Cadence (steps/min) and relative intensity in 61 to 85-year-olds: the CADENCE-Adults study.

BACKGROUND: We previously demonstrated that a heuristic (i.e., evidence-based, rounded yet practical) cadence threshold of ≥ 100 steps/min was associated with absolutely-defined moderate intensity physical activity (i.e., ≥ 3 metabolic equivalents [METs]) in older adults 61-85 years of age. Although it was difficult to ascertain achievement of absolutely-defined vigorous (6 METs) intensity, ≥ 130 steps/min was identified as a defensible threshold for this population. However, little evidence exists regarding cadence thresholds and relatively-defined moderate intensity indicators, including ≥ 64% heart rate [HR] maximum [HRmax = 220-age], ≥ 40% HR reserve [HRR = HRmax-HRresting], and ≥ 12 Borg Scale Rating of Perceived Exertion [RPE]; or vigorous intensity indicators including ≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE. PURPOSE: To analyze the relationship between cadence and relatively-defined physical activity intensity and identify relatively-defined moderate and vigorous heuristic cadence thresholds for older adults 61-85 years of age. METHODS: Ninety-seven ostensibly healthy adults (72.7 ± 6.9 years; 49.5% women) completed up to nine 5-min treadmill walking bouts beginning at 0.5 mph (0.8 km/h) and progressing by 0.5 mph speed increments (with 2-min rest between bouts). Directly-observed (and video-recorded) steps were hand-counted, HR was measured using a chest-strapped monitor, and in the final minute of each bout, participants self-reported RPE. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds associated with relatively-defined moderate (≥ 64%HRmax, ≥ 40%HRR, and ≥ 12 RPE) and vigorous (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE) intensities. A compromise between the two analytical methods, including Youden's Index (a sum of sensitivity and specificity), positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. RESULTS: Across all relatively-defined moderate intensity indicators, segmented regression models and ROC curve analyses identified optimal cadence thresholds ranging from 105.9 to 112.8 steps/min and 102.0-104.3 steps/min, respectively. Comparable values for vigorous intensity indicators ranged between126.1-132.1 steps/min and 106.7-116.0 steps/min, respectively. Regardless of the relatively-defined intensity indicator, the overall best heuristic cadence threshold aligned with moderate intensity was ≥ 105 steps/min. Vigorous intensity varied between ≥ 115 (greater sensitivity) or ≥ 120 (greater specificity) steps/min. CONCLUSIONS: Heuristic cadence thresholds align with relatively-defined intensity indicators and can be useful for studying and prescribing older adults' physiological response to, and/or perceived experience of, ambulatory physical activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Cadence-based classification of moderate-intensity overground walking in 41- to 85-year-old adults.

BACKGROUND: Walking cadence (steps/min) has emerged as a valid proxy of physical activity intensity, with consensus across numerous laboratory-based treadmill studies that ≥100 steps/min approximates absolutely defined moderate intensity (≥3 metabolic equivalents; METs). We recently reported that this cadence threshold had a classification accuracy of 73.3% for identifying moderate intensity during preferred pace overground walking in young adults. The purpose of this study was to evaluate and compare the performance of a cadence threshold of ≥100 steps/min for correctly classifying moderate intensity during overground walking in middle- and older-aged adults. METHODS: Participants (N = 174, 48.3% female, 41-85 years of age) completed laboratory-based cross-sectional study involving an indoor 5-min overground walking trial at their preferred pace. Steps were manually counted and converted to cadence (total steps/5 min). Intensity was measured using indirect calorimetry and expressed as METs. Classification accuracy (sensitivity, specificity, accuracy) of a cadence threshold of ≥100 steps/min to identify individuals walking at ≥3 METs was calculated. RESULTS: The ≥100 steps/min threshold demonstrated accuracy of 74.7% for classifying moderate intensity. When comparing middle- vs. older-aged adults, similar accuracy (73.4% vs. 75.8%, respectively) and specificity (33.3% vs. 34.5%) were observed. Sensitivity was high, but was lower for middle- vs. older-aged adults (85.2% vs. 93.9%, respectively). CONCLUSION: A cadence threshold of ≥100 steps/min accurately identified moderate-intensity overground walking. Furthermore, accuracy was similar when comparing middle- and older-aged adults. These findings extend our previous analysis in younger adults and confirm the appropriateness of applying this cadence threshold across the adult lifespan.

