Baseline diet modifies the effects of dietary change.

The Dietary Approaches to Stop Hypertension (DASH) eating pattern has been shown to reduce blood pressure (BP) in previous clinical trials. In the PREMIER study, an established behavioural intervention, with or without DASH, promoted greater weight loss than an advice-only control group, but effects of the DASH intervention on BP were weaker. In these analyses, PREMIER data were used to evaluate whether change in dairy product or fruit and vegetable (FV) intake during the first six intervention months impacted changes in weight and/or BP. Study participants were classified as having low or high intakes of dairy products (<1·5 v. ≥1·5 servings/d) and FV (<5 v. ≥5 servings/d) at baseline and 6 months. For dairy products, in particular, participants with higher baseline intakes tended to decrease their intakes during the intervention. In these analyses, subjects consuming <1·5 dairy servings/d at baseline whose intake increased during the intervention lost more weight than those whose intake decreased or remained low throughout (10·6 v. 7·0 pounds (4·8 v. 3·2 kg) lost, respectively, P = 0·002). The same was true for FV intake (11·0 v. 5·9 pounds (5·0 v. 2·7 kg) lost, P < 0·001). We also found synergistic effects of dairy products and FV on weight loss and BP reduction. Specifically, subjects who increased their intakes of dairy products and also consumed ≥5 servings of FV/d lost more weight and had greater reductions in BP than other groups; in addition, higher FV intakes had the greatest benefit to BP among those consuming more dairy products. These results provide evidence that the DASH pattern was most beneficial to individuals whose baseline diet was less consistent with DASH.

Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in Older Men with Mobility Limitations.

OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is an important modulator of skeletal muscle mass loss in older people. The Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial was designed to assess the independent and combined effects of higher protein intake and a promyogenic agent, testosterone, on lean body mass, muscle strength and physical function in older men with mobility disability. The purpose of this paper is to describe the experimental design and nutrition intervention, including techniques used by research dietitians to develop and deliver energy and protein-specific meals to the homes of community-dwelling participants. Strategies to enhance long-term dietary compliance are detailed. DESIGN: Randomized, double-blind, placebo-controlled six-month intervention trial. SETTING: Participants were recruited from Boston MA USA and surrounding communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were recruited for this study. INTERVENTION: Here we report the successful implementation of a double-blind, placebo-controlled, parallel group, randomized controlled trial with a 6-month intervention period among community-living men, age 65 years and older with a mobility limitation. A controlled feeding plan was used to deliver required energy intakes and prescribed protein quantities of 0.8 or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A 2x2 factorial design was used to assess the effects of protein level alone and in combination with testosterone (vs. placebo) on changes in lean body mass (primary outcome), muscle strength, and physical function. RESULTS: A total of 154 men met the eligibility criteria; 112 completed a 2-week run-in period designed to evaluate compliance with the nutrition intervention. Of these, 92 subjects met compliance eligibility criteria and agreed to be randomized; 85% completed the full trial. The study successfully delivered three meals per day to subjects, with a high degree of compliance and subject satisfaction. Overall self-reported compliance rates were 80% and 93% for the meals and supplements, respectively. Details of compliance strategies are discussed. CONCLUSION: This community-based study design may serve as a model for longer-term nutritional interventions requiring monitoring of dietary compliance in a home-based feeding and supplementation trial.

Lean red meat consumption and lipid profiles in adolescent girls.

