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Obesity may be a modifiable risk factor for pelvic floor disorders.The objective of this study is to determine associations between weight, weight changes, and cumulative exposure to excess body mass index (BMI) from prepregnancy to 1 year postpartum on pelvic floor support and symptoms 1 year after first vaginal birth.In 645 primiparous women who gave birth vaginally, we assessed anatomic pelvic floor support, pelvic floor symptoms and BMI at the third trimester, 5 - 10 weeks, and 1 year postpartum; we also assessed BMI prepregnancy and predelivery. Using multivariable models, we determined associations between pelvic floor outcomes 1 year postpartum and BMI quartiles at different timepoints, gestational weight gain, and postpartum weight retention. We evaluated associations between stress urinary incontinence (SUI) and moderate/severe urinary incontinence (UI) 1 year postpartum and cumulative excess BMI from prepregnancy to 1-year postpartum (BMI1year).Body mass index was not associated with anatomic support, composite symptom burden, overactive bladder, anal incontinence, or constipation at any timepoint. Gestational weight gain and postpartum weight retention were not associated with any 1-year outcome. Body mass index at every timepoint was positively associated with SUI and moderate/severe UI; BMI1year was most predictive. Cumulative excess BMI was positively associated with SUI and moderate/severe UI but only slightly more predictive of these outcomes than BMI1year alone.Body mass index over the pregnancy trajectory was not associated with outcomes other than UI. The small advantage of cumulative exposure to excess BMI over BMI1year in predicting SUI and moderate/severe UI suggests that BMI1year adequately captures risk of these 1-year outcomes.

Little is known about early postpartum physical activity (PA). Objectives: We aimed to describe PA amount and types and compare moderate-vigorous PA (MVPA) at 12-25 (T1) and 33-46 days (T2) postpartum. Design: Cross-sectional study. Methods: Participants, primiparas delivered vaginally, wore wrist accelerometers and completed questionnaires. Median and interquartile range (IQR) describe minutes/day of PA intensities in total minutes, 5- and 10-minute bouts. Wilcoxon Signed Rank test compared MVPA. Results: 577 (age: 28.3 (SD: 5.1)) had accelerometry or questionnaire at either time-point. 405 had accelerometry at both timepoints. Median (IQR) total minutes/day for light, moderate, vigorous and MVPA were 295.8 (256.1-331.7), 54.6 (40-72.7), 0.4 (0.2-0.8), and 55.5 (40.4-74.3), respectively, at T1 and 329 (289.4-367.1), 63.6 (46.9-82.2), 0.6 (0.3-1.3), and 64.5 (47-84.8), respectively, at T2. Median (IQR) minutes/day for MVPA in 5- and 10-minute bouts were 1.6 (0-5.5) and 0 (0-3.8) at T1, and 3 (0-9.2) and 0 (0-5.5) at T2. At T1, 75% (406/541) and at T2, 72.4% (397/548) reported non-impact activities. At T1, 4% and at T2, 13% reported impact/straining activities. MVPA was greater at T2 than T1 (p< 0.0001) with medians (IQR) of: total: 64.7 (47-84.6) vs 56.5 (41-74.9) minutes; 5-minute bouts: 3 (0-9.8) vs 1.7 (0-5.6) minutes; and 10-minute bouts: 1.3(0-6) vs 0(0-3.8) minutes. Conclusion: Women had high daily MVPA, though MVPA in bouts remained low. Significant increases in MVPA from T1 to T2 were small, few women reported impact/straining activities. Realistic return to pre-pregnancy PA levels should recognize the relative lack of sustained/strenuous activity in early postpartum.

OBJECTIVES This study aimed to explore associations between relative and maximal intra-abdominal pressure (IAP) on pelvic floor outcomes in primiparas delivered vaginally. METHODS At 5-10 weeks and 1 year postpartum, we measured absolute IAP by vaginal sensor while participants lifted a weighted car seat (IAPLIFT) and performed isometric trunk flexion endurance (IAPTFE) and seated maximal strain (IAPSTRAIN). Primary outcomes, completed 1 year postpartum, included worse pelvic floor support (descent to or beyond the hymen) and positive symptom burden (bothersome symptoms in ≥2 of 6 domains on the Epidemiology of Prolapse and Incontinence Questionnaire). We calculated relative IAP (as absolute IAP/IAPSTRAIN). RESULTS Of 542 participants, 9.7% demonstrated worse support and 54.3% demonstrated symptom burden at 1 year postpartum. In multivariable analyses, absolute IAPLIFT and absolute IAPTFE at 5-10 weeks postpartum were not associated with worse support. As relative IAP at 5-10 weeks increased, the prevalence of worse support decreased (prevalence ratio [PR] of 0.77 [95% confidence intervals (CIs), 0.63-0.94] and PR of 0.79 [95% CI, 0.67-0.93]) per 10% increase for relative IAPLIFT and relative IAPTFE, respectively. This was largely due to IAPSTRAIN, which increased the prevalence of worse support (PR, 1.15 [95% CI, 1.06-1.25]) per 10 cm H2O increase. One year postpartum, only IAPSTRAIN increased the prevalence of worse support (PR, 1.11 [95% CI, 1.02-1.20]) per 10 cm H2O. Of all IAP measures at both time points, only absolute IAPLIFT at 1 year significantly increased the prevalence of symptom burden (PR, 1.11 [95% CI, 1.05-1.18]) per 10 cm H2O. CONCLUSIONS This exploratory analysis suggests that postpartum IAPSTRAIN may increase the prevalence of worse support in primiparas delivered vaginally.

Objective This study aimed to determine whether measures of muscular fitness modify the effect of intra-abdominal pressure (IAP) during lifting on pelvic floor support. Methods Participants, primiparous women 1 year after vaginal delivery, underwent the Pelvic Organ Prolapse Quantification examination, measurement of IAP via a vaginal sensor while lifting a weighted car seat, pelvic floor muscle force assessment using an instrumented speculum, grip strength using a hand dynamometer, and trunk flexor endurance by holding an isometric contraction while maintaining a 60-degree angle to the table. We dichotomized pelvic floor support as worse (greatest descent of the anterior, posterior, or apical vagina during maximal strain at or below the hymen) versus better (all points above the hymen). Results Of 825 participants eligible after delivery, 593 (71.9%) completed a 1-year study visit. Mean (SD) age was 29.6 (5.0) years. One year postpartum, 55 (9.3%) demonstrated worse support. There were no differences in IAP during lifting or in other measures of pelvic floor loading between women with better and worse support. In multivariable analyses, neither grip strength nor pelvic floor muscle force modified the effect of IAP on support. In women with trunk flexor endurance duration ≥13 minutes, the odds of worse support increased significantly as IAP increased. No fitness measure modified the effect of other measures of pelvic floor loading on support. Conclusions Primiparous women with higher IAP during lifting and greater muscular fitness did not have reduced odds of worse pelvic floor support compared with those with lower IAP at the same muscular fitness.

