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Danielle R Bouchard,1,2 Marie-France Langlois,3,4 Katherine Boisvert-Vigneault,3,4 Paul Farand,5 Mathieu Paulin,5 Jean-Patrice Baillargeon3,4 1Faculty of Kinesiology and Recreation Management, 2Health, Leisure and Human Performance Research Institute, University of Manitoba, Winnipeg, Manitoba, Canada; 3Departement of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Quebec, Canada; 4CRC Étienne LeBel, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; 5Departement of Medicine, Division of Cardiology, Université de Sherbrooke, Quebec, Canada Abstract: Most individuals do not reach the recommended physical activity level of at least 150 minutes of aerobic exercise (AE) at moderate-to-vigorous intensity per week. For example, only 13% of older Canadian adults reach World Health Organization physical activity guideline (PAG). One of the reasons might be a difficulty identifying the required intensity. Twenty-five inactive older adults received one session about the AE-PAG and how to use a tool or strategy to help them identify AE intensity: heart-rate (HR) monitor (% of maximal HR; N = 9); manual pulse (% of maximal HR; N = 8); or pedometer (walking cadence; N = 8). Participants had 8 weeks to implement their specific tool with the aim of reaching the PAG by walking at home. At pre- and post-intervention, the capacity to identify AE intensity and AE time spent at moderate-to-vigorous intensity were evaluated. Only the two groups using a tool increased total AE time (both P < 0.01), but no group improved the time spent at moderate-to-vigorous intensity. No significant improvement was observed in the ability to correctly identify AE intensity in any of the groups, but a tendency was observed in the pedometer group (P = 0.07). Using walking cadence with a pedometer should be explored as a tool to reach the PAG as it is inexpensive, easy to use, and seemed the best tool to improve both AE time and perception of intensity. Keywords: aging, pacing, aerobic exercise

AIM: To determine the independent effects of total and each health professional's frequency of contacts, on changes in anthropometric measures and physical capacity following a lifestyle intervention offered by a multi-disciplinary team in adults at high risk for type 2 diabetes. MATERIALS AND METHODS: A 12-month lifestyle intervention was performed in 48 adults with prediabetes. Participants were randomly assigned to either an individual counselling group (every six weeks)+an optional series of 25 group seminars (every week) or to the group seminars only. Physical activity level, energy intake, anthropometric measures, and physical capacity were assessed. RESULTS: Total frequency of contacts with any professional was associated with change in body weight, BMI and, waist circumference (all P<=.05). However, no frequency of contacts with a specific professional was associated with the studied outcomes, except for changes in physical capacity. The latest was significantly improved in participants who attended at least two group sessions with the kinesiologist (P=.02). DISCUSSION: To improve anthropometric measures, total contact frequency seems to be more important than contact frequency with any specific professionals. However, to improve physical capacity, meeting with a kinesiologist for two or more occasions, in group sessions, seems to be an effective strategy. [ABSTRACT FROM AUTHOR]

Objective: Injected volume and subcutaneous adipose tissue blood flow (ATBF) affect insulin absorption. Pharmacokinetics of short-acting insulin analogs were established by assessing injection of small doses in lean subjects, healthy or with type 1 diabetes. In obese patients, however, daily dosages are larger and ATBF is decreased. This study assessed the kinetics of a short-acting insulin analog in obese subjects with type 2 diabetes.Research Design and Methods: Euglycemic clamps after subcutaneous lispro injections were performed. Six healthy control subjects received 10 units. Seven obese (BMI 38.3 ± 7.0 kg/m(2)) subjects with type 2 diabetes received 10, 30, and 50 units. Plasma lispro was measured by specific radioimmunoassay and ATBF by the (133)Xe-washout technique.Results: ATBF was 64% lower in subjects with type 2 diabetes than in control subjects. After 10 units injection, time to lispro plasma peak (T(max)) was similar (48.3 vs. 55.7 min; control subjects versus type 2 diabetic subjects), although maximal concentration (C(max))/dose was 41% lower in subjects with type 2 diabetes, with lower and delayed maximal glucose infusion rate (GIR(max): 9.0 vs. 0.6 mg/kg/min, P < 0.0001, 69 vs. 130 min, P < 0.0001, respectively). After 30- and 50-unit injections, T(max) (88.6 and 130.0 min, respectively) and time to GIR(max) (175 and 245 min) were further delayed and dose related (r(2) = 0.51, P = 0.0004 and r(2) = 0.76, P < 0.0001, respectively).Conclusions: Absorption and hypoglycemic action of increasing dosages of lispro are critically delayed in obese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester., Methods: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses., Results: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted β=0.026, 95 % CI: 0.003-0.050)., Conclusion: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester., Competing Interests: Declaration of Competing Interest The authors of this article declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Regional anesthesia may favour postoperative rehabilitation by inhibiting peripheral sensitization and secondary hyperalgesia. The literature on this subject is limited. In the present FUNCTION study, we sought to compare the functional recovery post orthopedic wrist surgery with regional versus general anesthesia., Methods: We conducted a single-centre prospective observational cohort study in adult patients with a distal radial fracture. Functional recovery was assessed with validated psychometrics questionnaires (Quick Disabilities of Arm, Shoulder and Hand [QuickDASH] and Patient-Rated Wrist Evaluation [PRWE]), range of motion, and grip strength. We used a linear mixed regression model to assess the impact of the anesthesia technique on functional recovery. Postoperative pain and patient satisfaction were evaluated using a visual analog scale., Results: We recruited 76 patients. At 12 weeks post surgery, there was no difference between the type of anesthesia and functional recovery with the QuickDASH (higher scores worse; regional anesthesia [RA], 22.7 vs general anesthesia [GA], 19.3; adjusted mean difference [aMD], -0.3; 95% confidence interval [CI], -9.6 to 9.0; P = 0.9) and PRWE (higher scores worse; RA group, 21.0 vs GA group, 20.5; aMD, -3.3; 95% CI, -12.1 to 5.6; P = 0.93) questionnaires. Range of motion, satisfaction, and postoperative pain were similar between groups. Right-hand grip strength was higher in the GA group., Conclusion: Regional anesthesia was not associated with improved functional recovery compared with general anesthesia. The dominance of the operated limb was a confusion factor in all evaluation modalities. Further research taking into account the dominance of the hand is necessary to establish the effects of regional anesthesia on functional recovery., Study Registration: ClinicalTrials.gov (NCT04541745); registered 9 September 2020., (© 2023. Canadian Anesthesiologists' Society.)

