Preliminary Evidence for Subdimensions of Geriatric Frailty: The MacArthur Study of Successful Aging

OBJECTIVES: To identify frailty subdimensions. DESIGN: Longitudinal cohort (MacArthur Study). SETTING: Three U.S. urban centers. PARTICIPANTS: One thousand one hundred eighteen high‐functioning subjects aged 70 to 79 in 1988. MEASUREMENTS: Participants with three or more of five Cardiovascular Health Study (CHS) frailty criteria (weight loss, weak grip, exhaustion, slow gait, and low physical activity) in 1991 were classified as having the CHS frailty phenotype. To identify frailty subdimensions, factor analysis was conducted using the CHS variables and an expanded set including the CHS variables, cognitive impairment, interleukin‐6 (IL‐6), C‐reactive protein (CRP), subjective weakness, and anorexia. Participants with four or more of 10 criteria were classified as having an expanded frailty phenotype. Predictive validity of each identified frailty subdimension was assessed using regression models for 4‐year disability and 9‐year mortality. RESULTS: Two subdimensions of the CHS phenotype and four subdimensions of the expanded frailty phenotype were identified. Cognitive function was consistently part of a subdimension including slower gait, weaker grip, and lower physical activity. The CHS subdimension of slower gait, weaker grip, and lower physical activity predicted disability (adjusted odds ratio (AOR)=1.7, 95% confidence interval (CI)=1.3–2.2) and mortality (AOR=1.5, 95% CI=1.3–1.8). Subdimensions of the expanded model with predictive validity were higher IL‐6 and CRP (AOR=1.2 for mortality); slower gait, weaker grip, lower physical activity, and lower cognitive function (AOR=1.8 for disability; AOR=1.5 for mortality), and anorexia and weight loss (AOR=1.2 for disability). CONCLUSION: This study provides preliminary empirical support for subdimensions of geriatric frailty, suggesting that pathways to frailty differ and that subdimension‐adapted care might enhance care of frail seniors.     

Reversible interconversion of carbon dioxide and formate by an electroactive enzyme

Carbon dioxide (CO₂) is a kinetically and thermodynamically stable molecule. It is easily formed by the oxidation of organic molecules, during combustion or respiration, but is difficult to reduce. The production of reduced carbon compounds from CO₂ is an attractive proposition, because carbon-neutral energy sources could be used to generate fuel resources and sequester CO₂ from the atmosphere. However, available methods for the electrochemical reduction of CO₂ require excessive overpotentials (are energetically wasteful) and produce mixtures of products. Here, we show that a tungsten-containing formate dehydrogenase enzyme (FDH1) adsorbed to an electrode surface catalyzes the efficient electrochemical reduction of CO₂ to formate. Electrocatalysis by FDH1 is thermodynamically reversible—only small overpotentials are required, and the point of zero net catalytic current defines the reduction potential. It occurs under thoroughly mild conditions, and formate is the only product. Both as a homogeneous catalyst and on the electrode, FDH1 catalyzes CO₂ reduction with a rate more than two orders of magnitude faster than that of any known catalyst for the same reaction. Formate oxidation is more than five times faster than CO₂ reduction. