Intermittent actuation attenuates fibrotic behaviour of myofibroblasts.

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood. Here, we use analytical, computational, and in vitro models to understand the response of human myofibroblasts (WPMY-1 stromal cell line) to intermittent actuation using soft robotics and investigate how actuation can alter the secretion of collagen and pro/anti-inflammatory cytokines by these cells. Our findings suggest that there is a mechanical loading threshold that can modulate the fibrotic behaviour of myofibroblasts, by reducing the secretion of soluble collagen, transforming growth factor beta-1 and interleukin 1-beta, and upregulating the anti-inflammatory interleukin-10. By improving our understanding of how cells involved in the FBR respond to mechanical actuation, we can harness this technology to improve functional outcomes for a wide range of implanted medical device applications including drug delivery and cell encapsulation platforms. STATEMENT OF SIGNIFICANCE: A major barrier to the successful clinical translation of many implantable medical devices is the foreign body response (FBR) and resultant deposition of a hypo-permeable fibrotic capsule (FC) around the implant. Perturbation of the implant site using intermittent actuation (IA) of soft-robotic implants has previously been shown to modulate the FBR and reduce FC thickness. However, the mechanisms of action underlying this response were largely unknown. Here, we investigate how IA can alter the activity of myofibroblast cells, and ultimately suggest that there is a mechanical loading threshold within which their fibrotic behaviour can be modulated. These findings can be harnessed to improve functional outcomes for a wide range of medical implants, particularly drug delivery and cell encapsulation devices.

Sodium bicarbonate induces alkalosis, but improves high-intensity cycling performance only when participants expect a beneficial effect: a placebo and nocebo study.

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid-base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid-base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15-0.74; Dextrose/Ergogenic: 0.45; 0.04-0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect.

Effect of menstrual cycle and contraceptive pill phase on aspects of exercise physiology and athletic performance in female athletes: protocol for the Feminae international multisite innovative project.

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.

Variability in variability: does variation in morphological and physiological traits differ between men and women?

Many researchers presume greater variability between female participants than between males due to the menstrual cycle. This view has encouraged a sex bias in health and medical research, resulting in considerable knowledge gaps with important clinical implications. Yet in another field-evolutionary biology-the received wisdom is the reverse: that men are more variable, possibly due to male heterogamety. To test these competing hypotheses, we compared variance between the sexes for 50 morphological and physiological traits, analysing data from the NHANES database. Nearly half the traits did not exhibit sexual dimorphism in variation, while 18 exhibited greater female variation (GFV), indicating GFV does not dominate human characteristics. Only eight traits exhibited greater male variation (GMV), indicating GMV also does not dominate, and in turn offering scant support for the heterogamety hypothesis. When our analysis was filtered to include only women with regular menstrual cycles (and men of equivalent age), the number of traits with GFV and GMV were low and not statistically different, suggesting that the menstrual cycle does not typically explain GFV when it occurs. In practical terms, health and medical researchers should no longer simply assume that female participants will induce additional variation in the traits of interest.

P1NP and ß-CTX-1 Responses to a Prolonged, Continuous Running Bout in Young Healthy Adult Males: A Systematic Review with Individual Participant Data Meta-analysis.

BACKGROUND: Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. This study aimed to quantify group responses and inter-individual variability of P1NP and ß-CTX-1 after prolonged, continuous running (60-120 min at 65-75% V̇O2max) in young healthy adult males using individual participant data (IPD) meta-analysis. METHODS: The protocol was designed following PRISMA-IPD guidelines and was pre-registered on the Open Science Framework prior to implementation ( https://osf.io/y69nd ). Changes in P1NP and ß-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and ß-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies. RESULTS: P1NP levels increased during and immediately after running, when the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 h and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·mL-1) and daily (- 0.4 ± 5.7 ng·mL-1) variation values. ß-CTX-1 levels decreased during and up to 4 h after running with distributions comparable to typical hourly variation (- 0.13 ± 0.11 ng·mL-1). There was no evidence of changes in ß-CTX-1 levels during the 4 days after the running bout, when distributions were also similar between the running data and typical daily variation (- 0.03 ± 0.10 ng·mL-1). CONCLUSION: Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in ß-CTX-1 identified in both control and running data, suggested that these changes were due to the markers' circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and ß-CTX-1, in this population.

Soft robot-mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery.

