Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.

Using a consumer-based wearable activity tracker for physical activity goal setting and measuring steps in pregnant women with gestational diabetes mellitus: exploring acceptance and validity.

BACKGROUND: Activity monitoring devices may be used to facilitate goal-setting, self-monitoring, and feedback towards a step-based physical activity (PA) goal. This study examined the performance of the wrist-worn Fitbit Charge 3™ (FC3) and sought opinions on walking and stepping-in-place from women with gestational diabetes (GDM). METHODS: Participants completed six 2-min metronome-assisted over ground bouts that varied by cadence (67, 84, or 100 steps per minute) and mode (walking or stepping-in-place; N = 15), with the sequence randomized. Steps were estimated by FC3 and measured, in duplicate, by direct observation (hand-tally device, criterion). Equivalence testing by the two one-sided tests (TOST) method assessed agreement within ± 15%. Mean absolute percent error (MAPE) of steps were compared to 10%, the accuracy standard of the Consumer Technology Association (CTA)™. A subset (n = 10) completed a timed, 200-m self-paced walk to assess natural walking pace and cadence. All participants completed semi-structured interviews, which were transcribed and analyzed using descriptive and interpretive coding. RESULTS: Mean age was 27.0 years (SD 4.2), prepregnancy BMI 29.4 kg/m2 (8.3), and gestational age 32.8 weeks (SD 2.6). The FC3 was equivalent to hand-tally for bouts of metronome-assisted walking and stepping-in-place at 84 and 100 steps per minute (i.e., P < .05), although walking at 100 steps per minute (P = .01) was no longer equivalent upon adjustment for multiple comparisons (i.e., at P < .007). The FC3 was equivalent to hand-tally during the 200-m walk (i.e., P < .001), in which mean pace was 68.2 m per minute (SD 10.7), or 2.5 miles per hour, and mean cadence 108.5 steps per minute (SD 6.5). For walking at 84 and 100 steps per minute, stepping-in-place at 100 steps per minute, and the 200-m walk, MAPE was within 10%, the accuracy standard of the CTA™. Interviews revealed motivation for PA, that stepping-in-place was an acceptable alternative to walking, and competing responsibilities made it difficult to find time for PA. CONCLUSIONS: The FC3 appears to be a valid step counter during the third trimester, particularly when walking or stepping-in-place at or close to women's preferred cadence.

Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemia.

BACKGROUND: Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. METHODS: A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations. RESULTS: Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. CONCLUSIONS: Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.

Association of Daily Step Count and Step Intensity With Mortality Among US Adults.

Importance: It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality. Objective: Describe the dose-response relationship between step count and intensity and mortality. Design, Setting, and Participants: Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015. Exposures: Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema. Results: A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11 999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12 000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12 000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34). Conclusions and Relevance: Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day.

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen.

In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP-/-]) were compared with wild type (WT) mice. Surprisingly, IP-/- mice had increased numbers of pulmonary CD3-NK1.1+Ly49b+ NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals. This phenomenon was associated with elevated CX3CL1 levels in the airways of IP-/- mice and treatment with a neutralizing Ab to CX3CL1 reduced IFN-γ production by the lung NK cells. Remarkably, IP-/- mice were less responsive to HDM challenge than WT counterparts because intranasal instillation of the allergen induced markedly reduced levels of airway eosinophils, CD4+ lymphocyte infiltration, and mucus production, as well as depressed levels of CCL2 chemokine and Th2 cytokines. NK cells were responsible for such attenuated responses because depletion of NK1.1+ cells in IP-/- mice restored both the HDM-induced lung inflammation and ILC2 numbers, whereas transfer of CD3-NK1.1+ NK cells into the airways of WT hosts suppressed the inflammatory response. Collectively, these data demonstrate a hitherto unknown role for PGI2 in regulating the number and properties of NK cells resident in lung tissue and reveal a role for NK cells in limiting lung tissue ILC2s and preventing allergic inflammatory responses to inhaled HDM allergen.