Objectives Intra-abdominal pressure (IAP) increases during physical activity. Activities with high IAP are often restricted for women because of potential pelvic floor overloading. Researchers categorize high IAP activities using absolute values (in centimeters of water). Although essential for descriptive purposes, absolute IAP may not be ideal for individualized exercise recommendations. For oxygen consumption, a well-established measure of fitness, exercise scientists use a percentage of the maximal value observed during exercise to create relative exercise intensity prescriptions for an individual. Relative exercise intensity correlates inversely to the maximal value observed. We explore whether this approach and response pattern extend to IAP observed during exercise. Methods Fifty-five women completed 16 exercises while wearing a vaginal sensor to measure IAP. The highest mean IAP occurred during seated Valsalva/strain (IAPSTRAIN). We calculated relative IAP (in percent) for each participant by dividing the maximal IAP during each exercise by IAPSTRAIN. We examined relationships between relative IAP and IAPSTRAIN for each activity using Pearson r correlations. Results Mean age was 30.4 ± 9.4 years, and body mass index was 22.4 ± 2.6 kg/m. For most women, IAP was greater during strain than during exercises. Relative IAPs negatively correlated with IAPSTRAIN. Excluding one exercise because of small sample sizes, r for all others ranged from -0.35 to -0.80, all statistically significant. Conclusions The relative IAP responses to many exercises exhibit an inverse relationship to the highest IAP values during strain, consistent with other variables measured during exercise. Relative IAP may provide an alternative to absolute IAP in understanding IAP's effect on pelvic floor health.

Post-operative changes in moderate-to-vigorous physical activity (MVPA) may contribute to improved weight loss and long-term weight maintenance of individuals after bariatric surgery. Patients experience minimal changes in MVPA 6 months after surgery, but no studies have investigated early changes in physical activity after surgery. This study aims to assess MVPA changes during the rapid weight loss phase through self-reporting and objective measures.Physical activity patterns were assessed as minutes per day spent doing MVPA. A walking cadence of ≥ 100 steps per minute defined MVPA. Individuals completing gastric bypass (N = 7) and sleeve gastrectomy (N = 17) procedures (21 females, 3 males, age 42.2 ± 12.6 years, body mass 121.8 ± 24.8 kg, BMI 44.0 ± 6.5) completed office visits at 12 ± 6 days pre- and 35 ± 10 days post-operative. Each wore an ActiGraph GT3X tri-axial accelerometer at the hip for 7 days before and again for 7 days 30.6 ± 10 days after surgery. Assessments also included a subjective question about their anticipated and perceived post-operative MVPA (scale of - 3 to 3 with 3 being much more physically active and - 3 being much less).Participants did not change their minutes per day of MVPA significantly (pre-operative 1.5 ± 2.1; post-operative 2.6 ± 5.6, NS). Participants predicted their post-operative physical activity level would increase (2.8 ± 0.4). The self-reported activity level on the same scale after surgery was significantly less than predicted (1.9 ± 1.0, p 0.05) but still suggested that participants thought they were more physically active.Consistent with reports 6 months after surgery, MVPA did not increase in the early post-operative period, despite patient expectations. The early post-operative period may be a time for behavioral intervention.

Objectives High intra-abdominal pressure (IAP) may influence the development of pelvic floor disorders. We and others have used intravaginal pressure transducers to measure IAP in women during exercise and daily activities, but utilizing the transducer for long-term measurements creates compliance issues. Waist-worn accelerometers are prominent in research and may be a reliable alternative for approximating IAP. We hypothesized that there are pair-wise positive correlations between the mean maximal accelerometer vector magnitude and 2 IAP measurements: mean maximal IAP and area under the curve (AUC). Methods Twenty-five women who regularly participated in exercise performed 13 activities. Intra-abdominal pressure was measured with an intravaginal transducer and acceleration with a waist-worn accelerometer. We determined the mean maximal IAP, AUC for IAP, and mean maximal accelerometer vector magnitude for each activity and participant. The relationship between IAP and acceleration was determined by computing the Pearson correlation coefficient (R) and the 95% confidence interval for mean maximal accelerometer vector magnitude versus mean maximal IAP and mean maximal accelerometer vector magnitude versus AUC for IAP. Results The R values were 0.7353 for mean maximal accelerometer vector magnitude versus mean maximal IAP (including walking) and 0.5059 for mean maximal accelerometer vector magnitude versus AUC for IAP (excluding walking). Walking at 3 speeds, analyzed separately, presented R values of 0.72208 for mean maximal IAP and 0.21678 for AUC. Conclusion Waist-worn accelerometers may provide a viable method for approximating mean maximal IAP in a population of women during most activities.

Objective The aim of the study was to determine whether measures of muscular strength and fitness are associated with pelvic floor muscle (PFM) force 1-year postpartum in a population of primiparous women who delivered vaginally. Methods This cross-sectional analysis is an ancillary study to an ongoing prospective cohort study and includes 203 primiparous women. Procedures collected 1-year postpartum included maximal PFM force, grip strength, trunk flexor muscle endurance, percent body fat, intra-abdominal pressure during trunk flexor endurance testing, intra-abdominal pressure during strain, and self-reported physical activity. Results The mean (SD) age was 29.8 (5.0) years and the mean (SD) body mass index was 24.5 (5.2) kg/m. Nineteen percent were of Hispanic ethnicity. The median (interquartile range) PFM force was 5.05 (2.86-7.94) N. The median (interquartile range) trunk flexor endurance time was 146.0 (78.0-267.0), whereas the mean (SD) grip strength and percent fat were 32.4 (6.4) kg and 29.4% (10.0), respectively.There were no statistically significant associations between PFM force and any of the measures tested on analyses unadjusted or adjusted for self-report of doing PFM exercises. Of other factors evaluated, non-Hispanic ethnicity, increasing age, self-reported family history of pelvic organ prolapse or urinary incontinence, and normal and obese body mass index (both compared with overweight) were associated with lower PFM force. Conclusions In primiparous women 1-year postpartum, we found no associations between PFM force and measures of strength and fitness. This study's results are consistent with existing literature that specific, targeted, and consistent pelvic floor exercises are the best way to improve PFM strength.

SUMMARYWe recently identified a new cellular structure in yeast, called the Mitochondrial-Derived Compartment (MDC), that forms on mitochondria in response to amino acid excess. While emerging evidence supports an important function for MDCs in protecting cells from metabolic stress, whether this system exists beyond yeast remains unclear. Here, we show that MDCs are conserved in mammals, and like their yeast counterparts, are responsive to the intracellular amino acid content. Specifically, we find that inhibition of protein translation stimulates formation of dynamic, micron-sized compartments that associate with the mitochondrial network. These compartments are enriched for the carrier receptor Tomm70A and other select mitochondrial outer and inner membrane cargo, associate with the ER membrane, and require the conserved GTPase Miro1 for formation. Mammalian MDCs are responsive to changes in amino acid levels during translation inhibition, and are not activated by other common cellular stressors. Thus, MDCs represent an evolutionarily conserved nutrient-responsive mitochondrial remodeling system.

