GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates.

INTRODUCTION: Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the ß-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic. AREAS COVERED: This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D. EXPERT OPINION: GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Longitudinal affective response to high-intensity interval training and moderate-intensity continuous training in overweight women with polycystic ovary syndrome: A randomised trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) experience general and PCOS-specific barriers that limit their engagement with exercise and contribute to high attrition from exercise programs, hindering the potential benefits of exercise to address their increased cardio-metabolic risk. A positive remembered affective response can predict future intentions and adherence to exercise prescription. OBJECTIVES: To compare the longitudinal changes in remembered affect to high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in women with PCOS and to determine whether longitudinal changes in remembered affect are correlated with changes in fitness, body mass index, adherence and exercise enjoyment. METHODS: Physically inactive, overweight women with PCOS were randomly assigned to 12 weeks of either HIIT (n = 15) or MICT (n = 14) (3 sessions per week). Remembered affective valence (Feeling Scale) was collected after each exercise session. Cardiorespiratory fitness (VO2peak) was assessed at baseline and post-intervention. Exercise enjoyment was assessed post-intervention. RESULTS: The longitudinal changes in the remembered affect were more positive in the HIIT group compared to MICT (ß = 0.017, p = 0.047). HIIT was also considered more enjoyable than MICT (p = 0.002). Adherence was high in both groups (>90%). We found a moderate correlation with longitudinal changes between the remembered affect and change in fitness (rs = 0.398) and exercise enjoyment (rs = 0.376) using the combined group, however, these were not statistically significant (p = 0.054 and p = 0.064, respectively). CONCLUSIONS: HIIT demonstrated a more positive longitudinal remembered affective response and greater exercise enjoyment compared to MICT in overweight women with PCOS.

Prevalence of diagnosable depression in patients awaiting orthopaedic specialist consultation: a cross-sectional analysis.

BACKGROUND: Musculoskeletal conditions, including osteoarthritis (OA), are a leading cause of disability and chronic pain, and are associated with high rates of comorbid depression. However, signs of depression are often masked by pain. The aim of this study was to determine the prevalence and severity of depression and pain in individuals awaiting specialist orthopaedic consultation. A secondary objective was to determine the relationship between pain and depression, irrespective of demographic factors and clinical diagnosis. METHODS: Cross-sectional analysis of individuals awaiting orthopaedic consultation at a public hospital in Melbourne, Australia. Relevant data were extracted from medical records and questionnaires. Descriptive statistics were used to summarise participant characteristics. The patient health questionnaire (PHQ-9) was used to assess depression and a numerical rating scale (NRS) was used to assess pain severity. Multiple linear regression analyses were used to establish the relationship between pain and depression. RESULTS: Nine hundred and eighty-six adults (mean ± standard deviation, age = 54.1 ± 15.7 years, 53.2% women) participated in the study. OA was present in 56% of the population and 34% of the entire population had moderate depression or greater, 19% of which met the criteria for major depressive disorder. Moderate-to-severe pain was present in 79% of individuals with OA and 55% of individuals with other musculoskeletal complaints. Pain was significantly associated with depression scores (ß = 0.84, adjusted R2 = 0.13, P < 0.001), and this relationship remained significant after accounting for gender, age, education and employment status, OA status, number of joints affected and waiting time (ß = 0.91, adjusted R2 = 0.19, P < 0.001). CONCLUSIONS: Depression affects one-third of individuals on an orthopaedic waitlist. A strong link between pain and depression in patients awaiting specialist orthopaedic consultation exists, indicating a need for an integrated approach in addressing pain management and depression to manage this complex and comorbid presentation.

Efficacy of high-intensity interval training for improving mental health and health-related quality of life in women with polycystic ovary syndrome.

Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% HRpeak, N = 15) or HIIT (> 90% HRpeak, N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ - 1.7, P = 0.005), anxiety (Δ - 3.4, P < 0.001) and stress (Δ - 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ - 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (ß = - 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings.Trial registration number: ACTRN12615000242527.

The engagement of tertiary students with an online mental health intervention during the coronavirus disease 2019 pandemic: A feasibility study.

Background: We discuss the feasibility of a brief, online mental health promotion programme for tertiary students and establish recommendations for future programmes. Methods: The programme 'Student Elevenses' was delivered at a tertiary education institution. 'Student Elevenses' aimed to promote student wellbeing during the coronavirus disease 2019 crisis, comprised of 10-15-min daily online micro-interventions targeting six lifestyle areas for wellbeing, and was delivered via video conference. Upon programme completion, all students were invited to complete barriers to engagement survey, irrespective of whether they had attended or heard of the programme. Descriptive statistics were calculated for demographics, as well as feasibility and acceptability outcomes including recruitment rates, attendance rates and reported barriers to attendance. Open-ended questions were coded for themes. Results: Less than 1% of those who consented to participate actually attended the programme, with attendance ranging from 2 to 17 participants. Participants were predominantly female (68%), domestic students (81%) and had a mean age of 29.5 years. The barriers students reported included fixed time, online format, a belief programme would not be helpful, preference for existing supports and perceived impacts of coronavirus disease 2019. Students recommended embedding support within policies/teaching, offering a range of supports and involving students in design. Conclusion: Barriers to mental health promotion via telehealth should be considered to promote accessibility and acceptability for tertiary students. Future programmes should consider reaching students through mandatory activities (e.g. lectures, tutorials) and should include student consultation and co-design to support the development of programmes that meet student needs and preferences.

Within-Person Associations Between Physical and Social Contexts With Movement Behavior Compositions in Adolescents: An Ecological Momentary Assessment Study Using a Compositional Data Analysis Approach.

BACKGROUND: External contexts, including the social and physical contexts, are independent predictors of momentary physical activity and sedentary behaviors. However, no studies to date have examined how external contexts are related to overall momentary movement behavior compositions using compositional data analysis. Therefore, this study aimed to determine differences in momentary movement behavior compositions between different social and physical contexts in adolescents. METHODS: Overall, 119 adolescents (mean age 14.7 y, SD = 1.44) provided details about their momentary physical and social contexts over 4 days using ecological momentary assessment. Sedentary behaviors, light-intensity physical activity, and moderate to vigorous physical activity were assessed using ActiGraph GT3X+ accelerometers. Compositional multivariate multilevel models were estimated to determine if movement behavior compositions differed between contexts. RESULTS: Participants engaged in significantly less sedentary behaviors when outdoors compared with indoors and replaced it with moderate to vigorous physical activity. Participants also engaged in significantly less sedentary behaviors when with friends or friends and family and replaced it with light-intensity physical activity. CONCLUSION: These results highlight the potential of targeting external contexts to increase physical activity and to reduce sedentary behavior in adolescents' daily lives. These factors could be targeted in mobile health and just-in-time adaptive interventions to improve young people's movement behavior compositions.