Energy Cost Expression for a Youth Compendium of Physical Activities: Rationale for Using Age Groups.

PURPOSE: This study compared the accuracy of physical activity energy expenditure (PAEE) prediction using 2 methods of accounting for age dependency versus 1 standard (single) value across all ages. METHODS: PAEE estimates were derived by pooling data from 5 studies. Participants, 6-18 years (n = 929), engaged in 14 activities while in a room calorimeter or wearing a portable metabolic analyzer. Linear regression was used to estimate the measurement error in PAEE (expressed as youth metabolic equivalent) associated with using age groups (6-9, 10-12, 13-15, and 16-18 y) and age-in-years [each year of chronological age (eg, 12 = 12.0-12.99 y)] versus the standard (a single value across all ages). RESULTS: Age groups and age-in-years showed similar error, and both showed less error than the standard method for cycling, skilled, and moderate- to vigorous-intensity activities. For sedentary and light activities, the standard had similar error to the other 2 methods. Mean values for root mean square error ranged from 0.2 to 1.7 youth metabolic equivalent across all activities. Error reduction ranged from -0.2% to 21.7% for age groups and -0.23% to 18.2% for age-in-years compared with the standard. CONCLUSIONS: Accounting for age showed lower errors than a standard (single) value; using an age-dependent model in the Youth Compendium is recommended.

Estimating physical activity in youth using an ankle accelerometer.

This study developed and validated a vector magnitude (VM) two-regression model (2RM) for use with an ankle-worn ActiGraph accelerometer. For model development, 181 youth (mean ± SD; age, 12.0 ± 1.5 yr) completed 30 min of supine rest and 2-7 structured activities. For cross-validation, 42 youth (age, 12.6 ± 0.8 yr) completed approximately 2 hr of unstructured physical activity (PA). PA data were collected using an ActiGraph accelerometer, (non-dominant ankle) and the VM was expressed as counts/5-s. Measured energy expenditure (Cosmed K4b2) was converted to youth METs (METy; activity VO2 divided by resting VO2). A coefficient of variation (CV) was calculated for each activity to distinguish continuous walking/running from intermittent activity. The ankle VM sedentary behavior threshold was ≤10 counts/5-s, and a CV≤15 counts/5-s was used to identify walking/running. The ankle VM2RM was within 0.42 METy of measured METy during the unstructured PA (P > 0.05). The ankle VM2RM was within 5.7 min of measured time spent in sedentary, LPA, MPA, and VPA (P > 0.05). Compared to the K4b2, the ankle VM2RM provided similar estimates to measured values during unstructured play and provides a feasible wear location for future studies.

"What Is a Step?" Differences in How a Step Is Detected among Three Popular Activity Monitors That Have Impacted Physical Activity Research.

(1) Background: This study compared manually-counted treadmill walking steps from the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or frequency (Hz) step-detection thresholds; and quantified key features of the acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7 ± 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2-4 mph) while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker testing to determine device-specific frequency and amplitude step-detection thresholds. Simulated signal testing was used to determine thresholds for the ActiGraph step algorithm. Steps during human testing were compared using bias and confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly different from the criterion. The DigiwalkerSW200 records steps for movements with a total acceleration of ≥1.21 g. The OmronHJ720ITC detects a step when movement has an acceleration ≥0.10 g with a dominant frequency of ≥1 Hz. The step-threshold for the ActiLife algorithm is variable based on signal frequency. Acceleration signals at the hip and wrist have distinctive patterns during treadmill walking. (4) Conclusions: Three common research-grade physical activity monitors employ different step-detection strategies, which causes variability in step output.

Effect of Adding Online Social Support Tools to an Adult Walking Program: A Pilot Randomized Controlled Trial.