Objective To estimate the association between habitus measures and pelvic floor support and symptoms in primiparous women 1 year after term vaginal delivery. Methods In this cross-sectional study including women enrolled at seven academic and community sites, we assessed pelvic floor support, weight, height, waist circumference, and percent fat using air displacement plethysmography and participants completed questionnaires, all at one year postpartum. We tested the association of quintiles of habitus measure, including body mass index (BMI), waist circumference, percent body fat, and waist/height ratio, with the primary outcomes: anatomic support, dichotomized as maximal vaginal descent less than 0 cm (better support) compared with 0 cm or more (worse support) per the pelvic organ prolapse quantification examination and symptom burden (positive with bothersome symptoms in two or more of six symptom domains), and on five secondary outcomes. The sample size provides 90% power to detect odds ratios (ORs) of 1.78 or greater between women at mean compared with mean+1 SD of habitus measure. Results Of 592 participants, 55 (9.3%) demonstrated worse support and 321 (54.2%) symptom burden. In multivariable analyses, habitus measures were not significantly associated with anatomic support or, except for the highest waist/height ratio quintile, with symptom burden. Compared with women in the first quintile of each habitus measure, those in most higher quintiles demonstrated elevated odds of moderate to severe urinary incontinence (UI); increased odds for stress urinary incontinence (SUI) were mainly limited to the highest quintile. After adjusting for percent body fat, the increased odds for BMI on SUI (OR 2.47, 95% CI 1.43-4.28) were no longer significant (OR 1.38, 95% CI 0.54, 3.51). Conclusion Habitus in primiparous patients at 1 year postpartum was not associated with anatomic support or symptom burden. Habitus was more associated with moderate to severe UI than mild UI. The association of higher BMI with SUI was attenuated by fitness, reflected by fat percentage.

Mitochondrial-derived compartments (MDCs) regulate the mitochondrial proteome in response to nutrient stress. English et al. now show that the ERMES complex and the conserved GTPase Gem1 promote MDC biogenesis at sites of contact between the endoplasmic reticulum and mitochondria., Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid overabundance stress. How cells form MDCs is unclear. Here, we show that MDCs are dynamic structures that form and stably persist at sites of contact between the ER and mitochondria. MDC biogenesis requires the ER–mitochondria encounter structure (ERMES) and the conserved GTPase Gem1, factors previously implicated in lipid exchange and membrane tethering at ER–mitochondria contacts. Interestingly, common genetic suppressors of abnormalities displayed by ERMES mutants exhibit distinct abilities to rescue MDC formation in ERMES-depleted strains and are incapable of rescuing MDC formation in cells lacking Gem1. Thus, the function of ERMES and Gem1 in MDC biogenesis may extend beyond their conventional role in maintaining mitochondrial phospholipid homeostasis. Overall, this study identifies an important function for ER–mitochondria contacts in the biogenesis of MDCs.

OBJECTIVE To determine whether 2 aspects of trunk recovery after childbirth, intraabdominal pressure (IAP) generation and trunk flexor endurance (TFE), predict measures of pelvic floor health 1 year postpartum. METHODS In this prospective cohort study, we enrolled nulliparas in their third trimester and followed up those delivered vaginally for 1 year. We measured IAP while lifting a weighted car seat (IAPLIFT), IAP during TFE testing (IAPTFE), and TFE duration 5 to 10 weeks postpartum and assessed pelvic floor support and symptoms 1 year postpartum. RESULTS Mean age of the 624 participants was 28.7 years. At 5 to 10 weeks postpartum, mean (SD) maximal IAPLIFT and IAPTFE were 47.67 (11.13) and 51.57 (12.34) cm H2O, respectively. Median TFE duration was 126 seconds (Interquartile range, 74-211). At 1 year postpartum, 9.3% demonstrated worse support (maximal vaginal descent at or below hymen) and 54% met criteria for symptom burden (bothersome symptoms in ≥2 domains of Epidemiology of Prolapse and Incontinence Questionnaire). In multivariable models, neither IAPLIFT nor IAPTFE were associated with worse support or symptom burden (P = 0.54-1.00). Trunk flexor endurance duration increased prevalence of worse support (prevalence ratio, 1.05; 95% confidence interval, 1.01-1.08) per 60-second increase, P = 0.005) but not symptom burden (prevalence ratio, 1.00; 95% confidence interval, 0.98-1.03; P = 0.92). CONCLUSIONS These results provide some reassurance to early postpartum women, who are unlikely to perform routine activities that generate IAP far outside the range tested. Further research is needed to understand why women with long TFE durations have increased prevalence of worse support.

Background: Exercise increases intra-abdominal pressure (IAP) acutely, which may impact the pelvic floor of women. IAP during exercise demonstrates high variability among women but is not routinely assessed. Assessing less invasive measures related to IAP during exercise may facilitate study of how IAP impacts the pelvic floor. Methods: The objective of this study was to investigate the relationship of heart rate and rating of perceived exertion (RPE) with IAP during a standard treadmill test. We describe the trend of IAP by predicted aerobic fitness during incremental exercise. IAP was measured using a validated transducer placed in the upper vagina. Heart rate and RPE were collected during the first 3 stages of the standard Bruce treadmill protocol. Relationships of heart rate and RPE with IAP were determined by Pearson correlation coefficients. Predicted aerobic fitness values for each participant were ranked in tertiles with IAP by treadmill stage. Results: Twenty-four women participated in this study (mean age: 24.7 ± 5.4 years; body mass index: 22.5 ± 2.2 kg·m−2). There were significant relationships between heart rate and IAP (r = 0.67, P < 0.001) and RPE and IAP (r = 0.60, P < 0.001) across treadmill stages. Tertiles of predicted aerobic fitness and IAP displayed similar trends as other exercise measures such as heart rate and ventilation during incremental exercise. Conclusion: Heart rate and RPE could be used as proxy measures of IAP during incremental exercise. Aerobic fitness may help explain IAP variability in women and provide context for future research on IAP and pelvic floor health.