Background: Healthy eating during pregnancy has favorable effects on glycemic control and is associated with a lower risk of gestational diabetes mellitus (GDM). According to Diabetes Canada, there is a need for an effective and acceptable intervention that could improve glucose homeostasis and support pregnant individuals at risk for GDM., Aims: This unicentric randomized controlled trial (RCT) aims to evaluate the effects of a nutritional intervention initiated early in pregnancy, on glucose homeostasis in 150 pregnant individuals at risk for GDM, compared to usual care., Methods: Population: 150 pregnant individuals ≥18 years old, at ≤14 weeks of pregnancy, and presenting ≥1 risk factor for GDM according to Diabetes Canada guidelines. Intervention: The nutritional intervention initiated in the first trimester is based on the health behavior change theory during pregnancy and on Canada's Food Guide recommendations. It includes (1) four individual counseling sessions with a registered dietitian using motivational interviewing (12, 18, 24, and 30 weeks), with post-interview phone call follow-ups, aiming to develop and achieve S.M.A.R.T. nutritional objectives (specific, measurable, attainable, relevant, and time-bound); (2) 10 informative video clips on healthy eating during pregnancy developed by our team and based on national guidelines, and (3) a virtual support community via a Facebook group. Control: Usual prenatal care. Protocol: This RCT includes three on-site visits (10-14, 24-26, and 34-36 weeks) during which a 2-h oral glucose tolerance test is done and blood samples are taken. At each trimester and 3 months postpartum, participants complete web-based questionnaires, including three validated 24-h dietary recalls to assess their diet quality using the Healthy Eating Food Index 2019. Primary outcome: Difference in the change in fasting blood glucose (from the first to the third trimester) between groups. This study has been approved by the Ethics Committee of the Centre de recherche du CHU de Québec-Université Laval., Discussion: This RCT will determine whether a nutritional intervention initiated early in pregnancy can improve glucose homeostasis in individuals at risk for GDM and inform Canadian stakeholders on improving care trajectories and policies for pregnant individuals at risk for GDM., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05299502, NCT05299502., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bernier, Plante, Lemieux, Robitaille, Lemieux, Desroches, Bélanger-Gravel, Maheux-Lacroix, Weisnagel, Demers, Camirand Lemyre, Boulet, Baillargeon and Morisset.)

Background and Objectives: Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life extends the window of cerebrovascular protection to the postmenopausal period. To investigate this, we examined the relationship between lifetime hormone exposure (LHE) and cerebral small vessel disease in more than 9,000 postmenopausal women in the UK-Biobank., Methods: The cohort consisted of women (aged 40-69 years) who attended one of 22 research centers across the United Kingdom between 2006 and 2010. Women were excluded if they were premenopausal when scanned, had missing reproductive history data, self-reported neurologic disorders, brain cancer, cerebral vascular incidents, head or neurologic injury, and nervous system infection. Endogenous LHE (LHE Endo ) was estimated by summing the number of years pregnant (LHE Parity ) with the duration of the reproductive period (LHE Cycle = age menopause - age menarche). Exogenous LHE (LHE Exo ) was estimated by summing the number of years on oral contraceptives and hormone replacement therapy. Cerebral small vessel disease was determined by estimating white matter hyperintensity volume (WMHV) from T2-fluid-attenuated inversion recovery brain MRI (acquired between 2014 and 2021), normalized to intracranial volume and log-transformed. Multiple linear regressions were used to assess the relationship between LHE Endo on WMHV adjusted for age, cardiovascular risk factors, sociodemographics, and LHE Exo ., Results: A total of 9,163 postmenopausal women (age 64.21 ± 6.81 years) were retained for analysis. Average LHE Endo was 39.77 ± 3.59 years. Women with higher LHE Endo showed smaller WMHV (adj- R 2 = 0.307, LHE Endo β = -0.007 [-0.012 to -0.002], p < 0.01). LHE Parity and LHE Cycle were independent contributors to WMHV (adj- R 2 = 0.308, p << 0.001; LHE Parity β = -0.022 [-0.042 to -0.002], p < 0.05; LHE Cycle β = -0.006 [-0.011 to -0.001], p < 0.05). LHE Exo was not significantly related to WMHV (LHE Exo β = 0.001 [-0.001 to 0.002], p > 0.05)., Discussion: Women with more prolonged exposure to endogenous hormones show relatively smaller burden of cerebral small vessel disease independent of the history of oral contraceptive use or hormone replacement therapy. Our results highlight the critical role endogenous hormones play in female brain health and provide real-world evidence of the protective effects premenopausal endogenous hormone exposure plays on postmenopausal cerebrovascular health., (© 2023 American Academy of Neurology.)

Background: Peripheral nerve block is a common anesthetic technique used during orthopedic upper limb surgery. Injection of local anesthetics around the target nerve inhibits the action of voltage-dependent sodium channels, inhibiting neurotransmission of pain impulses and providing motor immobility. Compared to general anesthesia, it could improve functional recovery by inhibiting nociceptive impulses and inflammation, thus reducing postoperative pain and immobilization and improving postoperative rehabilitation. This systematic review evaluates the impact of peripheral nerve block versus general anesthesia on postoperative functional recovery following orthopedic upper limb surgery., Methods: We searched CENTRAL, MEDLINE, CINHAL, EMBASE, and Scopus trial databases from inception until September 2021 for studies comparing peripheral nerve block to general anesthesia. We collected data on functional recovery, range of motion, patient satisfaction, quality of life, and return to work. We pooled studies using a random-effects model and summarized the quality of evidence with the GRADE approach., Results: We assessed 373 citations and 19 full-text articles for eligibility, and included six studies. Six studies reported on functional recovery, but failed to detect a significant superiority of peripheral nerve block over general anesthesia (3 RCT studies, N = 160; SMD -0.15; CI at 95% -0.60-0.3; I 2  = 45%; p = 0.07; low quality of evidence and 3 observational studies, N = 377; SMD -0.35; CI at 95% -0.71-0.01; I 2  = 64%; p = 0.06; very low quality of evidence)., Conclusions: Current literature is limited and fails to identify the benefit of peripheral nerve block on functional recovery. More studies are needed to assess the impact on long-term recovery. Considering the potential impact on clinical practice and training, a prospective study on functional recovery is ongoing (NCT04541745)., Trial Registration: PROSPERO ID CRD42018116298. Registered on December 4, 2018., (© 2023. The Author(s).)

