Alan Flint

Body-mass index and mortality among 1.46 million white adults.

BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

AC133-2, a Novel Isoform of Human AC133 Stem Cell Antigen

Human AC133 antigen, also called CD133, was recently identified as a hematopoietic stem cell marker. However, the molecular structure and function of this protein has remained unclear. Here we cloned and identified a novel isoform of AC133, which we named AC133-2. In comparison to the reported AC133 cDNA, which is referred to herein as AC133-1, a small exon of 27 nucleotides is deleted in AC133-2 by alternative mRNA splicing. Similar to the previously characterized AC133 antigen, recombinant AC133-2 expressed in 293 cells was glycosylated and transported to plasma membrane. AC133-2 mRNA was found predominant in a variety of human fetal tissue, adult tissues, and several carcinomas. In contrast, AC133-1 mRNA was more prominent in fetal brain and adult skeletal muscle but was not detected in fetal liver and kidney, adult pancreas, kidney, and placenta, suggesting different roles for the two isoforms in fetal development and mature organ homeostasis. Here, we demonstrate that AC133-2 is the isoform expressed on hematopoietic stem cells derived from fetal liver, bone marrow, and peripheral blood. The results indicate that AC133-2, not AC133-1, has been the cell surface antigen recognized by anti-AC133 monoclonal antibodies that are used for isolation of hematopoietic stem cells. To further investigate its expression in other stem cell populations, we found that AC133-2 co-expressed with β1 integrin in the basal layer of human neonatal epidermis. AC133-2+/β1 integrin+ cells proliferated and differentiated in culture, which coincided with a loss of AC133-2 and gain in a terminal differentiation marker involucrin. Taken together, these results suggest that AC133-2 is expressed in multiple stem cell niches and may provide a means to isolate specific stem cell subpopulations from human tissues.

Prospective Study of Breakfast Eating and Incident Coronary Heart Disease in a Cohort of Male US Health Professionals

Background— Among adults, skipping meals is associated with excess body weight, hypertension, insulin resistance, and elevated fasting lipid concentrations. However, it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease (CHD) risk. The objective of this study was to prospectively examine eating habits and risk of CHD. Methods and Results— Eating habits, including breakfast eating, were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer. During 16 years of follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for CHD, adjusted for demographic, diet, lifestyle, and other CHD risk factors. Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06–1.53). Compared with men who did not eat late at night, those who ate late at night had a 55% higher CHD risk (relative risk, 1.55; 95% confidence interval, 1.05–2.29). These associations were mediated by body mass index, hypertension, hypercholesterolemia, and diabetes mellitus. No association was observed between eating frequency (times per day) and risk of CHD. Conclusions— Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals.

Whole grains and incident hypertension in men

BACKGROUND Prospective data on the relation between whole grain intake and incident hypertension in men are limited, and no previous studies have quantitatively estimated total grams of whole grains in relation to risk of hypertension. OBJECTIVE The purpose of this study was to estimate the association of whole-grain intake (g/d) and risk of incident hypertension in a large prospective cohort of men. DESIGN The Health Professionals Follow-Up Study is a prospective cohort consisting of 51,529 male health professionals ranging in age from 40 to 75 y at enrollment in 1986. Baseline and updated measurement of whole-grain intake as well as important covariates were measured, and 31,684 participants without known hypertension, cancer, stroke, or coronary heart disease were followed prospectively for 18 y through 2004 for onset of hypertension. RESULTS A total of 9227 cases of incident hypertension were reported over the 18 y of follow-up. In multivariate-adjusted analyses, whole-grain intake was inversely associated with risk of hypertension, with a relative risk (RR) of 0.81 (95% CI: 0.75-0.87) in the highest compared with the lowest quintile (P for trend < 0.0001). In the multivariate model, total bran was inversely associated with hypertension, with a relative risk (RR) of 0.85 (95% CI: 0.78, 0.92) in the highest compared with the lowest quintile (P for trend: 0.002). CONCLUSIONS In summary, we found an independent inverse association between intake of whole grains and incident hypertension in men. Bran may play an important role in this association. These findings have implications for future dietary guidelines and prevention of hypertension.

