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8 Closing Session Dr. Haskell moderated the closing session of the workshop. Modera- tors of the earlier sessions (Drs. Morrow, Dishman, Brubaker, Macera, Freedson, Nelson, and Heath) provided summaries of the information presented, focusing on the nature, level, and strength of the evidence. A group discussion followed, and then Dr. Haskell provided an overall summary. This chapter integrates presentations made during the closing session. It covers risk reduction for a broad range of health conditions and selected populations, risk–benefit considerations of physical activity, and issues raised during the meeting. It also provides a summary of the final group discussion. The chapter concludes with closing remarks made by Dr. Haskell and RADM Penelope Slade Royall. SUMMARY OF PLENARY SESSIONS Physical Activity and Risk Reduction Adults Much evidence was presented that physical activity reduces the risk of developing many health conditions. Dr. Morrow illustrated this point with a graph such as that shown in Figure 8-1—a graph in which the spe- cific risk could be any one of many adverse health conditions, including cardiovascular disease, type 2 diabetes, osteoporosis, and many other conditions. This prototype graph is characterized by a large decrease in risk when the physical activity level increases from sedentary to moder- ate, and a further but smaller decrease in risk when the physical activity 141

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142 PHYSICAL ACTIVITY WORKSHOP “Risk” 40 Higher 35 30 25 20 15 10 5 Lower 0 Low Moderate High Fitness level FIGURE 8-1 A representation of the typical relationship between physical ac- tivity or fitness level and risk. NOTE: This general relationship appears to be applicable to the risk of mortality, cardio- vascular disease, hypertension, stroke, metabolic disorders, type 2 diabetes mellitus, im- paired bone health, impaired mental health status, impaired cognitive ability, some types of cancer, and impaired joint health. The general relationship appears to hold for males, females, persons in different age groups, persons with disabilities, and persons of differ- ent racial/ethnic groups. SOURCE: Morrow (2006). level increases from moderate to active. Regardless of the morbidity, mortality, or population group (with few exceptions), the evidence shows that those who are more physically active, get more exercise, or are more fit have lower risk. All types of physical activity seem to reduce health risks, and the greater the amount of physical activity—the more fit a per- son is—the lower the health risks, and one’s quality of life is better. Dr. Haskell summarized the amount and strength of the evidence re- lating physical activity to selected outcomes for unspecified demographic groups as shown in Table 8-1. Strength refers to both quality of data and the magnitude of the association observed. For example, a large effect adds to the strength of the data from an observational study, which ordi- narily is viewed as of lower quality than a randomized controlled trial.

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143 CLOSING SESSION TABLE 8-1 Summary of the Amount and Strength of Available Data Relating Physical Activity to Selected Outcomes, Unspecified Demographic Groups Amounta Strengthb Outcome All-cause mortality 1 1 Major Diseases Coronary heart disease 1 1 Cardiovascular disease 1 1 Type 2 diabetes mellitus 1 1 Cancer: colon and breast 1 2 Other cancer sites 2 3 Musculoskeletal Muscle qualityc 1 1 Muscle mass/sarcopeniad 1 1 Bone health (osteoporosis) 2 1 Osteoarthritis of knee and hip 2 3 Mental and Neurological Conditions Depression 1 1 Anxiety 1 2 Sleep quality 2 1 Alzheimer’s disease 2 2 Chronic fatigue syndrome 2 2 Parkinson’s disease 3 3 Weight-Related Conditions Prevention of weight regain 2 1 Contribution to long-term weight loss 1 2 Metabolic syndrome 2 1 Prevention of unhealthy weight gain 2 2 NOTE: Ratings are approximate; they are not based on a systematic review of the evi- dence and do not represent a conclusion or consensus reached at this Institute of Medi- cine workshop. a 1 = considerable data; 2 = some data; 3 = limited data. b 1 = high; 2 = moderate; 3 = low. c Applies to aerobic and resistance activity. d Applies to resistance activity.

