<p> PURPOSE: The purpose of this study was to determine if surgically-induced menopause in younger women affects substrate utilization during submaximal exercise while controlling for other potential confounds. METHODS: Thirteen untrained female subjects (33-50 years old) were recruited: oophorectomized (Group O = 5) and premenopausal controls (Group C = 8). Two separate visits included: body composition and maximal treadmill exercise test; followed by substrate utilization via open-circuit spirometry during 45 minutes of treadmill walking at 50% VO_2max. RESULTS: When controlling for multiple variables affecting whole-body substrate utilization (age, VO_2max, physical activity, body composition, fasting glucose, menstrual phase and diet), there was no difference in substrate utilization between pre- and postmenopausal women as measured by respiratory exchange ratio (RER) (0.83 &plusmn; 0.04 v 0.84 &plusmn; 0.03, <i>p</i>=0.47). CONCLUSIONS: Menopausal status does not appear to have an effect on substrate utilization during submaximal exercise in younger women.</p>

Repeated or prolonged activation of skeletal muscle results in an acute decline in the muscle's ability to produce force, which is typically referred to as fatigue. Muscle fatigue is likely related to the by-products of cellular metabolism, alterations in neural activation and diminished membrane excitability that have been shown to accompany repeated contractions. However, the complicated etiology of the fatigue process makes it difficult to understand the relative influence of these physiological responses. Computational modeling of the skeletal muscle response to repeated activation is an appealing means of gaining insight into the mechanisms of muscle fatigue. A reasonably comprehensive model would include components that represent motor neurons and populations of muscle fibers that reflect the range of metabolic and contractile characteristics known to exist in human skeletal muscle. Consideration of joint and connective tissue mechanical properties will add translational value by predicting whole joint segment behavior that can be validated by in vivo experimentation. The proposed dissertation project involved the development of a computational model incorporating multiple components meant to represent the function of the intact neuromuscular system. The complete model combines previously-validated models of neural activation and contractile behavior with a control function that attempts to match torque output to a pre-determined task. The model uses experimentally-derived functions describing metabolic cost and force inhibition to predict the loss of force generating capacity during repeated activation. Once tested using data from a group of adult men, the parameters of this model were altered to reflect age-related changes in the human neuromuscular system. The model's ability to predict the well-established phenomenon of age-related fatigue resistance during isometric contractions was then tested. The results from this series of studies support the utility of a computational approach to the investigation of muscle fatigue, and provide useful tools for future studies.

<p> Background: Data related to change in physical activity (PA) and sitting time (ST) and the association with mortality after first myocardial infarction (MI) in postmenopausal women are incomplete. A majority of the studies looking at sitting time and colorectal cancer (CRC) did not include physical activity as a potential confounder which is a significant limitation. We investigated the association between change in physical activity and sitting time among survivors of a first MI and all-cause, coronary heart disease (CHD), and cardiovascular disease mortality as well as the independent and joint associations of sitting time and physical activity with risk of incident colorectal cancer in postmenopausal women enrolled in the Women&rsquo;s Health Initiative Observational Study. </p><p> <i>Methods:</i> The WHI-OS cohort included 93,676 postmenopausal women, 50-79 years of age, enrolled between 1993 and 1998. Self-reported ST was reported at baseline, year 3 and year 6. Self-reported PA was reported at baseline and every year thereafter. All-cause, CHD and CVD mortality as well as incident colorectal cancer were the primary outcomes. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. </p><p> <i>Results:</i> Over a 13-year follow-up, 838 had a clinical MI during follow-up and adequate data on exposures. The risk of all-cause mortality was: 0.43 (0.28-0.70) for the increased activity group and 0.54 (0.38-0.76) for the active, no change group. Women who had pre-MI levels of sitting time &lt; 8 hrs/d had an 11% increased risk (HR= 1.11, 95% CI: 1.01, 1.23) of all-cause mortality for every 1 hr/d increase in sitting time. In the CRC analysis, 74,870 participants were included. Inactivity (&le; 1.7 MET-hrs/wk) was associated with increased risk of rectal cancer and marginally significant increase in CRC (HR=2.23, 95% CI: 1.32 &ndash; 3.79) and (HR=1.20, 95% CI: 0.98 &ndash; 1.48), respectively. </p><p> <i>Conclusions:</i> In conclusion, our findings support the hypothesis that meeting the recommended physical activity guidelines pre- and post-MI has a protective role against mortality in postmenopausal women. Also increased sitting time post-MI was associated with an increased risk of all-cause mortality. Lack of PA was associated with increased risk of rectal cancer and marginally significant increase in CRC.</p>