This pilot study examined the efficacy of providing access to online social support tools on adults' step counts during a technology-mediated walking intervention. Sixty-three insufficiently active adults were randomized to a 12-week walking intervention with (SUPPORT) or without (NO SUPPORT) access to online social support tools. Both groups received a pedometer, step goals, and access to relevant websites. The SUPPORT group also received access to online social support tools. A mixed-factor analysis of variance was conducted to examine within- and between-group differences in measures of daily steps, psychosocial indicators, and health. Both groups significantly (p < .05) increased their daily steps over time from baseline by 1,401 (SUPPORT) and 2,461 (NO SUPPORT), with no significant differences between groups. Psychosocial and health improvements were no greater for SUPPORT versus NO SUPPORT. The SUPPORT group's use of the online social support tools was low. Results suggest that giving adults access to online social support tools during a technology-mediated walking program did not lead to an enhanced increase in daily steps versus an identical program without these tools; however, the low use of these tools may have weakened their effect. Future studies should examine SUPPORT versus NO SUPPORT among groups with preexisting social ties.

Accelerometer-Derived Total Activity Counts, Bouted Minutes of Moderate to Vigorous Activity, and Insulin Resistance: NHANES 2003-2006.

INTRODUCTION: The objective of this study was to compare the associations of accelerometer-derived total activity counts per day and minutes of bouted moderate to vigorous physical activity (MVPA) with insulin resistance. METHODS: The sample included 2,394 adults (aged ≥20 y) from the 2003-2006 National Health and Nutrition Examination Survey. Time spent in MVPA, measured by using 2 cutpoints (≥2,020 counts/min [MVPA2,020] and ≥760 counts/min [MVPA760]), was calculated for bouts of at least 8 to 10 minutes. Total activity counts per day reflects the total amount of activity across all intensities. Insulin resistance was measured via the homeostatic model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). Two nested regression models regressed HOMA-IR and QUICKI, respectively, on minutes of bouted MVPA and total activity counts per day. We used an adjusted Wald F statistic to illustrate strength of association. RESULTS: After adjustment for covariates, total activity counts per day was more strongly associated with both HOMA-IR (adjusted Wald F = 36.83 , P < .001) and QUICKI (adjusted Wald F = 29.44, P < .001) compared with MVPA2,020 (HOMA-IR, adjusted Wald F = 4.00, P = .06; QUICKI, adjusted Wald F = 1.08, P = .31).Total activity counts per day was more strongly associated with both HOMA-IR (adjusted Wald F = 13.64, P < .001) and QUICKI (adjusted Wald F = 12.10, P < .001) compared with MVPA760 (HOMA-IR, adjusted Wald F = 1.13, P = .30; QUICKI, adjusted Wald F = 0.97, P = .33). CONCLUSION: Our study indicated that total activity counts per day has stronger associations with insulin resistance compared with minutes of bouted MVPA. The most likely explanation is that total activity counts per day captures data on light physical activity and intermittent MVPA, both of which influence insulin resistance.

Time-to-response toxicity analysis as a method for drug susceptibility assessment in salmon lice.

