Evaluation of the Spanish-Language Cancer Educational Webinar Series "Vamos a educarnos contra el cáncer" with the RE-AIM Framework.

The COVID-19 pandemic disrupted healthcare for patients with chronic diseases, including cancer. Barriers to healthcare increased, especially for racial and ethnic minorities. While many institutions developed webinars to educate community members, few webinars used a community-based participatory approach, employed a theory-based engagement design, and were evaluated. This manuscript reports the outcomes of "Vamos a educarnos contra el cáncer," a 2021 webinar series. Monthly educational webinars were conducted in Spanish on cancer-related topics. The presentations were delivered by Spanish-speaking content experts from different organizations. Webinars were conducted using the video conferencing platform Zoom. Polls were launched during the webinar to collect data and evaluate each webinar. The RE-AIM model of reach, effectiveness, adoption, implementation, and maintenance was used to evaluate the series. The SAS Analytics Software was used for analysis and data management. Two hundred ninety-seven people participated with over 3000 views of the webinar recordings (Reach); 90% rated the sessions as good or excellent (Effectiveness); 86% agreed to adopt or improve a cancer-related behavior, and 90% reported willingness to adopt or improve a cancer-related action for someone else (Adoption); 92% reported feeling engaged (Implementation). The series has produced a resource library, manual of operations, and agreement of the Hispanic/Latino Cancer Community Advisory Board (CAB) to continue the webinar series in the future (Maintenance). Overall, these results highlight the impact of this webinar series and provide a standard approach to planning, delivering, and evaluating webinars as a strategy for cancer prevention and control in a culturally appropriate manner.

Natural history of sleep disordered breathing in prepubertal children transitioning to adolescence.

Because there is a lack of agreed upon diagnostic criteria, it is critical to understand the natural history of obstructive sleep apnoea (OSA) in children in order to establish treatment strategies based on objective data.The Penn State Child Cohort is a representative, general-population sample of 700 elementary school children at baseline, of whom 421 were reassessed 8 years later, during adolescence.The remission of childhood apnoea-hypopnoea index (AHI) ≥2 events per h in adolescence was 52.9%. Using the higher threshold of AHI ≥5 events per h, remission was 100.0%, with 50.0% partially remitting to AHI 2- <5 events per h and the other half remitting to AHI <2 events per h. The incidence of adolescent AHI ≥2 events per h in those with childhood AHI <2 events per h was 36.5%, while the incidence of AHI ≥5 events per h in those with childhood AHI <5 events per h was 10.6%. This longitudinal study confirms that prepubertal OSA tends to resolve naturally during the transition to adolescence, and that primary snoring and mild sleep disordered breathing (SDB) do not appear to be strongly associated with progression to more severe SDB.The key risk factors for SDB in adolescence are similar to those found in middle-aged adults (i.e. male sex, older age and obesity). Moreover, consistent with recent studies in adults, this study includes the novel cross-sectional finding that visceral fat is associated with SDB as early as adolescence.

Abdominal obesity and metabolic syndrome burden in adolescents--Penn State Children Cohort study.

To investigate the association between abdominal obesity and metabolic syndrome (MetS) burden in a population-based sample of adolescents, we used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. Dual-energy x-ray absorptiometry (DXA) was used to assess abdominal obesity, as measured by android/gynoid fat ratio (A/G ratio), android/whole body fat proportion (A/W proportion), visceral (VAT) and subcutaneous fat (SAT) areas. Continuous metabolic syndrome score (cMetS), calculated as the sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components, was used to assess the MetS burden. Linear regression models were used to analyze the impact of DXA measures on cMetS components. All models were adjusted for age, race, sex, and general obesity. We found abdominal obesity is significantly associated with increased cMetS. With 1 standard deviation (SD) increase in A/G ratio, A/W proportion, VAT area, and SAT area, cMetS increased by 1.34 (SE=0.17), 1.25 (SE=0.19), 1.67 (SE=0.17), and 1.84 (SE=0.20) units, respectively. At individual component level, strongest association was observed between abdominal obesity and insulin resistance (IR) than lipid-based or blood pressure-based components. VAT and SAT had a stronger impact on IR than android ratio-based DXA measurements. In conclusion, abdominal obesity is associated with higher MetS burden in adolescent population. The association between abdominal obesity and IR measure is the strongest, suggesting the key impact of abdominal obesity on IR in adolescents MetS burden.

The circadian pattern of cardiac autonomic modulation and obesity in adolescents.