Walking cadence (steps/min) and intensity in 61-85-year-old adults: the CADENCE-Adults study.

BACKGROUND: Heuristic (i.e., evidence-based, rounded) cadences of ≥100 and ≥ 130 steps/min have consistently corresponded with absolutely-defined moderate (3 metabolic equivalents [METs]) and vigorous (6 METs) physical activity intensity, respectively, in adults 21-60 years of age. There is no consensus regarding similar thresholds in older adults. PURPOSE: To provide heuristic cadence thresholds for 3, 4, 5, and 6 METs in 61-85-year-old adults. METHODS: Ninety-eight community-dwelling ambulatory and ostensibly healthy older adults (age = 72.6 ± 6.9 years; 49% women) walked on a treadmill for a series of 5-min bouts (beginning at 0.5 mph with 0.5 mph increments) in this laboratory-based cross-sectional study until: 1) transitioning to running, 2) reaching ≥75% of their age-predicted maximum heart rate, or 3) reporting a Borg rating of perceived exertion > 13. Cadence was directly observed and hand-tallied. Intensity (oxygen uptake [VO2] mL/kg/min) was assessed with indirect calorimetry and converted to METs (1 MET = 3.5 mL/kg/min). Cadence thresholds were identified via segmented mixed effects model regression and using Receiver Operating Characteristic (ROC) curves. Final heuristic cadence thresholds represented an analytical compromise based on classification accuracy (sensitivity, specificity, positive and negative predictive value, and overall accuracy). RESULTS: Cadences of 103.1 (95% Prediction Interval: 70.0-114.2), 116.4 (105.3-127.4), 129.6 (118.6-140.7), and 142.9 steps/min (131.8-148.4) were identified for 3, 4, 5, and 6 METs, respectively, based on the segmented regression. Comparable values based on ROC analysis were 100.3 (95% Confidence Intervals: 95.7-103.1), 111.5 (106.1-112.9), 116.0 (112.4-120.2), and 128.6 steps/min (128.3-136.4). Heuristic cadence thresholds of 100, 110, and 120 were associated with 3, 4, and 5 METs. Data to inform a threshold for ≥6 METs was limited, as only 6/98 (6.0%) participants achieved this intensity. CONCLUSIONS: Consistent with previous data collected from 21-40 and 41-60-year-old adults, heuristic cadence thresholds of 100, 110, and 120 steps/min were associated with 3, 4, and 5 METs, respectively, in 61-85-year-old adults. Most older adults tested did not achieve the intensity of ≥6 METs; therefore, our data do not support establishing thresholds corresponding with this intensity level. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258 . Registered 24 December 2015.

Cadence (steps/min) and relative intensity in 21 to 60-year-olds: the CADENCE-adults study.

BACKGROUND: Heuristic cadence (steps/min) thresholds of ≥100 and ≥ 130 steps/min correspond with absolutely-defined moderate (3 metabolic equivalents [METs]; 1 MET = 3.5 mL O2·kg- 1·min- 1) and vigorous (6 METs) intensity, respectively. Scarce evidence informs cadence thresholds for relatively-defined moderate (≥ 64% heart rate maximum [HRmax = 220-age], ≥ 40%HR reserve [HRR = HRmax -HRresting, and ≥ 12 Rating of Perceived Exertion [RPE]); or vigorous intensity (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE). PURPOSE: To identify heuristic cadence thresholds corresponding with relatively-defined moderate and vigorous intensity in 21-60-year-olds. METHODS: In this cross-sectional study, 157 adults (40.4 ± 11.5 years; 50.6% men) completed up to twelve 5-min treadmill bouts, beginning at 0.5 mph and increasing by 0.5 mph. Steps were directly observed, HR was measured with chest-worn monitors, and RPE was queried in the final minute of each bout. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds, stratified by age (21-30, 31-40, 41-50, and 51-60 years). Reconciliation of the two analytical models, including trade-offs between sensitivity, specificity, positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. RESULTS: Across all moderate intensity indicators, the segmented regression models estimated optimal cadence thresholds ranging from 123.8-127.5 (ages 21-30), 121.3-126.0 (ages 31-40), 117.7-122.7 (ages 41-50), and 113.3-116.1 steps/min (ages 51-60). Corresponding values for vigorous intensity were 140.3-144.1, 140.2-142.6, 139.3-143.6, and 131.6-132.8 steps/min, respectively. ROC analysis estimated chronologically-arranged age groups' cadence thresholds ranging from 114.5-118, 113.5-114.5, 104.6-112.9, and 103.6-106.0 across all moderate intensity indicators, and 127.5, 121.5, 117.2-123.2, and 113.0 steps/min, respectively, for vigorous intensity. CONCLUSIONS: Heuristic cadence thresholds corresponding to relatively-defined moderate intensity for the chronologically-arranged age groups were ≥ 120, 120, 115, and 105 steps/min, regardless of the intensity indicator (i.e., % HRmax, %HRR, or RPE). Corresponding heuristic values for vigorous intensity indicators were ≥ 135, 130, 125, and 120 steps/min. These cadences are useful for predicting/programming intensity aligned with age-associated differences in physiological response to, and perceived experiences of, moderate and/or vigorous intensity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258 . Registered 24 December 2015.

