Defining the impact of continuous positive airway pressure therapy on diastolic function in adults with moderate-to-severe obstructive sleep apnea.

Although studies have shown that continuous positive airway pressure (CPAP) therapy to treat obstructive sleep apnea improves left ventricular diastolic function, modifiers of improvement are unknown. We explored race and pre-treatment 24-h non-dipping blood pressure status as modifiers of improved diastolic function. Participants (N = 220) with obstructive sleep apnea (apnea-hypopnea index ≥15 events/h) and hypertension were recruited to a cohort study that examined effects of 3-month CPAP therapy on 24-h blood pressure. Those who completed echocardiogram at baseline and follow-up were included in this analysis. Diastolic function parameters (E, A, e', E/A, E/e') were assessed. Race was categorised to African American versus others. Participants were categorised as nocturnal dippers (night-time blood pressure decrease by ≥10%) versus non-dippers. We compared changes in parameters of diastolic function by race and nocturnal dipping status. A total of 92 participants were included. They were men (86%), African American (67.4%), and current smoker (29.5%). Mean apnea-hypopnea index was 32.9 events/h. Mean CPAP usage was 3.15 h/day. After 3 months of CPAP treatment, there were significant improvements in measures of diastolic function: a median (interquartile range [IQR]) increase in E velocity by 4.00 (-5.75 to 13.75) cm/s, an increase in e' by 2.00 (0-4.00) cm/s, and a decrease in the E/e' ratio by 1.74 (-4.27 to 0.00) at follow-up (p < 0.05). These changes did not differ by race or nocturnal dipping status. Improvements in diastolic function after CPAP therapy did not differ by race or nocturnal dipping status. Further studies are needed to understand predictors of CPAP effects on diastolic function.

Asthma and Obstructive Sleep Apnea Overlap: What Has the Evidence Taught Us?

Obstructive sleep apnea (OSA) and asthma are highly prevalent chronic respiratory disorders. Beyond their frequent coexistence arising from their high prevalence and shared risk factors, these disorders feature a reciprocal interaction whereby each disease impacts the severity of the other. Emerging evidence implicates airway and systemic inflammation, neuroimmune interactions, and effects of asthma-controlling medications (corticosteroids) as factors that predispose patients with asthma to OSA. Conversely, undiagnosed or inadequately treated OSA adversely affects asthma control, partly via effects of intermittent hypoxia on airway inflammation and tissue remodeling. In this article, we review multiple lines of recently published evidence supporting this interaction. We provide a set of recommendations for clinicians involved in the care of adults with asthma, and identify critical gaps in our knowledge about this overlap.

The effects of separate and combined dietary weight loss and exercise on fasting ghrelin concentrations in overweight and obese women: a randomized controlled trial.

OBJECTIVE: Compensatory metabolic changes that accompany weight loss, for example, increased ghrelin, contribute to weight regain and difficulty in long-term weight loss maintenance; however, the separate effects of long-term caloric restriction and exercise on total circulating ghrelin in humans are unknown. DESIGN: A 12-month randomized controlled trial comparing: i) dietary weight loss with a 10% weight loss goal ('diet'; n = 118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week ('exercise'; n = 117); iii) dietary weight loss and exercise ('diet + exercise'; n = 117); or iv) no-lifestyle-change control (n = 87). PARTICIPANTS: 439 overweight or obese postmenopausal women (50-75 y). MEASUREMENTS: Fasting total serum ghrelin was measured by radioimmunoassay at baseline and 12 months. Fasting serum leptin, adiponectin and insulin were also measured. RESULTS: Fasting total ghrelin significantly increased in the diet + exercise arm (+7·4%, P = 0·008) but not in either the diet (+6·5%, P = 0·07) or exercise (+1·0%, P = 0·53) arms compared with control. Greater weight loss was associated with increased ghrelin concentrations, regardless of intervention. Neither baseline ghrelin nor body composition modified the intervention effects on changes in total ghrelin. The 12-month change in total ghrelin was inversely associated with changes in leptin, insulin and insulin resistance, and positively associated with change in adiponectin. CONCLUSIONS: Greater weight loss, achieved through a reduced calorie diet or exercise, is associated with increased total ghrelin concentrations in overweight or obese postmenopausal women.