PURPOSE: To assess the impact of obesity and population attributes on the circadian pattern of cardiac autonomic modulation (CAM) in a population-based sample of adolescents. METHODS: We used data from 421 adolescents who completed the follow-up exam in the Penn State Children Cohort study. CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat, normal R-R intervals from a 24-hour ECG, on a 30-minute basis. The HRV indices included frequency-domain (HF, LF, and LF/HF ratio) and time-domain (SDNN, RMSSD, and HR) variables. Nonlinear mixed-effect models were used to calculate a cosine periodic curve, each having three parameters quantifying its circadian period: M (mean levels of the HRV variables),  (amplitude of the oscillation), and θ (the time of the highest oscillation). RESULTS: The mean (SD) age was 16.9 (2.2) years, with 54 % male and 77 % white. The mean BMI percentile was 66, with 16 % obese (BMI percentile ≥ 95). Overall, HF (a marker of parasympathetic modulation) gradually increased from the late afternoon, reached peak amplitude around 3 a.m., and then decreased throughout the daytime until late afternoon. In contrast, obesity had adverse effects on all circadian parameters. The age, sex and race showed varying differences on the CAM circadian parameters. The adjusted means (95 %Cls) of M, Â, and θ for HF were 5.99 (5.79-6.19), 0.77 (0.66-0.89), 3:15 (2:15-4:15) a.m., and 6.21 (6.13-6.29), 0.66 (0.61-0.70), 2:45 (2:30-3:15) a.m. for obese and non-obese subjects, respectively. CONCLUSION: The circadian pattern of CAM can be quantified by the three cosine parameters. Obesity is associated with lower HRV even in young individuals like children/adolescents.

Assessing the Feasibility of a Faith-Based Colorectal Cancer Education and Screening Intervention for Latino Men in Pennsylvania.

Introduction: Limited health knowledge, literacy, engagement in preventive health services, participation in health promotion behaviors, and cultural factors place Latino men at high risk for colorectal cancer (CRC). This pilot study aimed to determine the feasibility and acceptability of a faith-based cancer education intervention focusing on Latino men between 45 and 74 years old. Methods: This pilot study used a single group pre- and post-intervention research design to compare changes in knowledge, perceived benefit of screening, perceived susceptibility and severity of CRC, and the completion of CRC screening after the intervention. Results: In this study, Latino men were willing to participate in a CRC educational intervention supported by a faith-based institution. The participants had limited knowledge about CRC, yet most recognized that screening is beneficial and that getting CRC is serious. Sixty percent of the participants completed the fecal immunochemical screening test, which showed that the intervention impacted the screening uptake among this group. Conclusion: The findings of this study support the further development of faith-based interventions focusing on Latino men.

The circadian pattern of cardiac autonomic modulation in a middle-aged population.

OBJECTIVES: To examine the circadian pattern of cardiac autonomic modulation (CAM) and its attributes in general population. METHODS: We obtained 24-h beat-to-beat RR data using a high resolution 12-lead Holter ECG in a community-dwelling sample of 115 non-smokers. We performed heart rate variability (HRV) analysis on the normal RRs from each 5-min segment to obtain time-specific HRV indices: high (HF; 0.15-0.40 Hz) and low (LF; 0.04-0.15 Hz) frequency powers, standard deviation of RR intervals (SDNN), and the square root of the mean of the sum of the squared differences of the adjacent RR intervals (RMSSD). For each individual, we fit the segment-specific HRV data to a cosine periodic function, and estimated 3 individual-level cosine function parameters to quantify the circadian variation: the mean (M), amplitude (A), and acrophase (θ). We then used a random-effects meta-analysis to summarize the M, A, and θ, and their 95% confidence intervals (CI). RESULTS: The mean age was 56 (SD 8) years, with 63% female and 76% white. The averages of M, A and θ (95%CI) of log HF were 3.59 (3.43-3.76) ms(2), 0.61 (0.54-0.68) ms(2), and 3:10 (2:25-3:55) AM, respectively, and that of RMSSD were 22.3 (20.5-24.1) ms, 6.5 (5.4-7.5) ms, 3:45 (2:55-4:35) AM, respectively. Older age is associated with lower mean of HRV. Males have higher oscillation amplitude than females. The acrophase of LF/HF was earlier in females than in males, and in younger individuals than in older individuals. CONCLUSIONS: The circadian pattern of CAM can be quantified by 3 cosine parameters of HRV, which are correlated with age and gender.