The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its effects via soft robotic actuations. Occlusion of the FSDSR porous membrane was monitored over 7 days in a rodent model using electrochemical impedance spectroscopy. The electrical resistance of the fibrotic capsule correlated to its increase in thickness and volume. Our FibroSensing membrane showed great sensitivity in detecting changes at the abiotic/biotic interface, such as collagen deposition and myofibroblast proliferation. The potential of the FSDSR to overcome fibrotic capsule formation and maintain constant drug dosing over time was demonstrated in silico and in vitro. Controlled closed loop release of methylene blue into agarose gels (with a comparable fold change in permeability relating to 7 and 28 days in vivo) was achieved by adjusting the magnitude and frequency of pneumatic actuations after impedance measurements by the FibroSensing membrane. By sensing fibrotic capsule formation in vivo, the FSDSR will be capable of probing and adapting to the foreign body response through dynamic actuation changes. Informed by real-time sensor signals, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrotic capsule formation.

Energy constraint and compensation: Insights from endurance athletes.

The Constrained Model of Total Energy Expenditure predicts that increased physical activity may not influence total energy expenditure, but instead, induces compensatory energetic savings in other processes. Much remains unknown, however, about concepts of energy expenditure, constraint and compensation in different populations, and it is unclear whether this model applies to endurance athletes, who expend very large amounts of energy during training and competition. Furthermore, it is well-established that some endurance athletes consciously or unconsciously fail to meet their energy requirements via adequate food intake, thus exacerbating the extent of energetic stress that they experience. Within this review we A) Describe unique characteristics of endurance athletes that render them a useful model to investigate energy constraints and compensations, B) Consider the factors that may combine to constrain activity and total energy expenditure, and C) Describe compensations that occur when activity energy expenditure is high and unmet by adequate energy intake. Our main conclusions are as follows: A) Higher activity levels, as observed in endurance athletes, may indeed increase total energy expenditure, albeit to a lesser degree than may be predicted by an additive model, given that some compensation is likely to occur; B) That while a range of factors may combine to constrain sustained high activity levels, the ability to ingest, digest, absorb and deliver sufficient calories from food to the working muscle is likely the primary determinant in most situations and C) That energetic compensation that occurs in the face of high activity expenditure may be primarily driven by low energy availability i.e., the amount of energy available for all biological processes after the demands of exercise have been met, and not by activity expenditure per se.

Use of factor analysis to model relationships between bone mass and physical, dietary, and metabolic factors in frail and pre-frail older adults.

Bone mass and quality decline with age, and can culminate in osteoporosis and increased fracture risk. This investigation modeled associations between bone and physical, dietary, and metabolic factors in a group of 200 pre-frail/frail older adults using factor analysis and structural equation modeling (SEM). Exploratory (EFA) and confirmatory factor analysis (CFA) were conducted to compose factors and to assess their robustness. SEM was used to quantify associations between bone and the other factors. Factors arising from EFA and CFA were: bone (whole body, lumbar and femur bone mineral density, and trabecular bone score; good fit), body composition - lean (lean mass, body mass, vastus lateralis, and femoral cross-sectional area; good fit), body composition - fat (total fat mass, gynoid, android, and visceral fat; acceptable fit), strength (bench and leg press, handgrip, and knee extension peak torque; good fit), dietary intake (kilocalories, carbohydrate, protein, and fat; acceptable fit), and metabolic status (cortisol, insulin-like growth factor 1 (IGF-1), growth hormone (GH), and free testosterone; poor fit). SEM using isolated factors showed that body composition (lean) (ß = 0.66, P < 0.001), body composition (fat) (ß = 0.36, P < 0.001), and strength (ß = 0.74, P < 0.001) positively associated with bone. Dietary intake relative to body mass negatively associated with bone (ß = -0.28, P = 0.001), whereas in absolute terms, it showed no association (ß = 0.01, P = 0.911). In a multivariable model, only strength (ß = 0.38, P = 0.023) and body composition (lean) (ß = 0.34, P = 0.045) associated with bone. Resistance training programs that focus on improving lean mass and strength in older individuals may benefit bone in this population.NEW & NOTEWORTHY We used factor analysis and structural equation modeling, which are rarely used in nutrition or exercise science, but constitute powerful tools that may overcome limitations of traditional analyses, combining individual related variables into factors or constructs of interest. Our investigation represents a starting point on this progressive pathway, providing useful insight and a working model for researchers and practitioners who wish to tackle complex problems such as the multifactorial causes of bone loss in older adults.