Walking cadence (steps/min) and intensity in 41 to 60-year-old adults: the CADENCE-adults study.

BACKGROUND: In younger adults (i.e., those < 40 years of age) a walking cadence of 100 steps/min is a consistently supported threshold indicative of absolutely-defined moderate intensity ambulation (i.e., ≥ 3 metabolic equivalents; METs). Less is known about the cadence-intensity relationship in adults of middle-age. PURPOSE: To establish heuristic (i.e., evidence-based, practical, rounded) cadence thresholds for absolutely-defined moderate (3 METs) and vigorous (6 METs) intensity in adults 41 to 60 years of age. METHODS: In this cross-sectional study, 80 healthy adults of middle-age (10 men and 10 women representing each 5-year age-group between 41 to 60 years; body mass index = 26.0 ± 4.0 kg/m2) walked on a treadmill for 5-min bouts beginning at 0.5 mph and increasing in 0.5 mph increments. Performance termination criteria included: 1) transitioning to running, 2) reaching 75% of age-predicted maximum heart rate, or 3) reporting a Borg rating of perceived exertion > 13. Cadence was directly observed (i.e., hand tallied). Intensity (i.e., oxygen uptake [VO2] mL/kg/min) was assessed with an indirect calorimeter and converted to METs (1 MET = 3.5 mL/kg/min). A combination of segmented regression and Receiver Operating Characteristic (ROC) modeling approaches was used to identify optimal cadence thresholds. Final heuristic thresholds were determined based on an evaluation of classification accuracy (sensitivity, specificity, positive and negative predictive value, overall accuracy). RESULTS: The regression model identified 101.7 (95% Predictive Interval [PI]: 54.9-110.6) and 132.1 (95% PI: 122.0-142.2) steps/min as optimal cadence thresholds for 3 METs and 6 METs, respectively. Corresponding values based on ROC models were 98.5 (95% Confidence Intervals [CI]: 97.1-104.9) and 117.3 (95% CI: 113.1-126.1) steps/min. Considering both modeling approaches, the selected heuristic thresholds for moderate and vigorous intensity were 100 and 130 steps/min, respectively. CONCLUSIONS: Consistent with our previous report in 21 to 40-year-old adults, cadence thresholds of 100 and 130 steps/min emerged as heuristic values associated with 3 and 6 METs, respectively, in 41 to 60-year-old adults. These values were selected based on their utility for public health messaging and on the trade-offs in classification accuracy parameters from both statistical methods. Findings will need to be confirmed in older adults and in free-living settings.

Walking cadence (steps/min) and intensity in 21-40 year olds: CADENCE-adults.

