Predicting cardiovascular risk using measures of regional and total body fat.

Excessive body fat is associated with increased risk for coronary heart disease (CHD). Various anthropometric methods are currently used to quantify regional and total body fat. The objectives of this study were to provide more insight into differences in cutoff points between methods for measuring total body fat and those for measuring regional body fat, independently and in combination, and to determine how well anthropometric and bioelectrical impedance methods of estimating body composition predict cardiovascular risk in a sample of unfit National Guard soldiers. Unfit healthy men (n = 123) and women (n = 32) between 21 and 55 years old from the Army National Guard were assessed for total and regional body fat. After having their degree of total and regional body fat assessed, the participants were categorized by level of body fat and 10-year CHD risk. Comparisons and predictions were made between degree of total as well as regional body fat and 10-year CHD risk estimated from Framingham Heart Study equations. A significant positive relationship was observed between waist circumference and 10-year CHD risk in men. When controlling for age, waist circumference was predictive of 10-year CHD risk, contributing to 6.4% of the variance, whereas waist-to-hip ratio did not contribute to the model significantly. The results of this study show that waist circumference is the best measure for identifying unfit male individuals at risk for CHD.

Ranpirnase Reduces HIV-1 Infection and Associated Inflammatory Changes in a Human Colorectal Explant Model.

Ranpirnase (RNP) is a low molecular weight type III endoribonuclease, which demonstrates broad antiviral and antitumor properties. We sought to characterize the antiviral activity of RNP against HIV-1 and to determine whether RNP modulates local inflammatory changes associated with HIV infection in the colorectal explant model. Colorectal explants were incubated for 2 h with HIV-1BaL, in the presence of increasing concentrations of RNP (0-60 µg/mL). After washing, explants were cultured for 14 days, with supernatant collected at days 3, 7, 10, and 14. All samples were assayed for HIV-1 p24. Additionally, 30 soluble inflammatory biomarkers were assayed in the day 3 supernatant sample. Other biopsies were stimulated with lipopolysaccharides (LPS) (10 µg/mL) in the presence of RNP and soluble biomarkers assayed at day 3. RNP inhibited productive infection of the colorectal explants with HIV-1BaL and induced a dose-dependent decrease in 15/30 biomarkers. Affected biomarkers included IP-10, MDC, MIP-1α, MIP-1ß, TARC, IL12-p40, IL-15, IL-17, IL-1α, IL-7, IFNγ, IL12-p70, IL-1ß, IL-4, IL-5, and TNF-ß. Similarly, RNP dose-dependent inhibition was demonstrated in 7/30 biomarkers after LPS stimulation, all of which overlapped with HIV-1BaL-induced biomarker changes. The ability of RNP to inhibit both colorectal explant HIV-1BaL infection and inflammatory changes associated with HIV-1 infection makes RPN a promising agent for topical rectal pre-exposure prophylaxis.

Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury.

BACKGROUND: Falls in older people have been characterized extensively in the literature, however little has been reported regarding falls in middle-aged and younger adults. The objective of this paper is to describe the perceived cause, environmental influences and resultant injuries of falls in 1497 young (20-45 years), middle-aged (46-65 years) and older (> 65 years) men and women from the Baltimore Longitudinal Study on Aging. METHODS: A descriptive study where participants completed a fall history questionnaire describing the circumstances surrounding falls in the previous two years. RESULTS: The reporting of falls increased with age from 18% in young, to 21% in middle-aged and 35% in older adults, with higher rates in women than men. Ambulation was cited as the cause of the fall most frequently in all gender and age groups. Our population reported a higher percentage of injuries (70.5%) than previous studies. The young group reported injuries most frequently to wrist/hand, knees and ankles; the middle-aged to their knees and the older group to their head and knees. Women reported a higher percentage of injuries in all age groups. CONCLUSION: This is the first study to compare falls in young, middle and older aged men and women. Significant differences were found between the three age groups with respect to number of falls, activities engaged in prior to falling, perceived causes of the fall and where they fell.

Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients.

The leading causes of death for individuals with Werner syndrome (WS) are myocardial infarction (MI) and stroke. The WS gene encodes a nuclear protein with both helicase and exonuclease activities. While individuals with WS have mutations that result in truncated, inactive proteins, several sequence variants have been described in apparently unaffected individuals. Some of these gene polymorphisms encode non-conservative amino acid substitutions, and it is expected that the changes would affect enzyme activity, although this has not been determined. Two research groups have studied the Cys/Arg 1367 polymorphism (located near the nuclear localization signal) in healthy and MI patients. Their results suggest that the Arg allele is protective against MI. We have characterized the Cys (C) and Arg (R) forms of the protein and find no notable difference in helicase and nuclease activities, or in nuclear/cytoplasmic distribution. The frequency of the C/R alleles in healthy individuals and subjects with coronary artery disease (CAD) drawn from the Baltimore Longitudinal Study of Aging (BLSA) was also examined. There was no indication that the R allele was protective against CAD. We conclude that the C/R polymorphism does not affect enzyme function or localization and does not influence CAD incidence in the BLSA cohort.

Physiological correlates of age-related decline in vibrotactile sensitivity.

The purpose of this study was to describe age-related changes in vibrotactile sensitivity in participants of the Baltimore Longitudinal Study of Aging and to identify factors that are associated with impairment in vibrotactile sensitivity independent of age. Participants (n=523, age: 26-95 years) underwent measurements of vibration perception threshold (VPT, 100Hz) under the 2nd metatarsal head, glucose tolerance, serum inflammatory markers, nerve conduction parameters, movement time and cognition. Univariate and multivariate regression analyses were performed to identify factors that predicted VPT independent of age. Structural equation modeling was used to describe relationships between these variables. VPT was progressively higher with older age. Adjusting for age and height, VPT was similar in men and women and the slope of age-related decline was similar in the two genders. Age, height, peroneal nerve conduction velocity and peroneal nerve amplitude were independent predictors of VPT. Structural equation model demonstrated a direct relationship between peripheral nerve function and VPT. Height and circulating inflammatory markers may influence age-related decline in vibrotactile sensitivity through their negative impacts on peripheral nerve function.

Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men.

Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.