Correction: Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0283394.].

Allied health professionals knowledge and clinical practice in telehealth exercise behavioural change for multiple sclerosis.

BACKGROUND: The growing importance of telehealth in multiple sclerosis (MS) necessitates an understanding of current practices and training needs of health professionals. We aimed to evaluate the knowledge, preparedness, and training preferences of Australian allied health professionals (AHPs) in telehealth exercise therapy and exercise behavioural change for MS patients to inform the development of educational training. METHODS: An online survey was completed by 58 Australian AHPs, including 34 physiotherapists, 14 exercise physiologists, and 10 occupational therapists, focusing on their current practices, preparedness, and training preferences in telehealth exercise and behavioural change for MS. The survey included multiple-choice, Likert scale, and free-text response questions. Data were analysed using binary and multinomial logistic regressions. RESULTS: Not all AHPs were aware of MS exercise guidelines (67% awareness), with exercise physiologists showing the highest familiarity. There was a significant understanding of the difference between physical activity and exercise, though definitions often lacked clarity. Most AHPs (91%) employed behavioural change strategies in their practice, especially goal-setting (95%), identifying facilitators (67%), and reinforcing progress (66%). While most (72%) felt prepared in promoting exercise to MS clients, there were differences in confidence levels concerning the prescription, modification, and teaching of telehealth exercise programs, with occupational therapists have significant less confidence in those domains compared to other AHPs. Most AHPs expressed interest in additional training, with a preference for online workshops focusing on exercise prescription for MS, behaviour change, and telehealth delivery methods. CONCLUSION: In our Australian AHP sample we identified that a quarter to a third of AHPs in MS care may not be confident or prepared to promote telehealth exercise and behavioural change to people with MS. Moreover, the findings highlight some disparity in knowledge and confidence levels amongst different AHPs concerning exercise therapy for MS, indicating the need for tailored multidisciplinary training programs. Such programs should address profession-specific educational gaps and training preferences, ensuring effective and safe telehealth exercise prescription in MS care.

Developing type 1 diabetes resources: a qualitative study to identify resources needed to upskill and support community sport coaches.

Introduction: Community sport coaches in Western Australia lack an understanding, the confidence, and knowledge in supporting young people with Type 1 diabetes (T1D). This study aims to identify what T1D educational resources are required to upskill coaches in Western Australia. Methods: Semi-structured online interviews were conducted with i) young people living with T1D, ii) parents of young people living with T1D and iii) community sport coaches. The questions explored i) past experiences of T1D management in community sport ii) the T1D information coaches should be expected to know about and iii) the format of resources to be developed. Thematic analysis of interview transcripts was performed, and the themes identified were used to guide resource development. Results: Thirty-two participants (16 young people living with T1D, 8 parents, 8 coaches) were interviewed. From the interviews, young people wanted coaches to have a better understanding of what T1D is and the effect it has on their sporting performance, parents wanted a resource that explains T1D to coaches, and sports coaches wanted to know the actions to best support a player living with T1D. All groups identified that signs and symptoms of hypoglycaemia and hyperglycaemia needed to be a key component of the resource. Sports coaches wanted a resource that is simple, quick to read and available in a variety of different formats. Conclusion: The interviews resulted in valuable information gained from all groups and have reinforced the need for the development of specific resources to increase community knowledge and provide support for players with T1D, parents and sport coaches.

The intensity of a resistance exercise session can be quantified by the work rate of exercise.

