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Background: Although nutrition and exercise both influence bone metabolism, little is currently known about their interaction, or whether nutritional intervention can modulate the bone biomarker response to acute exercise. Improved understanding of the relationships between nutrition, exercise and bone metabolism may have substantial potential to inform nutritional interventions to protect the bone health of exercising individuals, and to elucidate mechanisms by which exercise and nutrition influence bone. Objective: The aim was to synthesise available evidence related to the influence of nutrition on the response of the bone biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX-1) to acute exercise, using a systematic review and meta-analytic approach. Methods: Studies evaluating the influence of nutritional status or intervention on the bone biomarker response to an acute exercise bout were included and separated into four categories: (1) feeding status and energy availability, (2) macronutrients, (3) micronutrients and (4) other. Studies conducted on healthy human populations of any age or training status were included. Meta-analysis was conducted when data from at least five studies with independent datasets were available. In the case of insufficient data to warrant meta-analysis, results from individual studies were narratively synthesised and standardised mean effect sizes visually represented. Results: Twenty-two articles were included. Of these, three investigated feeding status or energy availability, eight macronutrients, eight micronutrients (all calcium) and six other interventions including dairy products or collagen supplementation. Three studies had more than one intervention and were included in all relevant outcomes. The largest and most commonly reported effects were for the bone resorption marker CTX-1. Meta-analysis indicated that calcium intake, whether provided via supplements, diet or in

Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes.

The idiom € more high-quality research is needed' has become the slogan for sport and exercise physiology-based research in female athletes. However, in most instances, it is challenging to address this gap of high-quality research in elite female athletes at a single study site due to challenges in recruiting enough participants with numerous menstrual cycle and contraceptive pill permutations. Accordingly, we have assembled an international multisite team to undertake an innovative project for female athletes, which investigates the effects of changes in endogenous and exogenous oestrogen and progesterone/progestins across the menstrual cycle and in response to second-generation combined monophasic contraceptive pill use, on aspects of exercise physiology and athletic performance. This project will employ the current gold-standard methodologies in this area, resulting in an adequately powered dataset. This protocol paper describes the consortium-based approach we will undertake during this study.

Background: Circulating biomarkers are often used to investigate the bone response to an acute bout of exercise, but heterogeneity in factors such as study design, quality, selected biomarkers, and exercise and participant characteristics render it difficult to synthesize and evaluate available evidence. Objective: The aim of this study was to quantify the effects of an acute exercise bout on bone biomarkers, along with the influence of potential moderators such as participant, exercise, and design characteristics, using a systematic review and meta-analytic approach. Methods: The protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines and prospectively published. Seven databases were systematically searched in accordance with predefined eligibility criteria. Bayesian three-level hierarchical meta-analysis models were used to explore the main effects of acute exercise on bone biomarkers, as well as potential moderating factors. Modelled effect sizes were interpreted according to three metrics, namely (1) evidence of an effect (defined by whether, or how much of, the credible interval [CrI] included zero); (b) the size of that effect (threshold values of 0.01, 0.2, 0.5 and 0.8 were used to describe effect sizes as very small, small, medium and large, respectively); and (c) the level of certainty in the estimated effect (defined using the GRADE framework). Results: Pooling of outcomes across all designs and categories indicated that an acute bout of exercise increased bone resorption (ES0.5 0.10, 95% CrI 0.00–0.20) and formation (ES0.5 0.05, 95% CrI 0.01–0.08) markers but the effects were very small and highly variable. Furthermore, moderator analyses revealed the source of some of this variability and indicated that exercise type and impact loading influenced the bone resorptive response. A moderate increase in C-terminal telopeptide of type 1 collagen (CTX-1) was observed in resp

