maturation based on their years from peak height velocity (PHV)., Main Outcome Measure(s):   Knee valgus was evaluated during the tuck-jump assessment via 2-dimensional analysis. Frontal-plane projection angles were subjectively classified as minor (<10°), moderate (10°-20°), or severe (>20°), and using these classifications, we scored knee valgus in the tuck jump as 0 ( no valgus), 1 ( minor), 2 ( moderate), or 3 ( severe)., Results:   A trend toward higher valgus scores was observed in the younger age groups and the pre-PHV group. The lowest frequency of no valgus occurred in the U18 and post-PHV groups. The highest percentages of severe scores were in the U13 and pre-PHV groups for the right limb. Knee-valgus scores were lower for both lower extremities in the U18 group than in all other age groups ( P < .001) except the U16 group. Scores were lower for the post-PHV than the pre-PHV group for the right limb ( P < .001) and both pre-PHV and circa-PHV groups for the left limb ( P < .001). Noteworthy interlimb asymmetries were evident in the U14, U15, and circa-PHV groups., Conclusions:   Reductions in knee valgus with incremental age and during the later stages of maturation indicated that this risk factor was more prevalent in younger players. Interlimb asymmetry may also emerge around the time of the peak growth spurt and early adolescence, potentially increasing the risk of traumatic injury.

There is an inherent risk of injury in male youth football; however, pertinent risk factors for injury have yet to be examined. This study used a prospective cohort design with 357 elite male youth football players (aged 10-18 years) assessed during the preseason period and then monitored during the season recording all non-contact lower extremity injuries. Screening tests included single leg hop for distance (SLHD); 75% of maximum hop and stick (75%Hop); single leg countermovement jump (SLCMJ); and the tuck jump assessment (TJ). Players were divided into subgroups based on chronological age. SLCMJ peak landing vertical ground reaction force (pVGRF) asymmetry was the most prominent risk factor (U11-U12s, OR 0.90, P = .04; and U15-U16s, OR 0.91, P < .001). Maturational offset (OR 0.58, P = .04), lower right leg SLCMJ pVGRF relative to body weight (OR 0.36, P = .03), and advanced chronological age (OR 3.62, P = .04) were also significantly associated with heightened injury risk in the U13-U14s, U15-U16s, and U18s, respectively. Univariate analyses showed combinations of anthropometric and movement screening risk factors were associated with heightened risk of lower extremity injury; however, there was variability across the different chronological age groups. Greater SLCMJ pVGRF asymmetry, lower right leg SLCMJ pVGRF %BW, later maturation, and advanced chronological age are potential risk factors for injury in elite male youth football players, although the strength of these relationships was often low to moderate. In addition, risk factors are likely to change at different stages of development., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Asymmetry is a risk factor for male youth soccer players. There is a paucity of data confirming the presence of asymmetry using practically viable screening tasks in players at different stages of maturation., Methods: A cross-sectional sample (N = 347) of elite male youth soccer players who were either pre-, circa-, or post-peak height velocity (PHV) completed the following assessments: single-leg Y-Balance anterior reach, single-leg hop for distance, single-leg 75% hop and stick, and single-leg countermovement jumps., Results: Single-leg countermovement jumps landing force asymmetry was higher in both circa- and post-PHV groups (P < .001; d = 0.41-0.43). Single-leg 75% hop and stick landing force asymmetries were also highest in circa-PHV players, but between-group comparisons were not statistically significant and effect sizes were small. Single-leg hop for distance and single-leg Y-Balance anterior reach asymmetries reduced with maturation; however, no group differences were significant, with small to trivial effect sizes (d ≤ 0.25)., Conclusion: Stage of maturation did not have a profound effect on asymmetry. Between-limb differences in functional performance seem to be established in early childhood; thus, targeted interventions to reduce this injury risk factor should commence in pre-PHV athletes and be maintained throughout childhood and adolescence to ensure asymmetry does not increase.