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144 PHYSICAL ACTIVITY WORKSHOP Dr. Haskell commented that, simply in terms of cardiovascular dis- ease and type 2 diabetes, the evidence on benefit from physical activity could be considered sufficient to justify new guidelines and that the evi- dence of benefit for a number of other conditions also is strong. Com- ments from other moderators highlighted type 2 diabetes, selected mental and neurological diseases, and weight-related conditions as conditions for which there is sufficient evidence of benefit. Type 2 diabetes Dr. Dishman noted that strong evidence from observa- tional studies and randomized controlled trials indicates that moderate to vigorous physical activity is associated with a reduced risk of developing type 2 diabetes, even among persons with impaired glucose tolerance, and that the effects usually are independent of weight loss. Moreover, some evidence indicates that physical activity and/or cardiorespiratory fitness favorably modifies cardiovascular events and mortality among persons with type 2 diabetes. Regular physical activity also favorably affects key features of the metabolic syndrome. Chronic effects of exer- cise include increased insulin sensitivity and responsiveness; improve- ments in other factors related to glucose use and storage, body fat, skeletal muscle, and lipemic control; and the reduction of comorbidities such as hypertension and systemic inflammation. Mental and neurological diseases Dr. Dishman summarized that there clearly is a sufficient amount and strength of evidence to justify a sys- tematic review of major depression, some anxiety and sleep disorders, self-esteem, selected features of cognitive function, and chronic pain (data not presented earlier due to lack of time). Evidence to judge dose– response is quite limited and mixed and will require systematic review. Dr. Dishman supplemented earlier presentations by pointing out the availability of a large body of evidence on mechanisms for cognitive and emotional responses to physical activity. Examples include the summary on the neurobiology of exercise by Dishman et al. (2006), studies of ex- ercise and neural plasticity (Anderson et al., 1996; Ang et al., 2003; Black et al., 1990; Carro et al., 2001; Cotman and Berchtold, 2002; Stummer et al., 1994; van Praag et al., 1999, 2005), and studies on the brain–behavior effects of physical activity (Chambliss et al., 2004; Dishman, 1997, Dishman et al., 1997; Greenwood et al., 2003; Russo- Neustadt et al., 2001; van Hoomissen et al., 2003; 2004; Yoo et al., 2000). However, the evidence is almost entirely from animal studies. This is a highly promising emerging area of study.

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145 CLOSING SESSION Weight-related conditions Dr. Brubaker noted that the increase in obe- sity rates has been accompanied by an increase in so-called unsuccessful attempts at weight loss. Nonetheless, evidence appears to be sufficient to support roles of physical activity for weight loss, the maintenance of weight loss, and the prevention of weight gain. Notably, a clinically sig- nificant weight loss of approximately 5 percent of body weight generally represents less weight loss than would be calculated based on energy balance models and much less than the client expects. Dr. Brubaker ad- dressed the difference in the amount of extra energy an individual may need to expend for different purposes: 700 to 1,000 kcal per week to pre- vent inappropriate weight gain versus 500 or 700 kcal per day (more than 2,000 kcal per week) to achieve weight loss and/or maintenance of weight loss. He pointed out that these estimates of energy expenditure may need careful consideration in the development of realistic guide- lines. Men appear to respond to physical activity interventions with more weight loss than do women. The mechanisms underlying this gender dif- ference are unclear and warrant further investigation. Although not all people respond to physical activity with weight loss, physical activity produces a variety of other health benefits (see above) independent of weight loss. Children and Youth Table 8-2 summarizes the information about evidence relating physi- cal activity to outcomes for youth. Very little evidence is available about dose–response. A summary of comments from Dr. Freesdon follows. Children and youth are basically healthy. Regular physical activity results in some improvements in the aerobic fitness and strength of healthy children and adolescents, but improvements in blood pressure and metabolic indicators are observed only in children with compro- mised health. Weight-bearing exercise has beneficial effects on bone, especially in prepubertal children. The need for different types of physi- cal activity varies with age. Physical inactivity and sedentary behaviors are highly prevalent and merit further attention.