Transforming growth factor ß1 impairs the transcriptomic response to contraction in myotubes from women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterised by a hormonal imbalance affecting the reproductive and metabolic health of reproductive-aged women. Exercise is recommended as a first-line therapy for women with PCOS to improve their overall health; however, women with PCOS are resistant to the metabolic benefits of exercise training. Here, we aimed to gain insight into the mechanisms responsible for such resistance to exercise in PCOS. We employed an in vitro approach with electrical pulse stimulation (EPS) of cultured skeletal muscle cells to explore whether myotubes from women with PCOS have an altered gene expression signature in response to contraction. Following EPS, 4719 genes were differentially expressed (false discovery rate <0.05) in myotubes from women with PCOS compared to 173 in healthy women. Both groups included genes involved in skeletal muscle contraction. We also determined the effect of two transforming growth factor ß (TGFß) ligands that are elevated in plasma of women with PCOS, TGFß1 and anti-Müllerian hormone (AMH), alone and on the EPS-induced response. While AMH (30 ng/ml) had no effect, TGFß1 (5 ng/ml) induced the expression of extracellular matrix genes and impaired the exercise-like transcriptional signature in myotubes from women with and without PCOS in response to EPS by interfering with key processes related to muscle contraction, calcium transport and actin filament. Our findings suggest that while the fundamental gene expression responses of skeletal muscle to contraction is intact in PCOS, circulating factors like TGFß1 may be responsible for the impaired adaptation to exercise in women with PCOS. KEY POINTS: Gene expression responses to in vitro contraction (electrical pulse stimulation, EPS) are altered in myotubes from women with polycystic ovary syndrome (PCOS) compared to healthy controls, with an increased expression of genes related to pro-inflammatory pathways. Transforming growth factor ß1 (TGFß1) upregulates genes related to extracellular matrix remodelling and reduces the expression of contractile genes in myotubes, regardless of the donor's health status. TGFß1 alters the gene expression response to EPS, providing a possible mechanism for the impaired exercise adaptations in women with PCOS.

The acute affective response to physical activity in people with depression: A meta-analysis.

BACKGROUND: Little is known about the acute affective response to physical activity in people with depression, which may have implications for acute symptom management and may also be a mechanism that explains the antidepressant effects of physical activity. This study aimed to quantitatively synthesize existing research on the acute affective response to physical activity in people with depression. METHODS: Five online databases were searched to July 2021 to identify studies that examined pre-post changes in affective states following a bout of moderate-to-vigorous physical activity in people with depression. The affective response to physical activity was synthesized using a random-effects meta-analysis with a robust variance estimator. RESULTS: A total of 18 studies were included in the meta-analysis. Results showed that people with depression experienced a favourable affective response following an acute bout of physical activity (SMD = 0.585, 95% confidence interval = [0.456, 0.714], 95% prediction interval = [-0.079, 1.249]). Moderator analysis indicated this effect was consistent across different types of affective states, exercise conditions, and participant characteristics. Additionally, results were robust to changes in the study protocol and publication bias. LIMITATIONS: Only within-person pre-post changes in affective responses were examined. No comparisons were made with control conditions. CONCLUSION: Acute bouts of physical activity can significantly improve affective states in people with depression. Future research should examine the effect of physical activity on affective states in non-experimental settings and examine whether the affective response to physical activity is a predictor of the long-term antidepressant effects of physical activity interventions.

Digital self-management interventions for osteoarthritis: a systematic scoping review of intervention characteristics, adherence and attrition.

BACKGROUND: Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. METHODS: Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. RESULTS: Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates < 20%, with contact and support from researchers not appearing to influence adherence or attrition. CONCLUSIONS: Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence.

Maternal metabolic factors and the association with gestational diabetes: A systematic review and meta-analysis.

Gestational diabetes (GDM) is associated with several adverse outcomes for the mother and child. Higher levels of individual lipids are associated with risk of GDM and metabolic syndrome (MetS), a clustering of risk factors also increases risk for GDM. Metabolic factors can be modified by diet and lifestyle. This review comprehensively evaluates the association between MetS and its components, measured in early pregnancy, and risk for GDM. Databases (Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, and Cochrane Library) were searched from inception to 5 May 2021. Eligible studies included ≥1 metabolic factor (waist circumference, blood pressure, fasting plasma glucose (FPG), triglycerides, and high-density lipoprotein cholesterol), measured at <16 weeks' gestation. At least two authors independently screened potentially eligible studies. Heterogeneity was quantified using I2 . Data were pooled by random-effects models and expressed as odds ratio and 95% confidence intervals (CIs). Of 7213 articles identified, 40 unique articles were included in meta-analysis. In analyses adjusting for maternal age and body mass index, GDM was increased with increasing FPG (odds ratios [OR] 1.92; 95% CI 1.39-2.64, k = 7 studies) or having MetS (OR 2.52; 1.65, 3.84, k = 3). Women with overweight (OR 2.17; 95% CI 1.89, 2.50, k = 12) or obesity (OR 4.34; 95% CI 2.79-6.74, k = 9) also were at increased risk for GDM. Early pregnancy assessment of glucose or the MetS, offers a potential opportunity to detect and treat individual risk factors as an approach towards GDM prevention; weight loss for pregnant women with overweight or obesity is not recommended. Systematic review registration: PROSPERO CRD42020199225.

