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Saurabh S Thosar,1– 4 Daniel Chess,1 Nicole P Bowles,1 Andrew W McHill,1,2 Matthew P Butler,1,5 Jonathan S Emens,1,6 Steven A Shea1,4 1Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA; 2School of Nursing, Oregon Health & Science University, Portland, OR, USA; 3Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA; 4OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR, USA; 5Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; 6Portland VA Medical Center, Portland, OR, 97239, USACorrespondence: Saurabh S ThosarOregon Institute of Occupational Health Sciences, 3181 S.W. Sam Jackson Park Road, Mail Code 606, Portland, OR, 97239, USATel +1 503 494-2064Fax +1 503 494-4278Email thosar@ohsu.eduPurpose: Sleep efficiency is inversely associated with cardiovascular risk. Brachial artery diameter and flow-mediated dilation (FMD) are noninvasive cardiovascular disease markers. We assessed the associations between sleep efficiency and these vascular markers in midlife adults, including people with sleep apnea.Patients and Methods: Thirty (18 males) participants completed an in-laboratory 8-hour sleep opportunity beginning at their habitual bedtimes. Polysomnography was used to assess sleep patterns and sleep efficiency (time asleep/time in bed). We measured systolic and diastolic blood pressure, heart rate, and baseline diameter, and FMD immediately upon awakening in the morning. Mixed model analyses, adjusting for apnea-hypopnea and body mass indices, were used to assess the relationship between overnight sleep efficiency and cardiovascular markers. We also explored sex differences.Results: Sleep efficiency was negatively associated with baseline brachial artery diameter (p = 0.005), systolic BP (p = 0.01), and diastolic BP (p = 0.02), but not flow-mediated dilation or heart rate (p > 0.05). These relationships were confirmed with correlations between sleep efficiency and baseline diameter (r = − 0.52, p = 0.004), systolic BP (r = − 0.43, p = 0.017), and diastolic BP (r = − 0.43, p = 0.019). There was a sex-specific interaction trend for sleep efficiency and arterial diameter (p = 0.07) and a significant sex-specific interaction (p < 0.05) for BP, such that the relationships between sleep efficiency and cardiovascular markers were significant in women but not in men.Conclusion: In midlife adults, poor sleep efficiency is associated with increased brachial artery diameter and blood pressure, effects that were primarily driven by significant associations in women. These associations could underlie the observed increase in cardiovascular risk in adults with poor sleep and cardiovascular disease.Keywords: sleep efficiency, midlife adults, obstructive sleep apnea, morning cardiovascular risk, polysomnography, sex differences

Saurabh S Thosar,1– 4 Meera C Bhide,1 Isabel Katlaps,1 Nicole P Bowles,1 Steven A Shea,1,4 Andrew W McHill1,2 1Oregon Institute of Occupational Health Sciences; 2School of Nursing; 3Knight Cardiovascular Institute, School of Medicine; 4OHSU-PSU School of Public Health, Oregon Health and Science University, Portland, OR, 97239, USACorrespondence: Saurabh S ThosarOregon Institute of Occupational Health Sciences, 3181 SW Sam Jackson Park Road, L606/RJH1586, Portland, OR, 97239, USATel +1 503 494-2064Fax +1 503 494-4278Email thosar@ohsu.eduPurpose: Sedentary behavior and suboptimal sleep increase risks for chronic diseases. We hypothesized that sedentary behavior and sleep affect each other and that an underlying sleep disorder would alter these relationships. To test these hypotheses, we studied the bidirectional relationships between sedentary behavior and sleep (duration and efficiency) in healthy controls (HC) and people with untreated obstructive sleep apnea (OSA).Patients and Methods: Fifty-two volunteers (18 HC, 19 mild OSA [apnea/hypopnea index [AHI] range 5– 14.9/hour], 15 moderate OSA [AHI range 15– 29.9/hour]) were studied with actigraphy and sleep diaries across ∼ 9 consecutive nights of self-selected consistent ∼ 8-hour sleep episodes at home (range 4– 21/nights per person). We analyzed whether total time asleep and sleep efficiency affected the subsequent daytime sedentary duration while controlling for body mass index and whether the severity of OSA altered this relationship. We also tested the reverse relationship, namely whether daytime sedentary duration affected the subsequent night’s sleep and if any such relationship differed with OSA severity.Results: Overnight sleep duration and efficiency negatively predicted the subsequent day’s sedentary duration in HC (p< 0.02), but not in people with mild or moderate OSA (p> 0.05). There was no significant reverse relationship between daytime sedentary duration and the subsequent night’s sleep duration or efficiency (p≥ 0.2).Conclusion: In healthy adults, short nighttime sleep predicts a longer duration of sedentary behavior on a subsequent day, but we did not observe this relationship in people with OSA. The mechanisms underlying this association in healthy individuals and its disruption in the presence of OSA need to be studied.Keywords: sitting time, sedentary behavior, cardiometabolic risk, sleep quality, chronic diseases, sleep disorders

Saurabh S Thosar,1–4 Daniel Chess,1 Nicole P Bowles,1 Andrew W McHill,1,2 Matthew P Butler,1,5 Jonathan S Emens,1,6 Steven A Shea1,4 1Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA; 2School of Nursing, Oregon Health & Science University, Portland, OR, USA; 3Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA; 4OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR, USA; 5Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; 6Portland VA Medical Center, Portland, OR 97239, USACorrespondence: Saurabh S ThosarOregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Mail Code 606, Portland, OR 97239, USATel +1 503 494-2064Fax +1 503 494-4278Email thosar@ohsu.edu View the original paper by Dr Thosar and colleagues This is in response to the Letter to the Editor

