Sarinnapha Vasunilashorn

Use of the Short Physical Performance Battery Score to Predict Loss of Ability to Walk 400 Meters: Analysis From the InCHIANTI Study

BACKGROUND Early detection of mobility limitations remains an important goal for preventing mobility disability. The purpose of this study was to examine the association between the Short Physical Performance Battery (SPPB) and the loss of ability to walk 400 m, an objectively assessed mobility outcome increasingly used in clinical trials. METHODS The study sample consisted of 542 adults from the InCHIANTI study aged 65 and older, who completed the 400 m walk at baseline and had evaluations on the SPPB and 400 m walk at baseline and 3-year follow-up. Multiple logistic regression models were used to determine whether SPPB scores predict the loss of ability to walk 400 m at follow-up among persons able to walk 400 m at baseline. RESULTS The 3-year incidence of failing the 400 m walk was 15.5%. After adjusting for age, sex, education, body mass index, Mini-Mental State Examination, number of medical conditions, and 400 m walk gait speed at baseline, SPPB score was significantly associated with loss of ability to walk 400 m after 3 years. Participants with SPPB scores of 10 or lower at baseline had significantly higher odds of mobility disability at follow-up (odds ratio [OR] = 3.38, 95% confidence interval [CI]: 1.32-8.65) compared with those who scored 12, with a graded response across the range of SPPB scores (OR = 26.93, 95% CI: 7.51-96.50; OR = 7.67, 95% CI: 2.26-26.04; OR = 8.28, 95% CI: 3.32-20.67 for SPPB < or = 7, SPPB 8, and SPPB 9, respectively). CONCLUSIONS The SPPB strongly predicts loss of ability to walk 400 m. Thus, using the SPPB to identify older persons at high risk of lower body functional limitations seems a valid means of recognizing individuals who would benefit most from preventive interventions.

The rise and fall of excess male infant mortality

The male disadvantage in infant mortality underwent a surprising rise and fall in the 20th century. Our analysis of 15 developed countries shows that, as infant mortality declined over two centuries, the excess male mortality increased from 10% in 1751 to >30% by approximately 1970. Remarkably, since 1970, the male disadvantage in most countries fell back to lower levels. The worsening male disadvantage from 1751 until 1970 may be due to differential changes in cause-specific infant mortality by sex. Declines in infant mortality from infections and the shift of deaths to perinatal conditions favored females. The reduction in male excess infant mortality after 1970 can be attributed to improved obstetric practices and neonatal care. The additional male infants who survived because of better conditions were more likely to be premature or have low birth weight, which could have implications for their health in later life. This analysis provides evidence of marked changes in the sex ratio of mortality at an age when behavioral differences should be minimal.

High-Resolution CT Scan Findings in Patients With Symptomatic Scleroderma-Related Interstitial Lung Disease

BACKGROUND Lung disease has become the leading cause of mortality and morbidity in scleroderma (SSc) patients. The frequency, nature, and progression of interstitial lung disease seen on high-resolution CT (HRCT) scans in patients with diffuse SSc (dcSSc) compared with those with limited SSc (lcSSc) has not been well characterized. METHODS Baseline HRCT scan images of 162 participants randomized into a National Institutes of Health-funded clinical trial were compared to clinical features, pulmonary function test measures, and BAL fluid cellularity. The extent and distribution of interstitial lung disease HRCT findings, including pure ground-glass opacity (pGGO), pulmonary fibrosis (PF), and honeycomb cysts (HCs), were recorded in the upper, middle, and lower lung zones on baseline and follow-up CT scan studies. RESULTS HRCT scan findings included 92.9% PF, 49.4% pGGO, and 37.2% HCs. There was a significantly higher incidence of HCs in the three zones in lcSSc patients compared to dcSSc patients (p = 0.034, p = 0.048, and p = 0.0007, respectively). The extent of PF seen on HRCT scans was significantly negatively correlated with FVC (r = - 0.22), diffusing capacity of the lung for carbon monoxide (r = - 0.44), and total lung capacity (r = - 0.36). A positive correlation was found between pGGO and the increased number of acute inflammatory cells found in BAL fluid (r = 0.28). In the placebo group, disease progression was assessed as 30% in the upper and middle lung zones, and 45% in the lower lung zones. No difference in the progression rate was seen between lcSSc and dcSSc patients. CONCLUSIONS PF and GGO were the most common HRCT scan findings in symptomatic SSc patients. HCs were seen in more than one third of cases, being more common in lcSSc vs dcSSc. There was no relationship between progression and baseline PF extent or lcSSc vs dcSSc. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00004563.