Risks of pelvic organ prolapse and urinary incontinence increase after the first vaginal delivery. During the early postpartum period, a time of active regeneration and healing of the pelvic floor, women may be particularly vulnerable to greater pelvic floor loading.This prospective cohort study aimed to determine whether objectively measured moderate to vigorous physical activity in the early postpartum period predicts pelvic floor support and symptoms 1 year after the first vaginal birth.We enrolled nulliparous women in the third trimester, later excluding those who had a cesarean or preterm delivery. Participants wore triaxial wrist accelerometers at 2 to 3 weeks and 5 to 6 weeks postpartum for ≥4 days. Primary outcomes, assessed 1 year postpartum, included (1) pelvic floor support on Pelvic Organ Prolapse Quantification examination, dichotomized as maximal vaginal descent of0 cm (better support) vs ≥0 cm (worse support); and (2) pelvic floor symptom burden, considered positive with report of ≥1 bothersome symptom in ≥2 of 6 domains, assessed using the Epidemiology of Prolapse and Incontinence Questionnaire. The primary predictor was average daily moderate to vigorous physical activity. Because we could not eliminate women with pelvic floor changes before pregnancy, we modeled prevalence, rather than risk, ratios for each outcome using modified Poisson regression.Of 825 participants eligible after delivery, 611 completed accelerometry and 1-year follow-up; 562 completed in-person visits, and 609 completed questionnaires. The mean age was 28.9 years (standard deviation, 5.01). The mean for moderate to vigorous physical activity measured in minutes per day was 57.3 (standard deviation, 25.4) and 68.1 (standard deviation, 28.9) at 2 to 3 weeks and 5 to 6 weeks, respectively. One year postpartum, 53 of 562 participants (9.4%) demonstrated worse vaginal support and 330 of 609 participants (54.2%) met criteria for pelvic floor symptom burden. In addition, 324 (53.1%), 284 (46.6%), 144 (23.6%), and 25 (4.1%) reported secondary outcomes of stress urinary incontinence, overactive bladder, anal incontinence, and constipation, respectively, and 264 (43.4%), 250 (41.0%), and 89 (14.6%) reported no, mild, or moderate to severe urinary incontinence, respectively. The relationship between moderate to vigorous physical activity and outcomes was not linear. On the basis of plots, we grouped quintiles of moderate to vigorous physical activity into 3 categories: first and second quintiles combined, third and fourth quintiles combined, and fifth quintile. In final multivariable models, compared with women in moderate to vigorous physical activity quintiles 3 and 4, those in the lower 2 (prevalence ratio, 0.55; 95% confidence interval, 0.31-1.00) and upper quintile (prevalence ratio, 0.70; 95% confidence interval, 0.35-1.38)) trended toward lower prevalence of worse support. However, we observed the reverse for symptom burden: compared with women in quintiles 3 and 4, those in the lower 2 (prevalence ratio, 1.20; 95% confidence interval, 1.02-1.41) and upper quintile prevalence ratio 1.34 (95% confidence interval, 1.11-1.61) demonstrated higher prevalence of symptom burden. Moderate to vigorous physical activity did not predict any of the secondary outcomes. The presence of a delivery factor with potential to increase risk for levator ani muscle injury did not modify the effect of moderate to vigorous physical activity on outcomes.Except for support, which was worse in women with moderately high levels of activity, early postpartum moderate to vigorous physical activity was either protective or had no effect on other parameters of pelvic floor health. Few women performed substantial vigorous activity, and thus, these results do not apply to women performing strenuous exercise shortly after delivery.

Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a new cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid elevation. MDCs protect cells from amino acid toxicity, but how cells form MDCs is unclear. Here, we show that MDCs are micron-sized, lumen-containing organelles that form at sites of contact between the ER and mitochondria. Upon formation, MDCs stably persist at ER-mitochondria contacts for extended periods of time. MDC formation requires the ER-mitochondria encounter structure (ERMES) and GTP hydrolysis by the conserved GTPase Gem1. Unexpectedly, MDC formation is not linked to the role of ERMES/Gem1 in the maintenance of mitochondrial phospholipid homeostasis. Our results identify an important role for ER-mitochondria contacts in the biogenesis of MDCs.Abbreviations used in this paper: ERMES, ER-mitochondria encounter structure; IMM, inner mitochondrial membrane; MDC, mitochondrial-derived compartment; OMM, outer mitochondrial membrane.SummaryEnglish et al. use super-resolution imaging to show that mitochondrial-derived compartments are lumen-containing organelles that form at sites of contact between the ER and mitochondria. Mitochondrial-derived compartment biogenesis requires a noncanonical function of the ERMES complex and the conserved GTPase Gem1.

SUMMARYAmino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, themitochondrial-derivedcompartment (MDC), is a dynamic, lumen-containing organelle that functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and remove Tom70, a surface receptor required for import of nutrient carriers of the SLC25 family. MDC formation is regulated by levels of mitochondrial carriers, and its activation by amino acids occurs simultaneously with removal of plasma membrane-localized transporters via the multi-vesicular body (MVB) pathway. Combined loss of MDC and MVB formation renders cells sensitive to elevated amino acids, suggesting these pathways operate as a coordinated network to protect cells from amino acid toxicity.

Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery.

Childhood obesity is a major focus of public health. The purpose of this study was to determine whether after-school physical activity and dietary habits predict cardio-metabolic risk in a sample of ethnic minority elementary school-aged children from low-income schools. Participants were a convenience sample of 92 children (3rd-6th grades) recruited from four Title I schools located in a metropolitan area from the Mountain West region of the United States. Children completed portions of the After School Student Questionnaire (ASSQ) and Physical Activity Questionnaire for Children (PAQ-C) to measure after-school physical activity and nutrition, respectively. Blood pressure, waist circumference and cardio-metabolic blood markers were collected in a fasted state to calculate a continuous metabolic syndrome (MetS) composite score. Predictive relationships were analyzed using a multiple linear regression model. Neither physical activity or nutrition scores were predictive of a MetS score. However, there was a linear, positive, and moderate correlation between physical activity and nutrition scores (r = 0.29, p < 0.05). The findings indicate that cardio-metabolic health cannot be predicted based on self-reported after-school physical activity and nutrition habits. There are many challenges that arise when analyzing cardio-metabolic health in children; however, this is an area of research that needs further analysis. A clearer understanding of these relationships can aid in identifying risk factors for disease at an earlier age and aid in future intervention development.

Many undergraduate students in kinesiology are interested in clinical careers and seek research opportunities for advanced study and unique learning experiences. This article describes a process of engaging undergraduate students in a multi-disciplinary, National Institutes of Health (NIH)-funded program project investigating factors that may affect pelvic floor support and symptoms in primiparous women during the first year postpartum. Students complete general and protocol-specific training prior to engagement, have specific tasks that reinforce skill development and require independence, and are invited to participate in additional opportunities with the investigative team. The topic of pelvic floor health is novel to most students and participation in this research expands their knowledge beyond a mainstream kinesiology curriculum. Institutionalizing this type of program could formalize undergraduate student research experiences and facilitate ongoing clinical research efforts with a kinesiolo...

OBJECTIVES: To describe change in trunk flexor endurance and intra-abdominal pressure (IAP) associated with trunk flexor assessment and explore factors associated with change in trunk flexor endurance during the first postpartum year. DESIGN: Ancillary analysis of an ongoing prospective cohort study. METHODS: Participants (N=282) were primiparous women delivered vaginally. They completed trunk flexor endurance testing while assessing IAP, body habitus measures (body mass index, waist circumference, and body composition), and questionnaires 5–10 weeks and 11–15 months postpartum. We investigated change in trunk flexor endurance by quartile of improvement and factors associated with improvement (Q4 vs. Q1-Q3) using multivariable models, adjusted for baseline endurance. RESULTS: Mean age was 28±5 years. The median (IQR) trunk flexor hold time increased from early to late postpartum (129/IQR=68, 217 vs 148/IQR= 80, 265 seconds, p = 0.01) and mean (SD) IAP decreased (55/SD=13 vs 48/SD=14 cmH(2)0, p < 0.0001). The most improved group (Q4) increased endurance time by 176 seconds (95% CI=103, 254), were less likely to be Hispanic, more likely to be older, more educated, and have lower measures of body habitus than women in Q1-Q3. CONCLUSION: Trunk flexor endurance increased and IAP decreased over one year postpartum. Lower body habitus and higher age early postpartum predicted greatest improvement in trunk flexor endurance at 1 year.