Osteoarthritis prevalence and modifiable factors: a population study.

BACKGROUND: This study's objectives were to investigate the prevalence of self-reported knee and hip osteoarthritis (OA) stratified by age and sex and to examine the association of modifiable factors with knee and hip OA prevalence. The study was conducted using randomly sampled data gathered from four communities in the province of Alberta, Canada. METHODS: A large adult population sample (N = 4733) of individuals ≥18 years were selected. Health-related information was collected through telephone interviews and community measurement clinics for which a sub-sample (N = 1808) attended. Participants self-reported OA during telephone interviews. Clinic interviews further assessed if the diagnosis was made by a health care professional. Statistical analyses compared prevalence of OA between sexes and across age categories. Associations between modifiable factors for OA and the prevalence of knee and hip OA were assessed using binary logistic regression modelling. RESULTS: Overall prevalence of self-reported OA in the total sample was 14.8 %, where 10.5 % of individuals reported having knee OA and 8.5 % reported having hip OA. Differences in prevalence were found for males and females across age categories for both knee and hip OA. In terms of modifiable factors, being obese (BMI >30 kg/m2) was significantly associated with the prevalence of knee (OR: 4.37; 95 % CI: 2.08,9.20) and hip (OR: 2.52; 95 % CI: 1.17,5.43) OA. Individuals who stand or walk a lot, but do not carry or lift things during their occupational activities were 2.0 times less likely to have hip OA (OR: 0.50; 95 % CI: 0.26,0.96). Individuals who usually lift or carry light loads or have to climb stairs or hills were 2.2 times less likely to have hip OA (OR: 0.45; 95 % CI: 0.21,0.95). The odds of having hip OA were 1.9 times lower in individuals consuming recommended or higher vitamin C intake (OR: 0.52; 95 % CI: 0.29,0.96). Significant differences in prevalence were found for both males and females across age categories. CONCLUSION: The prevalence of knee and hip OA obtained in this study is comparable to other studies. Females have greater knee OA prevalence and a greater proportion of women have mobility limitations as well as hip and knee pain; it is important to target this sub-group.

Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.

INTRODUCTION: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. METHODS: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. CONCLUSIONS: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.

Weight, inflammation, cancer-related symptoms and health related quality of life among breast cancer survivors.

Maintaining weight is important for better prognosis of breast cancer survivors. The associations between weight and cancer-related symptoms are not known. We examined associations among weight, weight change, inflammation, cancer-related symptoms, and health-related quality of life (HRQOL) in a cohort of stage 0-IIIA breast cancer survivors. Participants were recruited on average 6 months (2­12 months) after diagnosis. Height, weight, and C-reactive protein (CRP) were assessed at approximately 30 months post-diagnosis; cancer-related symptoms (chest wall and arm symptoms, vasomotor symptoms, urinary incontinence, vaginal symptoms, cognition/mood problems, sleep, sexual interest/function), and HRQOL (SF-36) were assessed at approximately 40 months post-diagnosis. Weight was measured at baseline in a subset. Data on 661 participants were evaluable for body mass index (BMI); 483 were evaluable for weight change. We assessed associations between BMI (<25.0, 25.0­29.9, ≥30.0 kg/m2), post-diagnosis weight change (lost ≥5 %, weight change <5 %, gained ≥5 %), and CRP (tertile) with cancer-related symptoms and HRQOL using analysis of covariance. Higher symptoms scores indicate more frequent or severe symptoms. Higher HRQOL scores indicate better HRQOL. Compared with those with BMI <25 kg/m2, women with BMI ≥30 kg/m2 had the following scores: increased for arm symptoms (+25.0 %), urinary incontinence (+40.0 %), tendency to nap (+18.9 %), and poorer physical functioning (−15.6 %, all p < 0.05). Obese women had lower scores in trouble falling asleep (−9.9 %; p < 0.05). Compared with weight change <5 %, participants with ≥5 % weight gain had lower scores in physical functioning (−7.2 %), role-physical (−15.5 %) and vitality (−11.2 %), and those with weight loss ≥5 % had lower chest wall (−33.0 %) and arm symptom scores (−35.5 %, all p < 0.05). Increasing CRP tertile was associated with worse scores for chest wall symptoms, urinary incontinence, physical functioning, role-physical, vitality and physical component summary scores (all P trend < 0.05). Future studies should examine whether interventions to maintain a healthy weight and reduce inflammation could alleviate cancer-related symptoms and improve HRQOL.