The salmon louse Lepeophtheirus salmonis (Krøyer, 1837) is an ectoparasite causing infections of wild and farmed Atlantic salmon (Salmo salar L.) in the Northern hemisphere. While L. salmonis control at commercial mariculture sites increasingly employs non-medicinal approaches, such as cage designs reducing infection rates and biological control through cleaner fish, anti-parasitic drugs are still a requirement for effective fish health care. With only a limited range of salmon delousing agents available, all of which have been in use for more than a decade, drug resistance formation has been reported for different products. Successful resistance management requires reliable susceptibility assessment, which is usually achieved through L. salmonis bioassays. These tests involve the exposure of parasites to different drug concentrations and require significant numbers of suitable L. salmonis stages. The present study reports an alternative bioassay that is based on time-to-response toxicity analyses and can be carried out with limited parasite numbers. The assay determines the median effective time (ET50), i.e., the time required until impaired swimming and/or attachment behaviour becomes apparent in 50% of parasites, by conducting repeated examinations of test animals starting at the time point where exposure to a set drug concentration commences. This experimental approach further allows the estimation of the apparent drug susceptibility of individual L. salmonis by determining their time to response, which may prove useful in experiments designed to elucidate associations between genetic factors and the drug susceptibility phenotype of parasites. Three laboratory strains of L. salmonis differing in susceptibility to emamectin benzoate were characterised using standard 24 h bioassays and time-to-response toxicity assays. While both the median effective concentration (EC50) and the ET50 showed variability between experimental repeats, both types of bioassay consistently discriminated susceptible and drug-resistant L. salmonis laboratory strains. STATEMENT OF RELEVANCE: Infections by sea lice cause significant costs to the global salmon farming industry, which have been estimated to exceed €300 million per year worldwide. Control of sea lice still relies to a significant extent on chemical delousing; however, chemical control is threatened by resistance formation. Resistance can be combated by rotation between different drugs and strategic implementation of non-medicinal strategies. However, resistance management requires reliable and feasible methods of susceptibility assessment. The present study is a technical note introducing a novel approach to susceptibility assessments in sea lice. The method can be applied in susceptibility assessments on farms, where it offers the advantage of a reduced requirement of parasites for testing. In addition, the novel method allows deriving the times of parasite require to show a response after drug treatment has started, thus providing a variable characterizing the drug susceptibility phenotype of individual parasites. Accordingly, the bioassay approach presented here will be useful for studies aiming at unravelling the genetic determinants of drug resistance.

Psycho-Physiological Effects of Television Viewing During Exercise.

We propose that enjoyment is an important factor in the adoption and long-term maintenance of exercise. Television (TV) viewing is believed to be a highly enjoyed leisure-time activity, combining it with exercise may make for a more enjoyable exercise experience. The objective of this study was to examine the effects of television (TV) viewing on psychological and physiological variables during a moderate-intensity exercise bout. Twenty-eight insufficiently active (<150 minutes per week of moderate intensity PA and/or 75 minutes of vigorous PA) adults (Age: M = 47.4 ± 7.6 years) participated in this study. Each participant performed three separate 30-minute walking bouts on a motorized treadmill. During each bout, participants watched a program they selected (30-minute scripted show) (self-selected TV condition), a British Broadcasting Corporation (BBC) nature program (standardized TV condition), or no TV program (no TV condition). Participants were unable to select the nature program as their self-selected program, as it was not a 30-minute scripted program. A Polar Heart Rate (HR) monitor and validated surveys on affect and enjoyment were used. Participants reported greater enjoyment of exercise for both self-selected and standardized TV conditions (97.1 ± 15.2 and 92.7 ± 15.2), compared to the No TV condition (77.5 ± 13.4, p < 0.001). The two TV conditions resulted in similar levels of focus on TV viewing (self-selected TV: 81.2 ± 19.7; standardized TV: 79.1 ± 14.2, p > 0.05) and dissociation from walking (self-selected TV: 38.1 ± 6.7 and standardized TV: 33.2 ± 3.9); they also resulted in more dissociation than the no TV condition (TV: 72.6 ± 5.6, p = 0.002). The findings indicate that TV viewing, regardless of whether the programming is self-selected or standardized, associates with greater enjoyment of exercise.

Introducing novel approaches for examining the variability of individuals' physical activity.