Objective To describe sleep quality and sleep duration in primiparous women 6 months postpartum and to determine whether sleep quality is associated with 24-hour physical activity assessed using triaxial wrist accelerometry and a novel analytic technique, functional data analysis (FDA). Methods Six months postpartum, participants wore a triaxial wrist accelerometer for 7 days and completed the Pittsburgh Sleep Quality Index (PSQI). We categorized sleep quality as good (score ≤5) or poor (>5). Data were summarized as vector magnitude of accelerations net of local gravity, or “Euclidean Norm Minus One” (ENMO, mg), in 5-second epochs. Using FDA, we modeled ENMO as a continuously changing, functional outcome predicted by sleep quality. We also compared mean total ENMO per 24-hour day, mean minutes of moderate to vigorous physical activity (MVPA) and of light activity/day, and mean minutes of MVPA in 10-minute bouts/day by sleep quality. Results Of 365 women that completed the PSQI, 215 (59%) reported poor sleep quality. Two hundred ninety-six women completed both the PSQI and valid accelerometry. With the exception of one brief period around noon, sleep quality was not significantly associated with 24-hour physical activity according to FDA. Women with poor sleep quality had slightly greater total mean activity, minutes of light activity, and minutes of MVPA per day, but no difference in minutes of MVPA in at least 10-minute bouts. Conclusion Poor sleep quality is common 6 months postpartum. We identified no clinically significant differences in physical activity metrics between women with good and poor quality sleep.

Background There are few studies that objectively assess physical activity using accelerometry in postpartum women and none that do so before 3 months postpartum. It is not known whether accelerometry can be successfully used in the early postpartum period and thus benefit studies designed to assess the health benefits and risks of early physical activity. Wear compliance may be substantially lower several weeks after childbirth, given the overwhelming nature of the early postpartum period, particularly for first time mothers. The aims of this study were to 1) describe the methods used to facilitate protocol compliance of wrist-worn accelerometry, 2) describe device usage and wear time in early postpartum primiparous women and 3) to place the compliance characteristics of early postpartum primiparous women in our study in context with that of other studies of postpartum women and standards published by large, physical activity surveillance studies. Methods Participants were primiparous women who were enrolled at 3rd trimester in a larger ongoing prospective cohort study, delivered vaginally, and lived in a 60 mile radius of the research site. The parent study was designed to evaluate the effects of early physical activity on pelvic floor health. Participants wore a wrist accelerometer (ActiGraph™ GT3XLink device) over two 7-day periods, 2–3 weeks and 5–6 weeks postpartum. We developed a protocol based on best practices to enhance compliance in this population. The Choi (2011) algorithm was used to determine wear time. Results Of all participants, 82.6% (166 of 201 eligible) and 70.1% (141 of 201 eligible) at 2–3 and 5–6 weeks, respectively, received and wore a functional device in the correct study time-frame for at least 7 days. Of participants that received a functional device, 94.3% (166/176) and 86.5% (141/163) wore the device for at least 7 days, with mean wear times of 1348.0 (135.8) minutes/day and 1313.5 (152) minutes/day, respectively. At 2–3 weeks, 96.1% and 90.4% met the NHANES and Whitehall II Study wear standards, respectively, while at 5–6 weeks, 93.9% and 84.1% did so. Conclusion Despite challenges in conducting physical activity research in postpartum women, adherence to wrist-worn accelerometry is high with this protocol.

Exercise in healthy female adults around the menopausal transition has been routinely examined in leisure activities alone, potentially discounting the physical activity (PA) that is accumulated in household and outdoor domains. The purpose of this study was to quantify PA in healthy middle-aged women and to examine the extent to which the Center for Disease Control (CDC) PA guidelines were met through leisure, household, and outdoor activities. Methods: 440 healthy women, 51–64 years old, BMI ≥18.5 or < 40 kg/m2, participated in the study using the Lifetime Physical Activity Questionnaire (LPAQ) to quantify PA. Results: 25.91% met the CDC PA guidelines if leisure time alone was examined. When multiple domains were included, 73.41% of the women met the PA guidelines. This percentage is much higher than the reported 20.6% of U.S. adults who met the guidelines in 2011. PA in women may be underrepresented in data limited to leisure time PA.

Background:Few have examined predictive relationships between physical activity (PA) and health using electronic health records (EHRs) of patient-reported PA.Objective:Assess initial predictive validity of the Physical Activity “Vital Sign” (PAVS) recorded in EHRs with BMI and disease burden.Methods:EHRs were from November 2011 to November 2013 (n = 34,712). Differences in not meeting Physical Activity Guidelines (PAG) were tested using chi-square analysis between being normal weight versus overweight/obese, and scoring below versus above the 50th percentile of the Charlson Comorbidity Index (CCI). Repeated measures logistic regression was used to determine odds of BMI and CCI classifications according to responses to the PAVS as not meeting PAG.Results:Patients who did not meet PAG according to the PAVS were more likely than normal weight patients to have a higher BMI (BMI 25.0–29.9, OR = 1.19, P = .001; BMI 30.0–34.9, OR = 1.39, P < .0001; BMI 35.0–39.9, OR = 2.42, P < .0001; BMI ≥ 40, OR = 3.7, P < .0001) and also higher disease burden (above 50th percentile for CCI, OR = 1.8, P < .0001).Conclusions:The strong association of the PAVS found with patient BMI and moderately-strong association with disease burden supports initial predictive validity of the PAVS recorded in EHRs. PA recorded in EHRs may be vastly useful for assessing patient disease and cost burdens attributed independently to PA behavior.

Mitochondrial inheritance, genome maintenance, and metabolic adaptation all depend on organelle fission by Dynamin-Related Protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogs Mitochondrial Dynamics 49 and 51 (MID49/MID51) and Mitochondrial Fission Factor (MFF), but the mechanisms by which these proteins recruit DRP1 and regulate its activities are unknown. Here we present a cryoEM structure of human, full-length DRP1 bound to MID49 and an analysis of structure- and disease-based mutations. We report that GTP binding allosterically induces a remarkable elongation and rotation of the G-domain, Bundle-Signaling Element (BSE) and connecting hinge loops of DRP1. In this nucleotide-bound conformation, a distributed network of multivalent interactions promotes DRP1 copolymerization into a linear filament with MID49, MID51 or both. Subsequent GTP hydrolysis and exchange within the filament leads to receptor dissociation, shortening through disassembly, and concomitant curling of DRP1 oligomers into closed rings. The dimensions of the closed DRP1 rings are consistent with DRP1-constricted mitochondrial tubules observed in human cells. These structures are the first views of full-length, receptor- and nucleotide-bound dynamin-family GTPases and—in comparison with nucleotide-free crystal structures—teach us how these molecular machines perform mechanical work through nucleotide-driven allostery.