Patterns of energy allocation during energetic scarcity; evolutionary insights from ultra-endurance events.

Exercise physiologists and evolutionary biologists share a research interest in determining patterns of energy allocation during times of acute or chronic energetic scarcity. Within sport and exercise science, this information has important implications for athlete health and performance. For evolutionary biologists, this would shed new light on our adaptive capabilities as a phenotypically plastic species. In recent years, evolutionary biologists have begun recruiting athletes as study participants and using contemporary sports as a model for studying evolution. This approach, known as human athletic palaeobiology, has identified ultra-endurance events as a valuable experimental model to investigate patterns of energy allocation during conditions of elevated energy demand, which are generally accompanied by an energy deficit. This energetic stress provokes detectable functional trade-offs in energy allocation between physiological processes. Early results from this modelsuggest thatlimited resources are preferentially allocated to processes which could be considered to confer the greatest immediate survival advantage (including immune and cognitive function). This aligns with evolutionary perspectives regarding energetic trade-offs during periods of acute and chronic energetic scarcity. Here, we discuss energy allocation patterns during periods of energetic stress as an area of shared interest between exercise physiology and evolutionary biology. We propose that, by addressing the ultimate "why" questions, namely why certain traits were selected for during the human evolutionary journey, an evolutionary perspective can complement the exercise physiology literature and provide a deeper insight of the reasons underpinning the body's physiological response to conditions of energetic stress.

Dietary ß-Alanine Intake Assessed by Food Records Does Not Associate With Muscle Carnosine Content in Healthy, Active, Omnivorous Men and Women.

ß-Alanine (BA) is one of the most widely used sport supplements, due to its capacity to improve high-intensity exercise performance by increasing muscle carnosine (MCarn) content, and consequently, the buffering capacity of the muscle. BA is also available in a variety of animal foods, but little is currently known about the influence of dietary BA intake on MCarn. The aim of the current study was to compile a detailed summary of available data on the BA content of commonly consumed foods, and to explore whether associations could be detected between self-reported dietary BA intake and skeletal MCarn in a group of 60 healthy, active, omnivorous men and women. Dietary BA intake was assessed via 3-day food records, and MCarn content assessed by high-performance liquid chromatography. A series of univariate and multivariate linear regression models were used to explore associations between estimated dietary BA and MCarn. No evidence of associations between dietary BA intake and MCarn were identified, with effect sizes close to zero calculated from models accounting for key demographic variables (f2 ≤ 0.02 for all analyses). These findings suggest that capacity to increase MCarn via dietary strategies may be limited, and that supplementation may be required to induce increases of the magnitude required to improve performance.

The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.

The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.

Towards a Whole Sample Imaging Approach Using Diffusion Tensor Imaging to Examine the Foreign Body Response to Explanted Medical Devices.

Analysing the composition and organisation of the fibrous capsule formed as a result of the Foreign Body Response (FBR) to medical devices, is imperative for medical device improvement and biocompatibility. Typically, analysis is performed using histological techniques which often involve random sampling strategies. This method is excellent for acquiring representative values but can miss the unique spatial distribution of features in 3D, especially when analysing devices used in large animal studies. To overcome this limitation, we demonstrate a non-destructive method for high-resolution large sample imaging of the fibrous capsule surrounding human-sized implanted devices using diffusion tensor imaging (DTI). In this study we analyse the fibrous capsule surrounding two unique macroencapsulation devices that have been implanted in a porcine model for 21 days. DTI is used for 3D visualisation of the microstructural organisation and validated using the standard means of fibrous capsule investigation; histological analysis and qualitative micro computed tomography (microCT) and scanning electron microscopy (SEM) imaging. DTI demonstrated the ability to distinguish microstructural differences in the fibrous capsules surrounding two macroencapsulation devices made from different materials and with different surface topographies. DTI-derived metrics yielded insight into the microstructural organisation of both capsules which was corroborated by microCT, SEM and histology. The non-invasive characterisation of the integration of implants in the body has the potential to positively influence analysis methods in pre-clinical studies and accelerate the clinical translation of novel implantable devices.

Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform.

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 Bone Biomarker Response to an Acute Bout of Exercise: A Systematic Review with Meta-Analysis.