Background: Interactions between genes and early-life exposures during conception, fetal life, infancy, and early childhood have been shown to affect an individual's health later in life. Maternal undernutrition and obesity, gestational diabetes, and impaired growth in utero and in early life are associated with adiposity and overweight and obesity in childhood, which are risk factors for poor health trajectories and non-communicable diseases. In Canada, China, India, and South Africa, 10-30% of children aged 5-16 years are overweight or obese., Methods: The application of developmental origins of health and disease principles offers a novel approach to prevention of overweight and obesity and reduction of adiposity by delivering integrated interventions across the life course, starting before conception and continuing through early childhood. The Healthy Life Trajectories Initiative (HeLTI) was established in 2017 through a unique collaboration between national funding agencies in Canada, China, India, South Africa, and WHO. The aim of HeLTI is to evaluate the effect of an integrated four-phase intervention starting preconceptionally and continuing through pregnancy, infancy, and early childhood on reducing childhood adiposity (fat mass index) and overweight and obesity, and optimising early child development, nutrition, and other healthy behaviours., Findings: Approximately 22 000 women are being recruited in Shanghai (China), Mysore (India), Soweto (South Africa), and across various provinces of Canada. Women who conceive (an expected 10 000) and their children will be followed up until the child reaches the age of 5 years., Interpretation: HeLTI has harmonised the intervention, measures, tools, biospecimen collection, and analysis plans for the trial to be run across four countries. HeLTI will help establish whether an intervention aimed at addressing maternal health behaviours, nutrition, and weight; providing psychosocial support to reduce maternal stress and prevent mental illness; optimising infant nutrition, physical activity, and sleep; and promoting parenting skills can reduce the intergenerational risk of excess childhood adiposity and overweight and obesity across diverse settings., Funding: Canadian Institutes of Health Research; National Science Foundation of China; Department of Biotechnology, India; and South African Medical Research Council., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: There is a lack of cost-effective and readily available access to evidence-based information to manage healthy behaviours for pregnant individuals. Mobile health (mHealth) tools offer a cost-effective, interactive, personalized option that can be delivered anywhere at a time most convenient for the user. This study protocol was primarily developed to, i) assess the feasibility of the SmartMoms Canada intervention in supporting participants to achieve gestational weight gain (GWG) guidelines. The secondary objectives are to, ii) assess user experience with the app, measured by adherence to the program via app software metrics and frequency of use, iii) determine the impact of SmartMoms Canada app usage on the adoption of healthful behaviours related to nutrition, physical activity and sleep habits, improvements in health-related quality of life, pregnancy-related complications, and symptoms of depression, and iv) investigate the potential extended effects of the app on postpartum health-related outcomes., Methods: This is a feasibility trial. Pregnant individuals aged 18-40 years with pre-gravid body mass index between 18.5 and 39.9 kg/m 2 , carrying a singleton fetus, having Wi-Fi access, and at ≤20 weeks' gestation will be recruited. Eligible people will be followed from recruitment until 12 months postpartum., Discussion: SmartMoms Canada is the first bilingual Canadian-centric app designed for pregnant people. This mHealth intervention, with its ability to supply frequent interactions, provides pregnancy- related health knowledge to users, potentially leading to an improvement in pregnancy-related outcomes and behaviours, and, ultimately a reduction in the present economic burden related to in-person interventions., Trial Registration: ISRCTN, ISRCTN16254958. Registered 20 December 2019, http://www.isrctn.com/ ISRCTN16254958., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Dietary and/or physical activity interventions are often recommended for women with overweight or obesity as the first step prior to fertility treatment. However, randomised controlled trials (RCTs) so far have shown inconsistent results. Therefore, we propose this individual participant data meta-analysis (IPDMA) to evaluate the effectiveness and safety of dietary and/or physical activity interventions in women with infertility and overweight or obesity on reproductive, maternal and perinatal outcomes and to explore if there are subgroup(s) of women who benefit from each specific intervention or their combination (treatment-covariate interactions)., Methods and Analysis: We will include RCTs with dietary and/or physical activity interventions as core interventions prior to fertility treatment in women with infertility and overweight or obesity. The primary outcome will be live birth. We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials and trial registries to identify eligible studies. We will approach authors of eligible trials to contribute individual participant data (IPD). We will perform risk of bias assessments according to the Risk of Bias 2 tool and a random-effects IPDMA. We will then explore treatment-covariate interactions for important participant-level characteristics., Ethics and Dissemination: Formal ethical approval for the project (Venus-IPD) was exempted by the medical ethics committee of the University Medical Center Groningen (METc code: 2021/563, date: 17 November 2021). Data transfer agreement will be obtained from each participating institute/hospital. Outcomes will be disseminated internationally through the collaborative group, conference presentations and peer-reviewed publication., Prospero Registration Number: CRD42021266201., Competing Interests: Competing interests: AH reports consultancy for Ferring with respect to the development of a lifestyle app. BWM is supported by an NHMRC Investigator grant (GNT1176437). BWM reports personal fees from ObsEva and Merck, and travel support from Merck, outside the submitted work. RW reports grants from the NHMRC. TM is supported by a Future Leader in Diabetes Award from the European Foundation for the Study of Diabetes/Novo Nordisk Foundation (NNF19SA058975) and grants from the regional health authority in Central Norway. ATK reports personal fees from Merck for lectures. The other authors do not have competing interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Women with obesity are at a higher risk of infertility as well as gestational and neonatal complications. Lifestyle changes are universally recommended for women with obesity seeking fertility treatments, but such intervention has only been assessed in very few robust studies. This study's objectives are therefore to assess the clinical outcomes and cost-effectiveness of an interdisciplinary lifestyle intervention (the Fit-For-Fertility Programme; FFFP) targeting women with obesity and subfertility in a diverse population., Methods and Analysis: This pragmatic multicentre randomised controlled trial (RCT) will include 616 women with obesity (body mass index ≥30 kg/m 2 or ≥27 kg/m 2 with polycystic ovary syndrome or at-risk ethnicities) who are evaluated at a Canadian fertility clinic for subfertility. Women will be randomised either to (1) the FFFP (experimental arm) alone for 6 months, and then in combination with usual care for infertility if not pregnant; or (2) directly to usual fertility care (control arm). Women in the intervention group benefit from the programme up to 18 months or, if pregnant, up to 24 months or the end of the pregnancy (whichever comes first). Women from both groups are evaluated every 6 months for a maximum of 18 months. The primary outcome is live birth rate at 24 months. Secondary outcomes include fertility, pregnancy and neonatal outcomes; lifestyle and anthropometric measures; and cost-effectiveness. Qualitative data collected from focus groups of participants and professionals will also be analysed., Ethics and Dissemination: This research study has been approved by the Research Ethics Board (REB) of Centre intégré universtaire de santé et des services sociaux de l'Estrie-CHUS (research coordinating centre) on 10 December 2018 and has been or will be approved successively by each participating centres' REB. This pragmatic RCT will inform decision-makers on improving care trajectories and policies regarding fertility treatments for women with obesity and subfertility., Trial Registration Number: NCT03908099., Protocol Version: 1.1, 13 April 2019., Competing Interests: Competing interests: Ferring has provided an unrestricted grant for the trial, without influencing the design or conduct of the trial, or the analysis or dissemination of the study’s results., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives., Objective: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters., Design: Cross-sectional study., Setting: Seven academic centers in North America, South America, and Europe., Patients: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT)., Main Outcome Measures: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels., Results: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040)., Conclusions: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Preconception lifestyle interventions appear promising to reduce pregnancy complications, prevent adult cardiometabolic diseases, and prevent childhood obesity. These interventions have almost exclusively been studied in populations of obese infertile women. The development of preconception lifestyle interventions targeting a broader population of overweight and obese women without a history infertility and their partners is needed. Methods: This study is a multicenter open label parallel group randomized controlled trial. Sixty-eight non-infertile women with overweight or obesity in the preconception period and their partners will be recruited from the Sherbrooke and Quebec City regions. The couples will be randomized in a 1:1 ratio to receive the Healthy for my Baby intervention or standard care in the preconception period and pregnancy. Women and their partners will be invited to take part in this lifestyle intervention which includes motivational interviews and daily self-monitoring of lifestyle goals through a mobile phone application. The primary endpoint of this study is the diet quality of women during the preconception period, which will be evaluated using the C-HEI 2007 score at baseline, 2, 4- and 6-months following study enrolment. Women's dietary quality will also be evaluated through the measure of urinary biomarkers of habitual dietary intake at baseline and 2 months in preconception, and 24-26 weeks in pregnancy. Additional indicators of women's lifestyle as well as anthropometric measures will be documented in preconception and pregnancy. For the pregnancy period, the main secondary endpoint is the pattern of gestational weight gain. Pregnancy and neonatal complications will also be evaluated. For partners, diet quality, other lifestyle habits, and anthropometric measures will be documented in the preconception and pregnancy periods. Discussion: This study will evaluate the effectiveness of a low-cost intervention designed to improve diet and other lifestyle characteristics of women in the preconception period who are overweight or obese. If the Healthy for my Baby intervention is efficacious regarding dietary measures, larger trials will be needed to evaluate the impact of this intervention on the rates of pregnancy complications, childhood obesity, and adult cardiometabolic disease. Clinical Trial Registration: clinicaltrials.gov (NCT04242069)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hardy, Lloyd, Morisset, Camirand Lemyre, Baillargeon and Fraser.)