BACKGROUND: Epidemiological studies of red meat consumption often fail to distinguish between leaner and fattier or processed cuts of meat. Red meat has also been frequently linked with less healthy diet patterns. Data exploring the health effects of lean red meat in younger individuals are scarce, particularly in the context of a healthy diet. The present study examined the effects of lean red meat in combination with higher intakes of fruit/nonstarchy vegetables on lipid profiles in older adolescent girls. METHODS: Data from 1461 girls who were followed for 10 years, starting at 9-10 years of age, in the National Heart Lung and Blood Institute Growth and Health Study were used. Diet was assessed using multiple sets of 3-day records collected over eight examination cycles. Outcome measures included fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides at age 18-20 years. RESULTS: After adjusting for age, race, socioeconomic status, height, activity level, hours of television per day, and intakes of whole grains and dairy foods using multivariable modelling, girls consuming ≥6 oz lean red meat per week combined with two or more servings of fruit/nonstarchy vegetables per day had LDL-C levels approximately 6-7 mg dL(-1) lower (P < 0.05) than girls with lower intakes of lean red meat and fruit/nonstarchy vegetables. In addition, girls with higher intakes of both were 33% less likely (odds ratio = 0.67, 95% confidence interval = 0.48-0.94) to have an LDL-C ≥110 mg dL(-1) and 41% less likely (odds ratio = 0.59, 95% confidence interval = 0.42-0.83) to have an elevated LDL : HDL ratio (≥2.2) at the end of adolescence. CONCLUSIONS: These analyses suggest that lean red meat may be included in a healthy adolescent diet without unfavourable effects on lipid values.

Functional properties of behaviour problems depending on level of intellectual disability.

BACKGROUND: Behaviour problems are common among individuals with intellectual disabilities (ID) especially in those with more severe forms. The determination of the functional profile of a targeted behaviour has important implications for the design of customised behavioural interventions. METHOD: We investigated the relationship between the level of ID and the functional profile of aggression, stereotypy and self-injurious behaviour (SIB) using the Questions about Behavioural Function (QABF). Two staff members at two time points completed the QABF for each of 115 adults with varying levels of ID participating in a day training and habilitation programme. RESULTS AND CONCLUSIONS: Our results suggest that there is a differential relationship between the functions of behaviour problems and level of ID. While SIB is more often seen by raters to be maintained by escape of social demands and by attaining access to tangible items with the decline of the intellectual level, aggressive and stereotypic behaviours were identified more often as serving multiple functions equally across functioning level.

Eating patterns and lipid levels in older adolescent girls.

BACKGROUND AND AIMS: Few studies have evaluated the effects of food-based eating patterns on adolescent lipid levels. This study examines whether usual adolescent eating patterns (ages 9-17 years) predict lipid levels at 18-20 years of age. METHODS AND RESULTS: This study uses previously collected data from the longitudinal NHLBI Growth and Health Study in which 2379 girls were enrolled at ages 9-10 years and followed for ten years. Food-based eating patterns were derived from multiple 3-day diet records. After adjusting for age, race, socioeconomic status, height, physical activity, and television viewing, girls with higher intakes of dairy, fruit and non-starchy vegetables had about a 40-50% reduced risk an LDL-C ≥ 170 mg/dL and non-HDL-C ≥ 145 mg/dL. Diets characterized by higher intakes of dairy and whole grains had similar benefits on TC and LDL-C. Girls consuming more fruits and non-starchy vegetables as well as more whole grains were much less likely to have high-risk lipid levels. Lean meat, poultry and fish when consumed in the context of other healthy eating patterns had no adverse effects on lipid levels in late adolescence. In fact when consumed with higher amounts of fruit and non-starchy vegetables, lean meat, poultry and fish had beneficial effects on HDL. Finally, dietary patterns that included more whole grains tended to be associated with lower TG levels. CONCLUSION: Healthy childhood eating patterns characterized by higher intakes of a variety of fruits, vegetables, whole grains, dairy, lean meat, poultry and fish are important modifiable predictors of lipid levels in late adolescence.

BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults.

