Search

Introduction: Professional identity formation (PIF) is an ongoing, self-reflective process involving habits of thinking, feeling and acting like a physician and is an integral component of medical education. While qualitative work has suggested that PIF is informed by professionalism, resilience, and leadership, there is a dearth of quantitative work in this area. Multiple methods build rigor and the present study aimed to quantitatively assess the relative psychometric contributions of professionalism, resilience, and leadership constructs to informing PIF, using a latent factor analysis approach., Methods: We analyzed data from the PILLAR study, which is an online cross-sectional assessment of a pre-clinical cohort of medical students in the RCSI University of Medicine and Health Sciences, Dublin, using established and validated quantitative measures in each area of interest: PIF, professionalism, leadership and resilience. A total of 76 items, combining four validated scales, along with a selection of demographic questions, were used. The hypothesis that PIF is informed by, and correlates with, professionalism, resilience and leadership was examined by conducting a confirmatory factor analysis of a proposed three-factor higher-order model. Model estimation used Maximum Likelihood Method (MLM) with geomin rotation. The hypothesized (measurement) model was examined against an alternative (saturated) model, as well as a three-factor model., Results: Latent variable analysis from 1,311 students demonstrated that a three-factor higher-order model best fit the data; suggesting PIF is informed by professionalism, resilience, and leadership, and that these constructs are statistically distinct and account for differential aspects of PIF. This higher-order model of PIF outperformed both the saturated model and the three-factor model. The analysis of which component may be the most or least influential was inconclusive, and the overall model was not influenced by year of training., Discussion: Building upon existing conceptual contentions, our study is the first to quantitatively support the contribution of professionalism, resilience, and leadership to the development of professional identity, and to delineate the inter-relationships between PIF and these constructs. This information can be used by medical educators when designing curricula and educational strategies intended to enhance PIF. Future work should seek to assess the influence of these constructs longitudinally., 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 Ryan, Moran, Byrne, Hickey, Boland, Harkin, Guraya, Bensaaud and Doyle.)

Objectives: With the rising global burden of stroke-related morbidity, and increased focus on patient-centered healthcare, patient reported outcome measures (PROMs) are increasingly used to inform healthcare decision-making. Some stroke patients with cognitive or motor impairments are unable to respond to PROMs, so proxies may respond on their behalf; the reliability of which remains unclear. The aim of the study is to update a 2010 systematic review to investigate the inter-rater reliability of proxy respondents answering PROMs for stroke patients., Materials and Methods: Studies on the reliability of proxy respondents in stroke were searched within CINAHL, Embase, PsycInfo, and WoS databases (01/07/22, 08/07/22). Fifteen studies were included for review. ICC and k-statistic were extracted for PROMs scales and categorized as poor (0.80). Bias was assessed using the CCAT., Results: Five studies reported PROMs with inter-rater reliability scores ranging from 0.80. Two studies reported activities of daily living (ADLs) scores ranging from 0.41 to 0.80 and 8 studies reported quality of life (QoL) measures with scores ranging from 0.80. Subcategories of these scales included physical (ICC/k-statistic 0.41- >0.8), cognitive (ICC/k-statistic 0.40-0.80), communication (ICC/k-statistic <0.4-0.80,) and psychological (ICC/k-statistic <0.40-0.60) measures., Conclusions: Proxy respondents are reliable sources for PROM reports on physical domains in ADLs, PROMs and QoL scales. Proxy reports for measures of communication and psychological domains had greater variability in reliability scores, ranging from poor to substantial; hence, caution should be applied when interpreting proxy reports for these domains., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations., Methods: We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables., Results: Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively., Conclusions: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women., (© 2023. The Author(s).)

Background: Medical students have reported high prevalence of mental health difficulties and burnout. However, there are limited investigations examining the association between resilience and these difficulties. We investigated: (1) depression, anxiety, personal and professional burnout, and comorbidity; (2) demographic and education characteristics associated with these outcomes; (3) the association between resilience and these outcomes; and (4) whether these results were attributable to sampling bias., Methods: Participants were n  = 521 medical students from RCSI University of Medicine and Health Sciences. Outcomes were measured using validated scales. We report descriptive statistics, and risk factors for the difficulties were investigated using generalized linear modelling., Results: One-in-three students reported incidence of depression or anxiety (24.5% co-morbidity). 8.9% of students reported all four difficulties. Difficulties were more common in female students and those in middle years of the programme. Resilience was negatively correlated with all outcomes and stable across demographic and educational variables. Weighting the data for sampling bias did not affect these results., Conclusions: Our results emphasise the high incidence of depression, anxiety, burnout, and comorbidity in students. We advocate for further investigation into the role of resilience as a modifiable factor that may ameliorate the incidence of depression, anxiety, and burnout in medical students.