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146 PHYSICAL ACTIVITY WORKSHOP TABLE 8-2 Summary of the Amount and Strength of the Available Data Relating Physical Activity to Selected Outcomes for Children and Youth Amounta Strengthb Outcome Fitness: strength and endurance 1 1 Skeletal health 2 2 Blood pressure in hypertensive youth 2 2 Weight loss in overweight/obesity 2 2 Metabolic syndrome factors 3 2 High-density lipoprotein cholesterol 2 3 Behavioral outcomes 2 3 Academic performance 2 3 Type 2 diabetes 4 NA NOTE: Ratings are approximate. They are not based on a comprehensive review of the evidence and do not represent a conclusion or consensus reached at this Institute of Medicine workshop. a 1 = considerable data; 2 = some data; 3 = limited data; 4 = very limited data. b 1 = high; 2 = moderate; 3 = low. NA = not applicable. Pregnant Women Physical activity appears to benefit women both during pregnancy and the postpartum period. Regular physical activity may lower one’s risk for gestational diabetes. Older Persons Considerable evidence points to the benefits of physical activity among persons ages 65 years and older, as shown in Table 8-3. High- lights of the comments made by Dr. Nelson appear below. Chronic illness Most chronic illnesses and other conditions place the greatest burden on older adults. The most notable of these are heart dis- ease, type 2 diabetes, osteoporosis, specific cancers, cognitive impair- ment, depression, and sleep problems. Evidence indicates that physical activity reduces the risk of developing many of these conditions and helps control signs and symptoms once a condition is established.

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147 CLOSING SESSION TABLE 8-3 Summary of the Amount and Strength of the Available Data Relating Physical Activity to Selected Outcomes, Persons Age 65 Years and Older Amounta Strengthb Outcome Coronary heart disease and cardiovascular disease 1 1 Diabetes mellitus 1 1 Osteoporosis 1 1 Sarcopenia (muscle wasting) 1 1 Fitness: endurance, strength, balance 1 1 Activities of daily living 1 1 Sleep quality 2 1 Cognitive function 1 2 Fall prevention 2 2 2 3 Disability NOTE: Ratings are approximate. They are not based on a comprehensive review of the evidence and do not represent a conclusion or consensus reached at this Institute of Medicine workshop. Wide variations in older persons’ ability to perform and in their response to activity call for caution in developing physical activity recommendations. a 1 = considerable data; 2 = some data; 3 = limited data; 4 = very limited data. b 1 = high; 2 = moderate; 3 = low. Physiological markers A large body of literature addresses physiologi- cal markers. It includes strong evidence both from observational and in- tervention studies that physical activity improves muscle mass and strength, bone, balance, and functional performance. Aerobic capacity declines in older adults; however, physically active older adults have higher oxygen capacity (VO2) than sedentary peers and some have higher VO2 than sedentary younger persons. A wide variety of physical activi- ties improve muscle mass and strength, bone, balance, and functional performance. Falls prevention A moderate amount of moderate to strong evidence addresses physical activity and the prevention of falls. Targeted physical activity interventions—especially those with a balance component— reduce falls in community-dwelling frail elders. Disability Physical activity influences all segments of the path to disabil- ity among older persons. High body fat content and poor quality of mus- cle increase the risk of disability. Well-designed randomized controlled trials are needed to better establish how various exercise regimens affect

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148 PHYSICAL ACTIVITY WORKSHOP the incidence of disability and hospitalization in older persons at high risk of becoming frail. Special considerations Consideration of the evidence relating to physi- cal activity in older adults merits attention to their great heterogeneity (many are in good health), body weight that is in flux, effects of intercur- rent illness, and specific medical conditions. Persons with Disabilities or Selected Chronic Conditions According to Dr. Heath, strong evidence documents that individuals with disabilities have the capacity to adapt to increased levels of physical activity and that increased levels of physical activity can produce the fol- lowing effects: • Improved cardiorespiratory fitness • Increases in muscular strength and endurance • Improved metabolic health (particularly carbohydrate and lipid metabolism) • Improved psychosocial status • Improved health-related quality of life Among persons with coronary heart disease, physical activity-based car- diac rehabilitation reduces all-cause mortality and cardiac mortality. A moderate amount of evidence documents that increases in physical activ- ity lead to beneficial changes in body composition, improved physical functioning, decreased fatigue, improved cardiovascular disease risk pro- file, and improved ventilation and decreased dyspnea (shortness of breath) among persons with heart failure and chronic obstructive pulmo- nary disease. Insufficient evidence is available to determine whether or not in- creases in physical activity influence treatment decisions, improve se- lected biomarkers, lead to lower recurrence rates and longer survival among cancer survivors, prevent and/or reduce the occurrence of secon- dary conditions, alter underlying disease processes, decrease disability, or improve function.