Weight and metabolic effects of dietary weight loss and exercise interventions in postmenopausal antidepressant medication users and non-users: a randomized controlled trial.

OBJECTIVE: Antidepressants may attenuate the effects of diet and exercise programs. We compared adherence and changes in body measures and biomarkers of glucose metabolism and inflammation between antidepressant users and non-users in a 12-month randomized controlled trial. METHODS: Overweight or obese, postmenopausal women were assigned to: diet (10% weight loss goal, N=118); moderate-to-vigorous aerobic exercise (225 min/week, N=117); diet+exercise (N=117); and control (N=87) in Seattle, WA 2005-2009. Women using antidepressants at baseline were classified as users (N=109). ANCOVA and generalized estimating equation approaches, respectively, were used to compare adherence (exercise amount, diet session attendance, and changes in percent calorie intake from fat, cardiopulmonary fitness, and pedometer steps) and changes in body measures (weight, waist and percent body fat) and serum biomarkers (glucose, insulin, homeostasis assessment-insulin resistance, and high-sensitivity C-reactive protein) between users and non-users. An interaction term (intervention×antidepressant use) tested effect modification. RESULTS: There were no differences in adherence except that diet session attendance was lower among users in the diet+exercise group (P<0.05 vs. non-users). Changes in body measures and serum biomarkers did not differ by antidepressant use (Pinteraction>0.05). CONCLUSION: Dietary weight loss and exercise improved body measures and biomarkers of glucose metabolism and inflammation independent of antidepressant use.

Revisiting Asthma Obstructive Sleep Apnea Overlap: Current Knowledge and Future Needs.

Asthma and obstructive sleep apnea are highly prevalent conditions with a high cost burden. In addition to shared risk factors, existing data suggest a bidirectional relationship between asthma and OSA, where each condition can impact the other. Patients with asthma often complain of sleep fragmentation, nocturnal asthma symptoms, daytime sleepiness, and snoring. The prevalence of OSA increases with asthma severity, as evidenced by multiple large studies. Asthma may lower the threshold for arousal in OSA, resulting in the hypopnea with arousal phenotype. Epidemiologic studies in adults have shown that OSA is associated with worse asthma severity, increased frequency of exacerbation, and poor quality of life. The current literature assessing the relationship among OSA, asthma, and CPAP therapy is heavily dependent on observational studies. There is a need for randomized controlled trials to minimize the interference of confounding shared risk factors.

Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device.

The dacryocystorhinostomy procedure creates a direct passageway between the lacrimal sac and nasal cavity, bypassing any nasolacrimal duct obstruction. Use of a continuous positive airway pressure device after dacryocystorhinostomy can cause nasolacrimal air regurgitation. Here, we report a case of air regurgitation after dacryocystorhinostomy that was successfully treated with placement of a Mini Monoka device, a silicone stent used in nasolacrimal surgery to prevent closure of the passageway, in a patient using a continuous positive airway pressure machine. Following the procedure, the patient was able to resume use of her continuous positive airway pressure device. CITATION: Srivatsan S, Mirza M, Imayama I, Setabutr P, Mahoney NR. Use of a nasolacrimal stent to treat air regurgitation after dacryocystorhinostomy in a patient using a continuous positive airway pressure device. J Clin Sleep Med. 2023;19(12):2123-2124.

Socioeconomic status impacts blood pressure response to positive airway pressure treatment.