Fine particulate air pollution is associated with higher vulnerability to atrial fibrillation--the APACR study.

The acute effects and the time course of fine particulate pollution (PM2.5) on atrial fibrillation/flutter (AF) predictors, including P-wave duration, PR interval duration, and P-wave complexity, were investigated in a community-dwelling sample of 106 nonsmokers. Individual-level 24-h beat-to-beat electrocardiogram (ECG) data were visually examined. After identifying and removing artifacts and arrhythmic beats, the 30-min averages of the AF predictors were calculated. A personal PM2.5 monitor was used to measure individual-level, real-time PM2.5 exposures during the same 24-h period, and corresponding 30-min average PM2.5 concentration were calculated. Under a linear mixed-effects modeling framework, distributed lag models were used to estimate regression coefficients (ßs) associating PM2.5 with AF predictors. Most of the adverse effects on AF predictors occurred within 1.5-2 h after PM2.5 exposure. The multivariable adjusted ßs per 10-µg/m³ rise in PM2.5 at lag 1 and lag 2 were significantly associated with P-wave complexity. PM2.5 exposure was also significantly associated with prolonged PR duration at lag 3 and lag 4. Higher PM2.5 was found to be associated with increases in P-wave complexity and PR duration. Maximal effects were observed within 2 h. These findings suggest that PM2.5 adversely affects AF predictors; thus, PM2.5 may be indicative of greater susceptibility to AF.

Working to Increase Stability through Exercise (WISE): screening, recruitment, and baseline characteristics.

BACKGROUND: The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania. METHODS: The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings. RESULTS: Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%). CONCLUSIONS: The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered.

Insulin resistance and circadian rhythm of cardiac autonomic modulation.

BACKGROUND: Insulin resistance (IR) has been associated with cardiovascular diseases (CVD). Heart rate variability (HRV), an index of cardiac autonomic modulation (CAM), is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. METHOD: Homeostasis models of IR (HOMA-IR), insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M), measures the overall average of a HRV index; amplitude (Â), measures the amplitude of the oscillation of a HRV index; and acrophase time (θ), measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. RESULTS: In persons without type diabetes, the multivariate adjusted ß (SE) of log HOMA-IR and M variable for HRV were -0.251 (0.093), -0.245 (0.078), -0.19 (0.06), -4.89 (1.76), -3.35 (1.31), and 2.14 (0.995), for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P < 0.05). None of the IR variables were significantly associated with  or θ of the HRV indices. However, in eight type 2 diabetics, the magnitude of effect due to higher HOMA-IR on M, Â, and θ are much larger. CONCLUSION: Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.

Sleep-disordered breathing in children is associated with impairment of sleep stage-specific shift of cardiac autonomic modulation.

We examined the effects of sleep stages and sleep-disordered breathing (SDB) on autonomic modulation in 700 children. Apnea hypopnea index (AHI) during one 9 h night-time polysomnography was used to define SDB. Sleep stage-specific autonomic modulation was measured by heart rate variability (HRV) analysis of the first available 5 min RR intervals from each sleep stage. The mean [standard deviation (SD)] age was 112 (21) months (49% male and 25% non-Caucasian). The average AHI was 0.79 (SD = 1.03) h(-1), while 73.0%, 25.8% and 1.2% of children had AHI <1 (no SDB), 1-5 (mild SDB) and >or=5 (moderate SDB), respectively. In the no SDB group, the high frequency (HF) and root mean square SD (RMSSD) increased significantly from wake to Stage 2 and slow wave sleep (SWS), and then decreased dramatically when shifting into rapid eye movement (REM) sleep. In the moderate SDB group, the pattern of HRV shift was similar to that of no SDB. However, the decreases in HF and RMSSD from SWS to REM were more pronounced in moderate SDB children [between-group differences in HF (-24% in moderate SDB versus -10% in no SDB) and RMSSD (-27% versus -12%) were significant (P < 0.05)]. The REM stage HF is significantly lower in the moderate SDB group compared to the no SDB group [mean (standard error): 4.49 (0.43) versus 5.80 (0.05) ms(2), respectively, P < 0.05]. Conclusions are that autonomic modulation shifts significantly towards higher parasympathetic modulation from wake to non-rapid eye movement sleep, and reverses to a less parasympathetic modulation during REM sleep. However, the autonomic modulation is impaired among children with moderate SDB in the directions of more reduction in parasympathetic modulation from SWS to REM sleep and significantly weaker parasympathetic modulation in REM sleep, which may lead to higher arrhythmia vulnerability, especially during REM sleep.

