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Key Points: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training-induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways. However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both. In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200-350 mmol kg -1 dry weight (dw), we demonstrate that acute post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability. Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within-day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover., Abstract: We examined the effects of post-exercise carbohydrate (CHO) and energy availability (EA) on potent skeletal muscle cell signalling pathways (regulating mitochondrial biogenesis and lipid metabolism) and indicators of bone metabolism. In a repeated measures design, nine males completed a morning (AM) and afternoon (PM) high-intensity interval (HIT) (8 × 5 min at 85% V ̇ O 2 peak ) running protocol (interspersed by 3.5 h) under dietary conditions of (1) high CHO availability (HCHO: CHO ∼12 g kg -1 , EA∼ 60 kcal kg -1 fat free mass (FFM)), (2) reduced CHO but high fat availability (LCHF: CHO ∼3 ( -1 , EA∼ 60 kcal kg -1 FFM) or (3), reduced CHO and reduced energy availability (LCAL: CHO ∼3 g kg -1 , EA∼ 20 kcal kg -1 FFM). Muscle glycogen was reduced to ∼200 mmol kg -1  dw in all trials immediately post PM HIT (P < 0.01) and remained lower at 17 h (171, 194 and 316 mmol kg -1  dw) post PM HIT in LCHF and LCAL (P < 0.001) compared to HCHO. Exercise induced comparable p38MAPK phosphorylation (P < 0.05) immediately post PM HIT and similar mRNA expression (all P < 0.05) of PGC-1α, p53 and CPT1 mRNA in HCHO, LCHF and LCAL. Post-exercise circulating βCTX was lower in HCHO (P < 0.05) compared to LCHF and LCAL whereas exercise-induced increases in IL-6 were larger in LCAL (P < 0.05) compared to LCHF and HCHO. In conditions where glycogen concentration is maintained within 200-350 mmol kg -1  dw, we conclude post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after HIT running attenuates bone resorption, effects that are independent of energy availability and circulating IL-6., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

One of the largest change operations to take place in South Australia was the moving of the Royal Adelaide Hospital (RAH) to its new site in 2017. Change can influence workplace effectiveness and staff satisfaction and morale. Understanding the stages of change, staff experience and carefully managing the process is important. This paper aims to describe the successful move of the radiation therapy department at the RAH to its new site, focusing on the staff experience and management strategies to ensure the success of the move. A four-stage model of change was used to guide understand, manage and reflect upon the transition of the RAH radiation therapy department to a new site. Key change events and management strategies are described and aligned with the four stages of change. The move to the new site was a great success with a transition period working across two sites enabling a slower ramp up of activity at the new site supporting staff and patients in adjusting to the new environment. The four-stage model of change assisted in the smooth implementation of a transition plan for radiation oncology. At the RAH, innovation and development are encouraged, along with management having a comprehensive understanding of organisational change enabling the radiation oncology department to successfully navigate rapid change., (© 2019 SA Health. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Histidine containing dipeptides (HCDs: carnosine, anserine and balenine) have numerous therapeutic and ergogenic properties, but there is a lack of consensus on the mechanistic pathways through which they function. Potential roles include intracellular buffering, neutralisation of reactive species, and calcium regulation. Comparative investigations of the HCD content of various species provide unique insight into their most likely mechanisms of action. This review chronologically describes how the comparative physiology studies, conducted since the beginning of the 20th century, have shaped our understanding of the physiological roles of HCDs. The investigation of a wide range of physiologically distinct species indicates that those species with a strong reliance on non-oxidative forms of energy production are abundant in HCDs. These include: whales who experience long periods of hypoxia while diving; racehorses and greyhound dogs who have highly developed sprint abilities, and chickens and turkeys whose limited capacity for flight is largely fuelled by their white, glycolytic, muscle. Additionally, a higher HCD content in the Type 2 muscle fibres of various species (which have greater capacity for non-oxidative metabolism) was consistently observed. The pKa of the HCDs render them ideally suited to act as intracellular physicochemical buffers within the pH transit range of the skeletal muscle. As such, their abundance in species which show a greater reliance on non-oxidative forms of energy metabolism, and which experience regular challenges to acid-base homeostasis, provides strong evidence that intracellular proton buffering is an important function of the HCDs in skeletal muscle., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Injuries are an inevitable consequence of athletic performance with most athletes sustaining one or more during their athletic careers. As many as one in 12 athletes incur an injury during international competitions, many of which result in time lost from training and competition. Injuries to skeletal muscle account for over 40% of all injuries, with the lower leg being the predominant site of injury. Other common injuries include fractures, especially stress fractures in athletes with low energy availability, and injuries to tendons and ligaments, especially those involved in high-impact sports, such as jumping. Given the high prevalence of injury, it is not surprising that there has been a great deal of interest in factors that may reduce the risk of injury, or decrease the recovery time if an injury should occur: One of the main variables explored is nutrition. This review investigates the evidence around various nutrition strategies, including macro- and micronutrients, as well as total energy intake, to reduce the risk of injury and improve recovery time, focusing upon injuries to skeletal muscle, bone, tendons, and ligaments.

Carnosine was originally discovered in skeletal muscle, where it exists in larger amounts than in other tissues. The majority of research into the physiological roles of carnosine have been conducted on skeletal muscle. Given this and the potential for muscle carnosine content to be increased with supplementation, there is now a large body of research examining the ergogenic effects (or otherwise) of carnosine. More recent research, however, points towards a potential for carnosine to exert a wider range of physiological effects in other tissues, including the brain, heart, pancreas, kidney and cancer cells. Taken together, this is suggestive of a potential for carnosine to have therapeutic benefits in health and disease, although this is by no means without complication. Herein, we will provide a review of the current literature relating to the potential therapeutic effects of carnosine in health and disease.

