Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stress.

Amino 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, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multivesicular body (MVB) pathway. The combined loss of vacuolar amino acid storage, MVBs, and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homeostasis through post-translational nutrient transporter remodeling.

Structural basis of mitochondrial receptor binding and constriction by DRP1.

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.

Germline ERBB3 mutation in familial non-small-cell lung carcinoma: expanding ErbB's role in oncogenesis.

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

Postpartum sedentary behaviour and pelvic floor support: A prospective cohort study.

We evaluated the association between sedentary time and pelvic floor support in primiparas delivered vaginally. The 532 participants (29.2 ± 4.9 years) wore wrist accelerometers 6 months postpartum to assess sedentary time, light physical activity (LPA) and moderate to vigorous physical activity (MVPA). We assessed pelvic floor support 1 year postpartum, considered worse if vaginal walls or apex prolapsed to or beyond the hymen. We used multivariable isotemporal substitution analyses to determine the prevalence of worse support when replacing sedentary time with equal time spent in either LPA or MVPA. In 1 year, 9.4% demonstrated worse pelvic floor support. Decreasing sedentary time by 30 min/day with a concomitant increase in MVPA, controlling for LPA, was associated with increased prevalence of worse support (PR 1.43 (95% CI 1.15, 1.77), P < 0.01). Decreasing the sedentary time by 30 min/day with a concomitant increase in LPA, controlling for MVPA, was not significant (PR 0.89 (95% CI 0.80, 0.99), P = 0.04, > pre-set alpha of 0.02). Increasing MVPA while decreasing LPA, controlling for sedentary time, also increased the prevalence of worse support (PR 1.66 (95% CI 1.28, 2.16), P < 0.001). In conclusion, decreasing sedentary time increased the prevalence of worse pelvic floor support when replaced by MVPA, but not LPA.

Early postpartum physical activity and pelvic floor support and symptoms 1 year postpartum.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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 of <0 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. RESULTS: 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. CONCLUSION: 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.

Characteristics Associated with Depression and Suicidal Thoughts Among Medical Residents: Results from the DEPRESS-Ohio Study.

OBJECTIVE: This study describes the characteristics that are associated with depression in residents and also examines resident perception of available mental health support. METHODS: Residents and their program directors from each of 10 specialties across all academic training institutions in Ohio were electronically surveyed over a 2-month period. Generalized logistic regression was used to test for association between risk factors and depression and, among depressed residents, with suicidal thoughts. RESULTS: Using the PHQ-9, 19% of residents met criteria for at least moderate depression and 31.1% of depressed residents had suicidal thoughts. Over 70% of depressed residents were not receiving treatment, including 70% of depressed residents with suicidal thoughts. Residents who were unaware of wellness programming or did not believe their program director would be supportive of a depressed resident were significantly more likely to be depressed. Residents who believed depression treatment would negatively impact medical licensure were significantly more likely to be depressed. Male program directors and those in their position for fewer than 5 years were significantly more likely to have depressed residents in their program. CONCLUSIONS: A substantial proportion of depressed residents have suicidal thoughts, and most are not receiving treatment. Depressed residents may perceive the availability of support from their program director differently than their non-depressed colleagues, and may perceive greater risk to medical licensure if they seek treatment.

Perceptions of Residents and Their Training Directors Regarding Wellness Education, Program Support, and Access to Depression Treatment: the DEPRESS-Ohio Study.

OBJECTIVE: This study determines the extent to which residents and their program directors have discordant perceptions regarding wellness, support, and treatment opportunities for trainees. In addition, the authors examined whether psychiatry residents differed in their perceptions compared with residents in other specialties. METHODS: Residents and their program directors from each of 10 specialties were electronically surveyed after IRB approval and giving informed consent. RESULTS: Of 42 program directors responding, over 92% indicated they provided wellness education and programming; however, a significantly lower percentage of 822 trainees were aware of this (81.2% and 74.9%, respectively). A similar disparity existed between program directors (PDs) who knew where to refer depressed residents for help (92.9%) and residents who knew where to seek help (71%). Moreover, 83.3% of program directors believed they could comfortably discuss depression with a depressed resident, but a lower percentage of their trainees (69.1%) felt their training directors would be supportive. A significantly greater percentage of program directors (40.5%) believed seeking treatment for depression might compromise medical licensure than did residents (13.0%). Psychiatry residents were significantly more aware of wellness, support, and access than were residents from other specialties. CONCLUSIONS: The availability of wellness education, programming, program director accessibility, and knowing where to ask for help if depressed does not seem to be adequately communicated to many residents. Moreover, program directors disproportionately see depression treatment as a risk to medical licensure compared with their residents. Psychiatry residents seem to be more aware of program director support and access to care than their colleagues.

