Proper control of R-loop homeostasis is required for maintenance of gene expression and neuronal function during aging.

Age-related loss of cellular function and increased cell death are characteristic hallmarks of aging. While defects in gene expression and RNA metabolism have been linked with age-associated human neuropathies, it is not clear how the changes that occur in aging neurons contribute to loss of gene expression homeostasis. R-loops are RNA-DNA hybrids that typically form co-transcriptionally via annealing of the nascent RNA to the template DNA strand, displacing the non-template DNA strand. Dysregulation of R-loop homeostasis has been associated with both transcriptional impairment and genome instability. Importantly, a growing body of evidence links R-loop accumulation with cellular dysfunction, increased cell death, and chronic disease onset. Here, we characterized the R-loop landscape in aging Drosophila melanogaster photoreceptor neurons and showed that bulk R-loop levels increased with age. Further, genome-wide mapping of R-loops revealed that transcribed genes accumulated R-loops over gene bodies during aging, which correlated with decreased expression of long and highly expressed genes. Importantly, while photoreceptor-specific down-regulation of Top3ß, a DNA/RNA topoisomerase associated with R-loop resolution, lead to decreased visual function, over-expression of Top3ß or nuclear-localized RNase H1, which resolves R-loops, enhanced positive light response during aging. Together, our studies highlight the functional link between dysregulation of R-loop homeostasis, gene expression, and visual function during aging.

Characterizing a gene expression toolkit for eye- and photoreceptor-specific expression in Drosophila.

Binary expression systems are a powerful tool for tissue- and cell-specific research. Many of the currently available Drosophila eye-specific drivers have not been systematically characterized for their expression level and cell-type specificity in the adult eye or during development. Here, we used a luciferase reporter to measure expression levels of different drivers in the adult Drosophila eye, and characterized the cell type-specificity of each driver using a fluorescent reporter in live 10-day-old adult males. We also further characterized the expression pattern of these drivers in various developmental stages. We compared several Gal4 drivers from the Bloomington Drosophila Stock Center (BDSC) including GMR-Gal4, longGMR-Gal4 and Rh1-Gal4 with newly developed Gal4 and QF2 drivers that are specific to different cell types in the adult eye. In addition, we generated drug-inducible Rh1-GSGal4 lines and compared their induced expression with an available GMR-GSGal4 line. Although both lines had significant induction of gene expression measured by luciferase activity, Rh1-GSGal4 was expressed at levels below the detection of the fluorescent reporter by confocal microscopy, while GMR-GSGal4 showed substantial reporter expression in the absence of drug by microscopy. Overall, our study systematically characterizes and compares a large toolkit of eye- and photoreceptor-specific drivers, while also uncovering some of the limitations of currently available expression systems in the adult eye.

The evolution of the steps program, 2003-2010: transforming the federal public health practice of chronic disease prevention.

The Steps program, formerly known as Steps to a HealthierUS, was the first Centers for Disease Control and Prevention (CDC) program to support a community-based, integrated approach to chronic disease prevention. Steps interventions addressed both diseases and risk factors, focusing on the 3 leading causes of preventable deaths in the United States--tobacco use, poor nutrition, and physical inactivity--and the associated chronic conditions of asthma, diabetes, and obesity. When Steps shifted from interventions focused on individual health-risk behaviors to the implementation of policy, systems, and environmental changes, the program became an integral part of changing the way CDC addressed chronic disease prevention. In this article, we describe the shift in intervention strategies that occurred among Steps communities, the model that was developed as Steps evolved, common interventions implemented before and after the shift in approach, challenges experienced by Steps communities, and CDC programs that were modeled after Steps.

Prevalence of selected risk behaviors and chronic diseases and conditions-steps communities, United States, 2006-2007.