Introduction Pelvic floor disorders (PFDs), including pelvic organ prolapse (POP), stress and urgency urinary incontinence, and faecal incontinence, are common and arise from loss of pelvic support. Although severe disease often does not occur until women become older, pregnancy and childbirth are major risk factors for PFDs, especially POP. We understand little about modifiable factors that impact pelvic floor function recovery after vaginal birth. This National Institutes of Health (NIH)-funded Program Project, ‘Bridging physical and cultural determinants of postpartum pelvic floor support and symptoms following vaginal delivery’, uses mixed-methods research to study the influences of intra-abdominal pressure, physical activity, body habitus and muscle fitness on pelvic floor support and symptoms as well as the cultural context in which women experience those changes. Methods and analysis Using quantitative methods, we will evaluate whether pelvic floor support and symptoms 1 year after the first vaginal delivery are affected by biologically plausible factors that may impact muscle, nerve and connective tissue healing during recovery (first 8 weeks postpartum) and strengthening (remainder of the first postpartum year). Using qualitative methods, we will examine cultural aspects of perceptions, explanations of changes in pelvic floor support, and actions taken by Mexican-American and Euro-American primipara, emphasising early changes after childbirth. We will summarise project results in a resource toolkit that will enhance opportunities for dialogue between women, their families and providers, and across lay and medical discourses. We anticipate enrolling up to 1530 nulliparous women into the prospective cohort study during the third trimester, following those who deliver vaginally 1 year postpartum. Participants will be drawn from this cohort to meet the project9s aims. Ethics and dissemination The University of Utah and Intermountain Healthcare Institutional Review Boards approved this study. Data are stored in a secure password-protected database. Papers summarising the primary results and ancillary analyses will be published in peer-reviewed journals.

The purpose of this study was to determine the level of knowledge that current and preservice high school (HS) physical educators and sport coaches possess regarding the principles and methods involved in youth resistance training (RT) and to determine if that knowledge was acceptable based on a predetermined criterion (passing score). A panel of 10 experts in RT or sport pedagogy used a Delphi technique to create a 90-question assessment (examination) that was administered to 287 HS physical educators and sport coaches and 140 university physical education teacher education (PETE) students. An analysis of the results revealed that neither group demonstrated the minimal knowledge necessary to design, implement, and supervise RT programs based on a passing score of 75%: HS physical educators/coaches, mean = 59.30, SD = 14.30, 95% confidence interval (CI) = 57.64-60.96], t(286) = -18.61, p = 0.000; university PETE students, mean = 56.61, SD = 16.59, 95% CI = 53.84-59.38, t(139) = -13.12, p = 0.000. The pass rate for physical educators and sport coaches was 14.3% and for university PETE students it was 20.7%. The results of this study indicate that both current and preservice physical educators and sport coaches need additional education and training specific to the design and implementation of RT programs for HS students. Given that school districts typically require their educators attend in-service training programs, it may be advisable to develop an in-service program that allows both current and preservice HS physical educators and sport coaches to earn an RT certification that specifically addresses the unique physical and psychosocial needs of school-aged youth.

Strenuous physical activity has been linked to pelvic floor disorders in women. Using a novel wireless intra-vaginal pressure transducer, intra-abdominal pressure was measured during diverse activities in a laboratory. Fifty-seven women performed a prescribed protocol using the intra-vaginal pressure transducer. We calculated maximal, area under the curve and first moment of the area intra-abdominal pressure for each activity. Planned comparisons of pressure were made between levels of walking and cycling and between activities with reported high pressure in the literature. Findings indicate variability in intra-abdominal pressure amongst individuals doing the same activity, especially in activities that required regulation of effort. There were statistically significant differences in maximal pressure between levels of walking, cycling and high pressure activities. Results for area under the curve and first moment of the area were not always consistent with maximal pressure. Coughing had the highest maximal pressure, but had lower area under the curve and first moment of the area compared to most activities. Our data reflect novel findings of maximal, area under the curve and first moment of the area measures of intra-abdominal pressure, which may have clinical relevance for how physical activity relates to pelvic floor dysfunction.

Background Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis. Methods Wild-type mice and mice with hepatocyte-specific HIF-1α knockout (Hif1a-/-hep) were fed a high trans-fat diet for six months, as a model of NAFLD. Hepatic fibrosis was evaluated by Sirius red stain and hydroxyproline assay. Liver enzymes, fasting insulin, and hepatic triglyceride content were also assessed. Hepatocytes were isolated from Hif1a-/-hep mice and wild-type controls and were exposed to sustained hypoxia (1% O2) or normoxia (16% O2) for 24 hours. The culture media was used to reconstitute type I collagen and the resulting matrices were examined for collagen cross-linking. Results Wild-type mice on a high trans-fat diet had 80% more hepatic collagen than Hif1a-/-hep mice (2.21 μg collagen/mg liver tissue, versus 1.23 μg collagen/mg liver tissue, p = 0.03), which was confirmed by Sirius red staining. Body weight, liver weight, mean hepatic triglyceride content, and fasting insulin were similar between groups. Culture media from wild-type mouse hepatocytes exposed to hypoxia allowed for avid collagen cross-linking, but very little cross-linking was seen when hepatocytes were exposed to normoxia, or when hepatocytes from Hif1a-/-hep mice were used in hypoxia or normoxia. Conclusions Hepatocyte HIF-1 mediates an increase in liver fibrosis in a mouse model of NAFLD, perhaps due to liver tissue hypoxia in hepatic steatosis. HIF-1 is necessary for collagen cross-linking in an in vitro model of fibrosis.

Activities thought to induce high intra-abdominal pressure (IAP), such as lifting weights, are restricted in women with pelvic floor disorders. Standardized procedures to assess IAP during activity are lacking and typically only focus on maximal IAP, variably defined. Our intent in this methods paper is to establish the best strategies for calculating maximal IAP and to add area under the curve and first moment of the area as potentially useful measures in understanding biologic effects of IAP. Thirteen women completed a range of activities while wearing an intra-vaginal pressure transducer. We first analyzed various strategies heuristically using data from 3 women. The measure that appeared to best represent maximal IAP was an average of the three, five or ten highest values, depending on activity, determined using a top down approach, with peaks at least 1 second apart using algorithms written for Matlab computer software, we then compared this strategy with others commonly reported in the literature quantitatively using data from 10 additional volunteers. Maximal IAP calculated using the top down approach differed for some, but not all, activities compared to the single highest peak or to averaging all peaks. We also calculated area under the curve, which allows for a time component, and first moment of the area, which maintains the time component while weighting pressure amplitude. We validated methods of assessing IAP using computer-generated sine waves. We offer standardized methods for assessing maximal, area under the curve and first moment of the area for IAP to improve future reporting and application of this clinically relevant measure in exercise science.

Many surgeons recommend rest and restricting activities to their patients after surgery. The aim of this review is to summarize the literature regarding types of activities gynecologic surgeons restrict and intra-abdominal pressure during specific activities and to provide an overview of negative effects of sedentary behavior (rest). We searched PubMed and Scopus for years 1970 until present and excluded studies that described recovery of activities of daily living after surgery as well as those that assessed intra-abdominal pressure for other reasons such as abdominal compartment syndrome and hypertension. For our review of intra-abdominal pressure, we excluded studies that did not include a generally healthy population, or did not report maximal intra-abdominal pressures. We identified no randomized trial or prospective cohort study that studied the association between postoperative activity and surgical success after pelvic floor repair. The ranges of intra-abdominal pressures during specific activities are large and such pressures during activities commonly restricted and not restricted after surgery overlap considerably. There is little concordance in mean peak intra-abdominal pressures across studies. Intra-abdominal pressure depends on many factors, but not least the manner in which it is measured and reported. Given trends towards shorter hospital stays and off work intervals, which both predispose women to higher levels of physical activity, we urge research efforts towards understanding the role of physical activity on recurrence of pelvic organ prolapse and urinary incontinence after surgery.