Acute effects of fine particulate air pollution on ST segment height: a longitudinal study.

BACKGROUND: The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. METHODS: We investigate the acute effects and the time course of fine particulate pollution (PM2.5) on myocardium ischemic injury as assessed by ST-segment height in a community-based sample of 106 healthy non-smokers. Twenty-four hour beat-to-beat electrocardiogram (ECG) data were obtained using a high resolution 12-lead Holter ECG system. After visually identifying and removing all the artifacts and arrhythmic beats, we calculated beat-to-beat ST-height from ten leads (inferior leads II, III, and aVF; anterior leads V3 and V4; septal leads V1 and V2; lateral leads I, V5, and V6,). Individual-level 24-hour real-time PM2.5 concentration was obtained by a continuous personal PM2.5 monitor. We then calculated, on a 30-minute basis, the corresponding time-of-the-day specific average exposure to PM2.5 for each participant. Distributed lag models under a linear mixed-effects models framework were used to assess the regression coefficients between 30-minute PM2.5 and ST-height measures from each lead; i.e., one lag indicates a 30-minute separation between the exposure and outcome. RESULTS: The mean (SD) age was 56 (7.6) years, with 41% male and 74% white. The mean (SD) PM2.5 exposure was 14 (22) µg/m3. All inferior leads (II, III, and aVF) and two out of three lateral leads (I and V6), showed a significant association between higher PM2.5 levels and higher ST-height. Most of the adverse effects occurred within two hours after PM2.5 exposure. The multivariable adjusted regression coefficients ß (95% CI) of the cumulative effect due to a 10 µg/m3 increase in Lag 0-4 PM2.5 on ST-I, II, III, aVF and ST-V6 were 0.29 (0.01-0.56) µV, 0.79 (0.20-1.39) µV, 0.52 (0.01-1.05) µV, 0.65 (0.11-1.19) µV, and 0.58 (0.07-1.09) µV, respectively, with all p < 0.05. CONCLUSIONS: Increased PM2.5 concentration is associated with immediate increase in ST-segment height in inferior and lateral leads, generally within two hours. Such an acute effect of PM2.5 may contribute to increased potential for regional myocardial ischemic injury among healthy individuals.

Examining Older Adults' Attitudes and Perceptions of Cancer Screening and Overscreening: A Qualitative Study.

INTRODUCTION/OBJECTIVES: Screening guidelines for breast, cervical, and colorectal cancer (CRC) are less clear for older adults due to the potential harms that may result from screening. Understanding older adults' attitudes and perceptions, especially racial/ethnic minority and underserved adults, of cancer screening can help health care providers determine how best to communicate with older adults about cancer screening and screening cessation. The objective of this study was to determine how older adults primarily from minority/underserved backgrounds perceive cancer screening and overscreening. METHODS: Four focus groups (n = 39) were conducted with adults (>=65 years of age) in 3 community settings in south-central Pennsylvania. Two focus groups were conducted in Spanish and translated to English upon transcription. Focus group data was managed and analyzed using QSR NVivo 12. Inductive thematic analysis was used to analyze the data where themes emerged following the coding process. RESULTS: The focus group participants had an average age of 74 years and were primarily female (74%) and Hispanic (69%), with 69% reporting having less than a high school degree. Four key themes were identified from the focus groups: (1) importance of tailored and targeted education/information; (2) impact of physician/patient communication; (3) impact of barriers and facilitators to screening on cancer screening cessation; and (4) awareness of importance of screening. Participants were more likely to be agreeable to screening cessation if they received specific information regarding their health status and previous medical history from their physician as to why screening should be stopped and told by their physician that the screening decision is up to them. CONCLUSIONS: Older adults prefer individualized information from their physician in order to justify screening cessation but are against incorporating life expectancy into the discussion. Future research should focus on developing interventions to test the effectiveness of culturally tailored screening cessation messages for older adults.

Metabolic syndrome clusters and the risk of incident stroke: the atherosclerosis risk in communities (ARIC) study.

