Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease Results From the Women's Health Initiative

ObjectivesThe aim of this study was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD).BackgroundSedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exist on the interrelationship between these 2 components of energy balance.MethodsParticipants in the prospective Women’s Health Initiative Observational Study (n = 71,018), 50 to 79 years of age and free of CVD at baseline (1993 to 1998), provided information on sedentary behavior, defined as hours of sitting/day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated.ResultsSitting ≥10 h/day compared with ≤5 h/day was associated with increased CVD risk (hazard ratio: 1.18, 95% confidence interval: 1.09 to 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (p for trend < 0.001). When women were cross-classified by sitting time and physical activity (p for interaction = 0.94), CVD risk was highest in inactive women (≤1.7 metabolic equivalent task-h/week) who also reported ≥10 h/day of sitting. Results were similar for coronary heart disease and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women 70 years of age and older compared with younger women.ConclusionsProlonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk

Pre-sleep feeding, sleep quality, and markers of recovery in division I NCAA female soccer players

Pre-sleep nutrition habits in elite female athletes have yet to be evaluated. A retrospective analysis was performed with 14 NCAA Division I female soccer players who wore a WHOOP, Inc. band – a wearable device that quantifies recovery by measuring sleep, activity, and heart rate metrics through actigraphy and photoplethysmography, respectively – 24 h a day for an entire competitive season to measure sleep and recovery. Pre-sleep food consumption data were collected via surveys every 3 days. Average pre-sleep nutritional intake (mean ± sd: kcals 330 ± 284; cho 46.2 ± 40.5 g; pro 7.6 ± 7.3 g; fat 12 ± 10.5 g) was recorded. Macronutrients and kcals were grouped into high and low categories based upon the 50th percentile of the mean to compare the impact of a high versus low pre-sleep intake on sleep and recovery variables. Sleep duration (p = 0.10, 0.69, 0.16, 0.17) and sleep disturbances (p = 0.42, 0.65, 0.81, 0.81) were not affected by high versus low kcal, PRO, fat, CHO intake, respectively. Recovery (p = 0.81, 0.06, 0.81, 0.92), RHR (p = 0.84, 0.64, 0.26, 0.66), or HRV (p = 0.84, 0.70, 0.76, 0.93) were also not affected by high versus low kcal, PRO, fat, or CHO consumption, respectively. Consuming a small meal before bed may have no impact on sleep or recovery

Myths and Methodologies: Reducing scientific design ambiguity in studies comparing sexes and/or menstrual cycle phases

In recent years, the increase in scientific literature exploring sex differences has been beneficial to both clinicians and allied health science professionals, although female athletes are still significantly under‐represented in sport and exercise science research. Women have faced exclusion throughout history though the complexities of sociocultural marginalization and biomedical disinterest in women's health. These complexities have contributed to challenges of studying women and examining sex differences. One underlying complexity to methodological design may be hormonal perturbations of the menstrual cycle. The biphasic responses of oestrogen and progesterone across the menstrual cycle significantly influence physiological responses, which contribute to exercise capacity and adaptation in women. Moreover, oral contraceptives add complexity through the introduction of varying concentrations of circulating exogenous oestrogen and progesterone, which may moderate physiological adaptations to exercise in a different manner to endogenous ovarian hormones. Thus, applied sport and exercise science research focusing on women remains limited, in part, by poor methodological design that does not define reproductive status. By highlighting specific differences between phases with regard to hormone perturbations and the systems that are affected, methodological inconsistencies can be reduced, thereby improving scientific design that will enable focused research on female athletes in sports science and evaluation of sex differences in responses to exercise. The aims of this review are to highlight the differences between endogenous and exogenous hormone profiles across a standard 28–32 day menstrual cycle, with the goal to improve methodological design for studies exploring sex differences, menstrual cycle phase differences and/or endogenous versus exogenous female sex hormones

Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer disease

Background—Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis. Methods and Results—Using summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels of association with C-reactive protein, low-density lipoprotein, high-density lipoprotein, and triglyceride single-nucleotide polymorphisms using a false discovery rate threshold <0.05. By conditioning on polymorphisms associated with the 4 phenotypes, we identified 55 loci associated with increased AD risk. We then conducted a meta-analysis of these 55 variants across 4 independent AD cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2 genome-wide significant variants on chromosome 4 (rs13113697; closest gene, HS3ST1; odds ratio=1.07; 95% confidence interval=1.05–1.11; P=2.86×10−8) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04–1.11; P=3.38×10−8). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains. Conclusions—We demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By conditioning on the genetic association with the cardiovascular phenotypes, we identify novel AD susceptibility loci, including 2 genome-wide significant variants conferring increased risk for AD.acceptedVersio

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Advancing Knowledge of the Bio-Cultural Complexities of Low Energy Availability: The Value of Mixed-Methods Approaches

Low energy availability (LEA) is a complex health condition that most commonly affects female athletes. Research on LEA is weighted to quantitative approaches, and few studies have employed qualitative methods to understand the development of LEA. Current research fails to understand the complexity of LEA by largely operating within isolated research paradigms. This paper aims to demonstrate the value of integrating a mixed-methods research approach to understand the influence of sporting cultures on the physiological experiences of female athletes with LEA. The mixed-methods approach implemented the use of physiological (quantitative) and socio-psychological (qualitative) data obtained from elite female athletes in three sports: triathlons and running, (n = 11), rugby sevens (n = 9), and track cycling (n = 10). The physiological data consisted of energy availability, haematological analysis, bone health, and body composition. The socio-psychological data consisted of individual semi-structured interviews with topics covering nutrition, body image, the impact of the sporting environment, and experience with LEA. The interview data were thematically analysed. By bringing qualitative and quantitative data together, this paper illustrates the complex relationship between sporting culture and the physiology of LEA. First, endurance athletes categorised as having an LEA showed a positive correlation between the relative energy intake (EI) and serum ferritin, with the interviews revealing a focus on a low body weight and reducing the EI. Second, the interviews with the rugby players showed a strong but hierarchical team culture, with the experienced players monitoring and controlling the EI of novice players. Third, among the cyclists, the EI was reduced in those categorised as having an LEA, with the interviews revealing a coach–athlete power relationship impacting dietary behaviours. To conclude, this paper demonstrates how mixed methods are important for capturing how different sporting cultures impact athletes’ socio-psychological and physiological experiences of LEA

Fluid intake behavior in athletes during typical training bouts

BACKGROUND: Hydration habits during training may differ depending on sports mode and individual characteristics. The aim of this study was to assess fluid intake behavior in a wide sample of Italian athletes during their regular training. METHODS: Data on hydration habits during training were collected from a random sample of competitive athletes. Hydration strategies and personal characteristics were queried via questionnaire, including athletes' quantity and type of fluid ingested during a typical training bout, sport characteristics (e.g. mode and training duration), and whether their coach encouraged them to drink during trainings. RESULTS: Three hundred and fifty-two competitive athletes participated to the study; two hundred eighty-nine athletes correctly completed all survey items (age: 8-63 years, median: 21\ub113 years). Athletes were involved in international (3.1%), national (34.1%) and regional (44.9%) competitions. Median fluid intakes during training were 0.25 L/h; 150 athletes reported fluid intake below the median, whilst 23 athletes (6.5% of total sample) reported fluid intake at or above currently published exercise hydration guidelines (NATA and ACSM). Binary logistic regression indicated that the number of pauses to drink (B=0.771, P=0.000), duration of a typical training bout (B=-2.237, P=0.000), and a coach's encouragement to drink (B=0.601, P=0.030) were each associated with fluid consumption above or below the median value. CONCLUSIONS: Athletes across all disciplines reported drinking less fluid during training than currently espoused in hydration guidelines. A coach's encouragement to drink, the number of pauses during training, and bout duration each influence total fluid volume consumed, regardless of competition level, sex or the age of an athlet