A brief history of TRIM5alpha

In spite of the fact that the first isolates of HIV-1 became available more than 20 years ago, there is still no robust animal model for HIV-1 replication and pathogenesis. This is largely due to the existence of multiple genetic barriers to HIV-1 replication in most nonhuman primates, including a severe block targeting the early, post-entry phase of the viral replication cycle. It is now known that a protein called TRIM5alpha mediates this early restriction in nonhuman primate cells. Tissue culture experiments, together with genetic association studies involving multiple HIV/AIDS cohorts, indicate that the human orthologue of TRIM5alpha does not have a significant impact on HIV-1 replication. However, most human alleles encode a functional protein that can restrict at least one retrovirus unrelated to HIV-1 (N-tropic murine leukemia virus), although one deleterious mutation (H43Y) is present at high frequency in human populations. Phylogenetic analyses of the TRIM5 locus reveal that prehistoric retroviral epidemics, not unlike the current HIV/AIDS pandemic, played a significant role in the evolutionary history of humans and their primate relatives. The discovery of TRIM5alpha's antiretroviral activity sparked the imaginations of many laboratories, and considerable effort has now been channeled into characterizing the protein and determining its possible mechanism(s) of action. It is hoped that research on TRIM5alpha will contribute to the establishment of new and improved models for HIV replication and AIDS pathogenesis, point the way towards novel therapeutic targets to stem the tide of the human AIDS epidemic, provide an experimental window onto the early, post-entry stages of the retroviral replication cycle, and even inspire the search for other cellular factors that modulate retroviral infection.     

Core beliefs in dieters and eating disordered women

OBJECTIVE: The current study aimed to investigate the difference in the levels of core beliefs between eating disordered women and those who showed milder forms of symptomatology. METHODS: Thirty-five eating disordered women, 16 symptomatic dieters, 39 normal dieters and 34 non-clinical comparison women completed questionnaires measuring eating symptomatology (Eating Disorders Inventory [EDI]), core beliefs (Young Schema Questionnaire [YSQ]), depression (The Beck Depression Inventory-II [BDI-II]) and self-esteem (Rosenberg Self-Esteem Inventory [RSE]). RESULTS: With the exception of Entitlement beliefs, there were significant differences in the levels of core beliefs across all four groups. In particular, symptomatic dieters and eating disordered women differed on 8 YSQ subscales despite showing very similar level of eating symptomatology. DISCUSSION: The current findings lend support to the discontinuity model that suggests that there are fundamental differences between women with a clinical eating disorder and those with milder eating psychopathology. The clinical and research implications of the present results were discussed.     

Eliminating health disparities: understanding this important phenomenon

Since the formation of the United States in early times, diversity has always been a reality. With the immigration of diverse whites from Europe, the importation of black slaves from Africa, and the presence of the preexisting Native American populations, diversity has long been a fact of life in this country. However, one of the long-standing priorities of the United States has been "good health" for all the people. The broad diversity of the population has presented a tremendous challenge to health care. This article addresses this important topic by looking at the concept of health disparity from a biopsychosocial perspective and further by describing disparities that are present in the United States among the 2 major ethnic minority groups, African Americans and Mexican Americans. Many other health disparities could be considered in other groups, but space limits of article allow only the 2 major ethnic minority groups to be addressed.     

Association between infant birth weight and maternal cardiovascular risk factors in the health, aging, and body composition study

PURPOSE: Mothers who deliver a low-birth-weight (LBW) infant may themselves be at excess risk for cardiovascular disease. We investigated whether older women who bore LBW infants had higher blood pressure, lipid, glucose, insulin, interleukin 6 (IL-6), and C-reactive protein concentrations, and pulse wave velocity compared to women with normal-weight births. METHODS: Participants were 446 women with a mean age of 80 years and 47% black. Women reported birth weight and complications for each pregnancy. Analysis was limited to first births not complicated by hypertension or preeclampsia. RESULTS: Women who had delivered a first-birth infant weighing less than 2500 g had a lower body mass index (BMI) compared with women with a normal-weight (>or=2500 g) infant (26.7 versus 28.4 kg/m2; p=0.02), but they had a larger abdominal circumference for BMI (97.9 versus 95.5 cm; p=0.05). They also were marginally more likely to be administered antihypertensive medication (p=0.06). After adjustment for BMI, race, and age, women with a history of a small infant had elevations in systolic blood pressure (p=0.05) and greater IL-6 levels (p=0.02) and were more insulin resistant (p=0.05) compared with women with a normal-weight infant. CONCLUSIONS: These findings suggest that a history of LBW delivery identifies women with elevated cardiovascular risk factors.     