Introduction: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk., Methods and Analysis: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study., Ethics and Dissemination: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation., Trial Registration Number: ChiCTR1800017773., Protocol Version: November 11, 2020 (Version #5)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary care providers' (PCPs) attitude toward obesity is often negative, and their confidence level for helping patients manage their weight is low. Continuing professional development (CPD) on the subject of obesity is often based on a single activity using a traditional passive approach such as lectures known to have little effect on performance or patient outcomes. The aim of this study was to evaluate the impact of an educational intervention for obesity management on PCPs' attitude, self-efficacy, practice changes and patient-related outcomes., Methods: Prospective interventional study with 12 months follow-up. A two-day clinical obesity preceptorship was offered where participants were actively involved in competence building using real-life situations, in addition to electronic networking tools, including a discussion forum and interactive monthly webinars. Thirty-five participants (12 nurses and 23 physicians) from seven Family medicine groups were enrolled. Questionnaires were used to evaluate the impact on primary care nurses' and physicians' attitudes and self-efficacy for obesity management. Practice changes and patient outcomes were evaluated using clinical vignettes, de-identified electronic patient records and qualitative analyses from group interviews., Results: Physicians' general attitude towards patients with obesity was improved (61 ± 22 mm vs 85 ± 17 mm, p <  0.001). Self-efficacy for obesity management and lifestyle counselling were also improved immediately and 1 year after the intervention (all Ps <  0.05). De-identified patient records and clinical vignettes both showed improvement in recording of weight, waist circumference and evaluation of readiness to change lifestyle (all Ps <  0.05) that was confirmed by group interviews. Also, 15% of patients who were prospectively registered for weight management had lost more than 5% of their initial weight at the time of their last visit (P <  0.0001, median follow-up of 152 days)., Conclusion: A multimodal educational intervention for obesity management can improve PCPs'attitude and self-efficacy for obesity management and lifestyle counselling. This translates into beneficial practice changes and patient-related outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT01385397 . Retrospectively registered, 28 June 2011.

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn's anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns' data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = -0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns' cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.