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149 CLOSING SESSION Physical Activity and Risk—Maximizing Benefits According to Dr. Macera, a large body of literature documents the risk of physical activity-related injuries. Strong evidence indicates that it is possible to reduce injury risks that otherwise may deter individuals from being active. A suggested approach in developing guidelines is to consider evidence of how to maximize the benefits of physical activity while minimizing the risks. Strong evidence is available to support the following points regard- ing physical activity and risk: Injury Risk • Any movement increases the risk for injury. • Activities such as running or vigorous sports are associated with more injuries than are such activities as walking. • Recreational and competitive runners have a high prevalence of injury (average about 45 percent per year). • Higher amounts of past physical activity protect against current injury. • Higher levels of physical fitness protect against injury. • Active individuals may have lower occurrence of overall injury. • A sedentary lifestyle is associated with an elevated risk of injury when actually engaging in physical activity. • In military settings with a standard exercise training protocol, women have higher injury rates than men; this effect diminishes when adjusted for fitness. • Extremes of flexibility (too loose or too tight) are associated with injury risk among military subjects. Cardiovascular Risk • Sudden cardiac arrest is more common during exercise than dur- ing sedentary activities. • The risk of cardiovascular adverse effects goes down with habit- ual activity.

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150 PHYSICAL ACTIVITY WORKSHOP • The relative risk of sudden death during vigorous exercise is lowest among people who exercise regularly (e.g., ≥ 5 times per week). Weaker evidence suggests that smoking may be associated with an elevated risk of injury and that very high or low body mass index (BMI) may be associated with increased risk. In general, the database of studies of physical activity and risk is rich, including many diverse settings and populations. Much of the evi- dence comes from military studies with prescribed training schedules and standard injury assessment procedures. Among the weaknesses of the evidence are a lack of a common injury definition, small sample sizes, and a limited range of ages of subjects. More information is needed on specific injury risks associated with special populations, long-term ef- fects of acute as well as overuse injuries, and effects of excessive physi- cal activity on eating disorders and joint problems In summary, a strong body of evidence about physical activity- related injuries and sudden cardiac events can be evaluated as a compo- nent of a process to develop physical activity guidelines. Most modifi- able risk factors for injury are related to frequency, intensity, duration, and type of activity. The injury experience of youth, older adults, and those with disabilities merits special attention. Issues Raised During the Workshop Over the course of the workshop, several issues were raised that war- rant further attention. Among these issues were those relating to improv- ing measurement (including the use of more objective measures of physical activity), consideration of both acute and chronic effects of physical activity, the scope and role of biomarkers in assessing benefit, exercise as medicine, message confusion, validity, and dose–response. According to Dr. Morrow, it can be useful to view physical activity as a medicine—one that has preventive, therapeutic, and treatment char- acteristics. Physical activity can help people stay healthy, and it can help people with many types of health problems become healthier. With regard to message confusion, the following words may have different meanings to different people: light, moderate, brisk, heavy, vig- orous, exercise, physical activity, typical, most, and average.