BACKGROUND: Previous studies have reported that walking cadence (steps/min) is associated with absolutely-defined intensity (metabolic equivalents; METs), such that cadence-based thresholds could serve as reasonable proxy values for ambulatory intensities. PURPOSE: To establish definitive heuristic (i.e., evidence-based, practical, rounded) thresholds linking cadence with absolutely-defined moderate (3 METs) and vigorous (6 METs) intensity. METHODS: In this laboratory-based cross-sectional study, 76 healthy adults (10 men and 10 women representing each 5-year age-group category between 21 and 40 years, BMI = 24.8 ± 3.4 kg/m2) performed a series of 5-min treadmill bouts separated by 2-min rests. Bouts began at 0.5 mph and increased in 0.5 mph increments until participants: 1) chose to run, 2) achieved 75% of their predicted maximum heart rate, or 3) reported a Borg rating of perceived exertion > 13. Cadence was hand-tallied, and intensity (METs) was measured using a portable indirect calorimeter. Optimal cadence thresholds for moderate and vigorous ambulatory intensities were identified using a segmented regression model with random coefficients, as well as Receiver Operating Characteristic (ROC) models. Positive predictive values (PPV) of candidate heuristic thresholds were assessed to determine final heuristic values. RESULTS: Optimal cadence thresholds for 3 METs and 6 METs were 102 and 129 steps/min, respectively, using the regression model, and 96 and 120 steps/min, respectively, using ROC models. Heuristic values were set at 100 steps/min (PPV of 91.4%), and 130 steps/min (PPV of 70.7%), respectively. CONCLUSIONS: Cadence thresholds of 100 and 130 steps/min can serve as reasonable heuristic thresholds representative of absolutely-defined moderate and vigorous ambulatory intensity, respectively, in 21-40 year olds. These values represent useful proxy values for recommending and modulating the intensity of ambulatory behavior and/or as measurement thresholds for processing accelerometer data. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02650258 ).

Associations of 25-Hydroxyvitamin D With the Blood Pressure Response to Maximal Exercise Among Healthy Adults.

Insufficient 25-hydroxyvitamin D [25(OH)D] levels are associated with high resting blood pressure (BP). However, the relationship between 25(OH)D and the peak systolic BP (SBP) response to exercise, a predictor of future hypertension, has yet to be investigated. We sought to examine the relationship among serum 25(OH)D and the peak SBP response to a graded exercise stress test (GEST) among a large sample (n = 417) of healthy men (49%) and women (51%) over a broad age range (20-76 years; mean age: 44.1 ± 0.8 years). We hypothesized that individuals with clinically insufficient 25(OH)D would have a greater peak SBP response to a GEST compared to individuals with sufficient 25(OH)D levels. Fasting serum 25(OH)D, anthropometrics, resting BP, and peak exercise SBP were obtained at the baseline visit of a larger clinical trial (STOMP; NCT01140308). Mean 25(OH)D levels were 36.1 ± 0.7 ng/ml, with ∼35% of individuals classified as insufficient (<30 ng/ml). Average resting BP was 119 ± 13 mmHg/75 ± 10 mmHg, with 52.3% considered to have normal BP, while 25.2% had elevated BP and 22.5% had established hypertension. The peak SBP response to a GEST was similar between individuals with sufficient (48 ± 19 mmHg) versus insufficient (48 ± 18 mmHg) 25(OH)D (p = 1.000). One unexpected finding emerged such that individuals with sufficient 25(OH)D had higher resting SBP (120 ± 14 mmHg vs. 117 ± 13 mmHg; p = .020) than individuals with insufficient 25(OH)D. In contrast to our hypothesis, 25(OH)D levels were not associated with the peak SBP response to a GEST. Baseline 25(OH)D levels were positively correlated with resting SBP; however, the magnitude of this effect is likely not clinically meaningful.

Extracellular matrix remodeling and its contribution to protective adaptation following lengthening contractions in human muscle.

This study determined the contribution of extracellular matrix (ECM) remodeling to the protective adaptation of human skeletal muscle known as the repeated-bout effect (RBE). Muscle biopsies were obtained 3 hours, 2 days, and 27 days following an initial bout (B1) of lengthening contractions (LCs) and 2 days following a repeated bout (B2) in 2 separate studies. Biopsies from the nonexercised legs served as controls. In the first study, global transcriptomic analysis indicated widespread changes in ECM structural, deadhesive, and signaling transcripts, 3 hours following LC. To determine if ECM remodeling is involved in the RBE, we conducted a second study by use of a repeated-bout paradigm. TNC immunoreactivity increased 10.8-fold following B1, was attenuated following B2, and positively correlated with LC-induced strength loss (r(2) = 0.45; P = 0.009). Expression of collagen I, III, and IV (COL1A1, COL3A1, COL4A1) transcripts was unchanged early but increased 5.7 ± 2.5-, 3.2 ± 0.9-, and 2.1 ± 0.4-fold (P < 0.05), respectively, 27 days post-B1 and were unaffected by B2. Likewise, TGF-ß signaling demonstrated a delayed response following LC. Satellite cell content increased 80% (P < 0.05) 2 days post-B1 (P < 0.05), remained elevated 27 days post-B1, and was unaffected by B2. Collectively, the data suggest sequential ECM remodeling characterized by early deadhesion and delayed reconstructive activity that appear to contribute to the RBE.