Maternal dietary habits influence maternal and foetal health, representing a pathway for intervention to maximise pregnancy outcomes. Advice on energy intake is provided on a trimester basis, with no additional calories required in the first trimester and an additional 340 kcal d -1 and 452 kcal d -1 needed for the second and third trimesters. Energy intake depends on pre-gravid body mass index (BMI); underweight women are recommended an increase of 150, 200 and 300 kcal d -1 during the first, second and third trimester, normal weight women an increase of 0, 350 and 500 kcal d -1 and obese women an increase of 0, 450 and 350 kcal day -1 . The recommendations for carbohydrate and protein intake are 175 g d -1 and 0.88-1.1 g kgBM d -1 , with no change to fat intake. The number of pre-gravid obese women is rising; therefore, we need to regulate weight in women of childbearing age and limit gestational weight gain to within the recommended ranges [overweight women 6.8-11.3 kg and obese women 5.0-9.1 kg]. This can be achieved using nutritional interventions, as dietary changes have been shown to help with gestational weight management. As pregnancy has been identified as a risk factor for the development of obesity, normal weight women should gain 11.5-16.0 kg during pregnancy. While some research has shown that dietary interventions help to regulate gestational weight gain and promote postpartum weight loss to some extent, future research is needed to provide safe and effective guidelines to maximise these effects, while benefitting maternal and foetal health.

β-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day -1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day -1 ) improved isometric, but not isokinetic or isotonic endurance performance.

We investigated the changes in bone characteristics and body composition of elite speed skaters across two competitive seasons. Twelve elite speed skaters (age 23±4 years; height 1.73±0.09 m; body mass 68.5±8.8 kg; mean±1 SD) were assessed by DXA and pQCT for Bone Mineral Density (BMD), Bone Mineral Content (BMC), area, bone strength, cortical thickness and density at four points over the course of four competitive seasons. Body composition data was also collected. A main effect of time was shown for whole body BMC, right leg BMC, and trabecular area (P<0.05). Whole body BMC was higher during pre-season and end of season in comparison to mid-season (1.0%, P=0.007; 0.8%, P=0.017), right leg BMC was higher at the pre-season scan in comparison to the post pre-season scan (1.8%,P=0.020) and trabecular area was higher during the mid-season and end of season when compared to the pre-season (1.4%, P=0.012; 1.0%, P=0.003). Seasonal changes in bone characteristics and body composition are shown in elite speed skaters over a competitive season. The changes are thought to be a result of fluctuations in training load. These data may have implications for training design and injury risk management in elite sport., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50-85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case-control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene-environment interactions-in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically "extreme" population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.

Purpose: Cross-sectional studies suggest that training can increase muscle carnosine (MCarn), although longitudinal studies have failed to confirm this. A lack of control for dietary β-alanine intake or muscle fiber type shifting may have hampered their conclusions. The purpose of the present study was to investigate the effects of high-intensity interval training (HIIT) on MCarn., Methods: Twenty vegetarian men were randomly assigned to a control (CON) (n = 10) or HIIT (n = 10) group. High-intensity interval training was performed on a cycle ergometer for 12 wk, with progressive volume (6-12 series) and intensity (140%-170% lactate threshold [LT]). Muscle carnosine was quantified in whole-muscle and individual fibers; expression of selected genes (CARNS, CNDP2, ABAT, TauT, and PAT1) and muscle buffering capacity in vitro (βmin vitro) were also determined. Exercise tests were performed to evaluate total work done, V˙O2max, ventilatory thresholds (VT) and LT., Results: Total work done, VT, LT, V˙O2max, and βmin vitro were improved in the HIIT group (all P < 0.05), but not in CON (P > 0.05). MCarn (in mmol·kg dry muscle) increased in the HIIT (15.8 ± 5.7 to 20.6 ± 5.3; P = 0.012) but not the CON group (14.3 ± 5.3 to 15.0 ± 4.9; P = 0.99). In type I fibers, MCarn increased in the HIIT (from 14.4 ± 5.9 to 16.8 ± 7.6; P = 0.047) but not the CON group (from 14.0 ± 5.5 to 14.9 ± 5.4; P = 0.99). In type IIa fibers, MCarn increased in the HIIT group (from 18.8 ± 6.1 to 20.5 ± 6.4; P = 0.067) but not the CON group (from 19.7 ± 4.5 to 18.8 ± 4.4; P = 0.37). No changes in gene expression were shown., Conclusions: In the absence of any dietary intake of β-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in βmin vitro appears to be small.