Alec M Berman, Saurabh S Thosar, Steven A SheaOregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, USAObstructive sleep apnea (OSA) is a complex disorder involving the cardiovascular (CV), pulmonary, and metabolic systems. Characterized by marked daytime fatigue and reduced quality of life, OSA is independently associated with increased risk of hypertension,1 cardiovascular disease (CVD),2 including myocardial infarction (MI)3 and ischemic stroke,4 metabolic syndrome,5 and all-cause mortality.6 Currently, the most common treatment for OSA is continuous positive airway pressure (CPAP) during sleep, though its efficacy in reducing daytime fatigue and CVD risk factors depends largely on compliance to therapy, which is poor in the general population.7 Lamberts et al8 performed a large epidemiological study of OSA, using the Danish National Patient Registry (NPR; ∼4.5 million; including 25,389 people diagnosed with OSA), which confirmed associations between OSA and risk of ischemic stroke and MI. Yet, that study failed to show that CPAP reduces the incidence of these adverse CV events.8 On the other hand, a more recent study, which examined the same Danish NPR across a very similar time period, revealed that in people with OSA, CPAP reduces all-cause mortality.9 This editorial evaluates these seemingly conflicting results, whereby CPAP appears to reduce mortality but not two of the largest contributors to mortality: stroke and MI.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status. NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

This study aimed to test whether bright light (BL) exposure attenuates the reduction in blood pressure (BP) postexercise compared to dim light (DL). Twenty healthy men (27 ± 5 years) randomly underwent two experimental sessions: one under BL (5000 lux) and another under dim light (DL <8lux). In each session, subjects executed a bout of aerobic exercise (cycle ergometer, 30 min, moderate intensity). BP (oscillometric) and heart rate (HR monitor) were measured, and rate-pressure-product (RPP) was calculated. Additionally, a 24-h ambulatory blood pressure monitoring (ABPM) was conducted after the sessions. Systolic BP decreased while HR increased significantly and similarly after the exercise in both sessions. Additionally, systolic BP levels were higher in BL than DL throughout the experimental session (P session  = 0.04). Diastolic (P interaction  = 0.02) and mean (P interaction  = 0.03) BPs decreased after exercise in DL (at 30 min), and increased in BL (at 60 and 90 min). RPP increased in both sessions postexercise, but with a main effect revealing higher levels throughout the experimental session in BL than DL (P session  = 0.04) and during the first 3 h of ABPM (p = 0.05). In healthy men, BL exposure increased systolic BP and cardiac work, and abolished the postexercise decreases of diastolic and mean BPs., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

At the start of the COVID-19 pandemic, many workplaces transitioned to remote work, which altered lifestyle behaviors. We conducted a meta-analysis to understand if the transition to working from home due to the pandemic affected workers' physical activity and sedentary behavior worldwide. We reviewed articles published between November 2019 and May 2022. Of an initial 3485 articles, a total of 17 were included, 15 of 17 were included for their physical activity (PA) comparisons ( n = 36,650), and 12 of 17 ( n = 57,254) were included for their sedentary behavior (SB) comparisons (10 studies have data for both PA and SB). This work is registered through PROSPERO (CRD42022356000). Working from home resulted in a significant decrease in PA (Hedge's g = -0.29, 95% CI [-0.41, -0.18]) and an increase in SB (Hedge's g = +0.36, 95% CI [0.20, 0.52]). Working from home impaired preventative activity behaviors, and these results are relevant to worker health as the future of work evolves beyond the pandemic.

Background: Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures)., Objective: We examined proximal and distal drivers of cardiovascular disease and elucidated the interactions between modifiable and non-modifiable risk factors., Methods: We used a machine learning approach on four cohorts (2005-2012) of the National Health and Nutrition Examination Survey data to examine the effects of risk factors on cardiovascular risk quantified by the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). We estimated a network of risk factors, computed their strength centrality, closeness, and betweenness centrality, and computed a Bayesian network embodied in a directed acyclic graph., Results: In addition to traditional factors such as body mass index and physical activity, race and ethnicity and exposure to heavy metals are the most adjacent drivers of PCE. In addition to the factors directly affecting PCE, sleep complaints had an immediate adverse effect on FRS. Exposure to heavy metals is the link between race and ethnicity and FRS., Conclusion: Heavy metal exposures and race/ethnicity have similar proximal effects on cardiovascular disease risk as traditional clinical and lifestyle risk factors, such as physical activity and body mass. Our findings support the inclusion of diverse racial and ethnic groups in all cardiovascular research and the consideration of the social environment in clinical decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bowles, He, Huang, Stecker, Seixas and Thosar.)