PROBLEM: At least one chronic disease or condition affects 45% of persons and account for seven of the 10 leading causes of death in the United States. Persons who suffer from chronic diseases and conditions, (e.g., obesity, diabetes, and asthma) experience limitations in function, health, activity, and work, affecting the quality of their lives as well as the lives of their family. Preventable health-risk factors (e.g., insufficient physical activity, poor nutrition, and tobacco use and exposure) contribute substantially to the development and severity of certain chronic diseases and conditions. REPORTING PERIOD COVERED: 2006-2007 DESCRIPTION OF THE SYSTEM: CDC's Healthy Communities Program funds communities to address chronic diseases and related risk factors through policy, systems, and environmental change strategies. As part of the Healthy Communities Program, 40 Steps communities were funded nationwide to address six focus areas: obesity, diabetes, asthma, physical inactivity, poor nutrition, and tobacco use and exposure. During 2006-2007, 38 and 39 of the 40 communities conducted a survey to collect adult health outcome data. The survey instrument was a modified version of the Behavioral Risk Factor Surveillance System (BRFSS) survey, a state-based, random-digit-dialed telephone survey. The survey instrument collected information on chronic diseases and conditions, health risk behaviors, and preventive health practices related to Steps community outcomes from noninstitutionalized community members aged ≥18 years. RESULTS: Prevalence estimates of chronic diseases and conditions and risk behaviors varied among Steps communities that reported data for 2006 and 2007. The proportion of the population that achieved Healthy People 2010 (HP 2010) objectives also varied among the communities. In 2006, the estimated prevalence of respondents aged ≥18 years being overweight or obese as calculated from self-reported weight and height ranged from 51.8% to 73.7%. The nationwide 2006 BRFSS median was 62.3%; a total of 20 communities exceeded this median. In 2007, the estimated prevalence being overweight or obese ranged from 50.5% to 77.2%. The nationwide 2007 BRFSS median was 63.0%; a total of 18 communities exceeded this median. In 2006, the estimated prevalence of diagnosed diabetes (excluding gestational diabetes) ranged from 3.7% to 19.7%. None of the communities achieved the HP 2010 objective of increasing to 91% the proportion of adults with diabetes who have at least an annual clinical foot examination. Six communities reached the HP 2010 objective of increasing to 76% the proportion of adults with diabetes who have an annual dilated eye examination; 20 communities reached the HP 2010 objective of increasing to 65% the proportion of adults who have a glycosylated hemoglobin measurement (A1c) at least once a year. In 2007, the estimated prevalence of diagnosed diabetes (excluding gestational diabetes) ranged from 4.4% to 17.9%. None of the communities achieved the HP 2010 objective of increasing to 91% the proportion of adults with diabetes who have at least an annual clinical foot examination, eight communities achieved the HP 2010 objective of increasing to 76% the proportion of adults with diabetes who have an annual dilated eye examination, and 16 communities achieved the HP 2010 objective of increasing to 65% the proportion of adults who have an A1c at least once a year. In 2006, the prevalence of reported asthma ranged from 6.5% to 18.9%. Among those who reported having asthma, the prevalence of having no symptoms of asthma during the preceding 30 days ranged from 11.5% to 29.5% for five communities with sufficient data for estimates. In 2007, the estimated prevalence of reported asthma ranged from 7.5% to 18.9%. Among those who reported having asthma, the prevalence of having no symptoms of asthma during the preceding 30 days ranged from 10.3% to 36.1% for 12 communities with sufficient data for estimates. In 2006, the prevalence of respondents who engaged in moderate physical activity for ≥30 minutes at least five times a week or who reported vigorous physical activity for ≥20 minutes at least three times a week ranged from 42.3% to 59.9%. The prevalence of consumption of fruits and vegetables at least five times/day ranged from 11.1% to 30.2%. In 2007, the prevalence of moderate or vigorous physical activity ranged from 40.6% to 69.8%; 25 communities reached the HP 2010 objective to increase the proportion of adults who engage in physical activity to 50%. The prevalence of consumption of fruits and vegetables ≥5 times/day ranged from 14.6% to 37.6%. In 2006, the estimated prevalence among respondents aged >18 years who reported having smoked >100 cigarettes in their lifetime and who were current smokers on every day or some days at the time of the survey ranged from 12.5% to 48.0%. Among smokers, the prevalence of having stopped smoking for ≥1 day because of trying to quit smoking during the previous 12 months ranged from 48.4% to 67.9% for 31 communities. No communities reached the HP 2010 target of increasing to 75% smoking cessation attempts by adult smokers. In 2007, the estimated prevalence of current smokers ranged from 11.2% to 33.7%. Two communities reached the HP 2010 objective to reduce the proportion of adults who smoke. Among smokers, the prevalence of having stopped smoking for ≥1 day because of trying to quit smoking during the preceding 12 months ranged from 50.8% to 69.6% for 26 communities. No communities reached the HP 2010 objective of increasing to 75% smoking cessation attempts by adult smokers. INTERPRETATION: The findings in this report indicate variations in health risk behaviors, chronic diseases and conditions, and use of preventive health screenings and health services among Steps communities. These findings underscore the continued need to evaluate prevention interventions at the community level and to design and implement policies to promote and encourage healthy behaviors. PUBLIC HEALTH ACTION: Steps BRFSS data monitored the prevalence of health behaviors, conditions, and use of preventive health services. CDC (at the national level), and Steps staff at state, local, and tribal levels can use BRFSS data to demonstrate accountability to stakeholders; monitor progress in meeting objectives; focus activities on policy, systems and environmental change strategies with the greatest promise of results; identify collaboration opportunities; and identify and disseminate successes and lessons learned.