Purpose: We aimed to explore the effects of low energy availability (EA)[15 kcal·kg lean body mass (LBM) -1 ·d -1 ] achieved by diet or exercise on bone turnover markers in active, eumenorrheic women., Methods: By using a crossover design, ten eumenorrheic women (VO 2 peak : 48.1 ± 3.3 ml·kg -1 ·min -1 ) completed all three, 3-day conditions in a randomised order: controlled EA (CON; 45 kcal·kgLBM -1 ·d -1 ), low EA through dietary energy restriction (D-RES; 15 kcal·kgLBM -1 ·d -1 ) and low EA through increasing exercise energy expenditure (E-RES; 15 kcal·kgLBM -1 ·d -1 ), during the follicular phase of three menstrual cycles. In CON, D-RES and E-RES, participants consumed diets providing 45, 15 and 45 kcal·kgLBM -1 ·d -1 . In E-RES only, participants completed supervised running sessions (129 ± 10 min·d -1 ) at 70% of their VO 2 peak that resulted in an exercise energy expenditure of 30 kcal·kg LBM -1 ·d -1 . Blood samples were collected at baseline (BASE) and at the end of the 3-day period (D6) and analysed for bone turnover markers (β-CTX and P1NP), markers of calcium metabolism (PTH, albumin-adjusted Ca, Mg and PO 4 ) and hormones (IGF-1, T 3 , insulin, leptin and 17β-oestradiol)., Results: In D-RES, P1NP concentrations at D6 decreased by 17% (BASE: 54.8 ± 12.7 μg·L -1 , D6: 45.2 ± 9.3 μg·L -1 , P < 0.001, d = 0.91) and were lower than D6 concentrations in CON (D6: 52.5 ± 11.9 μg·L -1 , P = 0.001). P1NP did not change significantly in E-RES (BASE: 55.3 ± 14.4 μg·L -1 , D6: 50.9 ± 15.8 μg·L -1 , P = 0.14). β-CTX concentrations did not change following D-RES (BASE: 0.48 ± 0.18 μg·L -1 , D6: 0.55 ± 0.17 μg·L -1 ) or E-RES (BASE: 0.47 ± 0.24 μg·L -1 , D6: 0.49 ± 0.18 μg·L -1 ) (condition × time interaction effect, P = 0.17). There were no significant differences in P1NP (P = 0.25) or β-CTX (P = 0.13) responses between D-RES and E-RES. Both conditions resulted in reductions in IGF-1 (-13% and - 23% from BASE in D-RES and E-RES, both P < 0.01) and leptin (-59% and - 61% from BASE in D-RES and E-RES, both P < 0.001); T 3 decreased in D-RES only (-15% from BASE, P = 0.002) and PO 4 concentrations decreased in E-RES only (-9%, P = 0.03)., Conclusions: Low EA achieved through dietary energy restriction resulted in a significant decrease in bone formation but no change in bone resorption, whereas low EA achieved through exercise energy expenditure did not significantly influence bone metabolism. Both low EA conditions elicited significant and similar changes in hormone concentrations., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine, in conjunction with a wider investigation, whether 11 genetic variants in the vicinity of vitamin D, collagen and Wnt signalling pathways were associated with stress fracture injury in the Stress Fracture Elite Athlete (SFEA) cohort., Design: Genotype-phenotype association study., Methods: Self-reported stress fracture history and demographic data were recorded in 518 elite athletes, 449 male and 69 female (mean age 24.2±5.5 years) from the SFEA cohort. Elite athletes were assigned to two groups based on history of stress fracture injury. Data were analysed for the whole cohort and sub-stratified in to male only and multiple stress fracture cases. Genotype was determined using a proprietary fluorescence-based competitive allele-specific polymerase chain reaction assay., Results: SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 were associated with stress fracture (p<0.05). In the whole cohort, rs1877632 heterozygotes and homozygotes of the rare allele combined made up 59% of stress fracture sufferers in comparison to 46% in the non-stress fracture group (p=0.05). In the multiple stress fracture cohort, homozygotes of the rare allele of rs10735810 and rs731236 showed an association with stress fracture when compared to those homozygotes for the common allele combined with heterozygotes (p=0.03; p=0.01). No significant associations were shown in the other SNPs analysed (p>0.05)., Conclusions: These data suggest an important role for SOST SNP rs1877632 and VDR SNPs rs10735810 and rs731236 in the pathophysiology of stress fracture. This might be due to the role of the SNPs in the regulation of bone remodelling and adaptation to mechanical loading, with potential implications for the prevention and treatment of stress fracture injuries., (Copyright © 2017. Published by Elsevier Ltd.)

Global rates of obesity continue to rise and are necessarily the consequence of a long-term imbalance between energy intake and energy expenditure. This is the result of an expansion of adipose tissue due to both the hypertrophy of existing adipocytes and hyperplasia of adipocyte pre-cursors. Exercise elicits numerous physiological benefits on adipose tissue, which are likely to contribute to the associated cardiometabolic benefits. More recently it has been demonstrated that exercise, through a range of mechanisms, induces a phenotypic switch in adipose tissue from energy storing white adipocytes to thermogenic beige adipocytes. This has generated the hypothesis that the process of adipocyte 'browning' may partially underlie the improved cardiometabolic health in physically active populations. Interestingly, 'browning' also occurs in response to various stressors and could represent an adaptive response. In the context of exercise, it is not clear whether the appearance of beige adipocytes is metabolically beneficial or whether they occur as a transient adaptive process to exercise-induced stresses. The present review discusses the various mechanisms (e.g. fatty acid oxidation during exercise, decreased thermal insulation, stressors and angiogenesis) by which the exercise-induced 'browning' process may occur., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals., Methods: We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals., Results: Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries., Conclusions: Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Context: Genotype plays an important role in influencing bone phenotypes, such as bone mineral density, but the role of genotype in determining responses of bone to exercise has yet to be elucidated., Objective: To determine whether 10 SNPs associated with genes in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt Signalling Pathways are associated with bone phenotypes in elite academy footballers (Soccer players) and to determine whether these genotypes are associated with training induced changes in bone. Design, participants, and methods: 99 elite academy footballers volunteered to participate. Peripheral computed tomography of the tibia (4%, 14%, 38% and 66% sites) was performed immediately before and 12 weeks after an increase in football training volume. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays., Results: No significant genotype by time interactions were shown for any of the SNPs analysed (P > .05). A main effect of genotype was shown. SOST SNP rs1877632 (trabecular density), P2X7R SNPs rs1718119 (cortical thickness and CSA), rs3751143 (SSI, CSA, cortical CSA and periosteal circumference) RANK/RANKL/OPG SNPs rs9594738 (periosteal circumference), rs1021188 (cortical thickness and CSA) and rs9594759 (cortical density) were associated with bone phenotypes (P < .05)., Conclusions: No association was shown between P2X7R, RANK/RANKL/OPG and Wnt Signalling SNPs and a change in bone phenotypes following 12 weeks of increased training volume in elite academy footballers. However, SNPs were associated with bone phenotypes pre training. These data highlight the complexity of the interaction between SNPs in the vicinity of the RANK/RANKL/OPG, P2X7R and Wnt metabolic regulatory pathways and bone phenotypes in elite academy footballers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown., Purpose: We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes., Methods: These studies were performed using a randomised, counterbalanced, crossover design. Eleven eumenorrheic women and eleven men completed two 5-day protocols of controlled (CON; 45kcal·kgLBM -1 ·d -1 ) and restricted (RES; 15kcal·kgLBM -1 ·d -1 ) EAs. Participants ran daily on a treadmill at 70% of their peak aerobic capacity (VO 2 peak) resulting in an exercise energy expenditure of 15kcal·kgLBM -1 ·d -1 and consumed diets providing 60 and 30kcal·kgLBM -1 ·d -1 . Blood was analysed for BTMs [β-carboxyl-terminal cross-linked telopeptide of type I collagen (β-CTX) and amino-terminal propeptide of type 1 procollagen (P1NP)], markers of calcium metabolism [parathyroid hormone (PTH), albumin-adjusted calcium (ACa), magnesium (Mg) and phosphate (PO 4 )] and regulatory hormones [sclerostin, insulin-like growth factor 1 (IGF-1), triiodothyronine (T 3 ), insulin, leptin, glucagon-like-peptide-2 (GLP-2)]., Results: In women, β-CTX AUC was significantly higher (P=0.03) and P1NP AUC was significantly lower (P=0.01) in RES compared to CON. In men, neither β-CTX (P=0.46) nor P1NP (P=0.12) AUCs were significantly different between CON and RES. There were no significant differences between sexes for any BTM AUCs (all P values>0.05). Insulin and leptin AUCs were significantly lower following RES in women only (for both P=0.01). There were no differences in any AUCs of regulatory hormones or markers of calcium metabolism between men and women following RES (all P values>0.05)., Conclusions: When comparing within groups, five days of low EA (15kcal·kgLBM -1 ·d -1 ) decreased bone formation and increased bone resorption in women, but not in men, and no sex specific differences were detected., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2',7'-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes.