The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma skin cancers centers on cumulative genomic instability caused by inefficient DNA repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent translesion replication past these DNA lesions generate distinct molecular signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since previous efforts to develop experimental strategies to enhance the repair capacity of basal keratinocytes have been limited, we have engineered the N-terminally truncated form (Δ228) UV endonuclease (UVDE) from Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT. Further, a NLS was engineered onto a pyrimidine dimer glycosylase from Paramecium bursaria chlorella virus-1 (cv-pdg-NLS). Purified enzymes were encapsulated into liposomes and topically delivered to the dorsal surface of SKH1 hairless mice in a UVB-induced carcinogenesis study. Total tumor burden was significantly reduced in mice receiving either UVDE-TAT or UVDE-NLS-TAT versus control empty liposomes and time to death was significantly reduced with the UVDE-NLS-TAT. These data suggest that efficient delivery of exogenous enzymes for the initiation of repair of UVB-induced DNA damage may protect from UVB induction of squamous and basal cell carcinomas.

Hopping, skipping, jumping and sprinting are common tasks in both active play and competitive sports. These movements utilise the stretch-shortening cycle (SSC), which is considered a naturally occurring muscle action for most forms of human locomotion. This muscle action results in more efficient movements and helps optimise relative force generated per motor unit recruited. Innate SSC development throughout childhood and adolescence enables children to increase power (jump higher and sprint faster) as they mature. Despite these improvements in physical performance, the underpinning mechanisms of SSC development during maturational years remain unclear. To the best of our knowledge, a comprehensive review of the potential structural and neuromuscular adaptations that underpin the SSC muscle action does not exist in the literature. Considering the importance of the SSC in human movement, it is imperative to understand how neural and structural adaptations throughout growth and maturation can influence this key muscle action. By understanding the factors that underpin functional SSC development, practitioners and clinicians will possess a better understanding of normal development processes, which will help differentiate between training-induced adaptations and those changes that occur naturally due to growth and maturation. Therefore, the focus of this article is to identify the potential underpinning mechanisms that drive development of SSC muscle action and to examine how SSC function is influenced by growth and maturation.

Nitrogen mustards (NMs) are DNA-alkylating compounds that represent the earliest anticancer drugs. However, clinical use of NMs is limited because of their own mutagenic properties. The mechanisms of NM-induced mutagenesis remain unclear. The major product of DNA alkylation by NMs is a cationic NM-N7-dG adduct that can yield the imidazole ring-fragmented lesion, N 5 -NM-substituted formamidopyrimidine (NM-Fapy-dG). Characterization of this adduct is complicated because it adopts different conformations, including both a canonical β- and an unnatural α-anomeric configuration. Although formation of NM-Fapy-dG in cellular DNA has been demonstrated, its potential role in NM-induced mutagenesis is unknown. Here, we created site-specifically modified single-stranded vectors for replication in primate (COS7) or Escherichia coli cells. In COS7 cells, NM-Fapy-dG caused targeted mutations, predominantly G → T transversions, with overall frequencies of ∼11-12%. These frequencies were ∼2-fold higher than that induced by 8-oxo-dG adduct. Replication in E. coli was essentially error-free. To elucidate the mechanisms of bypass of NM-Fapy-dG, we performed replication assays in vitro with a high-fidelity DNA polymerase, Saccharomyces cerevisiae polymerase (pol) δ. It was found that pol δ could catalyze high-fidelity synthesis past NM-Fapy-dG, but only on a template subpopulation, presumably containing the β-anomeric adduct. Consistent with the low mutagenic potential of the β-anomer in vitro , the mutation frequency was significantly reduced when conditions for vector preparation were modified to favor this configuration. Collectively, these data implicate the α-anomer as a major contributor to NM-Fapy-dG-induced mutagenesis in primate cells., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