Tudor-Locke and colleagues previously assessed steps/day for 1 year. The aim of this study was to use this data set to introduce a novel approach for the investigation of whether individual's physical activity exhibits periodicity fluctuating round a mean and, if so, the degree of fluctuation and whether the mean changes over time. Twenty-three participants wore a pedometer for 365 days, recorded steps/day and whether the day was a workday. Fourier transform of each participant's daily steps data showed the physical activity had a periodicity of 7 days in half of the participants, matching the periodicity of the workday pattern. Activity level remained stable in half of the participants, decreased in ten participants and increased in two. In conclusion, the 7-day periodicity of activity in half of the participants and correspondence with the workday pattern suggest a social or environmental influence. The novel analytical approach introduced herein allows the determination of the periodicity of activity, the degree of variability in activity that is tolerated during day-to-day life and whether the activity level is stable. Results from the use of these methodologies in larger data sets may enable a more focused approach to the design of interventions that aim to increase activity.

Predicting energy expenditure through hand rim propulsion power output in individuals who use wheelchairs.

AIM: To examine the relationship between hand rim propulsion power and energy expenditure (EE) during wheelchair wheeling and to investigate whether adding other variables to the model could improve on the prediction of EE. METHODS: Individuals who use manual wheelchairs (n=14) performed five different wheeling activities in a wheelchair with a PowerTap power meter hub built into the right rear wheel. Activities included wheeling on a smooth, level surface at three different speeds (4.5, 5.5 and 6.5 km/h), wheeling on a rubberised track at one speed (5.5 km/h) and wheeling on a sidewalk course that included uphill and downhill segments at a self-selected speed. EE was measured using a portable indirect calorimetry system. Stepwise linear regression was performed to predict EE from power output variables. A repeated-measures analysis of variance was used to compare the measured EE to the estimates from the power models. Bland-Altman plots were used to assess the agreement between the criterion values and the predicted values. RESULTS: EE and power were significantly correlated (r=0.694, p<0.001). Regression analysis yielded three significant prediction models utilising measured power; measured power and speed; and measured power, speed and heart rate. No significant differences were found between measured EE and any of the prediction models. CONCLUSION: EE can be accurately and precisely estimated based on hand rim propulsion power. These results indicate that power could be used as a method to assess EE in individuals who use wheelchairs.

Monitoring capabilities of the Omron HJ-720ITC pedometer.

PURPOSE: The purpose of our study was to examine the monitoring capabilities of the Omron HJ-720ITC pedometer and determine the feasibility of using it in physical activity interventions. METHODS: Using data from an 8-week lifestyle-intervention study, we tested the capabilities of the pedometer for recording physical activity data. Data from a total of 28 subjects were used in our analysis. The total number of patient steps per day was recorded over the duration of an intervention, as well as "aerobic steps per day" (ie, those taken at a cadence of > 60 steps per minute for ≥ 10 consecutive minutes). Daily wear time was computed in order to ascertain participant compliance in wearing the pedometer. In addition, aerobic steps per minute were computed, providing an assessment of activity intensity during continuous walking bouts. RESULTS: Total steps per day and aerobic steps per day increased from baseline assessment to Week 8. Participants exceeded 100 steps/minute for 89% of their aerobic minutes, suggesting that they were in the moderate-intensity range (3-6 metabolic equivalent tasks) when performing continuous bouts of walking (> 10 minutes). CONCLUSION: The new pedometer is a reasonably priced, wearable activity monitor that is feasible for use in clinical and research settings.

Comparative Analysis of ActiGraph Step Counting Methods in Adults: A Systematic Literature Review and Meta-Analysis.