The YMCA/Steps Community Collaboratives, 2004-2008.

Since the YMCA/Steps National Partnership began in 2004, the collaborative approach has built local synergy, linked content experts, and engaged national partners to concentrate on some of the most pressing health issues in the United States. Together, national and local partners used evidence-based public health programs to address risk factors such as poor nutrition, physical inactivity, and tobacco use. This article describes the YMCA/Steps National Partnership and focuses on the experiences and achievements of the YMCA/Steps Community Collaboratives, conducted with technical assistance from the National Association of Chronic Disease Directors between 2004 and 2008. We introduce some of the fundamental concepts underlying the partnership's success and share evaluation results.

A comprehensive worksite wellness program in Austin, Texas: partnership between Steps to a Healthier Austin and Capital Metropolitan Transportation Authority.

BACKGROUND: In 2003, Steps to a Healthier Austin was funded by the Centers for Disease Control and Prevention to implement chronic disease prevention and health promotion activities. We report Steps to a Healthier Austin's partnership with Health & Lifestyles Corporate Wellness, Inc (Health & Lifestyles), to provide a worksite wellness program for Capital Metropolitan Transportation Authority (Capital Metro), Austin's local transit authority. CONTEXT: Capital Metro employs 1,282 people. In 2003, Health & Lifestyles was hired to help promote healthier lifestyles, increase employee morale, and combat rising health care costs and absenteeism rates. METHODS: Health & Lifestyles provided consultations with wellness coaches and personal trainers, a 24-hour company fitness center, personalized health assessments, and preventive screenings. The program expanded to include healthier food options, cash incentives, health newsletters, workshops, dietary counseling, smoking cessation programs, and a second fitness center. CONSEQUENCES: Participants in the wellness program reported improvements in physical activity, healthy food consumption, weight loss, and blood pressure. Capital Metro's total health care costs increased by progressively smaller rates from 2003 to 2006 and then decreased from 2006 to 2007. Absenteeism has decreased by approximately 25% since the implementation of the program, and the overall return on the investment was calculated to be 2.43. INTERPRETATION: Since the implementation of the wellness program in 2003, Capital Metro has seen a reduction in costs associated with employee health care and absenteeism.

Youth risk behavior surveillance--selected Steps communities, United States, 2007.