Gaps Between Self-Rated Job Importance and Abilities for Community Health Workers in Massachusetts.

Introduction Community health workers (CHWs) serve increasingly active roles in clinical care and population health. To identify priorities for training programs, we developed a training needs assessment (TNA) tool by integrating and distilling core competencies previously identified by various national and state agencies. Methods CHWs were asked to self-rate, using a 4-point scale, the importance to their work and their ability to perform 49 competencies categorized under 10 domains. A difference score-Ability minus Importance-was calculated to determine relative Need. Results The 96 CHWs who completed the TNA were mostly female (80%) and Latino (40%). While CHWs indicated training was needed for all competencies, the scores ranged from -0.04 to -0.45, on a scale running from 0 to -3, where larger negative numbers indicate higher need. In general, there was a high level of congruence between individual competencies with high Need and domains with Need, with few outliers. Competencies with high Need scores related to culture, case assessment and coordination, and behavior change. CHWs rated client-based competencies higher than population health competencies in Ability scores (3.43 vs. 3.05, respectively) and Importance scores (3.70 vs. 3.35, respectively). However, overall Need scores showed no difference between client-based and public health-based competencies. Conclusion CHWs can successfully rate the importance of core competencies to their work and rank their ability to perform these competencies. Training needs generally favored clinical individual client-focused skills over prevention and public health competencies. Using scales that incorporate self-rated measures of core competency ability and importance can inform priorities for CHW training programs and contribute to successful curriculum development.

Effect of statins on skeletal muscle function.

BACKGROUND: Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. METHODS AND RESULTS: The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). CONCLUSIONS: These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Skeletal Muscle Function Is Altered in Male Mice on Low-Dose Androgen Receptor Antagonist or Estrogen Receptor Agonist.

In males, skeletal muscle function may be altered by shifts in either circulating testosterone or estrogen. We examined the effect of acute (2-week) exposures to 17α-ethinyl estradiol (EE2), an estrogen receptor (ER) agonist, or flutamide, an androgen receptor (AR) antagonist, on the contractile function of individual skeletal muscle fibers from slow-contracting soleus and fast-contracting extensor digitorum longus muscles from adult male mice. Single fiber specific tension (force divided by cross-sectional area) was decreased with flutamide treatment in all myosin heavy chain (MHC) fiber types examined (I, IIA, and IIB); similar effects were observed with EE2 treatment but only in the fastest-contracting MHC IIB fibers. The decreases in maximally Ca2+-activated specific tension were primarily a result of fewer strongly bound myosin-actin cross-bridges, with flutamide treatment also showing lower myofilament lattice stiffness. Myosin-actin cross-bridge kinetics were slower in MHC IIA fibers in flutamide-treated mice, but faster in EE2-treated mice, indicating that contractile velocity may be affected differently in this fiber type, which is commonly expressed in human skeletal muscle. Importantly, these effects were observed in the absence of outcomes previously used to evaluate ER agonists or AR antagonists in rodents including weight of reproductive organs or mammary gland morphology. Our findings indicate that substantial shifts in skeletal muscle function occur in male mice following acute exposures to low doses of a pharmacological ER agonist and an AR antagonist. These results suggest that countermeasures to maintain physical function may be needed early in situations that induce similar ER agonist and AR antagonist conditions.

Cadence (steps/min) as an indicator of the walk-to-run transition.