Background: School based running programmes, such as The Daily Mile™, positively impact pupils' physical health, however, there is limited evidence on psychological health. Additionally, current evidence is mostly limited to examining the acute impact. The present study examined the longer term impact of running programmes on pupil cognition, wellbeing, and fitness., Method: Data from 6,908 school pupils (mean age 10.2 ± 0.7 years), who were participating in a citizen science project, was examined. Class teachers provided information about participation in school based running programmes. Participants completed computer-based tasks of inhibition, verbal and visual-spatial working memory, as well as the Children's Feeling scale and Felt arousal scale to determine subjective wellbeing. A multistage 20-m shuttle run test was used to estimate fitness., Results: From our total sample of 6,908 school pupils, 474 participants had been taking part in a running programme for <2 months (Shorter term participation); 1,004 participants had Longer Term participation (>3 months); and 5,430 did not take part in a running programme. The Longer Term participation group had higher fitness levels than both other groups and this remained significant when adjusted for age, sex and SES. Moderated regression analysis found that for the Shorter Term participation group, higher shuttle distance was associated with better visual-spatial working memory. Effect sizes were small though., Conclusion: We identified small and selective positive impact of participation in school based running programmes on fitness and cognition. While no long term benefit was identified for cognition or wellbeing, the impact on fitness and short term benefit suggest schools should consider participation., Competing Interests: JB and CM currently sit on the research advisory group for The Daily Mile Foundation but did not at the time of study design and data collection. They receive no payment or expenses for this though and their role is to advise concerning research priorities only. The Daily Mile Foundation had no role in the present research. The remaining 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 © 2022 Booth, Chesham, Brooks, Gorely and Moran.)

Cyclical changes in hormone profiles across the menstrual cycle are associated with alterations in metabolic control. MicroRNAs (miRNAs) contribute to regulating metabolic control, including adipose tissue metabolism. How fluctuations in hormonal profiles across the menstrual cycle affect adipose tissue miRNA expression remains unknown. Eleven healthy, regularly menstruating females underwent four sampling visits across their menstrual cycle. Subcutaneous abdominal adipose tissue and venous blood samples were collected at each sampling visit. Luteinizing hormone (LH) tests, calendar counting, and serum hormone concentrations were used to determine menstrual cycle phases: early-follicular (EF), late-follicular (LF), postovulatory (PO), and midluteal (ML). Serum follicle-stimulating hormone, LH, estrogen, progesterone, and testosterone were determined using multiplex magnetic bead panels and enzyme-linked immunosorbent assays. Global adipose tissue miRNA expression levels were determined via microarray in a subset of participants ( n = 8) and 17 candidate miRNAs were validated by RT-qPCR in the whole cohort ( n = 11). Global analysis of adipose tissue miRNA expression identified 33 miRNAs significantly altered across the menstrual cycle; however, no significant differences remained after correcting for multiple testing ( P > 0.05). RT-qPCR analysis of candidate miRNAs revealed miR-497-5p expression was significantly altered across the menstrual cycle ([Formula: see text] = 0.18, P = 0.03); however, post hoc tests did not reveal any significant differences between menstrual cycle phases ( P > 0.05). miR-30c-5p was associated with testosterone concentration ( R 2 = 0.13, P = 0.033). These pilot data indicate differences in adipose tissue miRNAs in healthy women across the menstrual cycle and a weak association with ovarian hormones. Further research in larger sample sizes is required to confirm regulation of miRNA expression across the menstrual cycle.

Studies on adipose tissue are useful in understanding metabolic and other conditions. Human subcutaneous adipose tissue is accessible. With appropriate training and strict adherence to aseptic technique, subcutaneous adipose samples can be safely and efficiently obtained in a non-clinical setting by researchers. Following the administration of local anesthetic lateral to the umbilicus, a 14 G needle attached to a 5 or 10 mL syringe is inserted through the skin into the subcutaneous tissue. Under suction, the syringe is moved in a reciprocating, slicing motion to isolate fragments of adipose tissue. Withdrawing the plunger is enough to ensure that adipose tissue fragments are aspirated through the needle into the syringe. A single biopsy can collect about 200 mg of tissue. This biopsy technique is very safe for both participants and research staff. Following the biopsy, participants can resume most everyday activities, although they should avoid swimming and overly strenuous activities for 48 h to avoid excessive bleeding. Participants can safely undergo 2 biopsies within a single day, meaning that the technique can be applied in before-after acute intervention studies.