BACKGROUND AND PURPOSE: Little is known about the metabolic syndrome (MetS) and the risk of incident stroke. This study is designed to identify particular clusters of MetS components that carry the highest risk of incident stroke. METHODS: We analyzed the public use data from the population-based Atherosclerosis Risk in Communities study. At baseline, 14 993 stroke-free middle-aged individuals were followed-up over 9 years for incident stroke. MetS components were defined according to the National Heart, Lung, and Blood Institute/American Heart Association criteria. Incident stroke was identified using a standardized incident events identification and classification protocol. Proportional hazard models were used to assess the RRs and 95% CIs of ischemic stroke associated with MetS and its different clusters. RESULTS: At baseline, the prevalence of MetS was 39%. The mean age was 54, with 26% blacks and 55% females. The hazard ratio of incident ischemic stroke associated with MetS among women (hazard ratio, 2.41; 95% CI, 1.69 to 3.49) and men (hazard ratio, 2.11; 95% CI, 1.56-2.85) was similar. There was a dose-response relationship between the numbers of MetS components and the risk of incidence stroke. Persons with either elevated blood pressure or elevated fasting glucose in the clusters to form a MetS had the highest risk for incident stroke (hazard ratio, 2.74-4.16 comparing to the reference group) than MetS without these 2 components (hazard ratio,

Working to Increase Stability through Exercise (WISE): Study protocol for a pragmatic randomized controlled trial of a coached exercise program to reduce serious fall-related injuries.

Approximately one-third of older adults fall each year and fall-related injuries are a leading cause of death and disability among this rapidly expanding age group. Despite the availability of bisphosphonates to reduce fractures, concerns over side effects have dramatically reduced use, suggesting that other treatment options are needed. Though many smaller studies have shown that physical activity programs can reduce falls, no study has been adequately powered to detect a reduction in fall-related injuries. We present the design of a three-year randomized controlled clinical trial of 1130 adults age 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The main aim is to determine the impact of a community-based multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers (or delivered via DVD) and accompanied by coaching and oversight, by telephone and in-person, by a fitness professional. The main outcome measure is serious fall-related injuries. Secondary outcomes include health care utilization, bone and muscle mass, loneliness, health-related quality of life and mood. The study represents the first large clinical trial of a comprehensive physical activity program to reduce secondary injuries among patients with a history of fragility fracture.

Infectivity of herpes simplex virus type-1 (HSV-1) amplicon vectors in dendritic cells is determined by the helper virus strain used for packaging.

Herpes simplex virus type-1 (HSV-1) amplicon vectors are being explored for a wide range of potential applications, including vaccine delivery and immunotherapy of cancer. While extensive effort has been directed towards the improvement of the amplicon "payload" in these vectors, relatively little attention has been paid to the effect of the packaging HSV-1 strains on the biological properties of co-packaged amplicon vectors. We therefore compared the biological properties of amplicon stocks prepared using a panel of primary HSV-1 isolates, a molecularly cloned strain used to package helper-free amplicons (designated here as F5), and two laboratory isolates (KOS and strain 17, which is the parent of the F5 clone). This analysis revealed considerable inter-strain variability in the ability of amplicon stocks packaged by different primary HSV-1 isolates to efficiently transduce established cell lines and primary human dendritic cells (DC). Amplicons packaged by both the F5 molecularly cloned virus and its laboratory-adapted parent (strain 17) were very inefficient at transducing DC, when compared to amplicons packaged by KOS or by several of the primary virus isolates. These finding have important implications for the future development of improved amplicon-based vaccine delivery systems and suggest that DC tropism may be an instrinsic property of some HSV-1 strains, independent of passage history or molecular cloning.

Sleep variability and cardiac autonomic modulation in adolescents - Penn State Child Cohort (PSCC) study.

OBJECTIVE: To investigate the effects of objectively measured habitual sleep patterns on cardiac autonomic modulation (CAM) in a population-based sample of adolescents. METHODS: We used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. CAM was assessed by heart rate (HR) variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-h electrocardiogram, on a 30-min basis. The HRV indices included frequency domain (HF, LF, and LF/HF ratio), and time domain (SDNN, RMSSD, and heart rate or HR) variables. Actigraphy was used for seven consecutive nights to estimate nightly sleep duration and time in bed. The seven-night mean (SD) of sleep duration and sleep efficiency were used to represent sleep duration, duration variability, sleep efficiency, and efficiency variability, respectively. HF and LF were log-transformed for statistical analysis. Linear mixed-effect models were used to analyze the association between sleep patterns and CAM. RESULTS: After adjusting for major confounders, increased sleep duration variability and efficiency variability were significantly associated with lower HRV and higher HR during the 39-h, as well as separated by daytime and nighttime. For instance, a 1-h increase in sleep duration variability is associated with -0.14(0.04), -0.12(0.06), and -0.16(0.05) ms(2) decrease in total, daytime, and nighttime HF, respectively. No associations were found between sleep duration, or sleep efficiency and HRV. CONCLUSION: Higher habitual sleep duration variability and efficiency variability are associated with lower HRV and higher HR, suggesting that an irregular sleep pattern has an adverse impact on CAM, even in healthy adolescents.