Objectives: To compare: 1) 75 g oral glucose tolerance test (OGTT) and self-monitoring of blood glucose (SMBG) in identifying gestational diabetes mellitus (GDM) and other hyperglycemic statuses in pregnant women; 2) pregnancy outcomes according to glycemic status; and 3) participants' opinions regarding both methods., Methods: A prospective study in women with a 50 g glucose load test ≥7.2 mmol/L at 24 to 28 weeks' gestation and singleton pregnancy. Women underwent OGTT (blinded) at day 1, followed by 7 days of SMBG (4 daily measurements: fasting and 2 h postprandially) without modifying diet or lifestyle. GDM (OGTT+) was diagnosed using the criteria of the International Association of the Diabetes and Pregnancy Study Groups, while pregnancy hyperglycemia (SMBG+) was defined as ≥4/7 glucose values ≥5.3 after fasting or ≥6.7 mmol/L 2 h postprandially for any meal of the day. Equivalent management was provided to women with GDM and/or pregnancy-related hyperglycemia., Results: We divided 103 participants (age: 29.5±5.0 years; prepregnancy body mass index: 25.3±5.4 kg/m 2 ) into 4 groups according to test results: OGTT+/SMBG+ (n=12, 11.7%); OGTT+/SMBG- (n=14, 13.6%); OGTT-/SMBG+ (n=9, 8.7%); and OGTT-/SMBG- (n=68, 66.0%). Clinical characteristics and maternal outcomes were statistically similar between groups. Neonatal complication rates were greater in groups with hyperglycemia than in the OGTT-/SMBG- group, notably neonatal hypoglycemia (9/12, 7/14, 5/9 vs. 6/68; p<0.001). Participants reported no convenience difference between methods but would prefer OGTT for a future pregnancy., Conclusions: More than half of the women with OGTT+ were normoglycemic in daily life. Conversely, 11.7% of women with OGTT- had pregnancy hyperglycemia. OGTT+ and/or SMBG+ were equally associated with greater neonatal complications. This study suggests that alongside OGTT, SMBG could improve the care of pregnant women., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral nerve block is a single injection that inhibits the transmission of peripheral nerve impulses to the central nervous system. The inhibition of the nociceptive impulse may decrease the occurrence of muscle spasm following mobilization postoperatively. This mechanism may contribute to a better functional recovery following upper limb surgery. This systematic review will investigate the impact of peripheral nerve block on functional recovery after an upper limb surgery., Methods: We will search studies comparing peripheral nerve block to general anesthesia for upper limb surgery in the following databases: CENTRAL, MEDLINE (Ovid), CINAHL, EMBASE, and Scopus. In duplicate, independent reviewers will assess eligibility, evaluate risk of bias, and abstract data on type of peripheral nerve block and functional outcome. Where possible, we will pool results using a random effects model. For each outcome, we will assess the quality of evidence using GRADE methodology., Discussion: We aim to summarize the available evidence comparing functional recovery with peripheral nerve block versus general anesthesia for upper limb surgery. These data will inform the design of a trial on the topic., Systematic Review Registration: PROSPERO CRD42018116298.

The signaling mechanisms of the angiotensin II type 2 receptor (AT 2 R), a heptahelical receptor, have not yet been clearly and completely defined. In the present contribution, we set out to identify the molecular determinants involved in AT 2 R activation. Although AT 2 R has not been shown to engage G q/11 , G 12 , G i2 , and β-arrestin (βarr) pathways as does the AT 1 R upon angiotensin II (AngII) stimulation, the atypical positioning of helix VIII in the recently published AT 2 R structure may play a role in the receptor's capacity to couple to downstream effectors. In the AT 2 R structure, helix VIII points inwards and towards intracellular loop 3 (ICL3) to form tertiary interactions with transmembrane domain 6 (TM6), possibly impeding access to signaling effectors. On the other hand, in most class A GPCRs, helix VIII is found to be engaged in tertiary interactions with ICL1 and away from the effector binding site. Upon closer examination of the AT 2 R structure, we found that the residues contained within intracellular loop 1 (ICL1) may be involved in driving this unusual conformation of helix VIII. To explore this hypothesis, we designed a series of AT 1 R/AT 2 R receptor chimeras to validate the roles of ICL1 and helix VIII in AT 2 R signaling. Substituting the AT 1 R ICL1 into AT 2 R led to a mutant receptor that coupled to G i2 . The substitution of the helix VIII and C-terminal domains of AT 2 R into the AT 1 R backbone led to a mutant receptor that retained AT 1 R-like signaling properties. These results suggest that the C-terminal portion of AT 2 R is compatible with canonical GPCR signaling and that ICL1 of AT 2 R is involved in repositioning helix VIII, which impedes engagement of classical GPCR effectors such as G proteins or βarrs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To assess: 1-the spousal concordance of lifestyle and anthropometric characteristics between partners of infertile couples in which the woman is obese; and 2-in men, the influence of these characteristics on their conventional seminal parameters., Design: Cross-sectional study., Setting: Fertility clinic of the Centre hospitalier universitaire de Sherbrooke, Canada, between January 2012 and February 2015., Patients: 97 infertile heterosexual couples in which women were obese and seeking fertility treatments., Intervention: Not applicable., Main Outcome Measures: Weight and percentage of fat mass were evaluated using a scale with foot-to-foot bio-impedance. Abdominal obesity was estimated with waist circumference and lifestyle habits, by a self-reported questionnaire. Seminal parameters were analysed and collected according to the WHO guidelines (Kruger's strict criteria for seminal morphology)., Results: There was a significant spousal concordance for the percentage of fat mass, leisure activities and overall nutritional quality. Accordingly, male participants displayed anthropometric and lifestyle characteristics at higher risk than Canadian men of similar age. Moreover, BMI, daily consumption of fruits & vegetables and sleeping hours in men were independently associated to the total motile sperm count., Conclusion: This is the first study to report concordance for anthropometric and lifestyle characteristics between partners of infertile couples in which the woman is obese. These characteristics in men were more adverse than in the general population and were associated with reduced sperm quality. Altogether, our results suggest that male partners of infertile couples could benefit from participating in the lifestyle intervention that is already recommended for their spouse affected by obesity., Capsule: Because partners of subfertile couples in which the woman is obese share adverse anthropometric and lifestyle characteristics, male partners should be implicated in lifestyle interventions already indicated for their spouse., (Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Purpose: To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults., Methods: Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords 'hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy'. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism., Results: Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults., Main Conclusions: Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.

Competing Interests: Competing interests: None declared.

Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of androgen-secreting tissues to NEFA and/or defective NEFA metabolism, leading to lipotoxic effects. Indeed, lipotoxicity could trigger androgenic hyperresponsiveness to insulin, LH, and ACTH. In most PCOS women, lipotoxicity also causes insulin resistance, inducing compensatory hyperinsulinemia, and may thus further increase hyperandrogenemia. Many approaches aimed at insulin sensitization also reduce lipotoxicity and have been shown to treat PCOS hyperandrogenemia. Furthermore, our group and others found that angiotensin II type 2 receptor (AT2R) activation is able to improve lipotoxicity. We provided evidence, using C21/M24, that AT2R activation improves adipocytes' size and insulin sensitivity in an insulin-resistant rat model, as well as androgen levels in a PCOS obese rat model. Taken together, these findings point toward the important role of lipotoxicity in PCOS development and of the RAS system as a new target for the treatment of PCOS.

Objective: To determine how often primary health care providers (PHCPs) in family medicine groups (FMGs) assess physical activity (PA) levels, provide PA counseling (PAC), and refer patients to exercise professionals; to describe patients' PA levels, physical fitness, and satisfaction regarding their PA management in FMGs; to describe available PA materials in FMGs and PHCPs' PAC self-efficacy and PA knowledge; and to identify characteristics of patients and PHCPs that determine the assessment of PA and PAC provided by PHCPs., Design: Cross-sectional study using questionnaires and a medical chart audit., Setting: Ten FMGs within the Integrated University Health Network of the Centre hospitalier universitaire de Sherbrooke in Quebec., Participants: Forty FPs, 24 nurses, and 439 patients., Main Outcome Measures: Assessment of PA level and PAC provided by PHCPs., Results: Overall, 51.9% of the patients had had their PA level assessed during the past 18 months, but only 21.6% received PAC from at least 1 of the PHCPs. Similar percentages were found among the inactive (n = 244) and more active (n = 195) patients. The median PAC self-efficacy score of PHCPs was 70.2% (interquartile range 52.0% to 84.7%) and the median PA knowledge score was 45.8% (interquartile range 41.7% to 54.2%), with no significant differences between nurses and FPs. In multivariate analysis, 34% of the variance in PAC provided was explained by assessment of PA level, overweight or obese status, type 2 diabetes or prediabetes, less FP experience, lower patient annual family income, more nurse encounters, and a higher patient physical component summary of quality of life., Conclusion: The rates of assessment of PA and provision of PAC in Quebec FMGs were low, even though most of the patients were inactive. Initiatives to support PHCPs and more resources to assess PA levels and provide PAC should be implemented., (Copyright© the College of Family Physicians of Canada.)

Background: We and others have observed that young girls predisposed to polycystic ovary syndrome (PCOS) display defective insulin sensitivity, beta-cell function and non-esterified fatty acids (NEFA) suppressibility during early pubertal years, compared to controls. Our objective is to assess whether these differences in glucose and NEFA metabolisms persist after 5 years in late/post-puberty., Methods: We conducted a prospective cohort study between 2007 and 2015 with 4-6 years of follow-up in an academic institution research center. We compared 8 daughters and sisters of PCOS women (PCOSr) to 8 age-matched girls unrelated to PCOS (±1.5 years). Girls were assessed initially at 8-14 years old and re-assessed after a median follow-up of 5.4 years, at 13-21 years old. Our main measures were a frequently sampled intravenous glucose tolerance test (FSivGTT)-derived insulin sensitivity (IS) and beta-cell function (disposition index, DI FSivGTT ); and indices of NEFA suppression during FSivGTT (log n -linear slope of NEFA and T 50 of NEFA suppression)., Results: At follow-up, both PCOSr and controls had similar results: IS = 3.2 vs 3.4 (p = 0.88), DI FSivGTT  = 1926 vs 1380 (p = 0.44), log n -linear slope = -0.032 vs -0.032 (p = 0.88) and T 50 NEFA = 18.1 vs 20.8 min (p = 0.57). IS, DI FSivGTT and NEFA suppressibility were stable in PCOSr after 5 years, but decreased significantly in controls (all p < 0.05)., Conclusions: Impaired metabolism observed during early puberty in girls predisposed to PCOS remains stable after 5 years whereas control girls deteriorated their metabolic parameters. Therefore, both groups become comparable in late/post-puberty. Early puberty may thus represent a window during which metabolic alterations are transiently apparent in girls at risk of PCOS.

Background: Several studies have reported higher levels of Alanine aminotransferase (ALT) in women with polycystic ovary syndrome (PCOS) compared with control subjects. Plasma ALT levels are considered a marker of hepatic lipotoxicity because of their significant associations with different hepatic metabolic dysfunctions, such as hepatic steatosis and hepatic insulin resistance., Methods: Retrospective chart review aiming to assess, in PCOS women, the relationship between ALT levels and measures of lipotoxicity consequences that are available clinically, both during fasting and using the oral glucose tolerance test., Results: Women (n = 132) with PCOS, were in average 27.9 years of age, with a mean body mass index of 34.1 kg/m 2 and 49% had a metabolic syndrome (MetS). ALT levels were significantly correlated with homeostatic model assessment for insulin resistance (r = 0.42, P < 0.001), HDL-C (r = -0.31, P < 0.001), Matsuda index (-0.45, P < 0.001), insulin secretion-sensitivity index-2 (-0.26, P = 0.043), and free testosterone (0.38, P < 0.001), but not with fasting glucose and triglyceride levels. ALT cutoff ≥24 IU/L was associated with all these parameters, including fasting glucose (P = 0.021) and triglyceride levels (P = 0.041), and detected more women with the MetS (59.2% vs. 36.1%, P = 0.008) and whole-body insulin resistance (Matsuda index <12.3 L 2 ·10/mmol 2 , 85.3% vs. 51.9%, P = 0.004)., Conclusions: Plasma ALT levels seem to be a strong predictor not only of liver lipotoxicity but also of systemic lipotoxic consequences and hyperandrogenemia in women with PCOS. Although it requires validation in another study, an ALT cutoff of ≥24 IU/L may help clinicians identify women with increased metabolic risks.