Context: There is evidence demonstrating variation in insulin sensitivity across the menstrual cycle. However, to date, research has yielded inconsistent results., Objective: This study investigated variation in insulin sensitivity across the menstrual cycle and associations with body mass index (BMI), physical activity, and cardiorespiratory fitness (CRF)., Methods: Data from 1906 premenopausal women in NHANES cycles 1999 to 2006 were analyzed. Menstrual cycle day was assessed using questionnaire responses recording days since last period. Rhythmic variation of plasma glucose, triglycerides, and insulin, homeostatic model of insulin resistance (HOMA-IR), and adipose tissue insulin resistance index (ADIPO-IR) across the menstrual cycle were analyzed using cosinor rhythmometry. Participants were assigned low or high categories of BMI, physical activity, and CRF, and category membership included in cosinor models as covariates., Results: Rhythmicity was demonstrated by a significant cosine fit for glucose (P = .014) but not triglycerides (P = .369), insulin (P = .470), HOMA-IR (P = .461), and ADIPO-IR (P = .335). When covariates were included, rhythmicity was observed when adjusting for: 1) BMI: glucose (P < .001), triglycerides (P < .001), insulin (P < .001), HOMA-IR (P < .001), and ADIPO-IR (P < .001); 2) physical activity: glucose (P < .001), triglycerides (P = .006), and ADIPO-IR (P = .038); and 3) CRF: triglycerides (P = .041), insulin (P = .002), HOMA-IR (P = .004), and ADIPO-IR (P = .004). Triglyceride amplitude, but not acrophase, was greater in the high physical activity category compared to low (P = .018)., Conclusion: Rhythmicity in insulin sensitivity and associated metabolites across the menstrual cycle are modified by BMI, physical activity, and CRF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

The consistently observed age-accompanied diminution in mind-wandering stands seemingly opposed to accounts that present mind-wandering as a failure of executive control. This study examined the impact of aging on the frequency and phenomenology of mind-wandering and investigated distinct variables mediating age-related differences in unintentional and intentional mind-wandering. Thirty-four younger and 34 healthy older adults completed a neuropsychological test battery and contrast change detection task embedded with experience sampling probes asking participants to discriminate the nature of their thoughts. Results revealed age-related decreases in unintentional and intentional mind-wandering, but equivalent task accuracy. Parallel mediations demonstrated that older adults reduced their unintentional mind-wandering through having less anxiety and greater task engagement than younger adults. Despite the evidence of age-related decline on cognitive function tests, neither executive function nor task demand variables further contributed to the model. Our results adjudicate between competing theories, highlighting the roles of affective and motivational factors in unintentional mind-wandering. Intentional mind-wandering showed no significant associations with the neuropsychological measures; however, intentional mind-wandering was associated with more false alarms, which was mediated by greater reaction time variability (RTV). In the context of the exploitation/exploration framework, we suggest that younger adults were more inclined to intentionally mind-wander, indexed by increased RTV, while preserving comparable performance accuracy to older adults. Conversely, older adults exploited greater task focus, marked by reduced RTV, with less bias toward, or resources for, exploration of the mind-wandering space. Therefore, dispositional and strategic factors should be considered in future investigations of mind-wandering across the lifespan. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Understanding human physiological responses to high-fat energy excess (HFEE) may help combat the development of metabolic disease. We aimed to investigate the impact of manipulating the n-3PUFA content of HFEE diets on whole-body and skeletal muscle markers of insulin sensitivity. Twenty healthy males were overfed (150% energy, 60% fat, 25% carbohydrate, 15% protein) for 6 d. One group (n = 10) received 10% of fat intake as n-3PUFA rich fish oil (HF-FO), and the other group consumed a mix of fats (HF-C). Oral glucose tolerance tests with stable isotope tracer infusions were conducted before, and following, HFEE, with muscle biopsies obtained in basal and insulin-stimulated states for measurement of membrane phospholipids, ceramides, mitochondrial enzyme activities, and PKB and AMPKα2 activity. Insulin sensitivity and glucose disposal did not change following HFEE, irrespective of group. Skeletal muscle ceramide content increased following HFEE (8.5 ± 1.2 to 12.1 ± 1.7 nmol/mg, p = .03), irrespective of group. No change in mitochondrial enzyme activity was observed following HFEE, but citrate synthase activity was inversely associated with the increase in the ceramide content (r=-0.52, p = .048). A time by group interaction was observed for PKB activity (p = .003), with increased activity following HFEE in HF-C (4.5 ± 13.0mU/mg) and decreased activity in HF-FO (-10.1 ± 20.7 mU/mg) following HFEE. Basal AMPKα2 activity increased in HF-FO (4.1 ± 0.6 to 5.3 ± 0.7mU/mg, p = .049), but did not change in HF-C (4.6 ± 0.7 to 3.8 ± 0.9mU/mg) following HFEE. We conclude that early skeletal muscle signaling responses to HFEE appear to be modified by dietary n-3PUFA content, but the potential impact on future development of metabolic disease needs exploring., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: School-based physical activity and running programmes, such as The Daily Mile™, are increasing in popularity globally. The aim of this research was to examine the acute impact of such classroom physical activity breaks on cognition and affective wellbeing., Methods: A total of 5463 school pupils from 332 schools took part in a citizen science project with a repeated measures design. They completed tasks of cognition (inhibition, verbal, and visuo-spatial working memory) and the Children's Feeling Scale and Felt Arousal Scale before and after three different outdoor activities: a classroom break of 15 min of self-paced activity, a near maximal exhaustion activity (the bleep test), and a no-exercise control group where pupils sat or stood outside. Wellbeing and fitness were examined as mediators of the relationship between outdoor activity and cognition., Results: Fifteen minutes of self-paced outdoor activity was beneficial for pupils' cognition and wellbeing in comparison to both other activities (Cohen's d effect sizes ranging from 0.04 to 0.22; small). The relationship with cognition was not mediated by participants' fitness level and was only partially mediated by wellbeing. Change scores for alertness were higher after the bleep test compared to the control activity but similar for all other outcomes., Conclusions: Taking a break from the classroom to complete 15 min of self-paced physical activity should be considered a worthwhile activity by class teachers, school management, and policymakers. Additionally, more intense physical activity should not be considered to be detrimental.