Gender differences in reward-related decision processing under stress

Recent research indicates gender differences in the impact of stress on decision behavior, but little is known about the brain mechanisms involved in these gender-specific stress effects. The current study used functional magnetic resonance imaging (fMRI) to determine whether induced stress resulted in gender-specific patterns of brain activation during a decision task involving monetary reward. Specifically, we manipulated physiological stress levels using a cold pressor task, prior to a risky decision making task. Healthy men (n = 24, 12 stressed) and women (n = 23, 11 stressed) completed the decision task after either cold pressor stress or a control task during the period of cortisol response to the cold pressor. Gender differences in behavior were present in stressed participants but not controls, such that stress led to greater reward collection and faster decision speed in males but less reward collection and slower decision speed in females. A gender-by-stress interaction was observed for the dorsal striatum and anterior insula. With cold stress, activation in these regions was increased in males but decreased in females. The findings of this study indicate that the impact of stress on reward-related decision processing differs depending on gender.

Chapter 5 Biomarkers Related To Aging In Human Populations

Biomarkers are increasingly employed in empirical studies of human populations to understand physiological processes that change with age, diseases whose onset appears linked to age, and the aging process itself. In this chapter, we describe some of the most commonly used biomarkers in population aging research, including their collection, associations with other markers, and relationships to health outcomes. We discuss biomarkers of the cardiovascular system, metabolic processes, inflammation, activity in the hypothalamic-pituitary axis (HPA) and sympathetic nervous system (SNS), and organ functioning (including kidney, lung, and heart). In addition, we note that markers of functioning of the central nervous system and genetic markers are now becoming part of population measurement. Where possible, we detail interrelationships between these markers by providing correlations between high risk levels of each marker from three population-based surveys: the National Health and Nutrition Examination Survey (NHANES) III, NHANES 1999-2002, and the MacArthur Study of Successful Aging. NHANES III is used instead of NHANES 1999-2002 when specific markers of interest are available only in NHANES III and when we examine the relationship of biomarkers to mortality which is only known for NHANES III. We also describe summary measures combining biomarkers across systems. Finally, we examine associations between individual markers and mortality and provide information about biomarkers of growing interest for future research in population aging and health.

Aging in Place: Evolution of a Research Topic Whose Time Has Come

Over the past 30 years, policy makers and professionals who provide services to older adults with chronic conditions and impairments have placed greater emphasis on conceptualizing aging in place as an attainable and worthwhile goal. Little is known, however, of the changes in how this concept has evolved in aging research. To track trends in aging in place, we examined scholarly articles published from 1980 to 2010 that included the concept in eleven academic gerontology journals. We report an increase in the absolute number and proportion of aging-in-place manuscripts published during this period, with marked growth in the 2000s. Topics related to the environment and services were the most commonly examined during 2000–2010 (35% and 31%, resp.), with a substantial increase in manuscripts pertaining to technology and health/functioning. This underscores the increase in diversity of topics that surround the concept of aging-in-place literature in gerontological research.

Inflammation and infection do not promote arterial aging and cardiovascular disease risk factors among lean horticulturalists.