Role of chronic exercise on pelvic floor support and function.

PURPOSE OF REVIEW: To summarize recent literature about the potential role of chronic exercise on pelvic floor support and function. RECENT FINDINGS: Stress urinary incontinence is common during physical activity. Scant evidence suggests a dose-response association between higher volumes of exercise and urinary incontinence. Athletes do not appear to have greater pelvic floor muscle strength or worse pelvic floor support compared to nonathletes. Pelvic floor muscle electromyographic activity increases substantially as running speeds increase. SUMMARY: Based on the current literature, no strong conclusions can be drawn about whether chronic exercise exerts a positive or negative influence on pelvic floor support and function. Adopting longitudinal research methodology that prospectively monitors exercise exposure and subsequent changes in pelvic floor support and function would help to reduce selection bias associated with cross sectional studies on groups of athletes.

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease.

Physical activity and the pelvic floor.

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.

The impact of acute and chronic strenuous exercise on pelvic floor muscle strength and support in nulliparous healthy women.

BACKGROUND: Strenuous physical activity, which is known to increase intraabdominal pressure and theoretically places stress on the pelvic floor, may affect pelvic support in nulliparous women. OBJECTIVE: The aims of this study were to: (1) examine the differences in maximal vaginal descent (MVD), vaginal resting pressure (VRP), and pelvic floor muscle strength (PFMS) between women who habitually perform strenuous exercise vs women who refrain from performing strenuous exercise; and (2) compare MVD, VRP, and PFMS before and immediately following physical activity in the strenuous and nonstrenuous groups separately. STUDY DESIGN: Participants were healthy nulliparous women ages 18-35 years who were habitual strenuous or nonstrenuous exercisers. Women in the strenuous group participated in CrossFit (CrossFit, Inc., Washington, DC) at least 3 days per week for at least 6 months. We assessed anthropometric and body composition values using standardized procedures. Participants completed the Pelvic Organ Prolapse Quantification examination and pelvic muscle strength assessment before and again within 15 minutes of completing exercise (CrossFit for the strenuous group and self-paced walking for the nonstrenuous). A research nurse masked to study group assignment recorded MVD, defined as the greatest value of anterior, posterior, or apical support, and VRP and PFMS using a perineometer. Maximal PFMS was recorded as the highest pressure measured in 3 vaginal contraction trials. Data were analyzed using parametric and nonparametric tests as appropriate. P < .05 was considered significant. RESULTS: Seventy nulliparous women participated in the study, 35 in each group. The mean age was 24.77 ± 4.3 years. Compared to the nonstrenuous group, strenuous participants were heavier (64.70 ± 7.78 kg vs 60.6 ± 8.99 kg, P = .027), had lower percent body fat (23.36 ± 5.88% vs 27.55 ± 7.07%, P = .003), and had higher handgrip strength (20.78 ± 5.97 kg vs 16.04 ± 11.04 kg, P = .001). Before exercise, there were no significant differences in VRP (P = .167), MVD (P = .49), or maximal PFMS (P = .773) between the strenuous and nonstrenuous groups. Immediately following exercise, we observed significant increases in MVD in both the strenuous (P = .008) and nonstrenuous (P = .025) groups, indicating marginal decreases in support. VRP significantly decreased in both groups after exercise. Maximal PFMS did not change significantly in either group after exercise. CONCLUSION: After an exercise bout typical for each group, vaginal support and VRP decreased slightly in both groups. Based on preexercise measures, chronic strenuous exercise demonstrated neither beneficial nor deleterious effects on pelvic floor strength or support. While strenuous women had greater grip strength than nonstrenuous women, PFMS was not significantly greater, suggesting that targeted pelvic floor muscle strengthening, rather than general muscle fitness, is needed to maximize PFMS.