There is evidence across a range of bi-parental species that physiological changes may occur in partnered males prior to the birth of an infant. It has been hypothesised that these hormonal changes might facilitate care-giving behaviours, which could augment infant survival. The mechanism that induces these changes has not been identified, but evidence from several species suggests that odour may play a role. The current study investigated this in humans by recording testosterone and psychological measures related to infant interest and care in men (n = 91) both before and after exposure to odours from either pregnant women or non-pregnant control women. We found no evidence for an effect of odour cues of pregnancy on psychological measures including self-reported sociosexual orientation and social dominance scores, ratings of infant or adult faces, or testosterone levels. However, we found that brief exposure to post-partum odours significantly increased the reward value of infant faces. Our study is the first to show that the odour of peri-partum women may lead to upregulation of men's interest in infants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite the known benefits of a physically active lifestyle, there are few examples of interventions that have been successfully implemented at a population level over a long period of time. One such example is The Daily Mile, a school based physical activity initiative, where a teacher takes their class out daily during class time for a short bout of ambulatory activity. At one school, this activity appears has been sustained over a long period (6 years), has the whole school participating and is now incorporated into its daily routine. The aim of this paper was to understand how The Daily Mile was implemented in primary schools and to assess factors associated with its successful implementation., Methods: Semi-structured interviews with school staff who had a significant role in implementing The Daily Mile were conducted at four primary schools in central Scotland. Interviews were digitally recorded and transcribed verbatim. Data were analysed using thematic analysis and descriptive analysis and interpretation of data undertaken. Details regarding the school grounds and facilities were also noted during the interviews., Results: Having simple core intervention components, flexible delivery that supports teacher autonomy and being adaptable to suit the specific primary school context appear to be key aspects of The Daily Mile that are related to its implementation success. Other factors relating to how The Daily Mile was developed, trialled and rolled out might also have contributed towards its successful implementation., Conclusion: The Daily Mile appears to have several factors which may relate to its implementation success. These are important considerations for others looking to implement The Daily Mile effectively in their primary school or in other contexts., Competing Interests: The authors have declared that no competing interests exist.

Background: The Daily Mile is a physical activity programme made popular by a school in Stirling, Scotland. It is promoted by the Scottish Government and is growing in popularity nationally and internationally. The aim is that each day, during class time, pupils run or walk outside for 15 min (~1 mile) at a self-selected pace. It is anecdotally reported to have a number of physiological benefits including increased physical activity, reduced sedentary behaviour, increased fitness and improved body composition. This study aimed to investigate these reports., Methods: We conducted a quasi-experimental repeated measures pilot study in two primary schools in the Stirling Council area: one school with, and one without, intention to introduce the Daily Mile. Pupils at the control school followed their usual curriculum. Of the 504 children attending the schools, 391 children in primary classes 1-7 (age 4-12 years) at the baseline assessment took part. The follow-up assessment was in the same academic year. Outcomes were accelerometer-assessed average daily moderate to vigorous intensity physical activity (MVPA) and average daily sedentary behaviour, 20-m shuttle run fitness test performance and adiposity assessed by the sum of skinfolds at four sites. Valid data at both time points were collected for 118, 118, 357 and 327 children, respectively, for each outcome., Results: After correction for age and gender, significant improvements were observed in the intervention school relative to the control school for MVPA, sedentary time, fitness and body composition. For MVPA, a relative increase of 9.1 min per day (95% confidence interval or 95%CI 5.1-13.2 min, standardised mean difference SMD = 0.407, p = 0.027) was observed. For sedentary time, there was a relative decrease of 18.2 min per day (10.7-25.7 min, SMD = 0.437, p = 0.017). For the shuttle run, there was a relative increase of 39.1 m (21.9-56.3, SMD = 0.236, p = 0.037). For the skinfolds, there was a relative decrease of 1.4 mm (0.8-2.0 mm, SMD = 0.246, p = 0.036). Similar results were obtained when a correction for socioeconomic groupings was included., Conclusions: The findings show that in primary school children, the Daily Mile intervention is effective at increasing levels of MVPA, reducing sedentary time, increasing physical fitness and improving body composition. These findings have relevance for teachers, policymakers, public health practitioners, and health researchers.