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151 CLOSING SESSION Dr. Morrow pointed out that the evidence on benefits of physical ac- tivity appears to have external validity because it generalizes to mortality and to a wide variety of morbidities, different populations, and activity styles. Internal validity is strongly suggested by the convergence of find- ings from different types of studies. When examining dose–response data, consideration may be given to the duration of the physical activity bout, the intensity and frequency of the bouts, the number of kilocalories used, and/or the total volume of exercise. Several participants suggested giving consideration to the least amount of physical activity that will produce benefit. DISCUSSION Before closing the session, moderator William Haskell invited atten- dees to share new information about outcomes already discussed as well as new outcomes that they wanted to place on the record. The statements made should not be interpreted as representing recommendations or the consensus of the workshop. Physical Activity in Diverse Racial and Ethnic Groups Several examples were given of comparable results in studies that involved two or more racial/ethnic groups. Such studies include the Dia- betes Prevention Program (DPP Research Group, 2002), and the re- sponse of bone to an exercise intervention (MacKelvie et al., 2002). Health Benefits of Physical Activity for Children and Adolescents Preschool children, in particular, are an understudied group. The terms physical activity and fitness are not interchangeable in children and youth in the way they may be used for adults. Work by Dr. Catrine Tudor-Locke et al. (2006) and colleagues (Flohr et al., 2006) address the correspondence of a recommended number of steps per day for children and adolescents with the guideline to obtain 60 minutes of physical activ- ity daily.

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152 PHYSICAL ACTIVITY WORKSHOP Evidence Related to Additional Health Conditions A large bibliography that includes references on physical activity and pain soon will be available through the American Pain Society. The oc- currence of fibromyalgia appears to be increasing and merits attention. Benefits of Specific Types of Physical Activity Considerable discussion occurred in response to a question about evidence to support the development of guidelines that address specific types of physical activity. For example, what health-related conditions are likely to be most affected by resistance training, and what is the strength of the evidence? Useful sources of information include work by the following: • Cussler et al. (2003, 2005) and Lohman et al. (1995) regarding strength training and bone • Sigal (2004) regarding a trial of aerobic and resistance exercise related to diabetes • FitzGerald (2004) regarding strength training and all-cause mor- tality • Meyer (2006) regarding strength training in patients with chronic congestive heart failure • Singh et al. (2005) regarding strength training and depression in older persons • Castaneda et al. (2002) regarding strength training in Hispanics with diabetes • Faigenbaum et al. (2001) and colleagues (Hoffman et al., 2005) regarding children and youth Balance training and multimodal interventions—not just resistance train- ing—should be considered. However, relatively little evidence appears to be available that compares effects of different types of exercise. Interrelationships of Physical Activity and Nutrition Emphasis was placed on considering diet as well as physical activity with regard to weight-related benefits. A meta-analysis conducted by

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153 CLOSING SESSION Miller and colleagues (1997) and the report by Saris et al. (2003) from the International Obesity Taskforce provide pertinent information on the effects of physical activity on weight management. Physical activity and nutrition interact in many other conditions as well. Examples include the acquisition of lean body mass, diabetes mellitus, bone health, and meta- bolic syndrome. Strategy for Interpreting the Scientific Evidence Dr. Pate advised the application of a conservative strategy in inter- preting the literature, and the value of this approach was reinforced by Dr. Haskell. There is great variability in the strength of the evidence on physical activity in relation to benefit and risk. The strong evidence that has accumulated since prior efforts at guidelines development for three or four of the major chronic disease conditions in adults can serve as a basis for further development of such evidence-informed guidelines. Several persons pointed out the importance of developing clear evidence- based messages. CONCLUDING REMARKS Overall Summary Presenter: William Haskell With the substantial decrease in the amount of daily activity required for living among the U.S. population, physical inactivity has become a major public health problem. The problem continues to grow. Nonethe- less, the United States currently lacks up-to-date, comprehensive physi- cal activity guidelines for promoting health. Lack of such guidelines is a deterrent to the implementation of an effective national physical activity plan. Scientific data collected over the past five or six decades strongly support numerous health benefits of a physically active lifestyle through- out the life span. The nature of the evidence that can be accumulated re- garding behaviors—in this case, physical activity behaviors—makes it essential to take into account the strength of a variety of types of evi- dence (see Figure 1-1 in Chapter 1). The dose–response data that were presented indicate that the development of new or comprehensive guide-