Macro- and micronutrients in patients with congestive heart failure, particularly African-Americans

Not all patients with heart failure, defined as a reduced ejection fraction, will have an activation of the RAAS, salt and water retention, or the congestive heart failure (CHF) syndrome. Beyond this cardiorenal perspective, CHF is accompanied by a systemic illness that includes oxidative stress, a proinflammatory phenotype, and a wasting of soft tissues and bone. A dyshomeostasis of calcium, magnesium, zinc, selenium, and vitamin D contribute to the appearance of oxidative stress and to compromised endogenous defenses that combat it. A propensity for hypovitaminosis D, given that melanin is a natural sunscreen, and for secondary hyperparathyroidism in African-Americans make them more susceptible to these systemic manifestations of CHF-a situation which is further threatened by the calcium and magnesium wasting that accompanies the secondary aldosteronism of CHF and the use of loop diuretics.     

Effects of birth cohort and age on body composition in a sample of community-based elderly

BACKGROUND: The effect of the recent obesity epidemic on body composition remains unknown. Furthermore, age-related changes in body composition are still unclear. OBJECTIVE: The objective was to simultaneously examine the effects of birth cohort and age on body composition. DESIGN: A total of 1786 well-functioning, community-based whites and blacks (52% women and 35% blacks) aged 70-79 y from the Health, Aging, and Body Composition Study underwent dual-energy X-ray absorptiometry annually from 1997 to 2003. RESULTS: At baseline, mean +/- SD percentage body fat, fat mass, and lean mass (bone-free) were 28 +/- 5%, 24 +/- 7 kg, and 56 +/- 7 kg, respectively, for men and 39 +/- 6%, 28 +/- 9 kg, and 40 +/- 6 kg for women. Mixed models were used to assess the effects of cohort and age-related changes on body composition. Later cohorts in men had a greater percentage body fat (0.32% per birth year, P < 0.0001) than did earlier cohorts. This cohort effect was due to a greater increase in fat mass than in lean mass (0.45 kg and 0.17 kg/birth year, respectively). With increasing age, percentage body fat in men initially increased and then leveled off. This age-related change was due to an accelerated decrease in lean mass and an initial increase and a later decrease in fat mass. Similar but less extreme effects of cohort and age were observed in women. CONCLUSIONS: The combination of effects of both birth cohort and age leads to bigger body size and less lean mass in the elderly.     

Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern

Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.     

Willingness to participate in HIV vaccine trials: the impact of trial attributes

OBJECTIVES: To assess willingness to participate (WTP) in hypothetical Phase III preventive HIV vaccine trials, and the impact of trial attributes on WTP, among low socioeconomic, ethnically diverse adults from communities at elevated risk for HIV infection. METHOD: Participants (n=123; median age=38; 69% male; 37% Latino; 14% African-American) were recruited in Los Angeles in 2003 using multi-site, venue-based sampling. WTP was assessed for eight hypothetical HIV vaccine trials that varied across seven dichotomous attributes, using a 2(7-4) fractional factorial experimental design. Individual-specific impact of vaccine trial attributes on WTP was estimated using within-individual ANOVA and then meta-analyzed across individuals. RESULTS: Mean WTP for eight hypothetical vaccine trials ranged from 1.74 to 3.81 (1=highly unlikely, 5=highly likely). Lower WTP was associated with vaccine-induced infection risk (impact=0.88, p<0.0001), false HIV-positives (0.53, p<0.0001), no provision of free HIV medications (0.52, p<0.0001), and longer trial duration (0.27; p=0.0002). CONCLUSION: HIV vaccine trial attributes may strongly influence WTP. Although existing candidate vaccines cannot cause HIV infection, perceptions of risk may impede WTP. Eliciting trial preferences and concerns prior to trial implementation may enable accommodation of participant preferences and support tailored interventions to address concerns and misconceptions to facilitate enrollment in safe and ethical trials among vulnerable communities.     

Comparative immunogenicity of trivalent influenza vaccine administered by intradermal or intramuscular route in healthy adults

The present study was undertaken with controls using equal doses ID and IM plus the standard full dose IM to assess the role of route of vaccine in immunogenicity of inactivated influenza vaccine. The study was a prospective, randomized, active-controlled, open label clinical trial conducted in healthy young adult outpatients to compare the effect of route (IM versus ID) on antibody responses to influenza vaccine. Volunteers received 3, 6 or 9 microg of vaccine by ID or IM route; 15 microg IM was also studied. Low doses of vaccine given by either route were almost as immunogenic as the standard 15 microg IM dose of influenza vaccine. ID route was not superior to IM vaccine at inducing antibodies. ID vaccine induced significantly more local inflammatory response than IM vaccine.