PURPOSE: Athletes regularly perform resistance training, yet it is unknown how best to monitor its intensity. This study compared different resistance exercise intensity metrics to determine their sensitivity to manipulating work rate (via altering inter-set rest and load). METHODS: Following baseline testing for 10- and 3-repetition maximum (RM; squat and bench press), fourteen trained participants completed four volume-matched protocols in a randomised order: 3x10 with 85% 10RM, 60 s rest (3x1060s); 3x10 with 85% 10RM, 180 s (3x10180s); 8x3 with 85% 3RM, 120 s (8x3120s); 8x3 with 85% 3RM, 300 s (8x3300s). Internal intensity was quantified via rate of oxygen consumption ([Formula: see text]), heart rate, blood lactate concentration, and rating of perceived exertion (RPE). External intensity was assessed via previously developed "Training-Intensity" (TI) and "Intensity-Index" (II) metrics, and from exercise work rate (expressed as kg∙min-1 and joules∙min-1). RESULTS: Internal intensity and work-rate metrics were highest for 3x1060s, followed by 3x10180s, 8x3120s and 8x3300s (p≤0.027). TI and II were higher for 8x3 than 3x10 protocols (p<0.001), but not different within these configurations. Internal intensity measures were more strongly correlated with work rate (r = 0.37-0.96) than TI and II (r = -0.42-0.33) metrics. CONCLUSIONS: Work rate corroborated objective internal intensity metrics during resistance exercise, with the highest work rate session (3x1060s) also eliciting greater RPE scores than other protocols. In contrast, the TI and II did not agree with other intensity measures, likely because they do not consider rest periods. Practitioners can plan for the physiological and perceptual demands of resistance training by estimating work rate.

Physical Activity Management for Youth With Type 1 Diabetes: Supporting Active and Inactive Children.

Regular physical activity and exercise are important for youth and essential components of a healthy lifestyle. For youth with type 1 diabetes, regular physical activity can promote cardiovascular fitness, bone health, insulin sensitivity, and glucose management. However, the number of youth with type 1 diabetes who regularly meet minimum physical activity guidelines is low, and many encounter barriers to regular physical activity. Additionally, some health care professionals (HCPs) may be unsure how to approach the topic of exercise with youth and families in a busy clinic setting. This article provides an overview of current physical activity research in youth with type 1 diabetes, a basic description of exercise physiology in type 1 diabetes, and practical strategies for HCPs to conduct effective and individualized exercise consultations for youth with type 1 diabetes.

Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. METHODS: This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. RESULTS: 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. CONCLUSIONS: Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.

Comparative Effects of Contrast Training and Progressive Resistance Training on Strength and Power-Related Measures in Subelite Australian Rules Football Players.

ABSTRACT: Schneiker, KT, Fyfe, JJ, Teo, SYM, and Bishop, DJ. Comparative effects of contrast training and progressive resistance training on strength and power-related measures in subelite Australian Rules Football players. J Strength Cond Res 37(7): 1440-1448, 2023-The aim of this study was to determine whether contrast training (CST) elicits superior strength-related and power-related outcomes compared with progressive resistance training (PRT). Sixteen male amateur Australian Rules Football players (age, 19 ± 2 years; height, 183 ± 8 cm; body mass, 78.5 ± 8.8 kg; mean ± SD ) completed 2 weeks of standardized resistance training followed by 6 weeks of either CST or PRT. Both CST and PRT improved absolute (20 and 19%) and relative (19 and 16%) 1 repetition maximum (1RM) half squat strength, absolute (8.7 and 8.7%, respectively) and relative (8.2 and 6.1%, respectively) squat jump peak power, and 20-m sprint performance (5.4 and 4.7%, respectively), including both 0 to 5 m (15 and 14%, respectively) and 0 to 10 m (8.6 and 7.5%, respectively) splits. Vertical jump height only improved with CST (6.5%), whereas body mass only increased after PRT (1.9%). There were negative associations between the baseline power-to-strength ratio (PSR) and improvements in both absolute ( r2 = 0.51 and 0.72 for CST and PRT, respectively) and relative ( r2 = 0.65 and 0.60 for CST and PRT, respectively) squat jump peak power. There were no statistically significant (i.e., p ≥ 0.05) between-group differences for all training outcomes. Both interventions improved various strength-related and power-related measures, although a lower baseline PSR was associated with greater improvements in power-related outcomes after both interventions. Contrast training is therefore an effective alternative to progressive resistance training during relatively short-term (6-8 weeks) training periods in young, male, team-sport athletes, particularly in those with a lower power-to-strength ratio.