The purpose of this study was to examine the effects of a neuromuscular training (NMT) program on lower-extremity biomechanics in youth female netball athletes. The hypothesis was that significant improvements would be found in landing biomechanics of the lower-extremities, commonly associated with anterior cruciate ligament (ACL) injury, following NMT. Twenty-three athletes (age = 12.2 ± 0.9 years; height = 1.63 ± 0.08 m; mass = 51.8 ± 8.5 kg) completed two testing sessions separated by 7-weeks and were randomly assigned to either a experimental or control group. Thirteen athletes underwent 6-weeks of NMT, while the remaining 10 served as controls and continued their regular netball training. Three-dimensional lower-extremity kinematics and vertical ground reaction force (VGRF) were measured during two landing tasks, a drop vertical jump and a double leg broad jump with a single leg landing. The experimental group significantly increased bilateral knee marker distance during the bilateral landing task at maximum knee-flexion range of motion. Knee internal rotation angle during the unilateral landing task at maximum knee flexion-extension range of motion was significantly reduced ( p ≤ 0.05, g > 1.00). The experimental group showed large, significant decreases in peak vertical ground reaction force in both landing tasks ( p ≤ 0.05, g > -1.30). Control participants did not demonstrate any significant pre-to-post-test changes in response to the 6-week study period. Results of the study affirm the hypothesis that a 6-week NMT program can enhance landing biomechanics associated with ACL injury in 11-13 year old female netball athletes.

De Ste Croix, MBA, Hughes, JD, Lloyd, RS, Oliver, JL, and Read, PJ. Leg stiffness in female soccer players: intersession reliability and the fatiguing effects of soccer-specific exercise. J Strength Cond Res 31(11): 3052-3058, 2016-Low levels of leg stiffness and reduced leg stiffness when fatigue is present compromise physical performance and increase injury risk. The purpose of this study was to (a) determine the reliability of leg stiffness measures obtained from contact mat data and (b) explore age-related differences in leg stiffness after exposure to a soccer-specific fatigue protocol in young female soccer players. Thirty-seven uninjured female youth soccer players divided into 3 subgroups based on chronological age (under 13 [U13], under 15 [U15], and under 17 [U17] year-olds) volunteered to participate in the study. After baseline data collection, during which relative leg stiffness, contact time, and flight time were collected, participants completed an age-appropriate soccer-specific fatigue protocol (SAFT). Upon completion of the fatigue protocol, subjects were immediately retested. Intersession reliability was acceptable and could be considered capable of detecting worthwhile changes in performance. Results showed that leg stiffness decreased in the U13 year-olds, was maintained in the U15 age group, and increased in the U17 players. Contact times and flight times did not change in the U13 and U15 year-olds, but significantly decreased and increased, respectively, in the U17 age group. The data suggest that age-related changes in the neuromuscular control of leg stiffness are present in youth female soccer players. Practitioners should be aware of these discrepancies in neuromuscular responses to soccer-specific fatigue, and should tailor training programs to meet the needs of individuals, which may subsequently enhance performance and reduce injury risk.