BACKGROUND: It is unclear whether the increased risk of colon cancer associated with obesity differs for men and women, by distribution of body fat, or by location of the tumor. The primary goal of this study was to address these questions. METHODS: Eligible subjects from the Framingham Study cohort were classified according to body mass index (BMI) and waist size during two age periods: 30-54 y (n=3764) and 55-79 y (n=3802). All eligible men and women were cancer-free at baseline and had complete information on the following potential confounders: age, sex, education, height, activity, smoking, and alcohol. There were 157 incident lifetime cases of colon cancer among those followed beginning at 30-54 y of age and 149 lifetime cases among those whose follow up began at 55-79 y. Subjects were stratified further by gender, activity, and tumor location. The Cox Proportional Hazards Models were used to adjust for possible confounding by the above-described factors. RESULTS: A BMI >/=30 led to a 50% increased risk (95% CI: 0.92-2.5) of colon cancer among middle-aged (30-54 y) and a 2.4-fold increased risk (95% CI: 1.5-3.9) among older (55-79 y) adults. The BMI effect was stronger for men than for women and for cases occurring in the proximal colon. These adverse effects generally diminished when waist was added to the multivariable models. A larger waist size (>/=99.1 cm (39 in) and 101.6 cm (40 in) for women and men, respectively) was associated with a two-fold increased risk of colon cancer; this risk increased linearly with increasing waist size and was evident for both proximal and distal colon cancer. There was no attenuation of these effects when BMI was added to the multivariable models. A larger waist had a particularly adverse effect among sedentary subjects (relative risk (RR)=4.4 for middle-aged adults; RR=3.0 for older adults). CONCLUSION: These findings suggest that waist circumference is a stronger predictor of colon cancer risk than is BMI, and that central obesity is responsible for an increased risk of cancer of both the proximal and distal colon.

Television viewing and change in body fat from preschool to early adolescence: The Framingham Children's Study.

OBJECTIVE: To prospectively examine the relation between television watching and body fat change in children from preschool to early adolescence. METHODS: In a longitudinal study, 106 children were enrolled during preschool years (mean age 4.0 y) and followed into early adolescence (mean age 11.1 y). Parents completed an annual questionnaire on the child's television and video habits. Body mass index (BMI), triceps skinfolds, and sum of five skinfolds were recorded yearly at annual clinic visits. Longitudinal statistical analyses were carried out using mixed modeling procedures to control for potential confounding by a number of factors. RESULTS: Television watching was an independent predictor of the change in the child's BMI, triceps, and sum of five skinfolds throughout childhood. Its effect was only slightly attenuated by controlling for the baseline body fat, level of physical activity (as measured repeatedly by Caltrac accelerometer), percent of calories from fat, total calorie intake, or the parents' BMI or education. By age 11, children who watched 3.0 h or more of television per day had a mean sum of skinfolds of 106.2 mm, compared with a mean sum of skinfolds of 76.5 mm for those who watched less than 1.75 h per day (P=0.007). Furthermore, the adverse effect of television viewing was worse for those children who were also sedentary or had a higher-fat diet. CONCLUSIONS: Children who watched the most television during childhood had the greatest increase in body fat over time. Healthy lifestyle education designed to prevent obesity and its consequences should target television-watching habits of children.

HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres.

The centromere plays a critical role in the segregation of chromosomes during mitosis. In mammals, sister centromeres are resolved from one another in the G2 phase of the cell cycle. During prophase, chromosomes condense with sister centromeres oriented in a back to back configuration enabling only one chromatid to be captured by each half spindle. To study this process, we identified a centromere protein (CENP)-C-like protein, holocentric protein (HCP)-4, in Caenorhabditis elegans based on sequence identity, loss of function phenotype, and centromeric localization. HCP-4 is found in the cytoplasm during interphase, but is nuclear localized in mitosis, where it localizes specifically to the centromere. The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F-like protein, HCP-1, indicating an ordered assembly pathway. Loss of HCP-4 expression by RNA-mediated interference resulted in a failure to generate resolution of sister centromeres on chromosomes, suggesting that HCP-4 is required for sister centromere resolution. These chromosomes also failed to form a functional kinetochore. Thus, the CENP-C-like protein HCP-4 is essential for both resolution sister centromeres and attachment to the mitotic spindle.