Objective: Given the complex interaction among the circadian system, energy metabolism, and obesity, the authors tested whether having obesity impacts the circadian variation in energy and glucose metabolism in humans., Methods: Participants with BMI either in the healthy weight or obesity ranges were studied in a 5-day, in-laboratory protocol that equally distributed behaviors (i.e., sleep, eating, exercise) across 24 h. Energy metabolism was measured at rest and during a standardized exercise bout and blood was sampled before and after each identical study meal to assess glucose and insulin levels., Results: In those with a healthy weight, the circadian nadir of energy expenditure, during both rest and exercise, occurred when participants would normally be asleep. However, in those with obesity, this nadir appears to occur during the habitual wake period. Differences in glucose regulation also depended on the circadian phase, such that individuals with obesity appeared to have relatively greater glucose intolerance during the circadian day and produced less insulin during the circadian night., Conclusions: Obesity is associated with altered circadian energy and glucose metabolism. Understanding and addressing these associations could lead to strategies that improve body weight and metabolic health in people with obesity., (© 2023 The Obesity Society.)

Background: Active break programs at the workplace are a promising initiative for increasing workers' physical activity (PA) levels, health, work-ability (WA), and social relationship., Objective: To determine the impact of an Active Breaks workplace program based on Bandura's Social Cognitive Theory (SCT) aligned with Behavior Change Techniques (BCT) on PA levels, cardiorespiratory fitness (CRF), WA, and social relationships among university workers., Methods: #UCLMuévete is a quasi-experimental, 12-week intervention designed according to the TREND and TIDieR-PHP checklists. Sixty-nine university workers were recruited and placed into 17 teams of 3 to 5 people. Participants were instructed to take a 20-min active break every working day (walking, cycling, and functional training). The following variables were measured before and after the 12-week intervention: (1) Amount of PA with accelerometers, (2) CRF through the 6 Min-Walking Test (m), (3) Body composition (fat mass (gr), muscle mass (gr), and bone mineral content (g/cm3) through densitometry), (4) Stress with the BodyGuard2 device, (5) WA through Work Ability Index (WAI), and (6) Social relationships through an ad-hoc questionnaire. Part-time workers, pregnant women, and workers with physical disability were excluded., Results: Significant improvements were observed in the amount of daily moderate-to-vigorous PA (Difference (Dif)., women +8.05 and men +12.31 minutes; p < 0.05; ES = 0.224; 0.379), CRF (Dif., women +52.98 and men +25.53 meters; p < 0.05; ES = 0.578; 0.209), and (Dif., women +2.16 and men +2.39; p < 0.05; ES = 0.150; 0.177). No significant changes were observed in body composition and stress., Conclusion: 20 min/day of aerobic and strength active breaks, based on SCT aligned to BCTs, improves university workers' amount of PA, CRF, WAI, and social relationships.

Study Objectives: Averaged nighttime blood pressure (BP) is superior to daytime BP for cardiovascular risk stratification, and the relative change between daytime/nighttime BP (dipping%) significantly predicts cardiovascular risk. Newer reports suggest that 4 measurements at night may be enough for cardiovascular risk stratification. Since BP oscillates across the night, the temporal distribution of measurements across the night may impact nighttime BP and dipping%. Therefore, we compared average nighttime BP and dipping% when using measurements in the first half (1 st -half), second (2 nd -half), and a combination of both (combined)., Methods: Forty-three (17 females and twenty-six males) midlife adults aged 50±10 years old wore an ambulatory BP monitor for 24 hours at home, programmed to measure BP every 20 minutes when scheduled for daytime and every 30 minutes during a self-selected 8-hour nighttime for time-in-bed. We compared the nighttime BP averages and dipping% when using either the first four measurements from the 1 st -half or 2 nd -half of the nighttime and combined., Results: Nighttime Systolic BP was significantly different across 1 st -half, 2 nd -half, and combined (111±9 vs.107±11 vs. 109±9 mmHg, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each). Systolic BP dipping% was significantly different across 1 st -half, 2 nd -half, and combined (9.9±5.5 vs.13.5±6.4 vs. 11.7±5.0 %, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each. Diastolic BP and diastolic dipping% were similar across the three different bins., Conclusion: In midlife adults, systolic nighttime BP and dipping% may depend upon when BP measurements are taken during the night.

Background: Although the scientific literature has previously described the impact of worksite programs based on physical activity (WPPAs) on employees' productivity and health in different contexts, the effect of these programs has not been analyzed based on the characteristics or modalities of physical activity (PA) performed (e.g., aerobic exercise, strength training, flexibility). In addition, studies on WPPAs usually report health and productivity outcomes separately, not integrated into a single study. Knowing the health and economic-related impacts of a WPPAs could provide useful information for stakeholders and policy development., Objective: The purpose of this review was as follows: (1) to analyze the effect of different modalities of WPPAs on employees' productivity and health and (2) to investigate the economic impact of WPPAs., Methods: This systematic review is registered in PROSPERO (CRD42021230626) and complies with PRISMA guidelines. Only randomized controlled trials from 1997 to March 2021 were included. Two reviewers independently screened abstracts and full texts for study eligibility, extracted the data, and performed a quality assessment using the Cochrane Collaboration Risk-of-Bias Tool for randomized trials. Population, instruments, comparison, and outcome (PICO) elements were used to define eligibility criteria. Eight-hundred sixty relevant studies were found through electronic searches in PubMed, Web of Science, Medline, Scopus, and SPORTDiscus databases. Once the eligibility criteria were applied, a total of 16 papers were included., Results: Workability was the productivity variable most positively impacted by WPPAs. Cardiorespiratory fitness, muscle strength, and musculoskeletal symptoms health variables improved in all the studies included. It was not possible to fully examine the effectiveness of each exercise modality because of the heterogeneity in methodology, duration, and working population. Finally, cost-effectiveness could not be analyzed because this information was not reported in most studies., Conclusion: All types of WPPAs analyzed improved workers' productivity and health. However, the heterogeneity of WPPAs does not allow to identify which modality is more effective., (© 2023. The Author(s).)