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154 PHYSICAL ACTIVITY WORKSHOP lines based on such new evidence would be feasible. The evidence pre- sented at the workshop clearly indicates that the large volume of high- quality data—much of it recent—could inform new physical activity guidelines. Next Steps Presenter: RADM Penelope Slade-Royall On behalf of the U.S. Department of Health and Human Services (DHHS), RADM Royall expressed thanks to all who took part in the workshop and provided outstanding information for the department’s consideration. She and her colleagues would consider the evidence pre- sented at this workshop and make recommendations to the Secretary of DHHS. Collaborators include Melissa Johnson from the President's Council on Physical Fitness and Sports, CAPT Richard Troiano from the Office of Disease Prevention and Health Promotion of the Office of Pub- lic Health and Science, and Harold W. (Bill) Kohl III from the Centers for Disease Control and Prevention. A decision about initiating the proc- ess of developing physical activities guidelines is expected to be released soon. REFERENCES Anderson BJ, Alcantara AA, Greenough WT. 1996. Motor-skill learning: Changes in synaptic organization of the rat cerebellar cortex. Neurobiol Learn Mem 66(2):221–229. Ang ET, Wong PT, Moochhala S, Ng YK. 2003. Neuroprotection associated with running: Is it a result of increased endogenous neurotrophic factors? Neuroscience 118(2):335–345. Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT. 1990. Learn- ing causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci USA 87(14):5568–5572. Carro E, Trejo JL, Busiguina S, Torres-Aleman I. 2001. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 21(15):5678–5684. Castaneda C, Layne J, Munoz-Orians L, Gordon P, Walsmith J, Foldvari M, Roubenoff R, Tucker K, Nelson M. 2002. High-intensity progressive resis- tance exercise training in Hispanic older adults with type 2 diabetes: A ran- domized controlled trial. Diabetes Care 25(12):2335–2341.

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155 CLOSING SESSION Chambliss HO, Van Hoomissen JD, Holmes PV, Bunnell BN, Dishman RK. 2004. Effects of chronic activity wheel running and imipramine on masculine copulatory behavior after olfactory bulbectomy. Physiol Behav 82(4): 593–600. Cotman CW, Berchtold NC. 2002. Exercise: A behavioral intervention to en- hance brain health and plasticity. Trends Neurosci 25(6):295–301. Cussler EC, Lohman TG, Going SB, Houtkooper LB, Metcalfe LL, Flint- Wagner HG, Harris RB, Teixeira PJ. 2003. Weight lifted in strength training predicts bone change in postmenopausal women. Med Sci Sports Exerc 35(1):10–17. Cussler EC, Going SB, Houtkooper LB, Stanford VA, Blew RM, Flint-Wagner HG, Metcalfe LL, Choi JE, Lohman TG. 2005. Exercise frequency and cal- cium intake predict 4-year bone changes in postmenopausal women. Osteopo- ros Int 16(12):2129–2141 Dishman RK. 1997. Brain monoamines, exercise, and behavioral stress: Animal models. Med Sci Sports Exerc 29(1):63–74. Dishman RK, Renner KJ, Youngstedt SD, Reigle TG, Bunnell BN, Burke KA, Yoo HS, Mougey EH, Meyerhoff JL. 1997. Activity wheel running reduces escape latency and alters brain monoamine levels after footshock. Brain Res Bull 42(5):399–406. Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, Gandevia SC, Gomez-Pinilla F, Greenwood BN, Hillman CH, Kramer AF, Levin BE, Moran TH, Russo-Neustadt AA, Salamone JD, Van Hoomis- sen JD, Wade CE, York DA, Zigmond MJ. 2006. Neurobiology of exercise. Obesity (Silver Spring) 14(3):345–356. DPP (Diabetes Prevention Program) Research Group. 2002. The Diabetes Pre- vention Program (DPP): Description of lifestyle intervention. Diabetes Care 25(12):2165–2171. Faigenbaum AD, Loud RL, O'Connell J, Glover S, O'Connell J, Westcott WL. 2001. Effects of different resistance training protocols on upper-body strength and endurance development in children. J Strength Cond Res 15(4):459–465. FitzGerald SJ, Barlow CE, Kampert JB, Morrow JR Jr, Jackson AW, Blair SN. 2004. Muscular fitness and all-cause mortality: Prospective observations. J Phys Activ Health 1:7–18. Flohr JA, Todd MK, Tudor-Locke C. 2006. Pedometer-assessed physical activ- ity in young adolescents. Res Q Exerc Sport 77(3):309–315. Greenwood BN, Foley TE, Day HE, Campisi J, Hammack SH, Campeau S, Maier SF, Fleshner M. 2003. Freewheel running prevents learned helpless- ness/behavioral depression: Role of dorsal raphe serotonergic neurons. J Neu- rosci 23(7):2889–2898. Hoffman JR, Kang J, Faigenbaum AD, Ratamess NA. 2005. Recreational sports participation is associated with enhanced physical fitness in children. Res Sports Med 13(2):149–161.