STUDY OBJECTIVES: Positive airway pressure (PAP) treatment of obstructive sleep apnea reduces blood pressure (BP). Retrospective data suggest that African Americans (AA), a group at high-risk for hypertensive organ dysfunction, may have a greater BP response to PAP therapy than European Americans (EA). We examined the difference in 24-hour BP response to 3 months of PAP treatment between AA and EA. METHODS: Participants (n = 259, 161 AA and 98 EA) with apnea-hypopnea index ≥ 15 events/h from 2 prospective cohorts were included. t-Tests and multiple linear regression were used to examine BP outcomes in AA vs EA, adjusting for PAP adherence, socioeconomic status, and baseline characteristics. RESULTS: Participants were middle aged (mean ± SD, 53.8 ± 9.3 years), 86% (227) men, apnea-hypopnea index 35.6 ± 19.2 events/h, and PAP adherence of 3.36 ± 2.24 h/day. The reductions in 24-hour systolic and diastolic BP (mm Hg) were not different in AA vs EA (systolic = -1.13 ± 12.1 vs -0.61 ± 12.8, P = .80 and diastolic = -0.74 ± 7.9 vs -0.80 ± 7.4, P = .96), and race was not a predictor of 24-hour systolic or diastolic BP reduction (P = .75 and 0.54). Socioeconomic status and PAP adherence demonstrated a significant interaction; low socioeconomic status was associated with an increase in 24-hour systolic BP (ß = 19.3, P = .03) in the absence of PAP use but a greater reduction in 24-hour systolic BP with higher PAP adherence (ß = -3.96, P = .03). CONCLUSIONS: Twenty-four hour BP response to PAP treatment is similar in AA and EA. Adherence to PAP treatment is more effective in improving 24-hour systolic BP in those with low SES. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Race and CPAP Effectiveness (RACE); URL: https://clinicaltrials.gov/ct2/show/NCT01960465; Identifier: NCT01960465 and Registry: ClinicalTrials.gov; Name: The Effects of Treating Obese and Lean Patients with Sleep Apnea (PISA); URL: https://clinicaltrials.gov/ct2/show/NCT01578031; Identifier: NCT01578031. CITATION: Imayama I, Gupta A, Yen PS, et al. Socioeconomic status impacts blood pressure response to positive airway pressure treatment. J Clin Sleep Med. 2022;18(5):1287-1295.

Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial.

BACKGROUND: Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL. METHODS: This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL. RESULTS: Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness. CONCLUSIONS: A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.

Effects of 12-month exercise on health-related quality of life: a randomized controlled trial.

OBJECTIVE: We investigated exercise effects on health-related quality of life (HRQOL) and exercise self-efficacy, and tested effect modification by baseline body mass index (BMI) and gender. METHODS: Middle-aged women (n=100) and men (n=102) were randomly assigned to either exercise (360 min/week of moderate-to-vigorous aerobic exercise) or control in Seattle, WA, from 2001 to 2004. Demographics, anthropometrics, exercise self-efficacy (5-item self-efficacy questionnaire) and HRQOL (SF-36) were assessed at baseline and 12 months. Analysis of covariance adjusting for baseline scores was used to compare HRQOL and exercise self-efficacy scores between the exercise and control groups. RESULTS: At 12 months, exercisers demonstrated higher exercise self-efficacy than controls (percent change from baseline: -6.5% vs. -15.0%, p < 0.01), without differences in HRQOL. Baseline BMI category and gender did not modify these effects. In exploratory analyses comparing exercisers and controls within subgroups defined by gender and BMI, 12-month HRQOL scores [role-physical (+7.0% vs. -13.1%), vitality (+15.6% vs. -4.2%), social functioning (+10.0% vs. -3.5%), and mental health (+6.8% vs. -2.9%)] were higher only among overweight male exercisers (p < 0.05, vs. control). CONCLUSION: Three hundred and sixty minutes per week of exercise, recommended for weight maintenance, did not have negative effects on exercise self-efficacy or HRQOL. This level of exercise may increase HRQOL among overweight men.

Determinants of quality of life in adults with type 1 and type 2 diabetes.