Competing Interests: We declare no competing interests.

Objectives: Ischemia with no obstructive coronary artery disease (INOCA) is a risk factor for major adverse cardiovascular events and is characterized by abnormal coronary microvascular tone. In patients with INOCA, adverse cardiovascular events most commonly occur in the morning compared to other times of the day and night., Materials and Methods: We tested whether coronary microvascular function varies diurnally with attenuation in the morning in patients with symptomatic coronary artery disease without significant (>50%) epicardial stenosis. We evaluated data from 17 patients studied in the AM (700-1159 h) and 11 patients in the PM (1200-1800 h). Coronary microvascular function was measured using perfusion contrast imaging at rest and after infusion of intravenous regadenoson. We calculated microvascular flow reserve as the ratio of hyperemic to resting flow. Along with independent sample t -tests, we performed bootstrapping procedures to test mean differences between AM and PM groups, using the bias-corrected and accelerated method with 5,000 bootstrapped samples., Results and Conclusion: The AM and PM groups were matched for demographic and existing risk factors. Coronary microvascular flow reserve was ∼33% higher in the AM compared to the PM ( P = 0.025, BCa 95% CI [0.25, 1.64]; Hedge's g = 0.89, 95% CI [0.11, 1.66]) as a result of significantly lower resting flow (∼50%) in the AM compared to the PM ( P = 0.03, M Diff = -56.65, BCa 95% CI [-118.59, -2.12]; Hedge's g = -0.86, 95% CI [-1.60, -0.06]). Our observations are of clinical value and can influence diagnosis and treatment in the clinic based on the time of day of measurements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thosar, Taqui, Davidson, Belcik, Hodovan, Rice and Lindner.)

Background: In humans, circulating cortisol usually peaks 30-60 min after awakening from nocturnal sleep, this is commonly referred to as the cortisol awakening response (CAR). We examined the extent to which the CAR is influenced by the circadian system, independent of behaviors including sleep., Materials and Methods: We examined the CAR in 34 adults (20 female) using two complementary multiday in-laboratory circadian protocols performed in dim light, throughout which behavioral factors were uniformly distributed across the 24-hour circadian cycle. Protocol 1 consisted of 10 identical consecutive 5-hour 20-minute sleep/wake cycles, and protocol 2 consisted of 5 identical consecutive 18-hour sleep/wake cycles. Salivary melatonin was used as the circadian phase marker (0° = dim light melatonin onset). During each sleep/wake cycle, salivary cortisol was measured upon scheduled awakening and 50-minutes later, with the change in cortisol defined as the CAR. Cosinor analyses were used to detect any significant circadian rhythmicity in the CAR. In secondary analyses, we adjusted the models for time awake before lights on, total sleep time, percent of rapid eye movement (REM) sleep, and percent of non-rapid eye movement (NREM) sleep., Results: Both protocols revealed a similar circadian rhythm in the CAR, with peaks occurring at a circadian phase corresponding to 3:40-3:45 a.m., with no detectable CAR during the circadian phases corresponding to the afternoon. In addition to the sinusoidal component of the circadian rhythm, total sleep time was also associated with the CAR for protocol 1. The percent of sleep spent in REM or NREM sleep were not associated with the CAR in either protocol., Conclusion: Our results show that the CAR exhibits a robust circadian rhythm that persists even after adjusting for prior sleep. Presuming that the CAR optimizes physiological responses to the anticipated stressors related to awakening, these findings may have implications for shift workers who wake up at unusual circadian phases. A blunted CAR in shift workers upon awakening in the evening may result in diminished responses to stressors., Competing Interests: Author AM is a consultant for Pure Somni. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bowles, Thosar, Butler, Clemons, Robinson, Ordaz, Herzig, McHill, Rice, Emens and Shea.)

Physiological function fluctuates across 24 h due to ongoing daily patterns of behaviors and environmental changes, including the sleep/wake, rest/activity, light/dark, and daily temperature cycles. The internal circadian system prepares the body for these anticipated behavioral and environmental changes, helping to orchestrate optimal cardiovascular and metabolic responses to these daily changes. In addition, circadian disruption, caused principally by exposure to artificial light at night (e.g., as occurs with night-shift work), increases the risk for both cardiovascular and metabolic morbidity and mortality. Regular exercise is a countermeasure against cardiovascular and metabolic risk, and recent findings suggest that the cardiovascular benefits on blood pressure and autonomic control are greater with evening exercise compared to morning exercise. Moreover, exercise can also reset the timing of the circadian system, which raises the possibility that appropriate timing of exercise could be used to counteract circadian disruption. This article introduces the overall functional relevance of the human circadian system and presents the evidence surrounding the concepts that the time of day that exercise is performed can modulate the cardiovascular and metabolic benefits. Further work is needed to establish exercise as a tool to appropriately reset the circadian system following circadian misalignment to preserve cardiovascular and metabolic health. © 2022 American Physiological Society. Compr Physiol 12:3621-3639, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