Context: The scientific literature shows conflicting evidence about the relationship between adiposity and bone mass in overweight and obese populations. The aim of this review was to quantify the correlation between adipose mass (absolute and relative) and bone mineral density (BMD) in overweight and obese populations. Three databases were searched electronically. In addition, reference lists of relevant articles were screened. A total of 16 studies, comprising 2587 participants and 75 correlation coefficients were selected for inclusion in the review. Data were extracted from each study using a standardized form. Multilevel modeling indicated opposing relationships between BMD and adiposity: absolute adiposity correlated positively, and relative adiposity negatively, with BMD. Sex and age were the primary moderators of these relationships. Strong evidence supported a negative relationship between relative adipose mass and BMD in men (R = -0.37; 95%CI, -0.57 to -0.12) and in those aged less than 25 years (R = -0.28; 95%CI, -0.45 to -0.08). To prevent bone loss in overweight and obese populations, nutrition- and exercise-based interventions that focus on a controlled reduction of adipose mass with concomitant preservation of lean mass are recommended. : PROSPERO no. CRD42015024313., (© The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 -8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Purpose: This study aimed to investigate the effect of feeding carbohydrate and protein (CHO + PRO), immediately or 2 h after an exhaustive run, on the bone turnover response in endurance runners., Methods: Ten men (age = 28 ± 5 yr, height = 1.74 ± 0.05 m, body mass [BM] = 69.7 ± 6.3 kg) performed treadmill running at 75% V˙O2max, until exhaustion, on three occasions. Blood was collected before and immediately, 1, 2, 3, 4, and 24 h postexercise, for measurement of β-CTX, P1NP, parathyroid hormone, PO4, ACa, and Ca. This was a randomized, counterbalanced, placebo-controlled, and single-blinded crossover study. The three trials were (i) placebo (PLA), where the PLA solution was ingested immediately and 2 h postexercise; (ii) immediate feeding (IF), where CHO + PRO (1.5 g·kg BM dextrose and 0.5 g·kg BM whey) was ingested immediately postexercise and PLA 2 h postexercise; and (iii) delayed feeding (DF), where PLA was ingested immediately postexercise and CHO + PRO solution 2 h postexercise. Data were analyzed using repeated-measures ANOVA and Tukey's HSD post hoc test., Results: At 1 and 2 h postexercise, β-CTX concentrations were lower in the IF trial compared with the DF and PLA trials (P ≤ 0.001). At 3 h postexercise, β-CTX concentrations were higher in the PLA trial compared with the IF (P ≤ 0.001) and DF trials (P = 0.026). At 4 h postexercise, β-CTX concentrations were lower in the DF trial compared with the IF (P = 0.003) and PLA trials (P ≤ 0.001). At 4 h postexercise, P1NP was higher in the IF trial compared with the DF (P = 0.026) and PLA trials (P = 0.001). At 3 h postexercise, parathyroid hormone was higher in the IF trial compared with the DF trial (P ≤ 0.001)., Conclusions: After exhaustive running, immediate ingestion of CHO + PRO may be beneficial, as it decreases bone resorption marker concentrations and increases bone formation marker concentrations, creating a more positive bone turnover balance.