There are conflicting models regarding the role of the Ypt11 GTPase in mitochondrial inheritance during yeast budding. This study demonstrates that Ypt11 function requires mitochondrial membrane targeting and GTPase domain–dependent effector interactions. In addition, the abundance of active Ypt11 forms is controlled by phosphorylation and degradation., The Rab GTPase Ypt11 is a Myo2-binding protein implicated in mother-to-bud transport of the cortical endoplasmic reticulum (ER), late Golgi, and mitochondria during yeast division. However, its reported subcellular localization does not reflect all of these functions. Here we show that Ypt11 is normally a low-abundance protein whose ER localization is only detected when the protein is highly overexpressed. Although it has been suggested that ER-localized Ypt11 and ER–mitochondrial contact sites might mediate passive transport of mitochondria into the bud, we found that mitochondrial, but not ER, association is essential for Ypt11 function in mitochondrial inheritance. Our studies also reveal that Ypt11 function is regulated at multiple levels. In addition to membrane targeting and GTPase domain–dependent effector interactions, the abundance of active Ypt11 forms is controlled by phosphorylation status and degradation. We present a model that synthesizes these new features of Ypt11 function and regulation in mitochondrial inheritance.

Introduction No tool currently used by primary health care providers to assess physical activity has been evaluated for its ability to determine whether or not patients achieve recommended levels of activity. The purpose of this study was to assess concurrent validity of physical activity self-reported to the brief (

A novel motif in the Insert B domain of the mitochondrial dynamin Dnm1 is essential for interaction with its adaptor Mdv1 during mitochondrial fission., To initiate mitochondrial fission, dynamin-related proteins (DRPs) must bind specific adaptors on the outer mitochondrial membrane. The structural features underlying this interaction are poorly understood. Using yeast as a model, we show that the Insert B domain of the Dnm1 guanosine triphosphatase (a DRP) contains a novel motif required for association with the mitochondrial adaptor Mdv1. Mutation of this conserved motif specifically disrupted Dnm1–Mdv1 interactions, blocking Dnm1 recruitment and mitochondrial fission. Suppressor mutations in Mdv1 that restored Dnm1–Mdv1 interactions and fission identified potential protein-binding interfaces on the Mdv1 β-propeller domain. These results define the first known function for Insert B in DRP–adaptor interactions. Based on the variability of Insert B sequences and adaptor proteins, we propose that Insert B domains and mitochondrial adaptors have coevolved to meet the unique requirements for mitochondrial fission of different organisms.

Introduction. Most dietary questionnaires are not created for use in a clinical setting for an adult health exam. We created the Healthy Eating Vital Sign (HEVS) to assess eating behaviors associated with excess weight. This study investigated the validity and reliability of the HEVS. Methods. Using a cross-sectional study design, participants responded to the HEVS and the Block Food Frequency Questionnaire (BFFQ). We analyzed the data descriptively, and, with Pearson’s correlation and Cronbach coefficient alpha. Results. We found moderate correlation (rho>0.3) between multiple items of the HEVS and BFFQ. The Cronbach's alpha was 0.49. Conclusion. Our results support the criterion validity and internal reliability of the HEVS as compared to the BFFQ. The HEVS can help launch a dialogue between patients and providers to monitor and potentially manage dietary behaviors associated with many chronic health conditions, including obesity.

One in four women has moderate to severe symptoms of at least one pelvic floor disorder. Lifetime physical activity, a modifiable risk factor, may theoretically predispose women to, or protect them from, developing pelvic floor disorders. It is neither feasible nor ethical to test this association using the most rigorous (level I) study design.The aim of this manuscript is to describe the methods for the PHysical ACtivity Study (PHACTS), which encompasses two case-control studies and the development of a registry, and to describe challenges and solutions to study progress to date. For each of the case-control studies, the primary aims are to determine, compared to controls with neither pelvic organ prolapse nor urinary incontinence, whether 1) pelvic organ prolapse or 2) stress urinary incontinence is associated with a) increased or decreased current leisure activity or b) increased or decreased overall lifetime activity (including leisure, household, outdoor, and occupational) measured in MET-hours per week, as well as in strenuous hours per week.To obtain 175 pelvic organ prolapse cases, 175 stress urinary incontinence cases, and an equal number of age, body mass index and recruitment site matched controls, we plan to enroll 1500 women from about 20 primary care level clinics.We have encountered various challenges leading to lessons learned about minimizing bias, recruitment from community clinics, the lifetime physical activity instrument used, and data management.Our experiences can help guide future investigators studying risk factors, particularly physical activity, and pelvic floor disorders.

To describe the development, feasibility and validity of a wireless intra-vaginal pressure transducer (IVT) which can be used to measure intra-abdominal pressure in real-world settings.A feasibility study was conducted in sixteen physically active women to determine retention and comfort of various IVT prototype designs during activity. A criterion validity study was conducted among women undergoing urodynamic testing to determine the accuracy of the IVT prototypes when compared to accepted clinical standards.A final prototype wireless IVT was developed after four design revisions of the second generation model. The feasibility study found that women reported the final prototype comfortable to wear and easily retained during physical activity. Intra-abdominal pressure measurements from the final prototype IVT compared favorably to standard urodynamic transducers, thus confirming evidence of its utility.We have successfully advanced the design of a wireless, intra-vaginal pressure transducer which provides accurate measures of intra-abdominal pressure. The final wireless IVT is better tolerated by patients and overcomes limitations of traditional urodynamic testing while laying the foundations for intra-abdominal pressure monitoring outside of the clinic environment.

In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against a primary role for ERMES in mitochondrial association with actin and mitochondrial movement. Finally, we show that ERMES complexes are long-lived, and do not depend on the presence of Gem1. Our findings suggest that the ERMES complex may have primarily a structural role in maintaining mitochondrial morphology.

Health clinic workers are potential agents of change for weight loss to patients, yet their behaviors are not well known. This study examined physical activity (PA) levels and dietary habits of health clinic workers who were and who were not trying to lose weight. Participants were 64 community health clinic workers (58 females and 6 males). Moderate-to-vigorous intensity (MVI) time spent in PA was assessed by triaxial accelerometry over 7 consecutive days. Dietary habits and weight loss efforts were determined by a food frequency questionnaire. Differences in MVI and nutrition variables were assessed by One-way ANOVA, comparing those trying to lose weight and those not trying to lose weight. 48 out of 64 health clinic workers (approximately 75%) indicated that they were currently trying to lose weight. There were significant differences (p < 0.05) in Body Mass Index (BMI), daily energy (Kcal) and fat (g) intake between those trying to lose weight and those not trying to lose weight. There were no significant differences in MVI, daily sugar intake (g), vegetable and fruit servings, and daily fiber intake (g) between groups. Health clinic workers trying to lose weight appear to be engaging in some appropriate dietary but not PA behaviors.