Objectives: Sedentary behavior is pervasive in the workplace and is harmful to health. Research on the effectiveness of comprehensive workplace interventions to reduce sedentary behavior and improve worker health and safety is crucial as sedentary jobs become more common., Methods: We developed a Total Worker Health intervention targeting sedentary behavior in call centers, and are evaluating intervention effectiveness in a randomized controlled trial. Four worksites will be randomly assigned to an intervention or control condition. The intervention condition includes the provision of active workstations along with programs and procedures at environmental, organizational, and individual levels. Control worksites will receive active workstations with no additional support, following common organizational practices., Results: Outcomes include objectively measured physical activity, biological markers of health, and self-report survey data at baseline, after the 6-month intervention or control period, and at a 12-month follow-up., Conclusions: The aims of the study are to determine whether a Total Worker Health intervention has stronger impacts on workplace sedentary behavior, uninterrupted bouts of sitting, and worker health and safety compared to a usual practice control condition. The study will inform future workplace sedentary behavior intervention and dissemination research, along with organizational best practices for reducing sedentary behavior in the workplace., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Endogenous circadian rhythms prepare the cardiovascular (CV) system for optimal function to match the daily anticipated behavioral and environmental cycles, including variable activities when awake during the day and recuperation when sleeping at night. The overall day-night patterns in most CV variables result from the summation of predictable circadian effects with variable behavioral and environmental effects on the CV system. The circadian system has also been implicated in the morning peak in the incidence of adverse CV events, including myocardial infarction, stroke, and sudden cardiac death. We discuss the resting and stress-reactive circadian control of CV physiology in humans and suggest future research opportunities, including improving CV therapy by optimally timing therapy relative to a person's internal body clock time., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The purpose of this study is to examine associations between objectively measured workplace sedentary behavior and physiological markers of health. We hypothesize that increased sedentary time and more frequent bouts of uninterrupted sitting are associated with increased hemoglobin A1c, increased blood pressure, and impaired endothelial function. Call center employees (N = 241) were enrolled from four worksites in the United States. Participants completed a survey and a physical health assessment. Sedentary behavior and sitting/standing time at work were quantified using an accelerometer. Hemoglobin A1c was measured using a finger-prick and portable analyzer. Blood pressure was measured with an automated cuff, and vascular endothelial function was assessed in a subsample of participants (n = 56) using EndoPAT. We analyzed data with two series of ordinary least squares regressions, first to examine relationships between bouts of uninterrupted sitting and physiological outcomes, and second to examine relationships between physical activity and sitting/standing time at work and physiological outcomes. The sample was primarily female, and on average was obese, prehypertensive, and prediabetic. There were no significant relationships between bouts of uninterrupted sitting or physical activity/sitting/standing time at work and physiological outcomes. In a sample that is predominantly sedentary, at risk for cardiovascular disease, and prediabetic, there are no significant associations between workplace sedentary behavior and physiological markers. The lack of associations could be related to either physiological adaptations or ceiling effects in this sample.

Cardiovascular disease is the leading cause of death in the world. In addition to non-modifiable factors such as age and sex, cardiovascular risk is also driven by behavioral, and therefore somewhat modifiable, factors such as physical activity, diet, and sleep. It is well established that sleep duration has a U-shaped association with mortality and cardiovascular disease, with recent evidence suggesting that this association is observed even while controlling for the effects of comorbid conditions. Whereas several biological mechanisms mediating the association between chronic short sleep duration and cardiovascular risk have been established, the biological mechanisms underlying the relationship between habitual long sleep (≥9 h) duration and cardiovascular risk, in the absence of other chronic diseases, are not well understood. This review will focus on summarizing the literature investigating the mechanisms underlying the association between habitual long sleep duration and cardiovascular risk. We will also propose the mechanistic pathways, distinct from the ones for short sleep, by which habitual long sleep can increase cardiovascular disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In humans, there is an endogenous, near 24-h (i.e., circadian) variation in mood with the best mood occurring during the circadian day and the worst mood occurring during the circadian night. Only positive affect, and not negative affect, has been shown to contribute to this circadian rhythm. We discovered a sharp circadian peak in negative affect during the circadian night coincident with a circadian trough in positive affect. These findings may help explain the association of depression with insomnia, the increased risk of suicide with nocturnal wakefulness, and the correlation between circadian misalignment and symptom severity in Major Depressive Disorder., (Published by Elsevier B.V.)

Obstructive sleep apnea (OSA) is associated with hypertension, cardiovascular disease, and a change in the 24 h pattern of adverse cardiovascular events and mortality. Adverse cardiovascular events occur more frequently in the middle of the night in people with OSA, earlier than the morning prevalence of these events in the general population. It is unknown if these changes are associated with a change in the underlying circadian rhythms, independent of behaviors such as sleep, physical activity, and meal intake. In this exploratory analysis, we studied the endogenous circadian rhythms of blood pressure, heart rate, melatonin and cortisol in 11 participants (48 ± 4 years; seven with OSA) throughout a 5 day study that was originally designed to examine circadian characteristics of obstructive apnea events. After a baseline night, participants completed 10 recurring 5 h 20 min behavioral cycles divided evenly into standardized sleep and wake periods. Blood pressure and heart rate were recorded in a relaxed semirecumbent posture 15 minutes after each scheduled wake time. Salivary melatonin and cortisol concentrations were measured at 1-1.5 h intervals during wakefulness. Mixed-model cosinor analyses were performed to determine the rhythmicity of all variables with respect to external time and separately to circadian phases (aligned to the dim light melatonin onset, DLMO). The circadian rhythm of blood pressure peaked much later in OSA compared to control participants (group × circadian phase, p < .05); there was also a trend toward a slightly delayed cortisol rhythm in the OSA group. Rhythms of heart rate and melatonin did not differ between the groups. In this exploratory analysis, OSA appears to be associated with a phase change (relative to DLMO) in the endogenous circadian rhythm of blood pressure during relaxed wakefulness, independent of common daily behaviors.