Cyclists in the Tour de France are endurance specialists. Twin and family studies have shown that approximately 50% of the variance in a number of performance-related phenotypes (whether measured at baseline, i.e., natural talent, or in response to training) including those important to cycling can be explained by genetic variation. Research into the specific genetic variants that are responsible has identified over 200 genes containing common genetic variants involved in the genetic predisposition to physical performance. However, typically these explain only a small portion of the variance, perhaps 1-2% and collectively they rarely explain anything approaching the 50% of the variance identified in the twin and family studies. Thus, there is a gap in our understanding of the relationship between heritability and performance. This gap may be bridged by investigation of rare variants or epigenetic variation or by altering study designs through increased collaborations to pool existing cohorts together. Initial findings from such efforts show promising results. This mini-review will touch on the genetics and epigenetics of sporting performance, how they relate to cyclists in the Tour de France and where best future efforts may be directed as well as discuss some preliminary research findings.

Rationale: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported., Objectives: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA)., Methods: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use., Measurements and Main Results: Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV 1 was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure "actual adherence" was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique., Conclusions: These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium., (Copyright © 2016 the American Physiological Society.)

Despite numerous attempts to discover genetic variants associated with elite athletic performance, an individual's trainability and injury predisposition, there has been limited progress to date. Past reliance on candidate gene studies focusing predominantly on genotyping a limited number of genetic variants in small, often heterogeneous cohorts has not generated results of practical significance. Hypothesis-free genome-wide approaches will in the future provide more comprehensive coverage and in-depth understanding of the biology underlying sports-related traits and related genetic mechanisms. Large, collaborative projects with sound experimental designs (e.g. clearly defined phenotypes, considerations and controls for sources of variability, and necessary replications) are required to produce meaningful results, especially when a hypothesis-free approach is used. It remains to be determined whether the novel approaches under current implementation will result in findings with real practical significance. This review will briefly summarize current and future directions in exercise genetics and genomics., (© 2016 S. Karger AG, Basel.)

DNA methylation is modifiable by acute and chronic exercise. DNA methyltransferases (DNMT) catalyze this process; however, there is a lack of literature concerning the specific mechanisms by which exercise-induced modifications occur. Interleukin 6 (IL-6) stimulation of various cell lines has been shown to augment DNMT expression and nuclear translocation, which suggests a possible pathway by which exercise is able to elicit changes in epigenetic enzymes. The present study sought to elucidate the response of the de novo methyltransferases DNMT3A and DNMT3B to circulatory factors found in plasma isolated from whole blood before and after 120-min of treadmill running at an intensity of 60% of individual velocity at V˙O2max (vV˙O2max) interspersed with 30-sec sprints at 90% of vV˙O2max every 10-min. Peripheral blood mononuclear cells (PBMCs) isolated from a resting participant were incubated with plasma isolated from exercising participants (n = 10) or recombinant IL-6 (rIL-6), followed by nuclear protein extraction and quantification of DNMT3A and DNMT3B concentrations. Nuclear concentrations of DNMT3B significantly decreased following the experimental protocol (P = 0.03), with no change observed in DNMT3A (P = 0.514).Various concentrations of rIL-6 caused an elevation in both DNMT3A and DNMT3B nuclear concentration compared with the blank control. The conflicting results between exercising and rIL-6 conditions suggests that IL-6 does regulate DNMT nuclear transport, however, other plasma mediators may also exert significant influence on the nuclear concentrations of these enzymes., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Aim: MicroRNAs (miRNAs) are stable in the circulation and are likely to function in inter-organ communication during a variety of metabolic responses that involve changes in gene expression, including exercise training. However, it is unknown whether differences in circulating-miRNA (c-miRNA) levels are characteristic of training modality., Methods: We investigated whether levels of candidate c-miRNAs differ between elite male athletes of two different training modalities (n = 10 per group)--endurance (END) and strength (STR)--and between these groups and untrained controls (CON; n = 10). Fasted, non-exercised, morning plasma samples were analysed for 14 c-miRNAs (miR-1, miR-16-2, miR-20a-1, miR-21, miR-93, miR-103a, miR-133a, miR-146a, miR-192, miR-206, miR-221, miR-222, miR-451, miR-499). Moreover, we investigated whether c-miRNA levels were associated with quantitative performance-related phenotypes within and between groups., Results: miR-222 was present at different levels in the three participant groups (p = 0.028) with the highest levels being observed in END and the lowest in STR. A number of other c-miRNAs were present at higher levels in END than in STR (relative to STR, ± 1 SEM; miR-222: 1.94 fold (1.73-2.18), p = 0.011; miR-21: 1.56 fold (1.39-1.74), p = 0.013; miR-146a: 1.50 fold (1.38-1.64), p = 0.019; miR-221: 1.51 fold (1.34-1.70), p = 0.026). Regression analyses revealed several associations between candidate c-miRNA levels and strength-related performance measures before and after adjustment for muscle or fat mass, but not following adjustment for group., Conclusion: Certain c-miRNAs (miR-222, miR-21, miR-146a and miR-221) differ between endurance- and resistance-trained athletes and thus have potential as useful biomarkers of exercise training and / or play a role in exercise mode-specific training adaptations. However, levels of these c-miRNAs are probably unrelated to muscle bulk or fat reserves.