Mitochondria undergo continuous cycles of homotypic fusion and fission, which play an important role in controlling organelle morphology, copy number, and mitochondrial DNA maintenance. Because mitochondria cannot be generated de novo, the motility and distribution of these organelles are essential for their inheritance by daughter cells during division. Mitochondrial Rho (Miro) GTPases are outer mitochondrial membrane proteins with two GTPase domains and two EF-hand motifs, which act as receptors to regulate mitochondrial motility and inheritance. Here we report that although all of these domains are biochemically active, only the GTPase domains are required for the mitochondrial inheritance function of Gem1p (the yeast Miro ortholog). Mutations in either of the Gem1p GTPase domains completely abrogated mitochondrial inheritance, although the mutant proteins retained half the GTPase activity of the wild-type protein. Although mitochondrial inheritance was not dependent upon Ca2+ binding by the two EF-hands of Gem1p, a functional N-terminal EF-hand I motif was critical for stable expression of Gem1p in vivo. Our results suggest that basic features of Miro protein function are conserved from yeast to humans, despite differences in the cellular machinery mediating mitochondrial distribution in these organisms.

The maintenance of correct mitochondrial shape requires numerous proteins that act on the surface or inside of the organelle. Although the soluble F-box protein Mfb1 was recently found to associate peripherally with mitochondria and to regulate organelle connectivity in budding yeast, how it localizes to mitochondria is unknown. Here, we show that two tetratricopeptide repeat proteins—the general preprotein import receptor Tom70 (a component of translocase of the outer membrane) and its paralogue Tom71—are required for Mfb1 mitochondrial localization. Mitochondria in cells lacking Tom70 and Tom71 form short tubules and aggregates, aberrant morphologies similar to those observed in the mfb1-null mutant. In addition, Mfb1 interacts with Tom71 in vivo, and binds to mitochondria through Tom70 in vitro. Our data indicate an unexpected role for Tom70 in recruitment of soluble proteins to the mitochondrial surface, and indicate that Tom71 has a specialized role in Mfb1-mediated mitochondrial morphogenesis.

Pelvic floor disorders are common, with 1 in 4 US women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse, or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review was to summarize studies reporting the association between physical activity and pelvic floor disorders. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include that urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high-intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this examination finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods.

Ouellette, KA, Brusseau, TA, Davidson, LE, Ford, CN, Hatfield, DL, Shaw, JM, and Eisenman, PA. Comparison of the effects of seated, supine, and walking interset rest strategies on work rate. J Strength Cond Res 30(12): 3396-3404, 2016-The idea that an upright posture should be maintained during the interset rest periods of training sessions is pervasive. The primary aim of this study was to determine differences in work rate associated with 3 interset rest strategies. Male and female members of the CrossFit community (male n = 5, female n = 10) were recruited to perform a strenuous training session designed to enhance work capacity that involved both cardiovascular and muscular endurance exercises. The training session was repeated on 3 separate occasions to evaluate 3 interset rest strategies, which included lying supine on the floor, sitting on a flat bench, and walking on a treadmill (0.67 m·s). Work rate was calculated for each training session by summing session joules of work and dividing by the time to complete the training session (joules of work per second). Data were also collected during the interset rest periods (heart rate [HR], respiratory rate [RR], and volume of oxygen consumed) and were used to explain why one rest strategy may positively impact work rate compared with another. Statistical analyses revealed significant differences (p ≤ 0.05) between the passive and active rest strategies, with the passive strategies allowing for improved work rate (supine = 62.77 ± 7.32, seated = 63.66 ± 8.37, and walking = 60.61 ± 6.42 average joules of work per second). Results also suggest that the passive strategies resulted in superior HR, RR, and oxygen consumption recovery. In conclusion, work rate and physiological recovery were enhanced when supine and seated interset rest strategies were used compared with walking interset rest.

Miro1 and 2 are (Rhot1 and 2) are two highly similar GTPases that are bound to the surface of mitochondria and possess EF-hand calcium binding motifs. Several groups have reported that Miro is involved in mitochondrial motility and inheritance, and particularly its calcium regulation, but the roles of the two isoforms have not been established. Genetic deletion of Miro1 in mouse is lethal at birth (Nguyen et al., 2014) and fibroblasts (MEFs) derived from Miro1 KO embryos show abnormal mitochondrial distribution, but the calcium-dependent inhibition of motility is unaffected and the respiratory and calcium buffering capacities are normal. Neuron-specific knockout of Miro1 leads to progressive deficits of upper motor neuron function, however mitochondria in processes of cortical neurons from Miro1 KO and wild-type embryos showed comparable calcium-sensitive motility inhibition. While no significant increase in Miro2 protein was observed in Miro1 KO MEFs, these data raise two possibilities: Miro1 and 2 are interchangeable with regard to calcium regulation of mitochondrial motility or Miro2 is the key player in this regard. To finally resolve this question, we are in the process of generating Miro2 KO and Miro1/2 KO cell lines.

In previous studies, researchers have identified a general low level of health-related fitness (HRF) knowledge among secondary students that can effect levels of physical activity (PA). An instructional strategy that may increase HRF knowledge without decreasing PA is the personalized system of instruction (PSI). Two classes from a private urban high school in a major city within the Mountain West region of the United States participated in the 6-week study. Group 1 (n = 24) completed a unit on personal fitness using the PSI model, and Group 2 (n = 29) used a traditional DI approach. Knowledge was assessed 3 times (pre, post, 3-week follow-up) using a 45-question standardized HRF knowledge test. Class time PA was reported using a modification of the SOFIT observation system. A 2 A— 3 ANOVA was used to compare HRF knowledge scores, showing a significant increase in Group 1 scores from pre- to posttest (p = 0.003) as well as significant increases in scores between Group 1 and Group 2 (p = 0.03). Physical activity results were compared using a pair-samples t test with outcomes revealing differences in class time PA levels (t = − 0.27, p = 0.79). These results indicate PSI is a successful model for increasing HRF knowledge while maintaining physical activity levels.

Mitochondrial division requires coordinated interactions among Fis1p, Mdv1p, and the Dnm1p GTPase, which assemble into fission complexes on the outer mitochondrial membrane. The integral outer membrane protein Fis1p contains a cytoplasmic domain consisting of a tetratricopeptide repeat (TPR)–like fold and a short NH2-terminal helix. Although it is known that the cytoplasmic domain is necessary for assembly of Mdv1p and Dnm1p into fission complexes, the molecular details of this assembly are not clear. In this study, we provide new evidence that the Fis1p–Mdv1p interaction is direct. Furthermore, we show that conditional mutations in the Fis1p TPR-like domain cause fission complex assembly defects that are suppressed by mutations in the Mdv1p-predicted coiled coil. We also define separable functions for the Fis1p NH2-terminal arm and TPR-like fold. These studies suggest that the concave binding surface of the Fis1p TPR-like fold interacts with Mdv1p during mitochondrial fission and that Mdv1p facilitates Dnm1p recruitment into functional fission complexes.