Load-velocity relationships and predicted maximal strength: A systematic review of the validity and reliability of current methods.

Maximal strength can be predicted from the load-velocity relationship (LVR), although it is important to understand methodological approaches which ensure the validity and reliability of these strength predictions. The aim of this systematic review was to determine factors which influence the validity of maximal strength predictions from the LVR, and secondarily to highlight the effects of these factors on the reliability of predictions. A search strategy was developed and implemented in PubMed, Scopus, Web of Science and CINAHL databases. Rayyan software was used to screen titles, abstracts, and full texts to determine their inclusion/eligibility. Eligible studies compared direct assessments of one-repetition maximum (1RM) with predictions performed using the LVR and reported prediction validity. Validity was extracted and represented graphically via effect size forest plots. Twenty-five eligible studies were included and comprised of a total of 842 participants, three different 1RM prediction methods, 16 different exercises, and 12 different velocity monitoring devices. Four primary factors appear relevant to the efficacy of predicting 1RM: the number of loads used, the exercise examined, the velocity metric used, and the velocity monitoring device. Additionally, the specific loads, provision of velocity feedback, use of lifting straps and regression model used may require further consideration.

Examining the effects of calorie restriction on testosterone concentrations in men: a systematic review and meta-analysis.

CONTEXT: Testosterone concentrations decline with age, and lower testosterone concentrations are associated with several morbidities, including sexual dysfunction, obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. OBJECTIVE: Because dietary habits play a critical role in weight regulation and T2DM management, the aim of this systematic review and meta-analysis was to summarize and critically evaluate the evidence from randomized controlled trials to determine the effects of calorie restriction (CR) on testosterone concentrations in men. DATA SOURCES: A literature search was conducted across 4 databases, from their inception until March 2020. DATA EXTRACTION: The screening and data extraction were completed by 2 authors independently, and in a blinded manner, according to a priori inclusion and exclusion criteria. DATA ANALYSIS: Of the 4198 studies identified from the initial search, 7 randomized controlled trials were included for data extraction. Significant increases in total testosterone concentrations were reported in 3 of 4 studies in which CR was examined with overweight or obese men, compared with the control groups. Significant decreases in total testosterone concentrations were reported in 2 of 3 studies in which the effects of CR were examined with normal-weight, healthy men, compared with the control groups. In all 4 studies that examined the effect of CR on sex hormone-binding globulin concentrations, the intervention significantly increased sex hormone-binding globulin concentrations compared with that of the control groups irrespective of body composition. CONCLUSION: This systematic review and meta-analysis provide some evidence that CR affects testosterone concentrations in men and this effect depends on their body mass index. PROSPERO registration no. CRD42020173102.

Effects of diurnal exercise timing on appetite, energy intake and body composition: A parallel randomized trial.

OBJECTIVE: To determine the effect of diurnal exercise timing on appetite, energy intake and body composition in individuals with overweight or obesity. METHODS: Forty sedentary, individuals with overweight or obesity (17 males, 23 females; age: 51 ± 13 years; BMI: 30.9 ± 4.2 kg/m2) were randomly allocated to complete a 12-week supervised multi-modal exercise training program performed either in the morning (amEX) or evening (pmEX). Outcome measures included appetite in response to a standardised test meal, daily energy intake (EI), body weight and body composition. Measures of dietary behaviour were assessed at baseline and post-intervention, along with habitual physical activity, sleep quality and sleep quantity. Significance was set at p ≤ .05 and Hedge's g effect sizes were calculated. RESULTS: Regardless of timing, exercise training increased perceived fullness (AUC; g = 0.82-1.67; both p < .01), decreased daily EI (g = 0.73-0.93; both p < .01) and body-fat (g = 0.29-0.32; both p <. 01). The timing of exercise did not change the daily EI or body-fat response to training (all p ≥ .27), however, perceived fullness increased in the amEX group (p ≤ .01). DISINHIBITION: (g = 0.35-1.95; p ≤ .01) and Hunger (g = 0.05-0.4; p = .02) behaviours decreased following exercise training, with Disinhibition demonstrating greater improvements in the pmEX group (p = .01). Objective and subjective sleep quantity increased with training (all p ≤ .01), but sleep quality was not reported to change. CONCLUSIONS: Multi-modal exercise training improved body composition and some appetite outcomes, although changes were inconsistent and largely independent of exercise-timing. In the absence of dietary manipulation, the effect of diurnal exercise timing on appetite and body composition appear trivial compared to the overall benefits of exercise participation.