The energy costs of athletic training can be substantial, and deficits arising from costs unmet by adequate energy intake, leading to a state of low energy availability, may adversely impact athlete health and performance. Life history theory is a branch of evolutionary theory that recognizes that the way the body uses energy—and responds to low energy availability—is an evolved trait. Energy is a finite resource that must be distributed throughout the body to simultaneously fuel all biological processes. When energy availability is low, insufficient energy may be available to equally support all processes. As energy used for one function cannot be used for others, energetic “trade-offs” will arise. Biological processes offering the greatest immediate survival value will be protected, even if this results in energy being diverted away from others, potentially leading to their downregulation. Athletes with low energy availability provide a useful model for anthropologists investigating the biological trade-offs that occur when energy is scarce, while the broader conceptual framework provided by life history theory may be useful to sport and exercise researchers who investigate the influence of low energy availability on athlete health and performance. The goals of this review are: (1) to describe the core tenets of life history theory; (2) consider trade-offs that might occur in athletes with low energy availability in the context of four broad biological areas: reproduction, somatic maintenance, growth, and immunity; and (3) use this evolutionary perspective to consider potential directions for future research.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long-term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. In this progress report, the design considerations and functional requirements of macroencapsulation systems are reviewed, specifically for stem-cell derived islets (SC-islets), highlighting distinct design parameters. Additionally, a perspective on the future for macroencapsulation systems is given, and how incorporating continuous sensing and closed-loop feedback can be transformative in advancing toward an autonomous biohybrid artificial pancreas., Juvenile Diabetes Research Fund (Grant 1-PNF-2019-778-S-B)

Energy is a finite resource that is competitively distributed among the body’s systems and biological processes. During times of scarcity, energetic “trade-offs” may arise if less energy is available than is required to optimally sustain all systems. More immediately essential functions are predicted to be prioritized, even if this necessitates the diversion of energy away from – and potential downregulation of – others. These concepts are encompassed within life history theory, an evolutionary framework with considerable potential to enhance understanding of the evolved biological response to periods of energy deficiency. Skeletal muscle is a particularly interesting tissue to investigate from this perspective, given that it is one of the largest and most energetically costly tissues within the body. It is also highly plastic, responsive to a broad range of stimuli, and contributes to many essential bodily functions, e.g., mechanical, regulatory and storage. These functions may be traded off against each other during periods of energy deficiency, with the nature of the trade-off’s dependent on the characteristics of the individual and the circumstances within which the deficit occurs. In this review, we consider the skeletal muscle response to periods of energy deficiency from a life history perspective, along with how this response may be influenced by factors including sex, age, body composition, training and nutritional status.

Freshwater turtles found in higher latitudes can experience extreme challenges to acid-base homeostasis while overwintering, due to a combination of cold temperatures along with the potential for environmental hypoxia. Histidine-containing dipeptides (HCDs; carnosine, anserine and balenine) may facilitate pH regulation in response to these challenges, through their role as pH buffers. We measured the HCD content of three tissues (liver, cardiac and skeletal muscle) from the anoxia-tolerant painted turtle (C. picta bellii) acclimated to either 3 or 20 °C. HCDs were detected in all tissues, with the highest content shown in the skeletal muscle. Turtles acclimated to 3 °C had more HCD in their skeletal muscle than those acclimated to 20 °C (carnosine = 20.8 ± 4.5 vs 12.5 ± 5.9 mmol·kg DM−1; ES = 1.59 (95%CI: 0.16–3.00), P = 0.013). The higher HCD content shown in the skeletal muscle of the cold-acclimated turtles suggests a role in acid-base regulation in response to physiological challenges associated with living in the cold, with the increase possibly related to the temperature sensitivity of carnosine's dissociation constant.

Efficient coupling of soft robotic cardiac assist devices to the external surface of the heart is crucial to augment cardiac function and represents a hurdle to translation of this technology. In this work, we compare various fixation strategies for local and global coupling of a direct cardiac compression sleeve to the heart. For basal fixation, we find that a sutured Velcro band adheres the strongest to the epicardium. Next, we demonstrate that a mesh-based sleeve coupled to the myocardium improves function in an acute porcine heart failure model. Then, we analyze the biological integration of global interface material candidates (medical mesh and silicone) in a healthy and infarcted murine model and show that a mesh interface yields superior mechanical coupling via pull-off force, histology, and microcomputed tomography. These results can inform the design of a therapeutic approach where a mesh-based soft robotic DCC is implanted, allowed to biologically integrate with the epicardium, and actuated for active assistance at a later timepoint. This strategy may result in more efficient coupling of extracardiac sleeves to heart tissue, and lead to increased augmentation of heart function in end-stage heart failure patients.