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156 PHYSICAL ACTIVITY WORKSHOP Lohman T, Going S, Pamenter R, Hall M, Boyden T, Houtkooper L, Ritenbaugh C, Bare L, Hill A, Aickin M. 1995. Effects of resistance training on regional and total bone mineral density in premenopausal women: A randomized pro- spective study. J Bone Miner Res 10(7):1015–1024. MacKelvie KJ, McKay HA, Petit MA, Moran O, Khan KM. 2002. Bone mineral response to a 7-month randomized controlled, school-based jumping interven- tion in 121 prepubertal boys: Associations with ethnicity and body mass in- dex. J Bone Miner Res 17(5):834–844. Meyer K. 2006. Resistance exercise in chronic heart failure—Landmark studies and implications for practice. Clin Invest Med 29(3):166–169. Miller WC, Koceja DM, Hamilton EJ. 1997. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise inter- vention. Int J Obes Relat Metab Disord 21(10):941–947. Morrow J. 2006. Physical activity, health promotion, and chronic disease pre- vention. Presentation at the Institute of Medicine Workshop on the Adequacy of Evidence for Physical Activity Guidelines Development. Washington, DC. October 23. Russo-Neustadt A, Ha T, Ramirez R, Kesslak JP. 2001. Physical activity- antidepressant treatment combination: Impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res 120(1):87–95. Saris WH, Blair SN, van Baak MA, Eaton SB, Davies PS, Di Pietro L, Fogel- holm M, Rissanen A, Schoeller D, Swinburn B, Tremblay A, Westerterp KR, Wyatt H. 2003. How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stock Conference and consensus statement. Obes Res 4(2):101–114. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. 2004. Physical ac- tivity/exercise and type 2 diabetes. Diabetes Care 27(10):2518–2539. Singh NA, Stavrinos TM, Scarbek Y, Galambos G, Liber C, Fiatarone-Singh MA. 2005. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. J Gerontol A Biol Sci Med Sci 60(6):768–776. Stummer W, Weber K, Tranmer B, Baethmann A, Kempski O. 1994. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ische- mia. Stroke 25(9):1862–1869. Tudor-Locke C, Lee SM, Morgan CF, Beighle A, Pangrazi RP. 2006. Children's pedometer-determined physical activity during the segmented school day. Med Sci Sports Exerc 38(10):1732–1738. Van Hoomissen JD, Chambliss HO, Holmes PV, Dishman RK. 2003. Effects of chronic exercise and imipramine on mRNA for BDNF after olfactory bulbec- tomy in rat. Brain Res 974(1-2):228–235. Van Hoomissen JD, Holmes PV, Zellner AS, Poudevigne A, Dishman RK. 2004. Effects of beta-adrenoreceptor blockade during chronic exercise on con- textual fear conditioning and mRNA for galanin and brain-derived neurotro- phic factor. Behav Neurosci 118(6):1378–1390.

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157 CLOSING SESSION van Praag H, Christie BR, Sejnowski TJ, Gage FH. 1999. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96(23):13427–13431. van Praag H, Shubert T, Zhao C, Gage FH. 2005. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25(38):8680–8685. Yoo HS, Tackett RL, Bunnell BN, Crabbe JB, Dishman RK. 2000. Antidepres- sant-like effects of physical activity vs. imipramine: Neonatal clomipramine model. Psychobiology 28(4):540–549.

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