Empower to connect and connect to empower: experience in using a humanistic approach to improve patients' access to, and experience of, care in isolation wards during the COVID-19 outbreak in Singapore.

Patients admitted to the isolation ward during the COVID-19 outbreak face multiple psychosocial stressors including the disruptive experience of being in quarantine, anxiety over contracting a newly emerging infectious disease and limited access to their healthcare team. This quality improvement project aims to leverage on technology to improve patients' access to, and experience of, care while in isolation.Patients admitted to two isolation wards in Singapore General Hospital (SGH) between 28 February and 19 March 2020 were each provided an iPad loaded with the MyCare application (app), curated materials and mobile games. During this period, 83 of them accessed the device and the app. MyCare app is an app developed by the nursing team in SGH as part of an existing interprofessional collaboration to help patients navigate their care during their inpatient stay. In response to COVID-19, MyCare app was supplemented with materials to address affected patients' informational and psychosocial needs. These materials included an information sheet on COVID-19, interviews with previous severe acute respiratory syndrome survivors, psychosocial support materials, and uplifting literature, illustrated storybooks and artwork.This paper describes the process of planning for, and executing, the intervention and reports the initial results of its effect. Initial feedback indicated a positive response to the intervention. 9 out of 10 respondents (90%) rated their hospital experience with a maximum of five stars and all 10 respondents (100%) rated the psychosocial support materials with five stars. Doctors managing the patients also observed a reduction in the number of commonly asked questions following the deployment of the iPad.This quality improvement project is ongoing with plans for further research to determine how to better support the psychosocial needs of patients in isolation during a novel disease outbreak. This report is written based on the Standards for Quality Improvement Reporting Excellence guidelines.

Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review.

Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.

An Intense, But Ecologically Valid, Resistance Exercise Session Does Not Alter Growth Factors Associated With Cognitive Health.

The purpose of this investigation was to assess the acute changes in growth factors associated with cognitive health following two ecologically valid, intense resistance exercise sessions. Twenty-nine late-middle-aged adults performed one session of either (a) moderate-load resistance exercise or (b) high-load resistance exercise. Venous blood was collected prior to warm-up, immediately following exercise and 30 min following exercise. Serum was analyzed for brain-derived neurotrophic factor, insulin-like growth factor 1, and vascular endothelial growth factor. Session intensity was determined by blood lactate concentration and session rating of perceived exertion. Postexercise blood lactate was greater following moderate-load when compared with high-load resistance exercise. Subjective session intensity was rated higher by the session rating of perceived exertion following moderate-load when compared with high-load resistance exercise. No differences were observed in serum growth factor levels between groups. Ecologically valid and intense moderate-load or high-load exercise methods do not alter serum growth factor levels in late-middle-aged adults.

The Effect of Exercise Timing on Glycemic Control: A Randomized Clinical Trial.