The feasibility of using rural health workers to determine cause of death in remote regions of Cameroon, West Africa.

The validity of the recent Global Burden of Disease Study (GBDS) was compromised by the lack of adult mortality data in developing countries, particularly in Sub-Saharan Africa. Verbal autopsies, in which health workers (HW), using questionnaires and algorithms, interview surviving family members to determine the cause of death, have proven useful in establishing priorities for the allocation of limited health care resources. Most reports, however, have come from large population centers. The feasibility of using health workers trained in verbal autopsy methodology to operate in remote rural areas of Africa has had limited testing. The records of 40 villagers who died in a Mission Hospital of the Northwest Province of Cameroon were reviewed, and the hospital discharge diagnosis, made by the attending physician, compared with that obtained by HW who administered a verbal autopsy to the family. In 70% of the cases the physician and HW were in exact agreement. Such a method, if confirmed in other studies among rural populations, may be an important approach to determining cause of death in many developing countries.

Parental eating attitudes and the development of obesity in children. The Framingham Children's Study.

OBJECTIVE: To investigate the extent to which parents' degree of dietary self-control, as measured by self-reported dietary restraint, disinhibition, and perceived hunger, affects the development of excess body fat in the child. DESIGN: Prospective observational study. SUBJECTS: Ninety-two 3-5y old children and their parents, enrolled in 1987 in the Framingham Children's Study. MEASUREMENTS: Self-reported levels of parental dietary restraint, disinhibition and perceived hunger were estimated using Stunkard and Messick's Three-Factor-Eating Questionnaire. Anthropometric measurements (height, weight and skinfold measurements at five sites) were obtained yearly for children and parents. The child's activity level was measured on multiple days each year using Caltrac accelerometers. Energy intake and percentage of calories from total fat were estimated from multiple sets of food diaries, collected each year. All analyses were adjusted for the following potential confounders: child's sex and baseline values for age, height, mean physical activity level, total calories and percentage of calories from fat as well as the educational levels of the parents at baseline. RESULTS: Over 6y, children's body fat increased linearly with increasing levels of self-reported parental disinhibition (eg 6y increase in the child's sum of five skinfolds was 34.4, 45.8 and 59.2 mm across increasing tertiles of parental disinhibition, P=0.012). Overall, children whose parents had higher dietary restraint scores had greater increases in body fatness than children whose parents had the lowest levels of restraint. When both parents had above average scores on dietary disinhibition or restraint, the children had greater increases in body fat (on all anthropometry measures) than when only one parent or when neither parent had high scores on those factors. Parental scores on the perceived hunger scale had no clear effect on body fat change of children. Since disinhibition and dietary restraint frequently co-exist, we then examined the joint effect of these two factors. The children with the greatest increases in body fat were those whose parents scored high on both factors. In the final analysis, we found that dietary restraint adversely affected the child's body fat only when associated with high parental disinhibition. CONCLUSION: This study suggests that parents who display high levels of disinhibited eating, especially when coupled with high dietary restraint, may foster the development of excess body fat in their children. This association may be mediated by direct parental role modeling of unhealthy eating behaviors, or through other indirect, and probably subconscious, behavioral consequences such as the suppression of the child's innate regulation of dietary intake.

A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus.