Alpha-actinin-3 (ACTN3) is an integral part of the Z line of the sarcomere. The ACTN3 R577X (rs1815739) polymorphism determines the presence or absence of functional ACTN3, which may influence the extent of exercise-induced muscle damage. This study aimed to compare the impact of, and recovery from, muscle-damaging eccentric exercise on subjects with or without functional ACTN3. Seventeen young men (20-33 years old), homozygous for the R (n = 9) or X (n = 8) alleles, performed two bouts of stretch-shortening exercise (50 drop jumps) two weeks apart. Muscle soreness, plasma creatine kinase (CK) activity, jump height, maximal voluntary isometric torque (MVC), peak concentric isokinetic torque (IT), and electrically stimulated knee extension torques at 20 and 100 Hz were measured at baseline and at a number of time points up to 14 days after each bout. There were no significant baseline differences between the groups. However, significant time point × genotype interactions were observed for MVC (p = 0.021) and IT (p = 0.011) for the immediate effect of eccentric exercise in bout 1. The RR group showed greater voluntary force decrements (RR vs. XX: MVC, -33.3% vs. -24.5%; IT, -35.9% vs. -23.2%) and slower recovery. A repeated-bout effect was clearly observed, but there were no differences by genotype group. The ACTN3 genotype modulates the response of muscle function to plyometric jumping exercise, although the differences are modest. The ACTN3 genotype does not influence the clearly observed repeated-bout effect; however, XX homozygotes recover baseline voluntary torque values faster and thus may be able to undertake more frequent training sessions.

The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population., (© 2011 Wiley-Liss, Inc.)

Daughters of diabetes patients have lower insulin sensitivity than women with no diabetes family history, but increase insulin sensitivity to a greater extent with exercise training. This study aimed to determine whether differences in circulating concentrations of adiponectin and leptin, and adipose tissue expression of their genes and receptors played a role. Women offspring of patients with type 2 diabetes mellitus (n = 34; age, 35.6 ± 7.0 years; body mass index, 28.1 ± 5.1 kg/m²) and matched controls with no diabetes family history (n = 36; age, 33.6 ± 6.1 years; body mass index, 27.3 ± 4.7 kg/m²) participated. Blood and abdominal subcutaneous adipose tissue samples were obtained at baseline and after a controlled 7-week endurance-type exercise intervention (sessions were performed at 65%-80% of maximum heart rate). At baseline, no significant differences were observed between groups in circulating leptin or adiponectin concentrations, or expression of their genes or receptors. In response to exercise, plasma leptin decreased more in offspring than controls (-32.2% vs -7.3%, P = .005 for interaction); and the long isoform of the leptin receptor messenger RNA (mRNA) increased significantly only in the offspring (+39.4%, P = .026 vs +7.7%, P = .892). Leptin mRNA decreased similarly in both groups (-24.7% vs -25.0%, P < .05 for both). Furthermore, changes in plasma leptin (r = -0.432, P < .001) and leptin mRNA (r = -0.298, P = .019) correlated significantly with changes in insulin sensitivity. Plasma adiponectin decreased similarly in both groups (-12.1% vs -15.2%, P < .01 for both), but no significant changes were observed in adiponectin-related gene expression. This work shows that exercise training has differing effects on leptin-related variables between women with and without a diabetes family history and suggests that these molecular differences may contribute to the differential effects of exercise training on insulin sensitivity between these 2 groups., (© 2011 Elsevier Inc. All rights reserved.)

A recent study investigating the molecular mechanisms of seed pod shattering has shown that the basic helix-loop-helix (bHLH) proteins INDEHISCENT and ALCATRAZ appear to regulate fruit patterning through gibberellic acid (GA)-DELLA signalling, revealing a central role for bHLH family members in GA response specificity.

Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N=1980) and 11-18-year-old Greek adolescents (N=949) were measured for adiposity-related phenotypes and genotyped at the FTO single-nucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P=0.001) and BMI (P=0.007). There was also a significant SNP(*)PA(*)gender interaction (P=0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P=0.016), but not females (P=0.15), and significant SNP(*)PA interaction in males (P=0.007), but not females (P=0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m(2) higher than T carriers (P=0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype.

Background: South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures., Methodology/principal Findings: Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml x kg(-1) x min(-1), p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg x kg(-1) x min(-1) at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg x kg(-1) x min(-1) at 25 ml O(2) x kg(-1) x min(-1), p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10-13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity., Conclusions/significance: These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.