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 response to cycling (ES0.5 0.65, 95% CrI 0.20-0.99), with greater durations and more work leading to larger CTX-1 increases. CTX-1 response peaked within 15 min and 2 h after the exercise bout. Other exercise types did not influence CTX-1. Changes to all bone formation markers were very small and transient, with the very small increases returning to baseline within 15 min of exercise cessation. No major trends for bone formation markers were identified across any of the moderating categories investigated. Certainty of evidence in most outcomes was deemed to be low or very low. CONCLUSION: The large influence of an acute bout of prolonged cycling on the bone resorption marker CTX-1, alongside the lack of a response of any biomarker to resistance or high-impact exercise types, indicate that these biomarkers may be more useful at investigating potentially osteolytic aspects of exercise, and raises questions about their suitability to investigate the osteogenic potential of different exercise types, at least in the short term and in response to a single exercise bout. Certainty in all outcomes was low or very low, due to factors including risk of bias, lack of non-exercise controls, inconsistency, imprecision and small-study effects. PROTOCOL REGISTRATION AND PUBLICATION: This investigation was prospectively registered on the Open Science Framework Registry ( https://osf.io/6f8dz ) and the full protocol underwent peer review prior to conducting the investigation.

Design and Verification of a Novel Perfusion Bioreactor to Evaluate the Performance of a Self-Expanding Stent for Peripheral Artery Applications.

Endovascular stenting presents a promising approach to treat peripheral artery stenosis. However, a significant proportion of patients require secondary interventions due to complications such as in-stent restenosis and late stent thrombosis. Clinical failure of stents is not only attributed to patient factors but also on endothelial cell (EC) injury response, stent deployment techniques, and stent design. Three-dimensional in vitro bioreactor systems provide a valuable testbed for endovascular device assessment in a controlled environment replicating hemodynamic flow conditions found in vivo. To date, very few studies have verified the design of bioreactors based on applied flow conditions and their impact on wall shear stress, which plays a key role in the development of vascular pathologies. In this study, we develop a computationally informed bioreactor capable of capturing responses of human umbilical vein endothelial cells seeded on silicone tubes subjected to hemodynamic flow conditions and deployment of a self-expanding nitinol stents. Verification of bioreactor design through computational fluid dynamics analysis confirmed the application of pulsatile flow with minimum oscillations. EC responses based on morphology, nitric oxide (NO) release, metabolic activity, and cell count on day 1 and day 4 verified the presence of hemodynamic flow conditions. For the first time, it is also demonstrated that the designed bioreactor is capable of capturing EC responses to stent deployment beyond a 24-hour period with this testbed. A temporal investigation of EC responses to stent implantation from day 1 to day 4 showed significantly lower metabolic activity, EC proliferation, no significant changes to NO levels and EC's aligning locally to edges of stent struts, and random orientation in between the struts. These EC responses were indicative of stent-induced disturbances to local hemodynamics and sustained EC injury response contributing to neointimal growth and development of in-stent restenosis. This study presents a novel computationally informed 3D in vitro testbed to evaluate stent performance in presence of hemodynamic flow conditions found in native peripheral arteries and could help to bridge the gap between the current capabilities of 2D in vitro cell culture models and expensive pre-clinical in vivo models.

Manufacturing, characterization, and degradation of a poly(lactic acid) warp-knitted spacer fabric scaffold as a candidate for tissue engineering applications.

Three-dimensional bioabsorbable textiles represent a novel technology for the manufacturing of tissue engineering scaffolds. In the present study, 3D bioabsorbable poly(lactic acid) (PLA) spacer fabric scaffolds are fabricated by warp-knitting and their potential for tissue engineering is explored in vitro. Changes in physical properties and mechanical performance with different heat setting treatments are assessed. To characterize the microenvironment experienced by cells in the scaffolds, yarn properties are investigated prior to, and during, hydrolytic degradation. The differences in yarn morphology, thermal properties, infrared spectra, and mechanical properties are investigated and monitored during temperature accelerated in vitro degradation tests in phosphate buffered saline (PBS) solution at 58 °C and pH 7.4 for 55 days. Yarn and textile cytocompatibility are tested to assess the effect of materials employed, manufacturing conditions, post processing and sterilization on cell viability, together with the cytocompatibility of the textile degradation products. Results show that the heat setting process can be used to modify scaffold properties, such as thickness, porosity, pore size and stiffness within the range useful for tissue regeneration. Scaffold degradation rate in physiological conditions is estimated by comparing yarn degradation data with PLA degradation data from literature. This will potentially allow the prediction of scaffold mechanical stability in the long term and thus its suitability for the remodelling of different tissues. Mouse calvaria preosteoblast MC3T3-E1 cells attachment and proliferation are observed on the scaffold over 12 days of in vitro culture by 4',6-diamidino-2-phenylindole (DAPI) fluorescent staining and DNA quantification. The present work shows the potential of spacer fabric scaffolds as a versatile and scalable scaffold fabrication technique, having the ability to create a microenvironment with appropriate physical, mechanical, and degradation properties for 3D tissue engineering. The high control and tunability of spacer fabric properties makes it a promising candidate for the regeneration of different tissues in patient-specific applications.