PURPOSE: The primary aim of this study was to compare steps per day across ActiGraph models, wear locations, and filtering methods. A secondary aim was to compare ActiGraph steps per day to those estimated by the ankle-worn StepWatch. METHODS: We conducted a systematic literature review to identify studies of adults published before May 12, 2022, that compared free-living steps per day of ActiGraph step counting methods and studies that compared ActiGraph to StepWatch. Random-effects meta-analysis compared ActiGraph models, wear locations, filter mechanisms, and ActiGraph to StepWatch steps per day. A sensitivity analysis of wear location by younger and older age was included. RESULTS: Twelve studies, with 46 comparisons, were identified. When worn on the hip, the AM-7164 recorded 123% of the GT series steps (no low-frequency extension (no LFE) or default filter). However, the AM-7164 recorded 72% of the GT series steps when the LFE was enabled. Independent of the filter used (i.e., LFE, no LFE), ActiGraph GT series monitors captured more steps on the wrist than on the hip, especially among older adults. Enabling the LFE on the GT series monitors consistently recorded more steps, regardless of wear location. When using the default filter (no LFE), ActiGraph recorded fewer steps than StepWatch (ActiGraph on hip 73% and ActiGraph on wrist 97% of StepWatch steps). When LFE was enabled, ActiGraph recorded more steps than StepWatch (ActiGraph on the hip, 132%; ActiGraph on the wrist, 178% of StepWatch steps). CONCLUSIONS: The choice of ActiGraph model, wear location, and filter all impacted steps per day in adults. These can markedly alter the steps recorded compared with a criterion method (StepWatch). This review provides critical insights for comparing studies using different ActiGraph step counting methods.

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology.

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (-50 and -29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced P(enh) and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (-12%), reduced total oxygen consumption rate (-8%), improved glucose tolerance, and reduced grip force (-14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction and thus reduced airway responsiveness; long-term lung pathology develops in the knockout mice due to impairment of energy-costly lung maintenance processes; and therefore, we propose mitochondrial oxidative phosphorylation as a novel target for the treatment of respiratory diseases, such as asthma.

Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies.

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow-stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFß stimulation and engraftment with myelofibrosis but not healthy donor-derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow-like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. SIGNIFICANCE: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics. See related commentary by Derecka and Crispino, p. 263. This article is highlighted in the In This Issue feature, p. 247.

Can sedentary behavior be made more active? A randomized pilot study of TV commercial stepping versus walking.

BACKGROUND: There is a growing problem of physical inactivity in America, and approximately a quarter of the population report being completely sedentary during their leisure time. In the U.S., TV viewing is the most common leisure-time activity. Stepping in place during TV commercials (TV Commercial Stepping) could increase physical activity. The purpose of this study was to examine the feasibility of incorporating physical activity (PA) into a traditionally sedentary activity, by comparing TV Commercial Stepping during 90 min/d of TV programming to traditional exercise (Walking). METHODS: A randomized controlled pilot study of the impact of 6 months of TV Commercial Stepping versus Walking 30 min/day in adults was conducted. 58 sedentary, overweight (body mass index 33.5 ± 4.8 kg/m2) adults (age 52.0 ± 8.6 y) were randomly assigned to one of two 6-mo behavioral PA programs: 1) TV Commercial Stepping; or 2) Walking 30 min/day. To help facilitate behavior changes participants received 6 monthly phone calls, attended monthly meetings for the first 3 months, and received monthly newsletters for the last 3 months. Using intent-to-treat analysis, changes in daily steps, TV viewing, diet, body weight, waist and hip circumference, and percent fat were compared at baseline, 3, and 6 mo. Data were collected in 2010-2011, and analyzed in 2011. RESULTS: Of the 58 subjects, 47 (81%) were retained for follow-up at the completion of the 6-mo program. From baseline to 6-mo, both groups significantly increased their daily steps [4611 ± 1553 steps/d vs. 7605 ± 2471 steps/d (TV Commercial Stepping); 4909 ± 1335 steps/d vs. 7865 ± 1939 steps/d (Walking); P < 0.05] with no significant difference between groups. TV viewing and dietary intake decreased significantly in both groups. Body weight did not change, but both groups had significant decreases in percent body fat (3-mo to 6-mo), and waist and hip circumference (baseline to 6-mo) over time. CONCLUSIONS: Participants in both the TV Commercial Stepping and Walking groups had favorable changes in daily steps, TV viewing, diet, and anthropometrics. PA can be performed while viewing TV commercials and this may be a feasible alternative to traditional approaches for increasing daily steps in overweight and obese adults. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01342471.