Objective- Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)-a robust cardiovascular risk marker-is impaired during this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate. Approach and Results- Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning ( P=0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon ( P≤0.01). Both systolic ( P=0.005) and diastolic blood pressure ( P=0.04) were rhythmic with peaks in the late afternoon. Conclusions- The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02202811.

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.

Adverse cardiovascular events, such as myocardial infarction and sudden cardiac death, occur more frequently in the morning. Prior studies have shown that vascular endothelial function (VEF), a marker of cardiovascular disease, is attenuated during physical inactivity and declines across the night. We sought to determine whether a morning attenuation in VEF is a result of prior sleep or the inactivity that inevitably accompanies sleep. After 1 wk of a rigorously controlled sleep-wake schedule and behaviors, 10 healthy participants completed a randomized crossover protocol in dim light and constant conditions, incorporating a night of 6 h of sleep opportunity and a night of immobility while they were supine and awake. VEF was measured in the dominant brachial artery as flow mediated dilation (FMD) before and after each 6-h trial. To avoid disturbing sleep and posture of the participants, blood was drawn using a 12-ft catheter from an adjoining laboratory room before, during, and after each 6-h trial, and plasma was analyzed for markers of oxidative stress [malondialdehyde adducts (MDA)], and endothelin-1. Contrary to expectation, both nocturnal sleep and nocturnal inactivity significantly increased FMD ( P < 0.05). There was no significant change in MDA or endothelin-1 within and between trials. Contrary to expectations based on prior studies, we found that overnight sleep or the inactivity that accompanies sleep did not result in attenuation in VEF in the morning hours in healthy people. Thus, it is plausible that the endogenous circadian system, a remaining factor not studied here, is responsible for the commonly observed decline in VEF across the night.

Purpose of Review: Given the emerging knowledge that circadian rhythmicity exists in every cell and all organ systems, there is increasing interest in the possible benefits of chronotherapy for many diseases. There is a well-documented 24-h pattern of blood pressure with a morning surge that may contribute to the observed morning increase in adverse cardiovascular events. Historically, antihypertensive therapy involves morning doses, usually aimed at reducing daytime blood pressure surges, but an absence of nocturnal dipping blood pressure is also associated with increased cardiovascular risk., Recent Findings: To more effectively reduce nocturnal blood pressure and still counteract the morning surge in blood pressure, a number of studies have examined moving one or more antihypertensives from morning to bedtime dosing. More recently, such studies of chronotherapy have studied comorbid populations including obstructive sleep apnea, chronic kidney disease, or diabetes. Here, we summarize major findings from recent research in this area (2013-2017). In general, nighttime administration of antihypertensives improved overall 24-h blood pressure profiles regardless of disease comorbidity. However, inconsistencies between studies suggest a need for more prospective randomized controlled trials with sufficient statistical power. In addition, experimental studies to ascertain mechanisms by which chronotherapy is beneficial could aid drug design and guidelines for timed administration.

All species organize behaviors to optimally match daily changes in the environment, leading to pronounced activity/rest cycles that track the light/dark cycle. Endogenous, approximately 24-hour circadian rhythms in the brain, autonomic nervous system, heart, and vasculature prepare the cardiovascular system for optimal function during these anticipated behavioral cycles. Cardiovascular circadian rhythms, however, may be a double-edged sword. The normal amplified responses in the morning may aid the transition from sleep to activity, but such exaggerated responses are potentially perilous in individuals susceptible to adverse cardiovascular events. Indeed, the occurrence of stroke, myocardial infarction, and sudden cardiac death all have daily patterns, striking most frequently in the morning. Furthermore, chronic disruptions of the circadian clock, as with night-shift work, contribute to increased cardiovascular risk. Here we highlight the importance of the circadian system to normal cardiovascular function and to cardiovascular disease, and identify opportunities for optimizing timing of medications in cardiovascular disease.

Background: The morning hours are associated with increased cardiovascular (CV) risk, and vascular endothelial function (VEF) is a strong predictor of CV disease. A diurnal rhythm in VEF has been established but the morning variation in VEF is not well-documented. Thus, we tested if VEF is impaired across the vulnerable morning period., Methods: After overnight fasts, eight healthy men (age 26.3 ± 3 yr) underwent assessments of VEF under standardized testing conditions every 2 h from 0700 to 1300 h on two separate days. VEF was estimated following 5 min brachial artery occlusions by hyperemic flow-mediated dilation (FMD)., Results: There was no significant change in FMD or hyperemic shear stimulus across the 6 h vulnerable period on either day, despite changes in physical activity and meals across these periods., Conclusion: In this healthy group of young men, VEF is stable across the vulnerable morning period when typical behaviors occurred (breakfast and physical activity). Future research should focus on the roles of sleep, physical inactivity during sleep and endogenous circadian rhythm in VEF.