Quantifying hopping and landing performances can assist coaches in identifying young male soccer players who may be at increased risk of injury. The influence of chronological age and maturation on these measures in this population is unknown. Single leg hop for distance (SLHD) and 75% horizontal hop and stick landing force (75%Hop) were examined in a cross-sectional sample (N=400) of elite male youth soccer players. Between-group differences for both chronological age (U11-U18) and stage of maturation (pre-, circa- or post-peak height velocity (PHV)) were analyzed. Absolute 75%Hop increased with both age and maturation. Apart from the U18s, pre-PHV and U11-U12 players displayed the greatest relative landing forces compared to all other groups (p<0.001; d=0.56-0.93). Absolute and relative SLHD were greatest in the U18s and post-PHV players (p<0.001; d=0.35-2.04). A trend showed increased SLHD with each consecutive age group although a reduction in performance was identified in the U13s (d=0.50-0.59). High volumes of accumulated soccer participation in the U18s may lead to altered landing strategies indicative of high injury risk. A temporary reduction in hop performance in the U13s may also be linked to a period of adolescent awkwardness., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations. Progressing alternative salt forms with improved solubility and dissolution properties can minimise this concern. This manuscript outlines a nonclinical approach comprising multiple biopharmaceutical, in vitro and physiologically based pharmacokinetic model (PBPK) modelling studies to enable selection of an alternative salt form for danirixin (DNX, GSK1325756), a pharmaceutical agent being developed for chronic obstructive pulmonary disease (COPD). The hydrobromide salt of DNX was identified as having superior biopharmaceutical properties compared to the free base (FB) form in clinical development and the impact of switching to the hydrobromide salt (HBr) was predicted by integrating the nonclinical data in a PBPK model (using GastroPlus™) to enable simulation of clinical drug exposure with FB and HBr salts in the absence and presence of a gastric acid reducing comedication (omeprazole, a proton pump inhibitor (PPI)). Subsequent investigation of DNX pharmacokinetics in a Phase 1 clinical study comparing FB with HBr salt forms confirmed that DNX HBr had reduced the variability of drug exposure and that exposure was not affected by PPI co-administration with DNX HBr. This case study therefore adds to the surprisingly few examples of a more soluble salt of a weak base translating to an improvement in human pharmacokinetics and illustrates a clear clinical benefit of salt selection during drug development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1) recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Here, we report that OGG1-deficient mice also display skeletal muscle pathologies, including increased muscle lipid deposition and alterations in genes regulating lipid uptake and mitochondrial fission in skeletal muscle. In addition, expression of genes of the TCA cycle and of carbohydrate and lipid metabolism are also significantly altered in muscle of OGG1-deficient mice. These tissue changes are accompanied by marked reductions in markers of muscle function in OGG1-deficient animals, including decreased grip strength and treadmill endurance. Collectively, these data indicate a role for skeletal muscle OGG1 in the maintenance of optimal tissue function.

Addition of hydroxyl radicals to the C8 position of 2'-deoxyguanosine generates an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2'-deoxyguanosine or N-(2-deoxy-d-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different conformations and in particular, can exist in an unnatural α anomeric configuration in addition to canonical β configuration. Previous studies reported that in 5'-TGN-3' sequences, Fapy-dG predominantly induced G → T transversions in both mammalian cells and Escherichia coli, suggesting that mutations could be formed either via insertion of a dA opposite the 5' dT due to primer/template misalignment or as result of direct miscoding. To address this question, single-stranded vectors containing a site-specific Fapy-dG adduct were generated to vary the identity of the 5' nucleotide. Following vector replication in primate cells (COS7), complex mutation spectra were observed that included ∼3-5% G → T transversions and ∼14-21% G → A transitions. There was no correlation apparent between the identity of the 5' nucleotide and spectra of mutations. When conditions for vector preparation were modified to favor the β anomer, frequencies of both G → T and G → A substitutions were significantly reduced. Mutation frequencies in wild-type E. coli and a mutant deficient in damage-inducible DNA polymerases were significantly lower than detected in COS7 and spectra were dominated by deletions. Thus, mutagenic bypass of Fapy-dG can proceed via mechanisms that are different from the previously proposed primer/template misalignment or direct misinsertions of dA or dT opposite to the β anomer of Fapy-dG. Environ. Mol. Mutagen. 58:182-189, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Hopper, A, Haff, EE, Barley, OR, Joyce, C, Lloyd, RS, and Haff, GG. Neuromuscular training improves movement competency and physical performance measures in 11-13-year-old female netball athletes. J Strength Cond Res 31(5): 1165-1176, 2017-The purpose of this study was to examine the effects of a neuromuscular training (NMT) program on movement competency and measures of physical performance in youth female netball players. It was hypothesized that significant improvements would be found in movement competency and physical performance measures after the intervention. Twenty-three junior female netball players (age, 12.17 ± 0.94 years; height, 1.63 ± 0.08 m; weight, 51.81 ± 8.45 kg) completed a test battery before and after a 6-week training intervention. Thirteen of these athletes underwent 6 weeks of NMT, which incorporated plyometrics and resistance training. Trained athletes showed significant improvements in 20-m sprint time, 505 agility time, countermovement jump height, and peak power (p ≤ 0.05, g > 0.8). In addition, trained athletes significantly improved their score in the Netball Movement Screening Tool (NMST) (p < 0.05, g > -1.30); while the athletes also demonstrated increased reach in the anterior and posteromedial directions for the right leg and left leg, and in the posterolateral direction for the left leg only in the Star Excursion Balance Test (SEBT) (p < 0.05, g > -0.03). Control subjects did not exhibit any significant changes during the 6-week period. Significant negative correlations were found between improved score on the NMST and decreased 5-, 10-, and 20-m sprint time, and 505 change of direction time (r > 0.4, p ≤ 0.05). Results of the study affirm the hypothesis that a 6-week NMT intervention can improve performance and movement competency in youth netball players.

Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB 1 ) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB 1 -induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB 1 -deoxyguanosine adduct (AFB 1 -Fapy-dG). Consistent with this in vitro result, newborn mice injected with AFB 1 show significant increases in the levels of AFB 1 -Fapy-dG in Neil1 -/- vs. wild-type liver DNA. Further, Neil1 -/- mice are highly susceptible to AFB 1 -induced HCCs relative to WT controls, with both the frequency and average size of hepatocellular carcinomas being elevated in Neil1 -/- The magnitude of this effect in Neil1 -/- mice is greater than that previously measured in Xeroderma pigmentosum complementation group A (XPA) mice that are deficient in nucleotide excision repair (NER). Given that several human polymorphic variants of NEIL1 are catalytically inactive for their DNA glycosylase activity, these deficiencies may increase susceptibility to AFB 1 -associated HCCs., Competing Interests: The authors declare no conflict of interest.

Meyers, RW, Oliver, JL, Hughes, MG, Lloyd, RS, and Cronin, JB. Influence of age, maturity, and body size on the spatiotemporal determinants of maximal sprint speed in boys. J Strength Cond Res 31(4): 1009-1016, 2017-The aim of this study was to investigate the influence of age, maturity, and body size on the spatiotemporal determinants of maximal sprint speed in boys. Three-hundred and seventy-five boys (age: 13.0 ± 1.3 years) completed a 30-m sprint test, during which maximal speed, step length, step frequency, contact time, and flight time were recorded using an optical measurement system. Body mass, height, leg length, and a maturity offset represented somatic variables. Step frequency accounted for the highest proportion of variance in speed (∼58%) in the pre-peak height velocity (pre-PHV) group, whereas step length explained the majority of the variance in speed (∼54%) in the post-PHV group. In the pre-PHV group, mass was negatively related to speed, step length, step frequency, and contact time; however, measures of stature had a positive influence on speed and step length yet a negative influence on step frequency. Speed and step length were also negatively influence by mass in the post-PHV group, whereas leg length continued to positively influence step length. The results highlighted that pre-PHV boys may be deemed step frequency reliant, whereas those post-PHV boys may be marginally step length reliant. Furthermore, the negative influence of body mass, both pre-PHV and post-PHV, suggests that training to optimize sprint performance in youth should include methods such as plyometric and strength training, where a high neuromuscular focus and the development force production relative to body weight are key foci.

The Tuck Jump Assessment (TJA) is a clinician-friendly screening tool that was designed to support practitioners with identification of neuromuscular deficits associated with anterior cruciate ligament injury. This study aimed to evaluate the inter- and intra-rater reliability of the modified scoring (0 to 2) TJA to add an additional range of objectivity for each criterion. A total of 24 elite youth volleyball athletes (12 males and 12 females) were included in this study. Each participant's recorded performance of the TJA was scored independently by two raters across ten criteria using the modified scale. The two raters then scored the same videos one week later. Another investigator who was blind to the identity of the raters analyzed the scores from both raters for each participant. Kappa coefficient ( k ) and percentage of exact agreement (PEA) for both intra- and inter-rater reliability were analyzed for each item. Intraclass correlation coefficients (ICC) were calculated to determine intra- and inter-rater reliability of the modified TJA total score. Intra- and inter-rater k was good to excellent for most items (0.65-0.91). Average PEA between the two raters and two sessions ranged from 83.3 to 100% in all scored items. The ICC for the total score was excellent in both inter- and inter-rater correlations (0.94-0.96). This research demonstrated that the modified version of the TJA predominantly shows good to excellent intra- and inter-rater reliability in all analyzed criteria.