Background: Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation., Methods: DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts. Glucose tolerance was assessed in all women using an oral glucose tolerance test at the second trimester of pregnancy. Participating women were extensively phenotyped throughout pregnancy, and placenta and cord blood samples were collected at birth., Results: We report that maternal glycemia at the second and third trimester of pregnancy are correlated with variations in DNA methylation levels at PRDM16, BMP7, and PPARGC1α and with cord blood leptin levels. Variations in PRDM16 and PPARGC1α DNA methylation levels were also correlated with cord blood leptin levels. Mediation analyses support that DNA methylation variations at the PPARGC1α gene locus explain 0.8 % of the cord blood leptin levels variance independently of maternal fasting glucose levels (p = 0.05)., Conclusions: These results suggest that maternal glucose in pregnancy could produce variations in DNA methylation in BAT-related genes and that some of these DNA methylation marks seem to mediate the impact of maternal glycemia on cord blood leptin levels, an adipokine regulating body weight.

Polycystic ovary syndrome (PCOS) is a common condition affecting women of reproductive age. This disorder is characterized by hyperandrogenism and anovulation and is frequently associated with comorbidities such as infertility, metabolic syndrome, type 2 diabetes, and cardiovascular risk factors. Although the causes of PCOS are unknown, this review focuses on the most accepted theory involving insulin action but will also elaborate on a novel concept: the role of lipotoxicity in the development of androgen overproduction, in addition to its known role in insulin resistance. This review will also shed a spotlight on 2 drugs that target lipotoxicity and are, therefore, known or promising for the treatment of PCOS manifestations: peroxisome proliferator-activated receptor γ and angiotensin II type 2 receptor agonists. This paper, therefore, emphasizes the need to further explore the pathophysiology of PCOS and particularly the role of lipotoxicity. Indeed, this new mechanism deserves attention to develop therapeutic approaches that will directly target the root of this condition and not only bandage its associated consequences.

Objective: To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance., Materials and Methods: Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function., Results: The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group., Conclusions: The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Background: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes., Methods/design: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women., Discussion: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics., Trial Registration: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Aim: To assess the associations between gestational diabetes mellitus (GDM) and DNA methylation levels at genes related to energy metabolism., Patients & Methods: Ten loci were selected from our recent epigenome-wide association study on GDM. DNA methylation levels were quantified by bisulfite pyrosequencing in 80 placenta and cord blood samples (20 exposed to GDM) from an independent birth cohort (Gen3G)., Results: We did not replicate association between DNA methylation and GDM. However, in normoglycemic women, glucose levels were associated with DNA methylation changes at LRP1B and BRD2 and at CACNA1D and LRP1B gene loci in placenta and cord blood, respectively., Conclusion: These results suggest that maternal glucose levels, within the normal range, are associated with DNA methylation changes at genes related to energy metabolism and previously associated with GDM. Maternal glycemia might thus be involved in fetal metabolic programming.

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m(2) were divided based on weight loss at 1 year: < 5% (non-responders, n 56) and ≥ 5% (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9.5% of their weight when compared with non-responders who lost only 0.8% of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P = 0.0003) and disposition index (P = 0.02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8.9 (SD 12.5) v. 3.6 (SD 10.7) nmol/l, P = 0.05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

Oral 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid was used to determine whether an increase in cardiac dietary fatty acid (DFA) metabolism in impaired glucose tolerance (IGT) is different in men and women. Myocardial DFA partitioning after 6 h was higher in IGT versus control subjects (P = 0.006) in both men (2.14 [95% CI 1.70-2.18] vs. 1.28 standard uptake value [SUV] units [0.80-1.76]) and women (1.95 [1.57-2.33] vs. 1.64 SUV units [1.32-1.96]) without difference between sexes. Myocardial DFA fractional uptake (Ki) between time 90 and 120 min postprandially was also higher in IGT versus control subjects (P < 0.001) in men (0.063 [0.032-0.095] vs. 0.016 min(-1) [0.007-0.025]) and women (0.050 [0.024-0.077] vs. 0.030 min(-1) [0.013-0.047]) without significant sex difference. Men had higher net myocardial DFA uptake between time 90 and 120 min driven by higher chylomicron-triglyceride (TG) levels. IGT-associated increased cardiac DFA partitioning was directly related to obesity in women, whereas it was associated with IGT per se in men. We conclude that early cardiac DFA uptake is higher in men driven by change in postprandial chylomicron-TG level but that increase in 6-h postprandial cardiac DFA partitioning nevertheless occurs with IGT both in men and women., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Acetylcholine (Ach) has vasodilatory actions. However, data are conflicting about the role of Ach in regulating blood flow in subcutaneous adipose tissue (ATBF). This may be related to inaccurate ATBF recording or to the responder/nonresponder (R/NR) phenomenon. We showed previously that healthy individuals are R (ATBF increases postprandially by >50% of baseline BF) or NR (ATBF increases ≤50% postprandially). Our objective was to assess the role of the cholinergic system on ATBF in R and NR subjects. ATBF was manipulated by in situ microinfusion of vasoactive agents (VA) in AT and monitored by the (133)Xenon washout technique (both recognized methods) at the VA site and at the control site. We tested incrementally increasing doses of Ach (10(-5), 10(-3), and 10(-1) mol/l; n = 15) and Ach receptor antagonists (Ra) before and after oral administration of 75-g glucose using atropine (muscarinic Ra; 10(-4) mol/l, n = 13; 10(-5) mol/l, n = 22) and mecamylamine (nicotinic Ra; 10(-3) mol/l, n = 15; 10(-4) mol/l, n = 10). Compared with baseline [2.41 (1.36-2.83) ml·100 g(-1)·min(-1)], Ach increased ATBF dose dependently [3.32 (2.80-5.09), 6.46 (4.36-9.51), and 10.31 (7.98-11.52), P < 0.0001], with no difference between R and NR. Compared with control side, atropine (both concentrations) had no effect on fasting ATBF; only atropine 10(-4) mol/l decreased post-glucose ATBF [iAUC: 1.25 (0.32-2.91) vs. 1.98 (0.64-2.94); P = 0.04]. This effect was further apparent in R. Mecamylamine had no impact on fasting and postglucose ATBF in R and NR. Our results suggest that the cholinergic system is implicated in ATBF regulation, although it has no role in the blunting of ATBF response in NR., (Copyright © 2015 the American Physiological Society.)