BACKGROUND: Limited evidence exists on the determinants of quality of life (QoL) specific to adults with type 1 diabetes (T1D). Further, it appears no study has compared the determinants of QoL between T1D and type 2 diabetes (T2D) groups. The objectives of this study were to examine: (1) determinants of QoL in adults with T1D; and, (2) differences in QoL determinants between T1D and T2D groups. METHODS: The Alberta Longitudinal Exercise and Diabetes Research Advancement (ALEXANDRA) study, a longitudinal study of adults with diabetes in Alberta, Canada. Adults (18 years and older) with T1D (N = 490) and T2D (N = 1,147) provided information on demographics (gender, marital status, education, and annual income), personality (activity trait), medical factors (diabetes duration, insulin use, number of comorbidities, and body mass index), lifestyle behaviors (smoking habits, physical activity, and diet), health-related quality of life (HRQL) and life satisfaction. Multiple regression models identified determinants of HRQL and life satisfaction in adults with T1D. These determinants were compared with determinants for T2D adults reported in a previous study from this population data set. Factors significantly associated with HRQL and life satisfaction in either T1D or T2D groups were further tested for interaction with diabetes type. RESULTS: In adults with T1D, higher activity trait (personality) score (ß = 0.28, p < 0.01), fewer comorbidities (ß = -0.27, p < 0.01), lower body mass index (BMI)(ß = -0.12, p < 0.01), being a non-smoker (ß = -0.14, p < 0.01), and higher physical activity levels (ß = 0.16, p < 0.01) were associated with higher HRQL. Having a partner (ß = 0.11, p < 0.05), high annual income (ß = 0.16, p < 0.01), and high activity trait (personality) score (ß = 0.27, p < 0.01) were significantly associated with higher life satisfaction. There was a significant age × diabetes type interaction for HRQL. The T2D group had a stronger positive relationship between advancing age and HRQL compared to the T1D group. No interaction was significant for life satisfaction. CONCLUSIONS: Health services should target medical and lifestyle factors and provide support for T1D adults to increase their QoL. Additional social support for socioeconomically disadvantaged individuals living with this disease may be warranted. Health practitioners should also be aware that age has different effects on QoL between T1D and T2D adults.

Determinants of quality of life in type 2 diabetes population: the inclusion of personality.

OBJECTIVE: The identification of factors that affect quality of life (QoL) is crucial to ameliorate the increasing burden of diabetes. This study tested a multi-dimensional model that consisted of factors across three domains (personal, medical, and lifestyle factors) to understand determinants of QoL in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,147 adults with type 2 diabetes completed a self-report survey which assessed demographic factors, personality (activity sub-trait), medical factors (diabetes duration, insulin use, number of comorbidities, and Body Mass Index), lifestyle behaviors (smoking, physical activity, and diet), and two indicators of QoL [i.e., health-related quality of life (HRQL) and life satisfaction (LS)]. RESULTS: The model explained 27.1 and 18.2% of the variance for HRQL and LS, respectively. Age was positively related to HRQL (ß = 0.14, P < 0.01). Personality (sub-activity trait) was the strongest, independent variable in both HRQL (ß = 0.25, P < 0.01) and LS (ß = 0.25, P < 0.01) after controlling for demographic, medical, and lifestyle factors. Physical activity was positively associated (ß = 0.14, P < 0.01) with HRQL but not with LS. CONCLUSIONS: Personality may be a useful screening tool to distinguish adults with type 2 diabetes who are at risk for poor QoL.

Pathways to well-being: Untangling the causal relationships among biopsychosocial variables.

RATIONALE: The biopsychosocial (BPS) model that challenged the historically dominant biomedical model remains influential today. This model considers biological, psychological, and social factors that can contribute to health and illness. Yet, a growing body of literature has been highly critical of the model for being too vague and for not providing details as to how the three factors of the model interact and contribute to health and illness. OBJECTIVE: Because biological, psychological, and social factors can be considered as distinct 'systems' that can be conceptually separated, defined, and measured, we sought to examine interrelationships among these factors. METHOD: By employing analytical reasoning and carefully considering relevant research evidence of direct pathways among biological, psychological, and social factors as applicable to an individual's health and well-being, this article introduces an updated theoretical model: the BPS-Pathways model. RESULTS: We present all six potential pathways among biological (B), psychological (P), and social (S) factors of the model, and explain how these pathways can potentially contribute to subjective well-being and to objective physical health outcomes. The influential pathways that lead to subjective well-being are S→P and B→P pathways, although these pathways can be impacted by psychological factors that differ among individuals. For objective health outcomes, the P→B and S→B pathways appear to be important, where the latter pathway is mediated by psychological factors. We additionally highlight the importance of systematically understanding subjective experience, which represents an epistemologically distinct domain, and describe how subjective experience can explain individual differences in causal pathways. CONCLUSIONS: The BPS-Pathways model presents a framework that can have important implications for clinical practice, as well as research, and can be useful for tailoring personalized medicine.