Nutritional recommendations for patients undergoing prolonged glucocorticoid therapy.

Glucocorticoid (GC) therapy is a common treatment used in rheumatic and autoimmune diseases, owing to its anti-inflammatory and immunosuppressive effects. However, GC therapy can also induce a number of adverse effects, including muscle and bone loss, hypertension, metabolic perturbations and increased visceral adiposity. We review available evidence in this area and provide nutritional recommendations that might ameliorate these adverse effects. Briefly, optimizing calcium, vitamin D, sodium and protein intake and increasing consumption of unprocessed and minimally processed foods, while decreasing the consumption of ultra-processed foods, might counteract some of the specific challenges faced by these patients. Importantly, we identify a dearth of empirical data on how nutritional intervention might impact health-related outcomes in this population. Further research is required to investigate the clinical and therapeutic efficacy of these theory-based recommendations.

Acute and post-acute COVID-19 presentations in athletes: a systematic review and meta-analysis.

OBJECTIVE: To describe acute/postacute COVID-19 presentations in athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The search was conducted in four databases (MEDLINE, EMBASE, SCOPUS, SPORTDiscus) and restricted to studies published from 2019 to 6 January 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were required to (1) include professional, amateur or collegiate/university athletes with COVID-19; (2) present data on acute/postacute COVID-19 symptoms and (3) have an observational design. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. RESULTS: 43 studies with 11 518 athletes were included. For acute presentation, the pooled event rates for asymptomatic and severe COVID-19 were 25.5% (95% CI: 21.1% to 30.5%) and 1.3% (95% CI: 0.7% to 2.3%), respectively. For postacute presentations, the pooled estimate of persistent symptoms was 8.3% (95% CI: 3.8% to 17.0%). Pooled estimate for myocardial involvement was 5.0% (95% CI: 2.5% to 9.8%) in athletes undergoing any cardiac testing, and 2.5% (95% CI: 1.0% to 5.8%) in athletes undergoing MRI, although clinical symptoms were not characterised. None of the studies with a control group (eg, non-infected athletes) could confirm a causal relationship between COVID-19 and myocardial involvement. CONCLUSION: This broad characterisation of COVID-19 presentations in athletes indicates that ~94% exhibited mild or no acute symptoms. The available evidence did not confirm a causal relationship between COVID-19 and myocardial involvement. A small proportion of athletes experienced persistent symptoms while recovering from infection, which were mostly mild in nature, but could affect return-to-play decisions and timing.

Medical devices, smart drug delivery, wearables and technology for the treatment of Diabetes Mellitus.

Diabetes mellitus refers to a group of metabolic disorders which affect how the body uses glucose impacting approximately 9% of the population worldwide. This review covers the most recent technological advances envisioned to control and/or reverse Type 1 diabetes mellitus (T1DM), many of which will also prove effective in treating the other forms of diabetes mellitus. Current standard therapy for T1DM involves multiple daily glucose measurements and insulin injections. Advances in glucose monitors, hormone delivery systems, and control algorithms generate more autonomous and personalised treatments through hybrid and fully automated closed-loop systems, which significantly reduce hypo- and hyperglycaemic episodes and their subsequent complications. Bi-hormonal systems that co-deliver glucagon or amylin with insulin aim to reduce hypoglycaemic events or increase time spent in target glycaemic range, respectively. Stimuli responsive materials for the controlled delivery of insulin or glucagon are a promising alternative to glucose monitors and insulin pumps. By their self-regulated mechanism, these "smart" drugs modulate their potency, pharmacokinetics and dosing depending on patients' glucose levels. Islet transplantation is a potential cure for T1DM as it restores endogenous insulin and glucagon production, but its use is not yet widespread due to limited islet sources and risks of chronic immunosuppression. New encapsulation strategies that promote angiogenesis and oxygen delivery while protecting islets from recipients' immune response may overcome current limiting factors.