Background: This study was designed to test the hypothesis that antioxidant Vitamin C prevents the impairment of endothelial function during prolonged sitting., Material and Methods: Eleven men (24.2 ± 4.4 yrs) participated in 2 randomized 3-h sitting trials. In the sitting without vitamin C (SIT) and the sitting with vitamin C (VIT) trial, participants were seated for 3 h without moving their legs. Additionally, in the VIT trial, participants ingested 2 vitamin C tablets (1 g and 500 mg) at 30 min and 1 h 30 min, respectively. Superficial femoral artery (SFA) flow-mediated dilation (FMD) was measured hourly for 3 h., Results: By a 1-way ANOVA, there was a significant decline in FMD during 3 h of SIT (p<0.001). Simultaneously, there was a significant decline in antegrade (p=0.04) and mean (0.037) shear rates. For the SIT and VIT trials by a 2-way (trial x time) repeated measures ANOVA, there was a significant interaction (p=0.001). Pairwise testing revealed significant between-SFA FMD in the SIT and VIT trial at each hour after baseline, showing that VIT prevented the decline in FMD 1 h (p=0.009), 2 h (p=0.016), and 3 h (p=0.004). There was no difference in the shear rates between SIT and VIT trials (p>0.05)., Conclusions: Three hours of sitting resulted in impaired SFA FMD. Antioxidant Vitamin C prevented the decline in SFA FMD, suggesting that oxidative stress may contribute to the impairment in endothelial function during sitting.

Unlabelled: Sitting time (ST) is associated with cardiovascular disease risk factors, whereas breaking ST has been reported to be beneficial for reducing cardiovascular risk., Purpose: The objective of this study is to examine the effects of breaking ST on superficial femoral artery (SFA) endothelial function., Hypotheses: 1) Prolonged sitting would induce endothelial dysfunction and changes in shear forces, and 2) breaking ST with brief periods of activity would prevent attenuation in endothelial function., Methods: Twelve nonobese men (24.2 ± 4.2 yr) participated in two randomized 3-h sitting trials. In the sitting (SIT) trial, subjects were seated on a firmly cushioned chair for 3 h without moving their lower extremities. In the breaking ST trial (ACT), subjects sat similar to the SIT trial but walked on a treadmill for 5 min at 2 mph at 30 min, 1 h 30 min, and 2 h 30 min during the sitting interval. SFA flow-mediated dilation (FMD) was assessed at baseline, 1 h, 2 h, and 3 h in each trial. Statistical analyses were performed using dependent variables SFA FMD and shear rates. Significance was set at P ≤ 0.05., Results: In the SIT trial, there was a significant decline in SFA FMD from baseline to 3 h (baseline, 4.72% ± 3.78%; 1 h, 0.52% ± 0.85%; 2 h, 1.66% ± 1.11%; 3 h, 2.2% ± 2.15; P < 0.05 by ANOVA) accompanied by a decline in mean shear rate and antegrade shear rate but no difference in shear rate (area under the curve). By two-way repeated-measures ANOVA, ACT prevented the sitting-induced decline in FMD (baseline, 4.5% ± 2.3%; 1 h, 5.04% ± 2.85%; 2 h, 5.28% ± 5.05%; 3 h, 6.9% ± 4.5%) along with no decline in shear rates., Conclusion: Three hours of sitting resulted in a significant impairment in shear rate and SFA FMD. When light activity breaks were introduced hourly during sitting, the decline in FMD was prevented.

Introduction: It is unknown if there are limb differences in vascular function during prolonged sitting., Purpose: This study was designed to test whether the effects of prolonged sitting on brachial artery (BA) and the superficial femoral artery (SFA) are similar., Methods: Twelve men (24.2 ± 4 yrs.) participated in a 3 hr prolonged sitting trial (SIT). SFA and BA flow mediated dilation (FMD) and respective flow patterns were measured at baseline, 1 hr, 2 hr and 3 hr., Results: By a one-way ANOVA there was a significant decline in SFA FMD during 3 hrs of SIT (p < 0.001). Simultaneously, there was a significant decline in antegrade (p = 0.04) and mean (0.037) shear rates. By a one way ANOVA there were no significant differences in BA FMD during 3 hrs of sitting. There were no changes in the shear rates in the BA except for a significant decrease in antegrade shear rate (p = 0.029) and a significant increase in oscillatory shear index (p = 0.034) during 3 hrs of sitting. Furthermore, there was no correlation between BA and SFA FMD measurements., Conclusion: Three hours of sitting resulted in impaired SFA FMD but not BA FMD. Although 3 hours of sitting did not impair BA FMD, it impaired shear patterns in the BA.

Sedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as 'sitting without otherwise being active.' This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions.