Skeletal muscle engraftment potential of adult mouse skin side population cells

Adult bone marrow and skeletal muscle have been shown to contain a subpopulation of cells, called side population (SP) cells, that can be isolated with the fluorescence-activated cell sorter. We used a similar method to identify SP cells in the skin of adult mice. These cells express surface markers similar to SP cells isolated from skeletal muscle, but differ from bone marrow SP cells and do not express hematopoietic markers. When transplanted into nonirradiated mdx mice, nuclei from donor skin SP cells are found within myofibers that express dystrophin. Thus, adult skin SP cells can engraft in dystrophic skeletal muscle even in the absence of total body irradiation.

Food-addiction scale measurement in 2 cohorts of middle-aged and older women

BACKGROUND Excess weight is a major threat to public health. An addiction-like tendency toward certain foods may contribute to overeating. OBJECTIVE We aimed to describe the prevalence and associated characteristics in relation to a food-addiction scale in middle-aged and older women. DESIGN We examined the prevalence and associated characteristics of a food-addiction scale measure in a cross-sectional analysis of 134,175 women participating in 2 ongoing prospective cohort studies of US nurses. RESULTS Overall, 7839 (5.8%) of the women surveyed met the criteria for food addiction measured by using the modified Yale Food Addiction Scale. The prevalence of food addiction was 8.4% in the younger cohort of women aged 45-64 y and 2.7% in the older cohort of women aged 62-88 y. In the multivariate model, body mass index (BMI; in kg/m²) ≥ 35.0 (compared with 18.5-22.9) was associated with food addiction, a prevalence ratio (PR) of 15.83 (95% CI: 12.58, 19.91) in the younger cohort of women, and a PR of 18.41 (95% CI: 11.63, 29.14) in the older cohort of women. Several other demographic characteristics and other factors were associated with the food-addiction measure in both cohorts of women. CONCLUSIONS To our knowledge, for the first time in a large, US-based population of women, we documented the prevalence of food addiction by using a novel measurement scale in middle-aged and older women. The results may provide insight into the strong association between behavioral attributes of food consumption and the development of obesity.

Muscle engraftment of myogenic progenitor cells following intraarterial transplantation.

Cell‐based therapy continues to be a promising avenue for the treatment of Duchenne muscular dystrophy (DMD), an X‐linked skeletal muscle–wasting disease. Recently, we demonstrated that freshly isolated myogenic progenitors contained within the adult skeletal muscle side population (SP) can engraft into dystrophic fibers of nonirradiated mdx5cv mice after intravenous transplantation. Engraftment rates, however, have not been therapeutically significant, achieving at most 1% of skeletal muscle myofibers expressing protein from donor‐derived nuclei. To enhance the engraftment of transplanted myogenic progenitors, an intraarterial delivery method was adapted from a previously described procedure. Cultured, lentivirus‐transduced skeletal muscle SP cells, derived from mdx5cv mice, were transplanted into the femoral artery of noninjured mdx5cv mice. Based on the expression of microdystrophin or green fluorescent protein (GFP) transgenes in host muscle, sections of the recipient muscles exhibited 5%–8% of skeletal muscle fibers expressing donor‐derived transgenes. Further, donor muscle SP cells, which did not express any myogenic markers prior to transplant, expressed the satellite cell transcription factor, Pax7, and the muscle‐specific intermediate filament, desmin, after extravasation into host muscle. The expression of these muscle‐specific markers indicates that progenitors within the side population can differentiate along the myogenic lineage after intraarterial transplantation and extravasation into host muscle. Given that femoral artery catheterization is a common, safe clinical procedure and that the transplantation of cultured adult muscle progenitor cells has proven to be safe in mice, our data may represent a step toward the improvement of cell‐based therapies for DMD and other myogenic disorders. Muscle Nerve, 2006

Effect of a pediatric practice-based smoking prevention and cessation intervention for adolescents: a randomized, controlled trial