The genetically programmed courtship song of male Drosophila melanogaster has a rhythmic repetitive structure of sound pulses that is a critical component of mate recognition. This study investigates the neuronal basis of courtship song production by using the GAL4 enhancer trap paradigm to drive the expression of UASG-tetanus toxin (TNT) and UASG-transformer (tra) in subsets of cells. Of the 727 enhancer trap lines screened for courtship song defects in this way, 38 produced a phenotype, and these were used to drive the expression of Green Fluorescent Protein (GFP), thereby implicating the corresponding neuronal structures. Twelve of 13 lines which gave vigorous courtship but did not produce song, showed GFP expression in the mushroom bodies (MBs) and the giant descending neuronal tract and/or the larval interhemispheric junction (IJ). Furthermore, the relevant DNA in which the enhancer trap was inserted was isolated and sequenced in 27 of the lines, and a number of candidate genes that have been implicated in Ras and hedgehog signalling were identified. Other candidate genes that could plausibly affect courtship song were involved in mesothoracic or axonal development.

The aim of the present study was to investigate the interaction between the angiotensin-converting enzyme 1 (ACE) I/D polymorphism and energy and macronutrient intakes on adiposity-related phenotypes among toddlers and preschoolers. A representative sample of 2374 Greek children aged 1 to 5 years old was examined (Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS)). Dietary and anthropometric (i.e. BMI, waist circumference (WC)) assessments were carried out using standard procedures. DNA samples were obtained from 2102 children and were genotyped for the ACE I/D polymorphism. Among the entire population, 17 % were 'at risk of overweight' and a similar percentage were 'overweight'. The frequencies of the II, ID and DD genotypes were 16, 46 and 38 %, respectively. Significant interactions were found between the ACE I/D polymorphism and total energy intake on WC (P = 0.004 for interaction) and the ACE I/D polymorphism and protein intake on BMI and being overweight (P < 0.05 for interaction). Furthermore, it was found that the ACE I/D polymorphism may modify the effect of fat intake on WC and BMI, but this interaction disappeared after adjustment for additional potential confounders. Stratified analyses revealed that total energy is correlated with WC and protein intake is associated with BMI and being overweight only among carriers of the D-allele (i.e. DD or ID genotypes). These results suggest that the ACE I/D polymorphism may act as a modifying factor in the response of adiposity-related phenotypes to diet.

Aims/hypothesis: Sedentary offspring of patients with type 2 diabetes are often more insulin-resistant than persons with no family history of diabetes, but when active or fit offspring of type 2 diabetic patients are compared with non-diabetic persons, differences in insulin resistance are less evident. This study aimed to determine the effects of an exercise training intervention on insulin sensitivity in both groups., Methods: Women offspring (n = 34) of type 2 diabetic patients (offspring age 35.6 +/- 7.0 years, BMI 28.1 +/- 5.1 kg/m(2)) and 36 matched female controls (age 33.6 +/- 6.1 years, BMI 27.3 +/- 4.7 kg/m(2)) participated. Body composition, fitness and metabolic measurements were made at baseline and after a controlled 7 week exercise intervention., Results: At baseline, insulin sensitivity index (ISI) was 22% lower in offspring than controls (p < 0.05), despite similar body fat and maximal oxygen uptake (.VO(2max)) values in the two groups. ISI increased by 23% (p < 0.05) in offspring following the exercise intervention, compared with 7% (NS) in the controls. Increases in .VO(2max) were similar in both groups (controls 12%, offspring 15%, p < 0.05 for both). Plasma leptin concentrations decreased significantly in the offspring (-24%, p < 0.01) but not in controls (0%, NS). Change in ISI correlated significantly with baseline ISI (r = -0.47, p < 0.0005) and change in leptin (r = -0.43, p < 0.0005). The latter relationship was not attenuated by adjustment for changes in body fat., Conclusions/interpretation: Offspring, but not controls, significantly increased ISI in response to an exercise intervention, indicating that insulin sensitivity is more highly modulated by physical activity in daughters of patients with type 2 diabetes than in women with no family history of the disease.

Objectives: To investigate the relationship between the angiotensin I-converting enzyme 1 (ACE) I/D polymorphism and adiposity-related phenotypes in a large cohort of toddlers and preschoolers., Methods: Body composition measurements and DNA samples were obtained from 2102 Greek children aged 1-6 years, as part of a large-scale epidemiological study (GENESIS). All children were genotyped for the ACE I/D polymorphism and gender- and age-stratified statistical analyses were performed., Results: In girls aged 4-6 years, the D-allele was associated with higher measurements of body mass index (BMI) (P=0.018), waist (P=0.001) and upper arm (P=0.013) circumferences, genotype accounting for 2.5, 4 and 3% of the phenotypic variance, respectively. In boys, the D-allele showed strong associations with lower BMI (P=0.001) at the age of 1-2 years that explained 17% of the phenotypic variance and with larger suprailiac skinfold (P=0.008) at 3-4 years old that explained 2% of the variance. No other significant associations between the ACE I/D polymorphism and adiposity-related phenotypes were found. In girls, the age at which significant associations were revealed coincided with the age at which BMI was observed to increase after its developmental nadir, but this feature of the association was not observed in boys., Conclusions: The ACE I/D polymorphism is associated with developmental and physiological changes in adiposity-related traits during early childhood in a gender- and age-specific manner.