BACKGROUND: Humans naturally transition from walking to running at a point known as the walk-to-run transition (WRT). The WRT commonly occurs at a speed of ∼2.1 m/s (m/s) or a Froude number (dimensionless value considering leg length) of 0.5. Emerging evidence suggests the WRT can also be classified using a cadence of 140 steps/min. An accurate cadence-based WRT metric would aid in classifying wearable technology minute-level step metrics as walking vs. running. PURPOSE: To evaluate performance of 1) WRT predictors directly identified from a treadmill-based dataset of sequentially faster bouts, and 2) accepted WRT predictors compiled from previous literature. METHODS: Twenty-eight adults (71.4% men; age = 36.6 ± 12.8 years, BMI = 26.2 ± 4.7 kg/m2) completed a series of five-minute treadmill walking bouts increasing in 0.2 m/s increments until they freely chose to run. Optimal WRT values for speed, Froude number, and cadence were identified using receiver operating characteristic (ROC) curve analyses. WRT value performance was evaluated via classification accuracy metrics. RESULTS: Overall accuracies (metric, percent) according to WRT predictors from previous literature were: speed (2.1 m/s, 55.0%), Froude number (0.5, 76.8%), and cadence (140 steps/min, 91.1%), and those from the dataset herein were: speed (1.9 and 2.0 m/s, 78.6%), Froude number (0.68, 77.3%), and cadence (134, 139, and 141 steps/min, 92.9%). The three equally accurate cadence values support a heuristic range of cadence-based WRT values in young and middle-aged adults: 135-140 steps/min. SIGNIFICANCE: A tight range of cadence values performed better as WRT predictors compared to either previously reported or directly identified speed or Froude number values. These findings have important implications for gait classification, especially considering cadence is a simple metric which can be readily assessed across settings using direct observation or wearable technologies.

Activation of nuclear factor-κB following muscle eccentric contractions in humans is localized primarily to skeletal muscle-residing pericytes.

Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. This study characterized the early molecular alterations in humans to eccentric contractions (ECs), a stimulus known to induce a muscle regenerative response. Thirty-five subjects completed 100 ECs of the knee extensors with 1 leg, and muscle biopsies were taken from both legs 3 h post-EC. The sample from the non-EC leg served as the control. We first conducted a well-powered transcriptomic screen and network analysis. Our screen identified significant changes in several transcripts with functions relating to inflammation, cell growth, and proliferation. Network analysis then identified the transcription factor NF-κB as a key molecular element affected by ECs. A transcription factor ELISA, using nuclear extracts from EC and control muscle samples, showed a 1.6-fold increase in NF-κB DNA binding activity following ECs. Immunohistochemical experiments localized the majority of NF-κB-positive nuclei to cells in the interstitium, which stained positive for the pericyte markers NG2 proteoglycan and alkaline phosphatase. Our results provide the first evidence of NF-κB activation in human muscle following ECs and suggest a novel role for muscle residing pericytes in the early adaptive response to ECs.

Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients.

OBJECTIVE: This study sought to determine whether aggressive glycemic control (90-120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycemic control (120-180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery. SUMMARY OF BACKGROUND DATA: Maintaining serum glucose levels between 120 and 180 mg/dL with continuous insulin infusions decreases morbidity in diabetic patients undergoing CABG surgery. Studies in surgical patients requiring prolonged ventilation suggest that aggressive glycemic control (<120 mg/dL) may improve survival; however, its effect in diabetic CABG patients is unknown. METHODS: Eighty-two diabetic patients undergoing CABG were prospectively randomized to aggressive glycemic control (90-120 mg/dL) or moderate glycemic control (120-180 mg/dL) using continuous intravenous insulin solutions (100 units regular insulin in 100 mL: normal saline) beginning at the induction of anesthesia and continuing for 18 hours after CABG. Primary end points were the incidence of major adverse events (major adverse events = 30-day mortality, myocardial infarction, neurologic events, deep sternal infections, and atrial fibrillation), the level of serum glucose, and the incidence of hypoglycemic events. RESULTS: There were no differences in the incidence of major adverse events between the groups (17 moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a lower mean glucose at the end of 18 hours of insulin infusion (135 ± 12 mg/dL moderate vs 103 ± 17 mg/dL aggressive; P < 0.0001). Patients with aggressive control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001). CONCLUSIONS: In diabetic patients undergoing CABG surgery, aggressive glycemic control increases the incidence of hypoglycemic events and does not result in any significant improvement in clinical outcomes that can be achieved with moderate control. Clinical Trials.gov (ID #NCT00460499).

A Transparent Method for Step Detection using an Acceleration Threshold.