PROBLEM: Priority health-risk behaviors, including tobacco use, unhealthy dietary behaviors, and physical inactivity often are established during childhood and adolescence, extend into adulthood, are interrelated, and are preventable. These behaviors contribute to chronic disease and other health conditions, including asthma. REPORTING PERIOD COVERED: January--May 2007. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors priority health-risk behaviors and the prevalence of obesity and asthma among youth and young adults. YRBSS includes a national school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education and health agencies. In 2007, as a component of YRBSS, communities participating in the Steps Cooperative Agreement Program (Steps Program) also conducted school-based surveys of students in grades 9--12 in their program intervention areas. These communities used a standard questionnaire that measured tobacco use, dietary behaviors, and physical activity and monitored the prevalence of obesity and asthma. This report summarizes results from surveys of students in 26 Steps communities that conducted surveys in 2007. RESULTS: Results from the 26 Steps communities indicated that a substantial proportion of adolescents engaged in health-risk behaviors that increased their likelihood of becoming obese. During 2007, across surveys, the percentage of high school students who had ever smoked at least one cigarette every day for 30 days ranged from 3.7% to 20.1% (median: 9.0%), the percentage who had eaten fruits and vegetables five or more times per day during the 7 days before the survey ranged from 13.9% to 23.9% (median: 17.9%), and the percentage who met recommended levels of physical activity ranged from 27.7% to 55.5% (median: 40.1%). Across surveys, the percentage of students who were obese ranged from 4.6% to 20.2% (median: 13.6%), and the percentage of students who had ever been told by a doctor or nurse that they had asthma ranged from 16.8% to 28.5% (median: 21.6%). INTERPRETATION: Although the prevalence of many health-risk behaviors and health conditions related to obesity and asthma varies across Steps communities, a substantial proportion of high school students engage in behaviors that place them at risk for chronic disease. PUBLIC HEALTH ACTION: Steps Program staff at the national, tribal, state, and local levels will use YRBSS data for decision making, program planning, and enhancing technical assistance to reduce tobacco use and exposure and to increase healthy eating and physical activity. These data will be used to help focus existing programs on activities that have shown the greatest promise of results, as well as identify populations of greatest need and opportunities for strategic collaboration to identify and disseminate lessons learned.

Prevalence of selected risk behaviors and chronic diseases--Behavioral Risk Factor Surveillance System (BRFSS), 39 steps communities, United States, 2005.

PROBLEM: Behavioral risk factors (e.g., tobacco use, poor diet, and physical inactivity) can lead to chronic diseases. In 2005, of the 10 leading causes of death in the United States, seven (heart disease, cancer, stroke, chronic lower respiratory diseases, diabetes, Alzheimer's disease, and kidney disease) were attributable to chronic disease. Chronic diseases also adversely affect the quality of life of an estimated 90 million persons in the United States, resulting in illness, disability, extended pain and suffering, and major limitations in daily living. REPORTING PERIOD COVERED: 2005. DESCRIPTION OF THE SYSTEM: CDC's Steps Program funds 40 selected U.S. communities to address six leading causes of death and disability and rising health-care costs in the United States: obesity, diabetes, asthma, physical inactivity, poor nutrition, and tobacco use. In 2005, a total of 39 Steps communities conducted a survey to collect adult health outcome data. The survey instrument was a modified version of the Behavioral Risk Factor Surveillance System (BRFSS) survey, a community-based, random-digit--dialing telephone survey with a multistage cluster design. The survey instrument collected information on health risk behaviors and preventive health practices among noninstitutionalized adults aged >/=18 years. RESULTS: Prevalence estimates of risk behaviors and chronic conditions varied among the 39 Steps communities that reported data for 2005. The proportion of the population that achieved Healthy People 2010 (HP 2010) objectives also varied among the communities. The estimated prevalence of obesity (defined as having a body mass index [BMI] of >/=30.0 kg/m(2) as calculated from self-reported weight and height) ranged from 15.6% to 44.0%. No communities reached the HP2010 objective of reducing the proportion of adults who are obese to 15.0%. The prevalence of diagnosed diabetes (excluding gestational diabetes) ranged from 4.3% to 16.6%. Eighteen communities achieved the HP2010 objective to increase the proportion of adults with diabetes who have at least an annual foot examination to 75.0%; five communities achieved the HP2010 objective to increase the proportion of adults with diabetes who have an annual dilated eye examination to 75.0%. The prevalence of reported asthma ranged from 7.0% to 17.6%. Among those who reported having asthma, the prevalence of having no symptoms of asthma during the preceding 30 days ranged from 15.4% to 40.3% for 10 communities with sufficient data for estimates. The prevalence of respondents who engaged in moderate physical activity for >/=30 minutes at least five times a week or who reported vigorous physical activity for >/=20 minutes at least three times a week ranged from 42.0% to 62.2%. The prevalence of consumption of fruits and vegetables at least five times a day ranged from 15.6% to 30.3%. The estimated prevalence among respondents aged >/=18 years who reported having smoked >/=100 cigarettes in their lifetime and who were current smokers on every day or some days at the time of the survey ranged from 11.0% to 39.7%. One community achieved the HP2010 objective to reduce the proportion of adults who smoke to 12.0%. Among smokers, the prevalence of having stopped smoking for >/=1 day as a result of trying to quit smoking during the previous 12 months ranged from 47.8% to 63.3% for 31 communities. No communities reached the HP2010 objective of increasing smoking cessation attempts by adult smokers to 75%. INTERPRETATION: The findings in this report indicate variations in health risk behaviors, chronic conditions, and use of preventive health screenings and health services. These findings underscore the continued need to evaluate intervention programs at the community level and to design and implement policies to reduce morbidity and mortality caused by chronic disease. PUBLIC HEALTH ACTION: Steps BRFSS data can be used to monitor the prevalence of specific health behaviors, diseases, conditions, and use of preventive health services. Steps Program staff at the national, state, local, and tribal levels can use BRFSS data to demonstrate accountability to stakeholders, monitor progress in meeting program objectives, focus programs on activities with the greatest promise of results, identify opportunities for strategic collaboration, and identify and disseminate successes and lessons learned.