This study was designed to evaluate the effects of maternal obesity and diabetes mellitus on the risk of nonchromosomal congenital defects. We used data from 22,951 pregnant women enrolled in a prospective cohort study of early prenatal exposures and pregnancy outcome. The relative risks [prevalence ratios (PRs)] of major nonchromosomal congenital defects associated with obesity and diabetes, alone or in combination, were calculated using multiple logistic regression analysis. In this study, in the absence of diabetes, obese women (body mass index > or =28) had no higher risk, overall, of having an offspring with a major defect [PR = 0.95; 95% confidence interval (CI) = 0.62-1.5]. Their offspring, however, did have a higher prevalence of certain types of defects, including orofacial clefts; club foot; cardiac septal defects; and, to a lesser extent, hydrocephaly and abdominal wall defects. Women with pre-existing or gestational diabetes who were not obese also had no excess risk overall of having offspring affected by a major defect (PR = 0.98; 95% CI = 0.43-2.2), although they did have a higher prevalence of musculoskeletal defects. The pregnancies of women who were both obese and diabetic were 3.1 times as likely (95% CI = 1.2-7.6) to result in an offspring with a defect than were those of nonobese, nondiabetic women, which suggests that obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies. The defects were largely craniofacial or musculoskeletal.

Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus?

Although rates of adult-onset diabetes mellitus increase with increasing obesity, there is little evidence that weight loss in overweight individuals can reduce their risk of developing diabetes. Using data from the Framingham Study, we examined the effects of sustained and nonsustained weight loss on risk of diabetes mellitus among 618 overweight (body mass index > or =27) subjects 30-50 years of age. To separate sustained from nonsustained weight loss, we examined weight change in two consecutive 8-year periods. Subjects who had stable weight (+/- 1 lb per year) during both periods served as the referent group for all analyses. Sustained weight loss led to a 37% lower risk of diabetes [relative risk (RR) = 0.63; 95% confidence interval = 0.34-1.2], and this effect was stronger for more obese (body mass index > or =29) subjects (RR = 0.38; 95% confidence interval = 0.18-0.81). Those who lost 8.1-15 lb had a 33% reduction in diabetes risk, whereas those losing more had a 51% reduction in risk. Regardless of the amount of weight lost, those who regained the lost weight had no reduction in diabetes risk (RR = 1.1 and 1.2 for those who lost 8.1-15 and >15 lb, respectively). We conclude that a modest amount of sustained weight loss can substantially reduce the risk of diabetes mellitus in overweight individuals.

HCP-1, a protein involved in chromosome segregation, is localized to the centromere of mitotic chromosomes in Caenorhabditis elegans.

To learn more about holocentric chromosome structure and function, we generated a monoclonal antibody (mAb), 6C4, that recognizes the poleward face of mitotic chromosomes in Caenorhabditis elegans. Early in mitosis, mAb 6C4 stains dots throughout the nucleoplasm. Later in prophase, mAb 6C4 stains structures on opposing faces of chromosomes which orient towards the centrosomes at metaphase. Colocalization with an antibody against a centromeric histone H3-like protein and the MPM-2 antibody, which identifies a kinetochore-associated phosphoepitope present in a variety of organisms, shows that the mAb 6C4 staining is present adjacent to the centromere. Expression screening using mAb 6C4 identified a protein in C. elegans that we named HCP-1 (for holocentric protein 1). We also identified a second protein from the C. elegans genome sequence database, HCP-2, that is 54% similar to HCP-1. When expression of HCP-1 is reduced by RNA interference (RNAi), staining with mAb 6C4 is eliminated, indicating that hcp-1 encodes the major mAb 6C4 antigen. RNAi with hcp-1 and hcp-2 together results in aberrant anaphases and embryonic arrest at approximately 100 cells with different amounts of DNA in individual nuclei. These results suggest that HCP-1 is a centromere-associated protein that is involved in the fidelity of chromosome segregation.

Effect of response to a low-fat diet among adolescent males on their adult blood cholesterol levels.