Habitual football participation has been shown to be osteogenic, although the specific volume of football participation required to cause bone adaptations are not well established. The aim of the present study is to investigate tibial bone adaptations in response to 12 weeks of increased training volume in elite adolescents who are already accustomed to irregular impact training. 99 male adolescent elite footballers participated (age 16±0 y; height 1.76±0.66 m; body mass 70.2±8.3 kg). Tibial scans were performed using peripheral quantitative computed tomography immediately before and 12 weeks after an increase in football training volume. Scans were obtained at 4, 14, 38 and 66% of tibial length. Trabecular density (mg/cm 3 ), cortical density (mg/cm 3 ), cross-sectional area, cortical area (mm 2 ), cortical thickness (mm) and strength strain index (mm 3 ) were assessed. Trabecular (4%) and cortical density (14, 38%), cortical cross-sectional area (14, 38%), total cross-sectional area (66%), cortical thickness (14, 38%) and strength strain index (14, 38%) increased following 12 weeks of augmented volume training (P<0.05). Increased density of trabecular and cortical compartments and cortical thickening were shown following an increased volume of training. These adaptive responses may have been enhanced by the adolescent status of the cohort, supporting the role of early exercise intervention in improving bone strength., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Skeletal muscle carnosine content can be increased through β-alanine (BA) supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity., Purpose: This study aimed to investigate the effects of 24 wk of BA supplementation on muscle carnosine content, gene expression, and high-intensity cycling capacity (CCT110%)., Methods: Twenty-five active males were supplemented with 6.4 g·d of sustained release BA or placebo for a 24 wk period. Every 4 wk participants provided a muscle biopsy and performed the CCT110%. Biopsies were analyzed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2, and PAT1)., Results: Carnosine content was increased from baseline at every time point in BA (all P < 0.0001; week 4 = +11.37 ± 7.03 mmol·kg dm, week 8 = +13.88 ± 7.84 mmol·kg dm, week 12 = +16.95 ± 8.54 mmol·kg dm, week 16 = +17.63 ± 8.42 mmol·kg dm, week 20 = +21.20 ± 7.86 mmol·kg dm, and week 24 = +20.15 ± 7.63 mmol·kg dm) but not placebo (all P > 0.05). Maximal increases were +25.66 ± 7.63 mmol·kg dm (range = +17.13 to +41.32 mmol·kg dm), and absolute maximal content was 48.03 ± 8.97 mmol·kg dm (range = 31.79 to 63.92 mmol·kg dm). There was an effect of supplement (P = 0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P = 0.05) with possible to almost certain improvements across all weeks., Conclusions: Twenty-four weeks of BA supplementation increased muscle carnosine content and improved high-intensity cycling capacity. The downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with BA supplementation, whereas the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of BA may also bear a major influence on muscle carnosine content.

Purpose: In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca 2+ ) handling. Accumulation of hydrogen cation (H + ) has been shown to impact Ca 2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca 2+ and H + coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions., Methods: Twenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day -1 of BA (n = 12) or placebo (PLA; n = 11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions., Results: BA supplementation had no effect on voluntary or electrically evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions during both resting (3 ± 13%; 19 ± 26%) and potentiated (1 ± 15%; 2 ± 20%) twitch contractions., Conclusions: The mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue., Trial Registration: The trial is registered with Clinicaltrials.gov, ID number NCT02819505.

Objective: To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance., Design: This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data., Data Sources: 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine')., Eligibility Criteria for Selecting Studies: Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses., Results: 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64))., Summary/conclusions: β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-alanine supplementation based on their chosen exercise modality., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

To defend against hydrogen cation accumulation and muscle fatigue during exercise, sodium bicarbonate (NaHCO 3 ) ingestion is commonplace. The individualized dose-response relationship between NaHCO 3 ingestion and blood biochemistry is unclear. The present study investigated the bicarbonate, pH, base excess and sodium responses to NaHCO 3 ingestion. Sixteen healthy males (23 ± 2 years; 78.6 ± 15.1 kg) attended three randomized order-balanced, nonblinded sessions, ingesting a single dose of either 0.1, 0.2 or 0.3 g·kg -1 BM of NaHCO 3 (Intralabs, UK). Fingertip capillary blood was obtained at baseline and every 10 min for 1 hr, then every 15 min for a further 2 hr. There was a significant main effect of both time and condition for all assessed blood analytes (p ≤ .001). Blood analyte responses were significantly lower following 0.1 g·kg -1 BM compared with 0.2 g·kg -1 BM; bicarbonate concentrations and base excess were highest following ingestion of 0.3 g·kg -1 BM (p ≤ .01). Bicarbonate concentrations and pH significantly increased from baseline following all doses; the higher the dose the greater the increase. Large interindividual variability was shown in the magnitude of the increase in bicarbonate concentrations following each dose (+2.0-5; +5.1-8.1; and +6.0-12.3 mmol·L -1 for 0.1, 0.2 and 0.3 g·kg -1 BM) and in the range of time to peak concentrations (30-150; 40-165; and 75-180 min for 0.1, 0.2 and 0.3 g·kg -1 BM). The variability in bicarbonate responses was not affected by normalization to body mass. These results challenge current practices relating to NaHCO 3 supplementation and clearly show the need for athletes to individualize their ingestion protocol and trial varying dosages before competition.

Context: The mechanism by which PTH is controlled during and after exercise is poorly understood due to insufficient temporal frequency of measurements., Objective: The objective of the study was to examine the temporal pattern of PTH, PO4, albumin-adjusted calcium, and Ca(2+) during and after exercise., Design and Setting: This was a laboratory-based study with a crossover design, comparing 30 minutes of running at 55%, 65%, and 75% maximal oxygen consumption, followed by 2.5 hours of recovery. Blood was obtained at baseline, after 2.5, 5, 7.5, 10, 15, 20, 25, and 30 minutes of exercise, and after 2.5, 5, 7.5, 10, 15, 20, 25, 30, 60, 90, and 150 minutes of recovery., Participants: Ten men (aged 23 ± 1 y, height 1.82 ± 0.07 m, body mass 77.0 ± 7.5 kg) participated., Main Outcome Measures: PTH, PO4, albumin-adjusted calcium, and Ca(2+) were measured., Results: Independent of intensity, PTH concentrations decreased with the onset of exercise (-21% to -33%; P ≤ .001), increased thereafter, and were higher than baseline by the end of exercise at 75% maximal oxygen consumption (+52%; P ≤ .001). PTH peaked transiently after 5-7.5 minutes of recovery (+73% to +110%; P ≤ .001). PO4 followed a similar temporal pattern to PTH, and Ca(2+) followed a similar but inverse pattern to PTH. PTH was negatively correlated with Ca(2+) across all intensities (r = -0.739 to -0.790; P ≤ .001). When PTH was increasing, the strongest cross-correlation was with Ca(2+) at 0 lags (3.5 min) (r = -0.902 to -0.950); during recovery, the strongest cross-correlation was with PO4 at 0 lags (8 min) (r = 0.987-0.995)., Conclusions: PTH secretion during exercise and recovery is controlled by a combination of changes in Ca(2+) and PO4 in men.