Step-based metrics provide simple measures of ambulatory activity, yet device software either includes undisclosed proprietary step detection algorithms or simply do not compute step-based metrics. We aimed to develop and validate a simple algorithm to accurately detect steps across various ambulatory and non-ambulatory activities. Seventy-five adults (21-39 years) completed seven simulated activities of daily living (e.g., sitting, vacuuming, folding laundry) and an incremental treadmill protocol from 0.22-2.2ms-1. Directly observed steps were hand-tallied. Participants wore GENEActiv and ActiGraph accelerometers, one of each on their waist and on their non-dominant wrist. Raw acceleration (g) signals from the anterior-posterior, medial-lateral, vertical, and vector magnitude (VM) directions were assessed separately for each device. Signals were demeaned across all activities and bandpass filtered [0.25, 2.5Hz]. Steps were detected via peak picking, with optimal thresholds (i.e., minimized absolute error from accumulated hand counted) determined by iterating minimum acceleration values to detect steps. Step counts were converted into cadence (steps/minute), and k-fold cross-validation quantified error (root mean squared error [RMSE]). We report optimal thresholds for use of either device on the waist (threshold=0.0267g) and wrist (threshold=0.0359g) using the VM signal. These thresholds yielded low error for the waist (RMSE<173 steps, ≤2.28 steps/minute) and wrist (RMSE<481 steps, ≤6.47 steps/minute) across all activities, and outperformed ActiLife's proprietary algorithm (RMSE=1312 and 2913 steps, 17.29 and 38.06 steps/minute for the waist and wrist, respectively). The thresholds reported herein provide a simple, transparent framework for step detection using accelerometers during treadmill ambulation and activities of daily living for waist- and wrist-worn locations.

Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals.

Results from the Diabetes Prevention Program highlight the effectiveness of metformin or regular physical activity in the prevention of type 2 diabetes. Independently, metformin and exercise increase insulin sensitivity, but they have not been studied in combination. To assess the combined effects, insulin-resistant subjects (n = 9) matched for weight, body fat, and aerobic fitness were studied before any treatment (B), after 2-3 wk of 2,000 mg/day metformin (MET), and after metformin plus 40 min of exercise at 65% Vo(2peak) (MET + Ex). A second group (n = 7) was studied at baseline and after an identical bout of exercise with no metformin (Ex). Biopsies of the vastus lateralis were taken at B, after MET, immediately after MET + Ex (group 1), or immediately after Ex (group 2). Insulin sensitivity was assessed 4 h postexercise with a euglycemic hyperinsulinemic (40 mU.m(2).min(-1)) clamp enriched with [6,6-(2)H]glucose. Insulin sensitivity was 54% higher after Ex (P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPKalpha2 activity was elevated threefold (P < 0.01) after Ex, but there was no increase with MET + Ex. These findings suggest that the combination of short-term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity, and the addition of metformin may attenuate the well-documented effects of exercise alone.

Expression of inducible nitric oxide synthase in conduits used in patients with diabetes mellitus undergoing coronary revascularization.

BACKGROUND: Expression of inducible nitric oxide synthase (iNOS) is a marker of vascular inflammation which can result in thrombosis and atherosclerosis. This study was undertaken to examine the difference in iNOS expression in the internal mammary artery (IMA) and saphenous veins (SVs) of patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery using both qualitative and quantitative methodology. METHODS: Segments of IMA and SV harvested in 100 diabetic patients with diabetes mellitus undergoing CABG surgery were fixed in formalin and immunostained to detect the presence of iNOS. Sections were graded using a qualitative score (0 = absence of iNOS expression to 3 = extensive expression of iNOS) and a quantitative computer-aided image analysis (area of staining/area of endothelium). Linear regression analyses were performed to assess the association of the degree of iNOS expression in both the IMA and SV with the type of diabetes control (insulin, oral, diet), and the serum levels of HbAlc, glucose, free fatty acids (ffa), C-reactive protein (CRP), and low-density liproprotein (LDL) at the time of conduit harvest. RESULTS: The degree of iNOS expression was significantly lower in the IMA compared to the SV by both qualitative (0.88 +/- 0.74 SD IMA vs. 1.38 +/- 0.68 SV; p < 0.0001) and quantitative (11.76 +/- 3.34% IMA vs. 17.10 +/- 2.54% SV; p = 0.01) methods. The Spearman rank correlation analysis showed a highly statistically significant association between the two methodologies (p < 0.0001). There was no correlation between iNOS expression in either the IMA or SV and the type of diabetes control, or levels of HA1c, glucose, ffa, and CRP. However, there was a significant (p = 0.04) correlation between LDL and iNOS expression in the SV graft, but not the IMA. CONCLUSIONS: iNOS expression is significantly decreased in the IMA compared to the SV in patients with diabetes mellitus undergoing CABG surgery. The degree of iNOS expression is unrelated to the level of glycemic control at the time of conduit harvest, but is associated with serum LDL levels in the SV, but not in the IMA grafts.