Metabolic syndrome burden in apparently healthy adolescents is adversely associated with cardiac autonomic modulation--Penn State Children Cohort.

BACKGROUND: Reduced cardiac autonomic modulation (CAM) has been associated with metabolic syndrome (MetS) in adults. However, the association between MetS component cluster and CAM has not been examined in adolescents. METHODS: We conducted a cross-sectional analysis using data from the Penn State Child Cohort follow-up examination. CAM was assessed by heart rate variability (HRV) analysis of 39-h RR intervals, including frequency (high frequency, HF; low frequency, LF; and LF/HF ratio) and time (SDNN, standard deviation of all RR intervals; RMSSD, square root of the mean of the sum of the squares of differences between adjacent RR intervals; and HR, heart rate) domain variables. To assess the MetS burden, we used continuous MetS score (cMetS)--sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components. Linear mixed-effect models were used to analyze the association between cMetS and CAM in the entire population and stratified by gender. RESULTS: After adjusting for age, sex, and race, cMetS was significantly associated with reduced HRV and higher HR. With 1 standard deviation increase in cMetS, there was a significant decrease in HF (-0.10 (SE = 0.02)), LF (-0.07 (SE = 0.01)), SDNN (-1.97 (SE = 0.50)), and RMSSD (-1.70 (SE = 0.72)), and increase in LF/HF (0.08 (SE = 0.02)) and HR (1.40 (SE = 0.26)). All cMetS components, with the exception of high-density lipoprotein (HDL), were associated with significantly decreased HRV and increased HR. High blood pressure (MAP) and triglyceride (TG) levels were also associated with an increase in LF/HF and decrease in RMSSD. An increase in high-density lipoprotein was only associated with higher LF and SDNN. Moreover, cMetS and HRV associations were more pronounced in males than in females. The associations between HRV and. MAP, TG, and HDL were more pronounced in females. CONCLUSIONS: cMetS score is associated with lower HRV, suggesting an adverse impact on CAM, even in apparently healthy adolescents.

Therapeutic levels of factor IX expression using a muscle-specific promoter and adeno-associated virus serotype 1 vector.

Extensive studies in animal models of the X-linked bleeding disorder hemophilia B (deficiency in functional coagulation factor IX, F.IX) have shown that muscle-directed adeno-associated (AAV)-mediated F.IX gene transfer can be used to treat this disease. However, large vector doses of AAV-2 vector are required for therapeutic levels of expression, and the number of vector doses that can be injected per intramuscular site is limited. Several studies have shown that some of these limitations can be overcome by use of AAV serotype 1 vector. Here, we demonstrate levels of F.IX transgene expression from a synthetic muscle-specific promoter (C5-12) that were higher than from the cytomegalovirus (CMV) immediate-early enhancer-promoter in cultured muscle cells in vitro and approximately 50% of CMV-driven expression in vivo in murine skeletal muscle after AAV-1 gene transfer. These data show for the first time that a tissue-specific promoter can be used to achieve therapeutic levels of muscle-derived F.IX expression in the context of viral gene transfer. However, use of a muscle-specific promoter did not prevent antibody formation in response to a murine F.IX transgene product in mice with F.IX gene deletion, indicating that the risk of humoral immune responses remains in the context of an immunologically unfavorable mutation.

Childhood obesity and autonomic dysfunction: risk for cardiac morbidity and mortality.

OPINION STATEMENT: The epidemic of childhood obesity is becoming a major predictor for risk of cardiovascular diseases (CVD) and mortality during adulthood. Alterations in the morphology of the heart due to obesity could be a predictor for the dysfunction of cardiac autonomic modulation (CAM). A number of epidemiologic studies have evaluated the effect of obesity and CAM in children, finding that obesity impaired the balance of CAM toward a sympathetic overflow and reduced parasympathetic modulation, a significant predictor of CVD morbidity and mortality in adults. Lifestyle modifications, for example long-term exercise programs, have been shown to improve CAM in the obese. This review discusses the recent evidence on childhood and adolescent obesity and its impact on CAM, as well as how early lifestyle changes could help improve CAM, which may in turn reduce the burden of CVD in adults.