High-intensity training elicits greater improvements in cardio-metabolic and reproductive outcomes than moderate-intensity training in women with polycystic ovary syndrome: a randomized clinical trial.

STUDY QUESTION: Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. WHAT IS KNOWN ALREADY: Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. STUDY DESIGN, SIZE, DURATION: This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. MAIN RESULTS AND THE ROLE OF CHANCE: Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (ß = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (ß = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (ß = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. WIDER IMPLICATIONS OF THE FINDINGS: Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: ACTRN12615000242527. TRIAL REGISTRATION DATE: 19 February 2015. DATE OF FIRST PATIENT'S ENROLMENT: 27 May 2016.

The Effect of Interventions That Target Multiple Modifiable Health Behaviors on Symptoms of Anxiety and Depression in Young People: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This meta-analysis aimed to determine the effect of interventions targeting multiple modifiable health behaviors (i.e., physical activity/sedentary behaviors, nutrition/diet, sleep, substance use) on depression and anxiety in young people. METHODS: A search of electronic databases from inception until May 2020 was conducted. Randomized controlled trials (RCTs) that explicitly targeted at least two modifiable health behaviors, measured anxiety or depression at baseline and after intervention using a validated instrument, and included participants with an average age between 12 and 25 years were included. The effect of interventions was synthesized using random effects meta-analysis. RESULTS: A total of 14 RCTs reporting on depression and six RCTs reporting on anxiety were included in the quantitative synthesis. Results showed that although interventions targeting multiple modifiable health behaviors did not produce significant reductions in symptoms of depression (g¯ = -.16, 95% confidence interval [CI] = [-.34, .02], 95% prediction interval [PI] = [-.80, .48], very low certainty evidence) or anxiety (g¯ = -.55, 95% CI = [-1.36, .26], 95% PI = [-3.48, 2.83], very low certainty evidence) across all young people, there was a significant difference in the effect of interventions on depression based on intervention type (Q = 8.37, df = 2, p = .012). Specifically, interventions targeting multiple modifiable health behaviors delivered to groups of young people with an elevated risk of depression had a favorable effect (g¯ = -.28, 95% CI = [-.52, -.05], 95% PI = [-1.04, .47]) on symptoms of depression compared with controls. CONCLUSIONS: Although not universally effective, this meta-analysis establishes the potential efficacy of targeted interventions aiming to improve multiple modifiable health behaviors to address depression in young people at elevated risk of depression. More research is needed to understand the effect of such interventions on symptoms of anxiety in young people.

Effectiveness of exercise interventions on mental health and health-related quality of life in women with polycystic ovary syndrome: a systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex condition, impacting cardio-metabolic and reproductive health, mental health and health-related quality of life. The physical health benefits of exercise for women with PCOS are well-established and exercise is increasingly being recognised as efficacious for improving psychological wellbeing. The aim of this review was to summarise the evidence regarding the effectiveness of exercise interventions on mental health outcomes in women with PCOS. METHODS: A systematic search of electronic databases was conducted in March of 2020. Trials that evaluated the effect of an exercise intervention on mental health or health-related quality of life outcomes in reproductive aged women with diagnosed PCOS were included. Methodological quality was assessed using the modified Downs and Black checklist. Primary outcomes included symptoms of depression and anxiety, and health-related quality of life. RESULTS: Fifteen articles from 11 trials were identified and deemed eligible for inclusion. Exercise demonstrated positive improvements in health-related quality of life in all of the included studies. Half of included studies also reported significant improvements in depression and anxiety symptoms. There was large variation in methodological quality of included studies and in the interventions utilised. CONCLUSIONS: The available evidence indicates that exercise is effective for improving health-related quality of life and PCOS symptom distress. Exercise also shows some efficacy for improving symptoms and/or prevalence of depression and anxiety in women with PCOS. However, due to large heterogeneity of included studies, conclusions could not be made regarding the impact of exercise intervention characteristics. High-quality trials with well reported exercise intervention characteristics and outcomes are required in order to determine effective exercise protocols for women with PCOS and facilitate translation into practice.