Despite the acknowledgment of exercise as a cornerstone in the management of type 2 diabetes (T2D), the importance of exercise timing has only recently been considered. PURPOSE: This study sought to determine the effect of diurnal exercise timing on glycemic control in individuals enrolled in a 12-wk supervised multimodal exercise training program. A secondary aim was to determine the effect of diurnal exercise timing on the circadian rhythm of wrist skin temperature. METHODS: Forty sedentary, overweight adults (mean ± SD, age = 51 ± 13 yr; body mass index = 30.9 ± 4.2 kg·m; women, n = 23) with and without (n = 20) T2D diagnosis were randomly allocated to either a morning (amEX) or an evening (pmEX) exercise training group. The supervised 12-wk (3 d·wk) program, comprised 30 min of moderate-intensity walking and 4 resistance-based exercises (3 sets, 12-18 repetitions each). Glycemic outcomes (glycated hemoglobin, fasting glucose, postprandial glucose) and wrist skin temperature were assessed at baseline and postintervention. RESULTS: Exercise training improved (main effect of time, all P < 0.01) all glycemic outcomes; however, this was independent of allocation to either the amEX (Hedge's g, 0.23-0.90) or the pmEX (Hedge's g, 0.16-0.90) group. Accordingly, the adopted exercise training program did not alter the circadian rhythm of skin temperature. When only T2D individuals were compared, amEX demonstrated greater effects (all Hedge's g) on glycated hemoglobin (amEX, 0.57; pmEX, 0.32), fasting glucose (amEX, 0.91; pmEX, 0.53), and postprandial glucose (amEX, 1.12; pmEX, 0.71) but was not statistically different. CONCLUSIONS: Twelve weeks of multimodal exercise training improved glycemic control and postprandial glycemic responses in overweight non-T2D and T2D individuals. However, no distinct glycemic benefits or alterations in circadian rhythm were associated with morning versus evening exercise, when performed three times per week in this cohort.

Twelve weeks of resistance training does not influence peripheral levels of neurotrophic growth factors or homocysteine in healthy adults: a randomized-controlled trial.

INTRODUCTION: There is growing evidence for a preventative effect of resistance training on cognitive decline through physiological mechanisms; yet, the effect of resistance training on resting growth factors and homocysteine levels is incompletely understood. This study aimed to investigate the effect of intense resistance training, for 12 weeks, on changes in peripheral growth factors and homocysteine in late middle-aged adults. METHODS: 45 healthy adults were enrolled into the single-site parallel groups' randomized-controlled trial conducted at the Department of Exercise Science, Strength and Conditioning Laboratory, Murdoch University. Participants were allocated to the following conditions: (1) high-load resistance training (n = 14), or (2) moderate-load resistance training (n = 15) twice per week for 12 weeks; or (3) non-exercising control group (n = 16). Data were collected from September 2016 to December 2017. Fasted blood samples were collected at baseline and within 7 days of trial completion for the analysis of resting serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1, vascular endothelial growth factor, and plasma homocysteine levels. RESULTS: No differences in baseline to post-intervention change in serum growth factors or plasma homocysteine levels were observed between groups. A medium effect was calculated for BDNF change within the high-load condition alone (+ 12.9%, g = 0.54). CONCLUSIONS: High-load or moderate-load resistance training twice per week for 12 weeks has no effect on peripheral growth factors or homocysteine in healthy late middle-aged adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616000690459.

Resistance training enhances delayed memory in healthy middle-aged and older adults: A randomised controlled trial.

OBJECTIVES: High-intensity exercise is a potential therapeutic tool to postpone or prevent the onset of cognitive decline. However, there is a lack of sufficient evidence regarding the longitudinal effects of structured resistance training on cognitive function in healthy adults. The purpose of this study was to investigate the effect of two ecologically valid, intense 12-week resistance training programs on cognitive function in late middle-aged adults. DESIGN: Single-site parallel randomised controlled trial at the Department of Exercise Science strength and conditioning laboratory. Groups allocated by minimisation randomisation. METHODS: Forty-five healthy adults (age range=41-69 years) were enrolled and randomised into (A) high-load, long rest resistance training (n=14), or (B) moderate-load, short rest resistance training (n=15) twice per week for 12 weeks, or a non-exercising control (n=16). Follow-up within seven days. Data were collected September 2016-December 2017. Cognitive function assessed using the CogState computerised battery. Assessors were blinded to participant group allocation. Secondary outcomes were maximal muscle strength and body composition. RESULTS: Forty-four participants were analysed in 2018. Delayed verbal memory performance was improved (p=0.02) in resistance training groups (g=0.67-0.79) when compared to the control group, with no differences between training groups. Likewise, increases in maximal muscle strength were observed (p<0.01) in resistance training groups when compared to the control group, with no differences between training groups. No differences in body composition were observed. There were no adverse events or side-effects of the intervention. CONCLUSIONS: 12 weeks of intense resistance training improves delayed verbal memory irrespective of training design (i.e., high-load vs. moderate-load). TRIAL REGISTRATION: This study is registered at www.anzctr.org.au ACTRN12616000690459.