The dog is a widely-used model for conducting metabolic studies. This is mainly due to its large size and its physiology which is relatively similar to that of humans. Here, we attempted to optimize a postprandial metabolic study protocol used in dogs. Following acclimatization, female mongrel dogs underwent 9 h profiling for time-course baseline plasma data on triglyceride, adrenocorticotropic hormone (ACTH) and cortisol levels. One week later, carotid and jugular catheters were surgically inserted for sampling and infusions. Initial post-operative care, based on the literature (Protocol 1), consisted of analgesia (buprenorphine every 8-12 h and 2-3 doses/day of acepromazine), restriction by Pavlov harness within cages, and a two- to three-day recovery period. Throughout the experiment, dogs received a lipid tracer diluted in 5% bovine serum albumin (BSA). Compared with baseline, animals vomited (n = 6/6) and exhibited high ACTH + cortisol levels (stress biomarkers), resulting in blunted triglyceride peak levels. To avoid these undesirable effects, post-operative care was modified (Protocol 2) as follows: animals (n = 19) were given a single dose of buprenorphine and no acepromazine, were unrestrained and free to move within cages, the recovery period was extended to seven days, and the lipid tracer was diluted in 0.002% versus 5% BSA. Using this modified protocol, postprandial plasma-triglyceride and ACTH/cortisol patterns were similar to baseline values. Controlling for stressors, as well as for factors which may alter proper digestion, is critical for all postprandial metabolic studies. Our results show that an optimized postprandial metabolic protocol used in dogs reduces experimental variability, while improving animal care and comfort., (© The Author(s) 2015.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Context: Although growing evidence points toward a role of lipotoxicity in the development of hyperandrogenesis, the main feature of polycystic ovary syndrome, few studies directly assessed this association in vivo in humans, and none targeted the ovarian milieu., Objective: The main objective of this study was to correlate follicular fluid (FF) T levels with lipids, lipid metabolites, and inflammation markers., Design: This was a cross-sectional study., Setting: Recruitment was performed in two fertility clinics at one private and one academic center., Participants: Eighty women requiring in vitro fertilization were recruited during one of their scheduled visit at the fertility clinic. All women aged between 18 and 40 years with a body mass index between 18 and 40 kg/m(2) were invited to participate., Intervention(s): There were no interventions., Main Outcome Measure(s): At the time of oocyte aspiration, FF was collected and analyzed for total T, lipids [nonesterified fatty acids (NEFAs) plus triglycerides], NEFA metabolites (acylcarnitines; markers of ineffective NEFAs β-oxidation), and inflammatory marker composition. The hypothesis being tested was formulated before the data collection., Results: FF T levels were significantly correlated with FF levels of lipids (r = 0.381, P = .001; independently of IL-6), acylcarnitines (r ≥ 0.255, all P = .008; not independently of lipids), and IL-6 (r = 0.300, P = .009, independently of lipids). Additionally, FF lipid levels were significantly and strongly correlated with acylcarnitines (r ≥ 0.594; all P < .001)., Conclusions: These results suggest that ovarian androgen production is related to intraovarian exposure to lipids, independently of inflammation and mainly through ineffective NEFA β-oxidation (as shown by higher acylcarnitine levels). Inflammation is also associated with intraovarian androgenesis, independently of lipids.

Background: In class II and III obese individuals, lifestyle intervention is the first step to achieve weight loss and treat obesity-related comorbidities before considering bariatric surgery. A systematic review, meta-analysis, and meta-regression were performed to assess the impact of lifestyle interventions incorporating a physical activity (PA) component on health outcomes of class II and III obese individuals., Methods: An electronic search was conducted in 4 databases (Medline, Scopus, CINAHL and Sportdiscus). Two independent investigators selected original studies assessing the impact of lifestyle interventions with PA components on anthropometric parameters, cardiometabolic risk factors (fat mass, blood pressure, lipid and glucose metabolism), behaviour modification (PA and nutritional changes), and quality of life in adults with body mass index (BMI) ≥ 35 kg/m2. Estimates were pooled using a random-effect model (DerSimonian and Laird method). Heterogeneity between studies was assessed by the Cochran's chi-square test and quantified through an estimation of the I²., Results: Of the 3,170 identified articles, 56 met our eligibility criteria, with a large majority of uncontrolled studies (80%). The meta-analysis based on uncontrolled studies showed significant heterogeneity among all included studies. The pooled mean difference in weight loss was 8.9 kg (95% CI, 10.2-7.7; p < 0.01) and 2.8 kg/m² in BMI loss (95% CI, 3.4-2.2; p < 0.01). Long-term interventions produced superior weight loss (11.3 kg) compared to short-term (7.2 kg) and intermediate-term (8.0 kg) interventions. A significant global effect of lifestyle intervention on fat mass, waist circumference, blood pressure, total cholesterol, LDL-C, triglycerides and fasting insulin was found (p<0.01), without significant effect on HDL-C and fasting blood glucose., Conclusions: Lifestyle interventions incorporating a PA component can improve weight and various cardiometabolic risk factors in class II and III obese individuals. However, further high quality trials are needed to confirm this evidence, especially beyond weight loss.

Polycystic ovary syndrome is a frequent disorder in women of reproductive age that consists of a heterogeneous combination of hyperandrogenism, chronic anovulation, and polycystic ovaries. Hyperandrogenism and anovulation are clearly linked to insulin resistance and compensatory hyperinsulinism, with an ovarian androgenic hyperresponsiveness to circulating insulin. Evidence is increasing that suggests that lipotoxicity, which is a key mechanism in the development of insulin resistance and type 2 diabetes, could also explain the androgen overproduction. During adolescence, diagnosis of polycystic ovarian syndrome (PCOS) may be difficult but is of importance because PCOS increases future risk of type 2 diabetes and metabolic complications. Metabolic perturbations begin early in adolescence and also exist in adolescent relatives of women with PCOS, even before clinical signs of PCOS. Screening for impaired glucose tolerance or type 2 diabetes is also important in this population, and treatment should focus on PCOS clinical manifestations as well as long-term metabolic risk.