Non-cell autonomous mechanisms control mitochondrial gene dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance and impaired energy metabolism in skeletal muscle, the aetiology of which is currently unclear. Here, we mapped the gene expression profile of skeletal muscle from women with PCOS and determined if cultured primary myotubes retain the gene expression signature of PCOS in vivo. Transcriptomic analysis of vastus lateralis biopsies collected from PCOS women showed lower expression of genes associated with mitochondrial function, while the expression of genes associated with the extracellular matrix was higher compared to controls. Altered skeletal muscle mRNA expression of mitochondrial-associated genes in PCOS was associated with lower protein expression of mitochondrial complex II-V, but not complex I, with no difference in mitochondrial DNA content. Transcriptomic analysis of primary myotube cultures established from biopsies did not display any differentially expressed genes between controls and PCOS. Comparison of gene expression profiles in skeletal muscle biopsies and primary myotube cultures showed lower expression of mitochondrial and energy metabolism-related genes in vitro, irrespective of the group. Together, our results show that the altered mitochondrial-associated gene expression in skeletal muscle in PCOS is not preserved in cultured myotubes, indicating that the in vivo extracellular milieu, rather than genetic or epigenetic factors, may drive this alteration. Dysregulation of mitochondrial-associated genes in skeletal muscle by extracellular factors may contribute to the impaired energy metabolism associated with PCOS.

Single Session and Short-Term Exercise for Mental Health Promotion in Tertiary Students: A Scoping Review.

Exercise can improve mental health; however many tertiary students do not reach recommended levels of weekly engagement. Short-term exercise may be more achievable for tertiary students to engage in to promote mental health, particularly during times of high stress. The current scoping review aimed to provide an overview of controlled trials testing the effect of short-term (single bout and up to 3 weeks) exercise across mental health domains, both at rest and in response to an experimentally manipulated laboratory stress task, in tertiary students. The search was conducted using 'Evidence Finder,' a database of published and systematic reviews and controlled trials of interventions in the youth mental health field. A total of 14 trials meet inclusion criteria, six measured mental health symptoms in response to an experimentally manipulated laboratory stress task and the remaining eight measured mental health symptoms. We found that short-term exercise interventions appeared to reduce anxiety like symptoms and anxiety sensitivity and buffered against a drop in mood following an experimentally manipulated laboratory stress task. There was limited available evidence testing the impacts of exercise on depression like symptoms and other mental health mental health domains, suggesting further work is required. Universities should consider implementing methods to increase student knowledge about the relationship between physical exercise and mental health and student access to exercise facilities.

Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFß) signalling. TGFß signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFß signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFß1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFß1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFß1. Collectively, our findings show that short-term treatment with TGFß1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFß signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects.

Poor reporting of physical activity and exercise interventions in youth mental health trials: A brief report.