Racial Differences in Functional and Sleep Outcomes with Positive Airway Pressure Treatment.

It is unclear if the response to positive airway pressure (PAP) treatment is different between African American (AA) and European Americans (EA). We examined whether race modifies the effects of PAP on sleep and daytime function. We assessed Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire, Psychomotor Vigilance Task and actigraphy in 185 participants with moderate-to-severe obstructive sleep apnea before and 3-4 months after PAP treatment. The participants were middle-aged (mean, 55.1 years), 83.8% men and 60.5% AA. Linear regression models were used to examine the effect of race on outcomes. The AA had smaller reductions in ESS (mean change (95% confidence interval, CI) AA, -2.30 [-3.35, -1.25] vs. EA, -4.16 [-5.48, -2.84] and frequency of awakenings (AA, -0.73 [-4.92, 3.47] vs. EA, -9.35 [-15.20, -3.51]). A race × PAP usage interaction term was added to the model to examine if the change in outcomes per 1 h increase in PAP usage differed by race. AA exhibited greater improvement in wake after sleep onset (ß (95% CI) AA, -8.89 [-16.40, -1.37] vs. EA, 2.49 [-4.15, 9.12]) and frequency of awakening (ß (95% CI) AA, -2.59 [-4.44, -0.75] vs. EA, 1.71 [-1.08, 4.50]). The results indicate the importance of race in evaluating outcomes following PAP treatment.

ATS Core Curriculum 2020. Adult Sleep Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3-4-year recurring cycle of topics. These topics will be presented at the 2020 Virtual Conference. Below is the adult sleep medicine core that includes topics pertinent to sleep-disordered breathing and insomnia.

SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells.

OBJECTIVE: Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol found in red wine, is known to activate sirtuin1 (SIRT1), a longevity gene. Previous studies have demonstrated that resveratrol extends the life span of diverse species through activation of SIRT1. It was also reported that inhibition of angiotensin II function by angiotensin II type I receptor (AT1R) antagonist prolonged rat life span. We, therefore, hypothesized that resveratrol may inhibit the renin-angiontein system and examined whether resveratrol affects AT1R expression in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Northern and Western blot analysis revealed that resveratrol significantly decreased the expression of AT1R at mRNA and protein levels in a dose- and time-dependent manner. Overexpression of SIRT1 reduced AT1R expression whereas nicotinamide, an inhibitor of SIRT1, increased AT1R expression and reversed the resveratrol-induced AT1R downregulation. AT1R gene promoter activity was decreased by resveratrol, but resveratrol did not affect the AT1R mRNA stability. Deletion analysis showed that the most proximal region of AT1R gene promoter containing Sp1 site is responsible for downregulation. Administration of resveratrol suppressed AT1R expression in the mouse aorta and blunted angiotensin II-induced hypertension. CONCLUSIONS: Resveratrol suppressed AT1R expression through SIRT1 activation both in vivo and in vitro. The inhibition of the renin-angiotensin system may contribute, at least in part, to the resveratrol-induced longevity and antiatherogenic effect of resveratrol.

Involvement of Mst1 in tumor necrosis factor-alpha-induced apoptosis of endothelial cells.

Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-alpha-induced apoptosis of ECs. Western blot analysis revealed that TNF-alpha induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-alpha-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting of propidium iodide-stained cells showed that TNF-alpha induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-alpha-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-alpha-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-alpha-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.