Adolescent same-sex and both-sex romantic attractions and relationships: implications for smoking.

OBJECTIVES: We examined cross-sectional and longitudinal associations between smoking and romantic attractions and relationships. METHODS: We used data from the National Longitudinal Study of Adolescent Health to assess associations of smoking at Waves I and II with same-sex, both-sex, and opposite-sex romantic attractions or relationships as determined at Wave I. We used logistic regression to predict smoking at Wave II by sexual orientation. RESULTS: Both adolescent boys and adolescent girls with both-sex attractions or relationships were significantly more likely than those with opposite-sex attractions or relationships to be current smokers. Adolescent boys and girls with both-sex attractions or relationships who were nonsmokers at Wave I were more likely to be current smokers at Wave II than those with opposite-sex attractions or relationships. CONCLUSIONS: Our findings support previous research on smoking among youths who report same-sex or both-sex romantic attractions or relationships and demonstrate the increased risk bisexual youths have for smoking initiation and smoking prevalence. Tobacco use prevention programs targeting gay and bisexual youths are warranted, particularly among adolescent girls and boys who have had both-sex romantic attractions or relationships.

Youth tobacco surveillance--United States, 2001-2002.

PROBLEM/CONDITION: Cigarette smoking is the leading preventable cause of death in the United States, accounting for approximately 440,000 deaths each year. The prevalence of cigarette smoking nationwide among high school students (grades 9-12) increased during the 1990s, peaking during 1996-1997, and then declined. Approximately 80% of tobacco users initiate use before age 18 years. An estimated 6.4 million children aged <18 years who are living today will die prematurely as adults because they began to smoke cigarettes during adolescence. The annual health-related economic cost associated with tobacco use exceeds 167 billion dollars. Because of these health and economic consequences, CDC has recommended that states establish and maintain comprehensive tobacco-control programs to reduce tobacco use among youth. REPORTING PERIOD: This report covers data collected during January 2001-December 2002. DESCRIPTION OF THE SYSTEM: The National Youth Tobacco Survey (NYTS) and state youth tobacco surveys (YTS) were developed to provide states with data to support the design, implementation, and evaluation of comprehensive tobacco-control programs. NYTS is representative of middle and high school students in the 50 states and the District of Columbia. During spring 2002, a total of 26,149 students in 246 schools completed NYTS questionnaires. Weighted data for the YTS were achieved by 13 states in 2001 and by 20 states in 2002; state sample sizes varied (range: 982-38,934). This report summarizes data from the 2002 NYTS and the 2001 and 2002 YTS. RESULTS AND INTERPRETATION: Findings from the 2002 NYTS indicate that current use of any tobacco product ranged from 13.3% among middle school students to 28.2% among high school students. Cigarette smoking was the most prevalent form of tobacco use, with 9.8% of middle school students and 22.5% of high school students reporting that they currently smoke cigarettes. Cigar smoking was the second most prevalent form of tobacco use, with 6.0% of middle school students and 11.6% of high school students reporting that they currently smoke cigars. Among current cigarette smokers, 41.8% of middle school students and 52.0% of high school students reported that they usually smoke Marlboro cigarettes. Black middle school and high school students who smoke were more likely to smoke Newport cigarettes than any other brand (58.3% and 66.8%, respectively). Among middle school students aged <18 years, 75.9% were not asked to show proof of age when they bought or tried to buy cigarettes, and 63.4% were not refused purchase because of their age. Among high school students aged <18 years, 58.5% were not asked to show proof of age when they bought or tried to buy cigarettes, and 60.6% were not refused purchase because of their age. Nearly half (49.6%) of middle school students and 62.1% of high school students who smoke reported a desire to stop smoking cigarettes, with 55.4% of