AIM: To describe the quality and completeness of the description and reporting of physical activity and exercise interventions delivered to young people to promote mental health or treat mental illness. METHODS: We conducted a series of scoping reviews identifying 64 controlled trials of physical activity and exercise interventions delivered to young people. We extracted: intervention characteristics, personnel and delivery format, the intensity, duration, frequency and type of physical activity or exercise. RESULTS: There was limited reporting of intervention details across studies; 52% did not provide information to confidently assess intervention intensity, 29% did not state who delivered the intervention, and 44% did not specify the intervention delivery format. CONCLUSIONS: We recommend that authors adhere to the CONSORT reporting requirements and its intervention reporting extensions, (a) the Template for Intervention Description and Replication, (b) Consensus for Exercise Reporting Template and (c) as part of this, detail the frequency, intensity, time and type of physical activity recommendations and prescriptions. Without this, future trials are unable to replicate and extend previous work to support or disconfirm existing knowledge, leading to research waste and diminishing translation and implementation potential.

Exercise Interventions in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Background: Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive and metabolic manifestations. Exercise training has consistently been found to result in improved clinical outcomes in women with PCOS, but shortfalls with exercise prescription are evident. The aim of this systematic review and meta-analysis was to identify exercise intervention characteristics that provide favourable outcomes in women with PCOS. Methods: A systematic review of published literature was conducted using EBSCOhost and Ovid Medline up to May 2019. The review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines as per our PROSPERO protocol (CRD42018088367). Randomised controlled trials, non-randomised controlled trials, and uncontrolled trials that evaluated an exercise intervention of at least moderate intensity in women with PCOS were included. Meta-analyses were performed using general linear mixed modelling and Bayesian inferences about effect magnitudes. Results: Thirty-three articles were identified for systematic review of which 19 were meta-analysed. Intervention duration ranged from 6 to 26 weeks. A total number of 777 women were included in the meta-analysis. The meta-analysis found that improvements in health outcomes are more dependent on exercise intensity rather than dose. Fixed effects analysis reported a moderate increase in VO2peak (24.2%; 90% CL, 18.5-30.1), and small reductions in HOMA-IR (-36.2%; 90% CL, -55.3 to -9.0), and waist circumference (-4.2%; 90% CL -6.0 to -2.3) as a result of vigorous intensity exercise. These results are confirmed in the predicted analysis which reported the greatest improvements in VO2peak, BMI, and waist circumference after vigorous intensity exercise alone or when combined with diet, particularly for women with clinically adverse baseline values. Conclusions: Exercise training in the management of PCOS is becoming more common. Results from our analysis support the use of exercise and suggest that vigorous intensity exercise may have the greatest impact on cardiorespiratory fitness, body composition, and insulin resistance. Our results indicate that, a minimum of 120 min of vigorous intensity per week is needed to provide favourable health outcomes for women with PCOS with studies of longer duration required to evaluate outcomes with sustained exercise.

Exercise Recommendations for Women with Polycystic Ovary Syndrome: Is the Evidence Enough?

In this opinion piece, we summarize, discuss implications of implementation, and critically evaluate our 2018 evidence-based guideline recommendations for exercise and physical activity in women with polycystic ovary syndrome (PCOS). We developed recommendations as part of a larger international guideline development project. The overall guideline scope and priorities were informed by extensive health professional and consumer engagement. The lifestyle guideline development group responsible for the exercise recommendations included experts in endocrinology, exercise physiology, gynecology, dietetics, and obstetrics, alongside consumers. Extensive online communications and two face-to-face meetings addressed five prioritized clinical questions related to lifestyle, including the role of exercise as therapy for women with PCOS. The guideline recommendations were formulated based on one narrative and two evidence-based reviews, before consensus voting within the guideline panel. The development process was in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to assess evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation, and recommendation strength. Given the evidence for exercise as therapy in PCOS being of low quality, a consensus recommendation was made based on current exercise guidelines for the general population. Women with PCOS and clinicians are forced to adopt generic approaches when recommending exercise therapy that perpetuates clinical management with pharmacological solutions. The current status of evidence highlights the need for greater international co-operation between researchers and funding agencies to address key clinical knowledge gaps around exercise therapy in PCOS to generate evidence for appropriate, scalable, and sustainable best practice approaches.