The purpose of this study was to predict drug content and hardness of intact tablets using artificial neural networks (ANN) and near-infrared spectroscopy (NIRS). Tablets for the drug content study were compressed from mixtures of Avicel PH-101, 0.5% magnesium stearate, and varying concentrations (0%, 1%, 2%, 5%, 10%, 20%, and 40% w/w) of theophylline. Tablets for the hardness study were compressed from mixtures of Avicel PH-101 and 0.5% magnesium stearate at varying compression forces ranging from 0.4 to 1 ton. An Intact Analyzer was used to obtain near infrared spectra from the tablets with varying drug contents, whereas a Rapid Content Analyzer (RCA) was used to obtain spectral data from the tablets with varying hardness. Two sets of tablets from each batch (i.e., tablets with varying drug content and hardness) were randomly selected. One set of tablets was used to generate appropriate calibration models, while the other set was used as the unknown (test) set. A total of 10 ANN calibration models (5 each with 10 and 160 inputs at appropriate wavelengths) and five separate 4-factor partial least squares (PLS) calibration models were generated to predict drug contents of the test tablets from the spectral data. For the prediction of tablet hardness, two ANN calibration models (one each with 10 and 160 inputs) and two 4-factor PLS calibration models were generated and used to predict the hardness of test tablets. The PLS calibration models were generated using Vision software. Prediction of drug contents of test tablets using the ANN calibration models generated with 10 inputs was significantly better than the prediction obtained with the ANN calibration models with 160 inputs. For tablets with low drug concentrations (less than or equal to 2% w/w) prediction of drug content was better with either of the two ANN calibration models than with the PLS calibration models. However, prediction of drug contents of tablets with greater than or equal to 5% w/w drug was better with the PLS calibration models than with the ANN calibration models. Prediction of tablet hardness was better with the ANN calibration models generated with either 10 or 160 inputs than with the PLS calibration models. This work demonstrated that a well-trained ANN model is a powerful alternative technique for analysis of NIRS data. Moreover, the technique could be used in instances when the conventional modeling of data does not work adequately.

Drug contents of intact tablets were determined using non-destructive near infrared (NIR) reflectance and transmittance spectroscopic techniques. Tablets were compressed from blends of Avicel PH-101 and 0.5% w/w magnesium stearate with varying concentrations of anhydrous theophylline (0, 1, 2, 5, 10, 20 and 40% w/w). Ten tablets from each drug content batch were randomly selected for spectral analysis. Both reflectance and transmittance NIR spectra were obtained from these intact tablets. Actual drug contents of the tablets were then ascertained using a UV-spectrophotometer at 268 nm. Multiple linear regression (MLR) models at 1116 nm and partial least squares (PLS) calibration models were generated from the second derivative spectral data of the tablets in order to predict drug contents of intact tablets. Both the reflectance and the transmittance techniques were able to predict the drug contents in intact tablets over a wide range. However, a comparison of the results of the study indicated that the lowest percent errors of prediction were provided by the PLS calibration models generated from spectral data obtained using the transmittance technique.

The near infrared (NIR) spectroscopic technique was used to determine copolymer ratios of polylactide-co-glycolide samples. Appropriate quantities of DL-polylactic acid and lactic-co-glycolic acid polymers with 86:14, 75:25, 64:36 and 52:48 lactide to glycolide ratios were dissolved in methylene chloride to obtain 5% (w/w) solutions. NIR spectra of the samples were obtained from the solutions using a Polyol Analyzer operated in the transmittance mode. Linear regression calibration models were generated at 2130 and 2288 nm from the second derivative spectral data obtained from the NIR technique. The lowest and highest standard errors of calibration (SEC) at 2130 nm were 1.29 and 1.63%, whereas those obtained from the calibration models generated at 2288 nm were 2.00 and 2.03%, respectively. Partial least squares (PLS) calibration models were also generated from the second derivative spectral data from 1100 to 2500 nm. The lowest and the highest SEC for the models were 1.46 and 1.53%, respectively. The calibration models were then used to predict the lactide contents of the unknown (test) samples. The highest percent error of prediction was 2.56% for samples with 86% lactide content when the linear regression calibration at 2130 nm was used, whereas the highest percent error of prediction was 1.56% for samples with 64% lactide content when the linear regression calibration at 2288 nm was used. The highest percent error of prediction was 1.73% for samples with 75% lactide content when the two-factor PLS calibration model was used.

The purpose of this study was to use near-infrared spectroscopy (NIRS) as a nondestructive technique to (a) differentiate three Avicel products (microcrystalline cellulose [MCC] PH-101, PH-102, and PH-200) in powdered form and in compressed tablets with and without 0.5% w/w magnesium stearate as a lubricant; (b) determine the magnesium stearate concentrations in the tablets; and (c) measure hardness of tablets compressed at several compression forces. Diffuse reflectance NIR spectra from Avicel powders and tablets (compression forces ranging from 0.2 to 1.2 tons) were collected and distance scores calculated from the second-derivative spectra were used to distinguish the different Avicel products. A multiple linear regression model was generated to determine magnesium stearate concentrations (from 0.25 to 2% w/w), and partial least squares (PLS) models were generated to predict hardness of tablets. The NIRS technique could distinguish between the three different Avicel products, irrespective of lubricant concentration, in both the powdered form and in the compressed tablets because of the differences in the particle size of the Avicel products. The percent error for predicting the lubricant concentration of tablets ranged from 0.2 to 10% w/w. The maximum percent error of prediction of hardness of tablets compressed at the various compression forces was 8.8% for MCC PH-101, 5.3% for MCC PH-102, and 4.6% for MCC PH-200. The NIRS nondestructive technique can be used to predict the Avicel type in both powdered and tablet forms as well as to predict the lubricant concentration and hardness.