Purpose: Few human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading., Methods: Tibial bone density and geometry were measured in 90 British Army male recruits (ages 21±3years, height: 1.78±0.06m, body mass: 73.9±9.8kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P<0.05)., Results: Bone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial-anterior and anterior-posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P<0.01)., Conclusions: In vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the effect of sprint interval training (SIT) in normoxia, vs. SIT in hypoxia alone or in conjunction with oral nitrate intake, on buffering capacity of homogenized muscle (βhm) and fiber type distribution, as well as on sprint and endurance performance., Methods: Twenty-seven moderately-trained participants were allocated to one of three experimental groups: SIT in normoxia (20.9% FiO2) + placebo (N), SIT in hypoxia (15% FiO2) + placebo (H), or SIT in hypoxia + nitrate supplementation (HN). All participated in 5 weeks of SIT on a cycle ergometer (30-s sprints interspersed by 4.5 min recovery-intervals, 3 weekly sessions, 4-6 sprints per session). Nitrate (6.45 mmol NaNO3) or placebo capsules were administered 3 h before each session. Before and after SIT participants performed an incremental VO2max-test, a 30-min simulated cycling time-trial, as well as a 30-s cycling sprint test. Muscle biopsies were taken from m. vastus lateralis., Results: SIT decreased the proportion of type IIx muscle fibers in all groups (P < 0.05). The relative number of type IIa fibers increased (P < 0.05) in HN (P < 0.05 vs. H), but not in the other groups. SIT had no significant effect on βhm. Compared with H, SIT tended to enhance 30-s sprint performance more in HN than in H (P = 0.085). VO2max and 30-min time-trial performance increased in all groups to a similar extent., Conclusion: SIT in hypoxia combined with nitrate supplementation increases the proportion of type IIa fibers in muscle, which may be associated with enhanced performance in short maximal exercise. Compared with normoxic training, hypoxic SIT does not alter βhm or endurance and sprinting exercise performance.

Introduction: Radiation therapy (RT), like many allied health professions, has lacked professional practice clarity, which until 2008 had not been comprehensively investigated. This manuscript describes the first phase of a three-phase project investigating the current and future practices of radiation therapists (RTs) in Australia. The aim of phase 1 was to define the practice of RTs in Australia., Methods: A quantitative approach was used to gain an understanding of RT practice. A national survey was distributed to RTs in Australia. Descriptive statistics and content analysis were used to analyse the data. RT practice was analysed in relation to core and non-core roles, where non-core roles were further divided into basic and advanced practices., Results: The data from the national survey were representative of the Australian RT population (n = 525). The current practice of RTs is presented in summary tables for each area of work (treatment, planning, simulation, mould room and general)., Conclusion: This study provided clarification of RT practice and indicated there was a desire to relinquish administrative roles to focus on RT-specific practice. There was evidence that some advanced roles were currently practiced in Australia; however, there was no structure to support these roles and they were based only on local need. This study identified that the profession needs to consider how they will maintain core RT practice, while encouraging the development of new roles, and whether some roles need to be relinquished.

Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. The aim of this study is to evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. In 210 Israeli Defense Forces (IDF) military conscripts, stress fracture injury was diagnosed (n = 43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n = 125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson's chi-squared (χ (2)) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. The variant allele of P2X7R SNP rs3751143 (Glu496Ala-loss of function) was associated with stress fracture injury, whilst the variant allele of rs1718119 (Ala348Thr-gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P < 0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P < 0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P < 0.05). The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury.

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

To test the hypothesis that daily weight-making is more problematic to health in male compared with female jockeys, we compared the bone density and resting metabolic rate (RMR) in weight-matched male and female Flat jockeys. RMR (kcal·kg(-1) lean mass) was lower in males compared with females as well as lower bone-density Z scores at the hip and lumbar spine. Data suggest the lifestyle of male jockeys compromise health more severely than females, possibly because of making weight more frequently.

Objectives: Intervention studies do not account for high within-individual variation potentially compromising the magnitude of an effect. Repeat administration of a treatment allows quantification of individual responses and determination of the consistency of responses. We determined the consistency of metabolic and exercise responses following repeated administration of sodium bicarbonate (SB)., Design and Methods: 15 physically active males (age 25±4 y; body mass 76.0±7.3 kg; height 1.77±0.05 m) completed six cycling capacity tests at 110% of maximum power output (CCT110%) following ingestion of either 0.3 g∙kg-1BM of SB (4 trials) or placebo (PL, 2 trials). Blood pH, bicarbonate, base excess and lactate were determined at baseline, pre-exercise, post-exercise and 5-min post-exercise. Total work done (TWD) was recorded as the exercise outcome., Results: SB supplementation increased blood pH, bicarbonate and base excess prior to every trial (all p ≤ 0.001); absolute changes in pH, bicarbonate and base excess from baseline to pre-exercise were similar in all SB trials (all p > 0.05). Blood lactate was elevated following exercise in all trials (p ≤ 0.001), and was higher in some, but not all, SB trials compared to PL. TWD was not significantly improved with SB vs. PL in any trial (SB1: +3.6%; SB2 +0.3%; SB3: +2.1%; SB4: +6.7%; all p > 0.05), although magnitude-based inferences suggested a 93% likely improvement in SB4. Individual analysis showed ten participants improved in at least one SB trial above the normal variation of the test although five improved in none., Conclusions: The mechanism for improved exercise with SB was consistently in place prior to exercise, although this only resulted in a likely improvement in one trial. SB does not consistently improve high intensity cycling capacity, with results suggesting that caution should be taken when interpreting the results from single trials as to the efficacy of SB supplementation., Trial Registration: ClinicalTrials.gov NCT02474628.