The functional allele (577R) of ACTN3, which encodes human alpha-actinin-3, has been reported to be associated with elite athletic status and with response to resistance training, while the nonfunctional allele (577X) has been proposed as a candidate metabolically thrifty allele. In a study of 992 adolescent Greeks, we show that there is a significant association (P=0.003) between the ACTN3 R577X polymorphism and 40 m sprint time in males that accounts for 2.3% of phenotypic variance, with the 577R allele contributing to faster times in an additive manner. The R577X polymorphism is not associated with other power phenotypes related to 40 m sprint, nor with an endurance phenotype. Furthermore, the polymorphism is not associated with obesity-related phenotypes in our population, suggesting that the 577X allele is not a thrifty allele, and thus the persistence of this null allele must be explained in other terms.

Genetic variation in the human Angiotensin I-Converting Enzyme (ACE) gene has been associated with many heritable traits, including physical performance. Herein we report the results of a study of several physical, physiological and skill parameters and lifestyle in 1,027 teenage Greeks. We show that there is a strong association (P < 0.001) between the ACE I/D (insertion/deletion) polymorphism and both handgrip strength and vertical jump in females, homozygotes for the I-allele exhibiting higher performance-related phenotype scores, accounting for up to 4.5% of the phenotypic variance. The association is best explained by a model in which the D-allele is dominant, with the mean phenotypic value in the I/D heterozygotes being close to that of the mean of the DD homozygotes. The association acts across the phenotype distribution in a classical polygenic manner. Other polymorphisms that define major ACE haplotypes in European populations (rs4424958, rs4311) show weaker associations with these performance-related phenotypes than does I/D. Similarly, diplotypes defined by these polymorphisms do not explain significantly larger amounts of the variance than I/D alone. As ACE I/D is the polymorphism most strongly associated with circulating ACE activity in European populations, we propose that the functional allelic differences that influence ACE activity also mediate the associations with the performance-related phenotypes studied here.

Genetic variation in the human angiotensin I-converting enzyme (ACE) gene has been associated with many heritable traits, including obesity. Herein, we report the results of a study of obesity-related phenotypes and lifestyle in 1016 teen-aged Greeks. We show that there is a strong association (p = 0.001) between subcutaneous fat and the ACE insertion/deletion (I/D) polymorphism in females, possession of genotypes containing the D allele being associated with increased fat thickness. This association is strongest in females who participate in no extra exercise and accounts for 6.5% of the phenotypic variance in fat thickness by ANOVA. The association is additive, with the mean phenotypic values in heterozygotes intermediate between the means of the two homozygotes, and the association acts at both extremes of the fat thickness distribution in a classical polygenic manner. Other ACE polymorphisms (rs4424958, rs4311) that define major haplotypes in European populations fail to provide stronger associations with the subcutaneous fat phenotype. Because ACE I/D is the polymorphism most strongly associated with circulating ACE levels in European populations, we propose that the functional allelic differences that influence circulating ACE levels also mediate the associations with the obesity-related phenotypes studied here.

Previous studies have hypothesised that mitochondrial DNA (mtDNA) polymorphisms may influence aerobic performance. The matrilineal inheritance and accumulation of polymorphisms in mtDNA means that mtDNA haplogroups, characterised by key polymorphisms, are often represented at different frequencies in different populations. The present study aimed to compare the mtDNA haplogroup distribution of elite Ethiopian athletes relative to the general Ethiopian population. The haplogroup distribution of 76 endurance athletes (E), members of the Ethiopian national athletics team, was compared to 108 members of the general Ethiopian population (C). DNA was extracted from buccal swabs and haplogroups assigned by sequencing part of the hypervariable sequence (HVS-I), followed by analysis of key coding-region polymorphisms. A high proportion of African 'L' haplogroups was found in athletes and controls (C=53%; E=55%). Haplogroup distribution of endurance runners did not differ from that of C (P=0.63). Elite Ethiopian athletes are not a mitochondrially distinct group relative to the Ethiopian population. It appears that environment and, perhaps, polymorphisms in the nuclear genome are more important determinants of Ethiopian running success than mtDNA polymorphisms.

Favourable genetic endowment has been proposed as part of the explanation for the success of East African endurance athletes, but no evidence has yet been presented. The Y chromosome haplogroup distribution of elite Ethiopian athletes (n=62) was compared with that of the general Ethiopian population (n=95) and a control group from Arsi (a region producing a disproportionate number of athletes; n=85). Athletes belonged to three groups: marathon runners (M; n=23), 5-km to 10-km runners (5-10K; n=21) and other track and field athletes (TF; n=18). DNA was extracted from buccal swabs and haplogroups were assigned after the typing of binary markers in multiplexed minisequencing reactions. Frequency differences between groups were assessed by using contingency exact tests and showed that Y chromosome haplogroups are not distributed amongst elite Ethiopian endurance runners in the same proportions as in the general population, with statistically significant (P<0.05) differences being found in four of the individual haplogroups. The geographical origins and languages of the athletes and controls suggest that these differences are less likely to be a reflection of population structure and that Y chromosome haplogroups may play a significant role in determining Ethiopian endurance running success.