Background Arterial aging is well characterized in industrial populations, but scantly described in populations with little access to modern medicine. Here we characterize health and aging among the Tsimane, Amazonian forager-horticulturalists with short life expectancy, high infectious loads and inflammation, but low adiposity and robust physical fitness. Inflammation has been implicated in all stages of arterial aging, atherogenesis and hypertension, and so we test whether greater inflammation associates with atherosclerosis and CVD risk. In contrast, moderate to vigorous daily activity, minimal obesity, and low fat intake predict minimal CVD risk among older Tsimane. Methods and Findings Peripheral arterial disease (PAD), based on the Ankle-Brachial Index (ABI), and hypertension were measured in Tsimane adults, and compared with rates from industrialized populations. No cases of PAD were found among Tsimane and hypertension was comparatively low (prevalence: 3.5%, 40+; 23%, 70+). Markers of infection and inflammation were much higher among Tsimane than among U.S. adults, whereas HDL was substantially lower. Regression models examine associations of ABI and BP with biomarkers of energy balance and metabolism and of inflammation and infection. Among Tsimane, obesity, blood lipids, and disease history were not significantly associated with ABI. Unlike the Tsimane case, higher cholesterol, C-reactive protein, leukocytes, cigarette smoking and systolic pressure among North Americans are all significantly associated with lower ABI. Conclusions Inflammation may not always be a risk factor for arterial degeneration and CVD, but instead may be offset by other factors: healthy metabolism, active lifestyle, favorable body mass, lean diet, low blood lipids and cardiorespiratory health. Other possibilities, including genetic susceptibility and the role of helminth infections, are discussed. The absence of PAD and CVD among Tsimane parallels anecdotal reports from other small-scale subsistence populations and suggests that chronic vascular disease had little impact on adult mortality throughout most of human evolutionary history.

Biodemography: New approaches to understanding trendsand differences in population health and mortality

The incorporation of biological information in large population surveys has expanded demographic analysis to clarify the meaning of observed trends and differences in population health and mortality. Levels of measured biological risk in the population were reduced in recent years largely because of the expanded use of prescription drugs. The increased use of antihypertensives and, to a lesser extent, lipid-lowering drugs was a likely cause of significant mortality reduction. Blacks and persons with lower educational attainment experience higher levels of biological risk factors, more diseases, and more frailty; these differences are the sources of higher mortality for these groups. Hispanics are less likely to have a higher prevalence of risk factors and diseases than the non-Hispanic population, providing further understanding of the “Hispanic paradox.” Almost every examined indicator of biological risk, disease, and frailty is related to higher mortality, indicating how incorporation of this information provides a fuller understanding of the morbidity process.

Blood lipids, infection, and inflammatory markers in the Tsimane of Bolivia

Objectives: Little is known about blood cholesterol (blood‐C) levels under conditions of infection and limited diet. This study examines blood‐C and markers of infection and inflammation in the Tsimane of the Bolivian Amazon, indigenous forager farmers living in conditions that model preindustrial European populations by their short life expectancy, high load of infections and inflammation, and limited diets.

Bacterial Cell Killing Mediated by Topoisomerase I DNA Cleavage Activity

DNA topoisomerases are important clinical targets for antibacterial and anticancer therapy. At least one type IA DNA topoisomerase can be found in every bacterium, making it a logical target for antibacterial agents that can convert the enzyme into poison by trapping its covalent complex with DNA. However, it has not been possible previously to observe the consequence of having such a stabilized covalent complex of bacterial topoisomerase I in vivo. We isolated a mutant of recombinant Yersinia pestis topoisomerase I that forms a stabilized covalent complex with DNA by screening for the ability to induce the SOS response in Escherichia coli. Overexpression of this mutant topoisomerase I resulted in bacterial cell death. From sequence analysis and site-directed mutagenesis, it was determined that a single amino acid substitution in the TOPRIM domain changing a strictly conserved glycine residue to serine in either the Y. pestis or E. coli topoisomerase I can result in a mutant enzyme that has the SOS-inducing and cell-killing properties. Analysis of the purified mutant enzymes showed that they have no relaxation activity but retain the ability to cleave DNA and form a covalent complex. These results demonstrate that perturbation of the active site region of bacterial topoisomerase I can result in stabilization of the covalent intermediate, with the in vivo consequence of bacterial cell death. Small molecules that induce similar perturbation in the enzyme-DNA complex should be candidates as leads for novel antibacterial agents.