BACKGROUND: While primary prevention of adult cardiovascular diseases should begin early, there are problems in identifying children at increased risk of future disease. METHODS: We did a follow-up study in 1991-1992 of 100 male former students at a boarding high school who had blood cholesterol measured in 1970-1971 both prior to and following a school-wide, reduced-fat dietary intervention. We compared adult cholesterol levels of the 50 subjects whose cholesterol decreased > or = 16.5% (the median decrease) following the 1970-1971 intervention (Diet-Sensitive) with the 50 whose response was < 16.5% (Non-Diet-Sensitive). RESULTS: Blood cholesterol of adults who were Diet-Sensitive in 1970-1971 was 4.2 mg/dl lower than their baseline values in adolescence, while adults classified as Non-Diet-Sensitive as adolescents showed a 15.9 mg/ dl increase in cholesterol over 21 years. Adjusting for baseline adolescent values, Non-Diet-Sensitive subjects were 4.8 (95% CI 1.4, 15.9) times as likely as Diet-Sensitive subjects to have adult cholesterol > or = 200 mg/ dl. Also, Diet-Sensitive adults on a low-fat diet had adult blood cholesterol levels > 20 mg/dl lower than Non-Diet-Sensitive adults on a similar diet (180.1 vs 202.1 mg/dl, respectively). CONCLUSIONS: Degree of response to a low-fat, low-cholesterol diet during adolescence may identify male subjects who will have differing patterns of cholesterol change over time.

A one year study of the macular pigment: the effect of 140 days of a lutein supplement.

A low density of macular pigment may represent a risk factor for age-related macular degeneration (AMD) by permitting greater blue light damage. This study was carried out to determine the effects on macular pigment optical density of dietary supplementation with lutein, one of the pigment constituents. Two subjects consumed lutein esters, equivalent to 30 mg of free lutein per day, for a period of 140 days. Macular pigment optical density was determined by heterochromatic flicker photometry before, during, and after the supplementation period. Serum lutein concentration was also obtained through the analysis of blood samples by high-performance liquid chromatography. Twenty to 40 days after the subjects commenced taking the lutein supplement, their macular pigment optical density began to increase uniformly at an average rate of 1.13+/-0.12 milliabsorbance units/day. During this same period, the serum concentration of lutein increased roughly tenfold, approaching a steady state plateau. The optical density curve eventually levelled off 40 to 50 days after the subjects discontinued the supplement. During the same 40 to 50 days, the serum concentration returned to baseline. Thereafter, little or no decrease in optical density was observed. The mean increases in the macular pigment optical density were 39% and 21% in the eyes of the two subjects respectively. In conclusion, the modest period of supplementation has been estimated to have produced in the subjects a 30 to 40% reduction in blue light reaching the photoreceptors, Bruch's membrane, and the retinal pigment epithelium, the vulnerable tissues affected by AMD.

Carotid endarterectomy in Oklahoma Medicare beneficiaries: patient characteristics and outcomes.

BACKGROUND AND OBJECTIVES: Ischemic stroke represents the third leading cause of death and the most common cause of permanent disability in the United States. Carotid endarterectomy has been widely utilized as a procedure to reduce the risk of stroke and represents the most commonly performed peripheral arterial surgery. This cooperative project was initiated to assess the appropriateness of carotid endarterectomies performed on Medicare beneficiaries and the postoperative outcomes (mortality and stroke) in these patients. METHODS: Retrospective review was performed on the inpatient medical records of 774 patients who underwent 813 carotid endarterectomy procedures in eight hospitals during calendar years 1993 and 1994. Medicare claims data were also analyzed for all carotid endarterectomies performed in Oklahoma during calendar years 1992 through 1995. RESULTS: A history of transient ischemic attack or stroke in the distribution of the operated carotid artery was documented in 57% of the cases. The majority of patients had preoperative ultrasound imaging of the carotid arteries and a preoperative angiogram was performed before 96% of the procedures. Accepted indications for the surgery were documented for 98% of the procedures. Stroke or death within 30 days of the date of the carotid endarterectomy occurred after 4.9% (0-8.8% by hospital) of the procedures. CONCLUSIONS: This project demonstrated considerable variation between hospitals in the outcomes of patients undergoing carotid endarterectomy and the potential for improved care of patients with regard to discharge planning, education, and use of anticoagulant or antiplatelet medications postoperatively.