middle school students and 53.1% of high school students reported having made at least one cessation attempt during the 12 months preceding the survey. Among students who have never smoked cigarettes, 21.3% of middle school students and 22.9% of high school students were susceptible to initiating cigarette smoking in the next year. Exposure to secondhand smoke (i.e., environmental tobacco smoke) was high. During the week before the survey, 1) 88.3% of middle school students and 91.4% of high school students who currently smoke cigarettes and 47.1% of middle school students and 53.3% of high school students who have never smoked cigarettes were in the same room with someone who was smoking cigarettes; 2) 81.7% of middle school students and 83.7% of high school students who currently smoke cigarettes and 31.5% of middle school students and 29.1% of high school students who have never smoked cigarettes rode in a car with someone who was smoking cigarettes; and 3) 71.5% of middle school students and 57.5% of high school students who currently smoke cigarettes and 33.3% of middle school students and 29.9% of high school students who have never smoked cigarettes lived in a home in which someone else smoked cigarettes. Media and advertising influence was also noted, with 58.1% of middle school students and 54.9% of high school students who currently use tobacco and 11.0% of middle school students and 13.7% of high school students who have never used tobacco reporting that they would wear or use an item with a tobacco company name or logo on it. Although 84.6% of middle school students and 91.2% of high school students had seen or heard antismoking commercials on television or radio, 89.9% of middle school students and 91.3% of high school students also had seen actors using tobacco on television or in the movies. PUBLIC HEALTH ACTIONS: Health and education officials use YTS and NYTS data to plan, evaluate, and improve national and state programs to prevent and control youth tobacco use. States can use these data in presentations to their state legislators to demonstrate the need for funding comprehensive tobacco-control programs, including tobacco cessation and prevention programs for youth.

Covariates of current cigarette smoking among secondary school students in Budapest, Hungary, 1999.

To date, few studies have examined the relationship between health behavior risk factors and cigarette smoking in Hungary. From 1995 to 1999, the prevalence of current smoking increased from 35.9 to 46.0% among secondary students in Budapest, Hungary. The objective of the present study was to examine the association between smoking and other health behavior risk factors among secondary school students in Budapest. Surveys were administered during regular classes in 21 traditional and nine vocational/technical schools containing Grades 9-12; 2410 students aged 15-18 years were included in the analysis. Overall, 44.9% of males and 46.9% of females were current smokers. Smoking increased with age and was significantly higher among vocational/technical (60.2%) than traditional (43.1%) students. The likelihood of smoking was significantly higher among students who rarely or never used a seatbelt when riding in a car driven by someone else, currently used alcohol, had engaged in episodic heavy drinking, had had four or more sex partners during their lifetime or did not participate in vigorous physical activity. Health-risk behaviors are frequently interrelated. Findings suggest that programs designed to prevent smoking should consider related health-risk behaviors as part of a comprehensive program.

Smoking cessation counseling: training and practice among women pediatricians.

We examined characteristics associated with smoking cessation counseling among a national sample of 579 women pediatricians. Fifty-two percent of women pediatricians had received at least some training in cessation counseling and 41% counseled smoking patients at least once per year. Prevalence of counseling increased by amount of training; 20.7% of those with no training counseled at least once per year versus 62.0% of those with extensive training. Pediatricians 50-70 years of age were 1.8 times as likely as those 30-39 years of age to perform frequent counseling (p<0.01). Programs to promote smoking cessation training and counseling among pediatricians are needed.