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse.

The two sides of the nervous system coordinate and integrate information via commissural neurons, which project axons across the midline. Commissural neurons in the spinal cord are a highly heterogeneous population of cells with respect to their birthplace, final cell body position, axonal trajectory, and neurotransmitter phenotype. Although commissural axon guidance during development has been studied in great detail, neither the developmental origins nor the mature phenotypes of commissural neurons have been characterized comprehensively, largely due to lack of selective genetic access to these neurons. Here, we generated mice expressing Cre recombinase from the Robo3 locus specifically in commissural neurons. We used Robo3 Cre mice to characterize the transcriptome and various origins of developing commissural neurons, revealing new details about their extensive heterogeneity in molecular makeup and developmental lineage. Further, we followed the fate of commissural neurons into adulthood, thereby elucidating their settling positions and molecular diversity and providing evidence for possible functions in various spinal cord circuits. Our studies establish an important genetic entry point for further analyses of commissural neuron development, connectivity, and function.

Long-Range Guidance of Spinal Commissural Axons by Netrin1 and Sonic Hedgehog from Midline Floor Plate Cells.

An important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a distance in vitro. netrin1 is also produced by ventricular zone (VZ) progenitors along the axons' route (VZ-netrin1). Recent studies using region-specific netrin1 deletion suggested that FP-netrin1 is dispensable and VZ-netrin1 sufficient for netrin guidance activity in vivo. We show that removing FP-netrin1 actually causes guidance defects in spinal cord consistent with long-range action (i.e., over hundreds of micrometers), and double mutant analysis supports that FP-netrin1 and Shh collaborate to attract at long range. We further provide evidence that netrin1 may guide via chemotaxis or haptotaxis. These results support the model that netrin1 signals at both short and long range to guide commissural axons in spinal cord.

Exercise Timing in Type 2 Diabetes Mellitus: A Systematic Review.

PURPOSE: The timing of exercise relative to meal consumption has recently been identified as potentially moderating the effectiveness of exercise on glycemic responses in type 2 diabetes mellitus (T2DM). The aim of this study was to systematically review the literature related to exercise timing, relative to meal consumption, and glycemic control in individuals with T2DM. METHODS: Systematic searches in PubMed, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov Registry databases were performed to identify articles published in English from inception to October 2017. Two authors independently extracted data and evaluated the quality of studies using the Cochrane Collaboration Data Collection Form and the Cochrane Collaboration Risk of Bias Assessment Tool, respectively. A qualitative synthesis was performed on the included studies, and results summarized in tables. RESULTS: Nineteen randomized controlled trials with a total of 346 participants were included. Improvements in glycemia (glucose concentrations and glucose area under the curve) and insulin area under the curve appeared more consistent when exercise was performed during the postmeal period as compared with the premeal period; however, this observation was largely based on indirect comparisons between studies. CONCLUSIONS: There is some evidence from randomized controlled trials that exercise performed 30 min after meal consumption may convey greater improvements in glycemic control for individuals with T2DM. However, there are only two studies that have directly assessed the role of exercise timing on glycemic management, and adopted methodologies are heterogeneous. Future low-risk trials in this field are warranted.