Acute exacerbation of COPD.

The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission.

Mitochondrial fission is mediated by the dynamin-related GTPases Dnm1/Drp1 (yeast/mammals), which form spirals around constricted sites on mitochondria. Additional membrane-associated adaptor proteins (Fis1, Mdv1, Mff, and MiDs) are required to recruit these GTPases from the cytoplasm to the mitochondrial surface. Whether these adaptors participate in both GTPase recruitment and membrane scission is not known. Here we use a yeast strain lacking all fission proteins to identify the minimal combinations of GTPases and adaptors sufficient for mitochondrial fission. Although Fis1 is dispensable for fission, membrane-anchored Mdv1, Mff, or MiDs paired individually with their respective GTPases are sufficient to divide mitochondria. In addition to their role in Drp1 membrane recruitment, MiDs coassemble with Drp1 in vitro. The resulting heteropolymer adopts a dramatically different structure with a narrower diameter than Drp1 homopolymers assembled in isolation. This result demonstrates that an adaptor protein alters the architecture of a mitochondrial dynamin GTPase polymer in a manner that could facilitate membrane constriction and severing activity.

Concurrent Validity of a Self-Reported Physical Activity "Vital Sign" Questionnaire With Adult Primary Care Patients.

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 (<30 sec) Physical Activity "Vital Sign" questionnaire (PAVS) compared with responses to the lengthier (3-5 min), validated Modifiable Activity Questionnaire (MAQ). METHODS: Agreement between activity reported to the PAVS and MAQ by primary care patients at 2 clinics in 2014 was assessed by using percentages and κ coefficients. Agreement consisted of meeting or not meeting the 2008 Aerobic Physical Activity Guidelines for Americans (PA Guidelines) of the US Department of Health and Human Services. We compared self-reported usual minutes per week of moderate-to-vigorous physical activity among patients at a primary care clinic in 2014 who reported to PAVS and to MAQ by using Pearson correlation and Bland-Altman plots of agreement. RESULTS: Among 269 consenting patients who reported physical activity, PAVS results agreed with those of MAQ 89.6% of the time and demonstrated good agreement in identifying patients who did not meet PA Guidelines recommendations (κ = 0.55, ρ = 0.57; P < .001). Usual minutes per week of moderate-to-vigorous physical activity reported to PAVS had a high positive correlation with the same reported to MAQ (r = 0.71; P < .001). CONCLUSION: PAVS may be a valid tool for identifying primary care patients who need counseling about physical activity. PAVS should be assessed further for agreement with repeated objective measures of physical activity in the patient population.

Comparison of the Effects of Seated, Supine, and Walking Interset Rest Strategies on Work Rate.

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.

Physical activity patterns in healthy middle-aged women.

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.

Lifetime physical activity and female stress urinary incontinence.

OBJECTIVE: We sought to estimate whether moderate/severe stress urinary incontinence (SUI) in middle-aged women is associated with overall lifetime physical activity (including leisure, household, outdoor, and occupational), as well as lifetime leisure (recreational), lifetime strenuous, and strenuous activity during the teen years. STUDY DESIGN: Recruitment for this case-control study was conducted in primary-care-level family medicine and gynecology clinics. A total of 1538 enrolled women ages 39-65 years underwent a Pelvic Organ Prolapse Quantification examination to assess vaginal support. Based on Incontinence Severity Index scores, cases had moderate/severe and controls had no/mild SUI. We excluded 349 with vaginal descent at/below the hymen (pelvic organ prolapse), 194 who did not return questionnaires, and 110 with insufficient activity data for analysis. In all, 213 cases were frequency matched 1:1 by age group to controls. Physical activity was measured using the Lifetime Physical Activity Questionnaire, in which women recall activity from menarche to present. We created separate multivariable logistic regression models for activity measures. RESULTS: SUI odds increased slightly with overall lifetime activity (odds ratio [OR], 1.20 per 70 additional metabolic equivalent of task-h/wk; 95% confidence interval [CI], 1.02-1.41), and were not associated with lifetime strenuous activity (OR, 1.11; 95% CI, 0.99-1.25). In quintile analysis of lifetime leisure activity, which demonstrated a nonlinear pattern, all quintiles incurred about half the odds of SUI compared to reference (second quintile; P = .009). Greater strenuous activity in teen years modestly increased SUI odds (OR, 1.37 per 7 additional h/wk; 95% CI, 1.09-1.71); OR, 1.75; 95% CI, 1.15-2.66 in sensitivity analysis adjusting for measurement error. The predicted probability of SUI rose linearly in women exceeding 7.5 hours of strenuous activity/wk during teen years. Teen strenuous activity had a similar effect on SUI odds when adjusted for subsequent strenuous activity during ages 21-65 years. CONCLUSION: In middle-aged women, a slight increased odds of SUI was noted only after substantially increased overall lifetime physical activity. Increased lifetime leisure activity decreased and lifetime strenuous activity appeared unrelated to SUI odds. Greater strenuous activity during teen years modestly increased SUI odds.