Radnor, JM, Lloyd, RS, and Oliver, JL. Individual response to different forms of resistance training in school-aged boys. J Strength Cond Res 31(3): 787-797, 2017-The aim of this study was to examine individual responses to different forms of resistance training on measures of jumping and sprinting performance in school-aged boys. Eighty boys were categorized into 2 maturity groups (pre- or post-peak height velocity [PHV]) and randomly assigned to a plyometric training, resistance training, combined training, or control group. Intervention groups participated in training twice weekly for 6 weeks, with measures of acceleration, maximal running velocity, squat jump height, and reactive strength index (RSI) collected preintervention and postintervention. In the pre-PHV cohort, plyometric training and combined training resulted in significantly more positive responders than the other 2 groups in both sprint variables (standardized residual values >1.96). In the post-PHV cohort, significantly more positive responders for acceleration and squat jump height resulted from traditional strength training and combined training groups, compared with other groups. Conversely, plyometric training and combined training resulted in a significantly greater number of positive responders than the other 2 groups for maximal velocity and RSI. Control participants rarely demonstrated meaningful changes in performance over the 6-week period. Irrespective of maturation, it would seem that combined training provides the greatest opportunity for most individuals to make short-term improvements in jump and sprint performance. Taking maturation into account, our data show that a plyometric training stimulus is important for individuals in the pre-PHV stage of development, whether as a stand-alone method or in combination with traditional strength training, when attempting to improve jumping and sprinting ability. However, individuals in the post-PHV stage require a more specific training stimulus depending on the performance variable that is being targeted for improvement.

Purpose: The aim of this study was to examine the influence of age and maturation upon magnitude of asymmetry in the force, stiffness and the spatiotemporal determinants of maximal sprint speed in a large cohort of boys., Methods: 344 boys between the ages of 11 and 16 years completed an anthropometric assessment and a 35 m sprint test, during which sprint performance was recorded via a ground-level optical measurement system. Maximal sprint velocity, as well as asymmetry in spatiotemporal variables, modeled force and stiffness data were established for each participant. For analysis, participants were grouped into chronological age, maturation and percentile groups., Results: The range of mean asymmetry across age groups and variables was 2.3-12.6%. The magnitude of asymmetry in all the sprint variables was not significantly different across age and maturation groups (p > .05), except relative leg stiffness (p < .05). No strong relationships between asymmetry in sprint variables and maximal sprint velocity were evident (r s < .39)., Conclusion: These results provide a novel benchmark for the expected magnitude of asymmetry in a large cohort of uninjured boys during maximal sprint performance. Asymmetry in sprint performance is largely unaffected by age or maturation and no strong relationships exist between the magnitude of asymmetry and maximal sprint velocity.

Early specialisation is characterised by formal participation in a single sport at the exclusion of others. Limited data are available to support this approach in the development of soccer players who attain elite status later in life. Of growing concern is the associated increased risk of injury and suggestions that single sport specialisation is a risk factor independent of age, growth, biological maturation and training volumes. In the United Kingdom, elite soccer organisations have recently adopted an early sport specialisation approach following the introduction of the Elite Player Performance Plan. A key tenet of this programme is increased opportunities for training through a marked rise in the specified on-pitch hours per week. The accumulation of high training hours may be less of a relevant marker for success, and the impact of such a significant increase in training volume for young athletes who are experiencing a range of growth and maturational processes is currently unknown. This critical commentary includes an evidence-based discussion of the effectiveness of early sport specialisation and the potential injury risks associated with such programmes placing a specific focus on elite male youth soccer players. Available data indicate that modifications to the existing Elite Player Performance Plan framework could enhance players' development and reduce injury risk. Proposed alterations include reduced volume of soccer-specific training at key stages of growth and maturation and guidelines for the provision of a greater variety of physical activities that are integrated within other programme components.