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO · kg body mass(-1) · h(-1)) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover., (Copyright © 2015 the American Physiological Society.)

Professions grapple with defining advanced practice and the characteristics of advanced practitioners. In nursing and allied health, advanced practice has been defined as 'a state of professional maturity in which the individual demonstrates a level of integrated knowledge, skill and competence that challenges the accepted boundaries of practice and pioneers new developments in health care'. Evolution of advanced practice in Australia has been slower than in the United Kingdom, mainly due to differences in demography, the health system and industrial relations. This article describes a conceptual model of advanced practitioner characteristics in the medical radiation professions, taking into account experiences in other countries and professions. Using the CanMEDS framework, the model includes foundation characteristics of communication, collaboration and professionalism, which are fundamental to advanced clinical practice. Gateway characteristics are: clinical expertise, with high level competency in a particular area of clinical practice; scholarship and teaching, including a masters qualification and knowledge dissemination through educating others; and evidence-based practice, with judgements made on the basis of research findings, including research by the advanced practitioner. The pinnacle of advanced practice is clinical leadership, where the practitioner has a central role in the health care team, with the capacity to influence decision making and advocate for others, including patients. The proposed conceptual model is robust yet adaptable in defining generic characteristics of advanced practitioners, no matter their clinical specialty. The advanced practice roles that evolve to meet future health service demand must focus on the needs of patients, local populations and communities.

The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4-6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4-6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine.

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2)., Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion., Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise., Conclusion: 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

β-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day of BA (n = 12) or placebo (PLA; n = 11). During each session, force was recorded during a series of knee extensor contractions: resting and potentiated twitches and octet (8 pulses, 300 Hz) contractions elicited via femoral nerve stimulation; tetanic contractions (1 s, 1-100 Hz) via superficial muscle stimulation; and maximum and explosive voluntary contractions. BA supplementation had no effect on the force-frequency relationship, or the force responses (force at 25 and 50 ms from onset, peak force) of resting or potentiated twitches, and octet contractions (P > 0.05). Resting and potentiated twitch electromechanical delay and time-to-peak tension were unaffected by BA supplementation (P > 0.05), although half-relaxation time declined by 7-12% (P < 0.05). Maximum and explosive voluntary forces were unchanged after BA supplementation. BA supplementation had no effect on evoked force responses, implying that altered calcium sensitivity and/or release are not the mechanisms by which BA supplementation influences exercise performance. The reduced half-relaxation time with BA supplementation might, however, be explained by enhanced reuptake of calcium, which has implications for the efficiency of muscle contraction following BA supplementation., (Copyright © 2015 the American Physiological Society.)

Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations., Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes., Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group and were sub-stratified into male and cases of multiple stress fracture groups. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays., Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (P<0.05). 8.1% of the stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (P<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes had suffered a stress fracture whilst 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188 and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (P<0.05)., Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health and offers potential targets for therapeutic interventions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the reliability of maximum voluntary isometric force (MVIF), cross-sectional area (CSA) and force per unit CSA measures, of the first dorsal interosseus (FDI) muscle, using a custom-built dynamometer and ultrasonography. Twenty-seven participants completed MVIF and CSA measurements on two separate occasions under the same conditions. Reliability was determined using paired samples t-tests, systematic bias ratio and ratio limits of agreement (RLoA), intra-class correlation (ICC) and coefficient of variation (CV). MVIF of the FDI muscle (mean ± s; 31.8 ± 7.6 N and 31.6 ± 7.3 N) was not different between trials (P = 0.63); RLoA between trials were 1.00 ×/÷ 1.09, ICC = 0.990 and CV = 3.22%. CSA of the FDI muscle (22.6 ± 6.9 and 22.9 ± 6.9 mm²) was also not different between trials (P = 0.31); RLoA between trials were 0.98 ×/÷ 1.19, ICC = 0.979 and CV = 6.61%. Force per unit CSA was not different between trials (1.49 ± 0.43 and 1.46 ± 0.44 N·mm²; P = 0.18), RLoA were 1.02 ×/÷ 1.17, ICC = 0.985 and CV = 5.76%. The techniques used to determine MVIF and CSA of the FDI muscle were reliable and can be combined to calculate force per unit CSA.

Purpose: To determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalemia or other metabolic responses is different between individuals who improve exercise capacity and those who do not., Methods: Twenty-one men completed 2 cycling-capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g/kg body mass of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess, and lactate were determined at baseline, preexercise, immediately postexercise, and 5 min postexercise., Results: SB supplementation did not significantly increase total work done (TWD; P = .16, 46.8 ± 9.1 vs 45.6 ± 8.4 kJ, d = 0.14), although magnitude-based inferences suggested a 63% likelihood of a positive effect. When data were analyzed without 4 participants who experienced GI discomfort, TWD (P = .01) was significantly improved with SB. Immediately postexercise blood lactate was higher in SB for the individuals who improved but not for those who did not. There were also differences in the preexercise-to-postexercise change in blood pH, bicarbonate, and base excess between individuals who improved and those who did not., Conclusions: SB improved high-intensity-cycling capacity but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that SB may not be beneficial to all individuals. Magnitude-based inferences suggested that the exercise effects are unlikely to be negative; therefore, individuals should determine whether they respond well to SB supplementation before competition.