OBJECTIVE. The purpose of this work was to determine whether a pediatric practice-based smoking prevention and cessation intervention increases abstinence rates among adolescents. METHODS. Eight pediatric primary care clinics were randomly assigned to either intervention or usual care control condition. The provider- and peer-delivered intervention tested was based on the 5A model recommended by the US Public Health Service clinical practice guidelines and the American Academy of Pediatrics and consisted of brief counseling by the pediatric provider followed by 1 visit and 4 telephone calls by older peer counselors aged 21 to 25 years. A consecutive sample of patients aged 13 to 17 years scheduled for an office visit was eligible regardless of smoking status. Of 2711 patients who agreed to participate, 2709 completed baseline assessments, and 2700 (99.6%) and 2690 (99.2%) completed 6- and 12-month assessments, respectively. RESULTS. Compared with the usual care condition, nonsmokers who received the provider- and peer-delivered intervention were significantly more likely to self-report having remained abstinent at 6-month and 12-month follow-up; smokers who received the provider- and peer-delivered intervention were more likely to report having quit at the 6-month but not the 12-month follow-up. A number of adolescent characteristics (eg, age, peer smoking, tobacco dependence, and susceptibility) were found to be predictive of abstinence at follow-up. CONCLUSIONS. A pediatric practice-based intervention delivered by pediatric providers and older peer counselors proved feasible and effective in discouraging the initiation of smoking among nonsmoking adolescents for 1 year and in increasing abstinence rates among smokers for 6 months.

Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men

PURPOSE Although studies have shown health benefits for moderate-intensity physical activity, there is limited evidence to support beneficial effects for high amounts of vigorous activity among middle-age and older men. The objective of this study was to examine the relationship between vigorous-intensity physical activity, compared with moderate-intensity activity, and risk of major chronic disease in men. METHODS We prospectively examined the associations between vigorous- and moderate-intensity physical activity and risk of major chronic disease among 44,551 men age 40-75 yr in 1986. Leisure-time physical activity was assessed biennially by questionnaire. During 22 yr of follow-up, we documented 14,162 incident cases of major chronic disease, including 4769 cardiovascular events, 6449 cancer events, and 2944 deaths from other causes. RESULTS The HR of major chronic disease comparing ≥ 21 to 0 MET.h.wk(-1) of exercise was 0.86 (95% confidence interval (CI), 0.81-0.91) for vigorous-intensity activity and 0.85 (95% CI, 0.80-0.90) for moderate activity. For cardiovascular disease (CVD), the corresponding HRs were 0.78 (95% CI, 0.70-0.86) and 0.80 (95% CI, 0.72-0.88), respectively. When examined separately, running, tennis, and brisk walking were inversely associated with CVD risk. Furthermore, more vigorous activity was associated with lower disease risk; the HR comparing >70 to 0 MET.h.wk(-1) of vigorous-intensity exercise was 0.79 (95% CI, 0.68-0.92; P < 0.0001 for trend) for major chronic disease and 0.73 (95% CI, 0.56-0.96; P < 0.0001 for trend) for CVD. CONCLUSIONS Vigorous- and moderate-intensity physical activities were associated with lower risk of major chronic disease and CVD. Increasing amounts of vigorous activity remained inversely associated with disease risk, even among men in the highest categories of exercise.

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men

Background: Although increased fruit intake reduces cardiovascular disease (CVD) risk, which fruits are most beneficial and what key constituents are responsible are unclear. Habitual intakes of flavonoids, specifically anthocyanins and flavanones, in which >90% of habitual intake is derived from fruit, are associated with decreased CVD risk in women, but associations in men are largely unknown. Objective: We examined the relation between habitual anthocyanin and flavanone intake and coronary artery disease and stroke in the Health Professionals Follow-Up Study. Design: We followed 43,880 healthy men who had no prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of validated food-frequency questionnaires. Results: During 24 y of follow-up, 4046 myocardial infarction (MI) and 1572 stroke cases were confirmed by medical records. Although higher anthocyanin intake was not associated with total or fatal MI risk, after multivariate adjustment an inverse association with nonfatal MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69, 0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke risk. Although flavanone intake was not associated with MI or total stroke risk, higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95% CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in participants aged ≥65 y (P-interaction = 0.04). Conclusions: Higher intakes of fruit-based flavonoids were associated with a lower risk of nonfatal MI and ischemic stroke in men. Mechanistic studies and clinical trials are needed to unravel the differential benefits of anthocyanin- and flavanone-rich foods on cardiovascular health.