Resistant starch alters colonic contractility and expression of related genes in rats fed a Western diet.

BACKGROUND AND AIM: Dietary fiber shortens gut transit time, but data on the effects of fiber components (including resistant starch, RS) on intestinal contractility are limited. We have examined RS effects in male Sprague-Dawley rats fed either a high-amylose maize starch (HAMS) or a wholemeal made from high-amylose wheat (HAW) on ileal and colonic contractility ex vivo and expression of genes associated with smooth muscle contractility. METHODS: Rats were fed diets containing 19 % fat, 20 % protein, and either low-amylose maize starch (LAMS), HAMS, wholemeal low-amylose wheat (LAW) or HAW for 11 week. Isolated ileal and proximal colonic sections were induced to contract electrically, or by receptor-independent (KCl) or receptor-dependent agents. Colonic gene expression was assessed using an Affymetrix microarray. RESULTS: Ileal contractility was unaffected by treatment. Maximal proximal colonic contractility induced electrically or by angiotensin II or carbachol was lower for rats fed HAMS and LAW relative to those fed LAMS (P < 0.05). The colonic expression of genes, including cholinergic receptors (Chrm2, Chrm3), serotonin receptors (Htr5a, Htr7), a protease-activated receptor (F2r), a prokineticin receptor (Prokr1), prokineticin (Prok1), and nitric oxide synthase 2 (Nos2), was altered by dietary HAMS relative to LAMS (P < 0.05). HAW did not significantly affect these genes or colonic contractility relative to effects of LAMS. CONCLUSIONS: RS and other fiber components could influence colorectal health through modulation of stool transit time via effects on muscular contractility.

Effects of walking speeds and carrying techniques on intra-abdominal pressure in women.

INTRODUCTION AND HYPOTHESIS: Walking speed and carrying technique affect intra-abdominal pressure (IAP) in women. In this study, we tested the feasibility of monitoring IAP outside the laboratory environment and compared IAP while study participants were (1) carrying 13.6 kg (similar to a 3-month old in car seat) in six different ways while walking 100 m; and (2) while walking 400 m at self-selected slow, normal, and fast paces. METHODS: Forty-six healthy women between 19 and 54 years completed the walking and lifting activities; the order for each was randomized. IAP was monitored with an intravaginal pressure transducer that wirelessly transmitted pressure data to a portable base station. We analyzed maximal peak IAP and area under the curve (AUC) IAP. RESULTS: Monitoring IAP outside of the laboratory was feasible. Mean maximal IAP during walking increased as pace increased: 42.5 [standard deviation (SD) 10.2], 50.5 (10.9), and 62.0 (12.1) cmH2O for slow, medium, and fast speeds, respectively: p < 0.0001 by mixed-model analysis of variance (ANOVA). The corresponding AUC of IAP for walking decreased as pace increased. The awkward carry, side carry, and front carry activities each resulted in higher mean maximal IAP [65.8 (10.6), 67.7 (12.8), and 77.3 (13.1) cmH2O, respectively] than the carry-in-backpack activity [55.5 (11.4) cmH2O; p < 0.0001]. CONCLUSION: Subtle variations in walking speed or method of carrying a toddler-size load can produce significant changes in IAP. Whether these changes increase the risk of pelvic floor disorders is not yet clear. However, these data suggest that further inquiry into optimal methods and appliances to assist women in carrying may create a lower IAP profile.