Context: Lower PTH concentrations reported in the hours after acute, endurance exercise compared with preexercise levels might be influenced by factors such as circadian fluctuations., Objective: The objective of the study was to compare postexercise PTH concentrations with a nonexercising control group., Design and Setting: A laboratory-based study with a crossover design, comparing a 60-minute (at 10:30 am) bout of treadmill running at 65% of the maximal rate of oxygen uptake (exercise) with semirecumbent rest (CON). Blood samples were obtained immediately before (baseline 10:15 am) and after (11:30 am) exercise and during recovery (12:30 am, 1:30 pm, and 2:15 pm)., Participants: Ten physically active men (mean ± 1 SD, age 26 ± 5 y; body mass 78.3 ± 5.8 kg; maximal rate of oxygen uptake 57.3 ± 6.9 mL/kg(-1) · min(-1)) participated in the study., Main Outcome Measures: PTH, albumin-adjusted calcium, and phosphate concentrations were measured., Results: PTH concentrations increased (+85%, P < .01) during exercise and were higher than in CON immediately at the end of exercise (4.5 ± 1.9 vs 2.6 ± 0.9 pmol/L(-1), P < .05). In the postexercise period (12:30-2:15 pm), PTH was not different compared with baseline but was lower compared with CON at 1:30 pm (-22%; P < .01) and tended to be lower at both 12:30 pm (-12%; P = .063) and 2:15 pm (-13%; P = .057). Exercise did not significantly affect the albumin-adjusted calcium concentrations, whereas phosphate was higher than CON immediately after exercise (1.47 ± 0.17 vs 1.03 ± 0.17 pmol/L(-1), P < .001) and was lower at 1:30 pm (-16%: P < .05)., Conclusions: Lower PTH concentrations after acute endurance running compared with a rested control condition suggest a true effect of exercise.

Recent investigations have suggested that highly trained athletes may be less responsive to the ergogenic effects of β-alanine (BA) supplementation than recreationally active individuals due to their elevated muscle buffering capacity. We investigated whether training status influences the effect of BA on repeated Wingate performance. Forty young males were divided into two groups according to their training status (trained: T, and non-trained: NT cyclists) and were randomly allocated to BA and a dextrose-based placebo (PL) groups, providing four experimental conditions: NTPL, NTBA, TPL, TBA. BA (6.4 g day(-1)) or PL was ingested for 4 weeks, with participants completing four 30-s lower-body Wingate bouts, separated by 3 min, before and after supplementation. Total work done was significantly increased following supplementation in both NTBA (p = 0.03) and TBA (p = 0.002), and it was significantly reduced in NTPL (p = 0.03) with no difference for TPL (p = 0.73). BA supplementation increased mean power output (MPO) in bout 4 for the NTBA group (p = 0.0004) and in bouts 1, 2 and 4 for the TBA group (p ≤ 0.05). No differences were observed in MPO for NTPL and TPL. BA supplementation was effective at improving repeated high-intensity cycling performance in both trained and non-trained individuals, highlighting the efficacy of BA as an ergogenic aid for high-intensity exercise regardless of the training status of the individual.

Purpose: To investigate the separate and combined effects of sodium bicarbonate and beta-alanine supplementation on repeated sprints during simulated match play performed in hypoxia., Methods: Study A: 20 recreationally active participants performed two trials following acute supplementation with either sodium bicarbonate (0.3 g·kg-1BM) or placebo (maltodextrin). Study B: 16 recreationally active participants were supplemented with either a placebo or beta-alanine for 5 weeks (6.4 g·day-1 for 4 weeks, 3.2 g·day-1 for 1 week), and performed one trial before supplementation (with maltodextrin) and two following supplementation (with sodium bicarbonate and maltodextrin). Trials consisted of 3 sets of 5 × 6 s repeated sprints performed during a football specific intermittent treadmill protocol performed in hypoxia (15.5% O2). Mean (MPO) and peak (PPO) power output were recorded as the performance measures., Results: Study A: Overall MPO was lower with sodium bicarbonate than placebo (p = .02, 539.4 ± 84.5 vs. 554.0 ± 84.6 W), although there was no effect across sets (all p > .05). Study B: There was no effect of beta-alanine, or cosupplementation with sodium bicarbonate, on either parameter, although there was a trend toward higher MPO with sodium bicarbonate (p = .07)., Conclusions: The effect of sodium bicarbonate on repeated sprints was equivocal, although there was no effect of beta-alanine or cosupplementation with sodium bicarbonate. Individual variation may have contributed to differences in results with sodium bicarbonate, although the lack of an effect with beta-alanine suggests this type of exercise may not be influenced by increased buffering capacity.

Introduction:  Documentation on the history of Australian radiotherapy is limited. This study provides radiation therapists' (RTs) perspectives of the people, workplace, and work practices in Australian radiotherapy centres from 1960 onwards. It provides a follow-up to our previous study: Australian radiation therapy: An overview - Part one, which outlines the history and development of radiotherapy from conception until present day., Methods:  Four focus groups were conducted on separate occasions in 2010, one in South Australia and three in Victoria, Australia. Participants who worked in radiotherapy were purposively selected to ensure a range of experience, age, and years of work., Results:  From a RT perspective, radiotherapy has evolved from a physically demanding 'hands-on' work environment, often with unpleasant sights and smells of disease, to a more technology-driven workplace., Conclusion:  Understanding these changes and their subsequent effects on the role of Australian RTs will assist future directions in advanced role development.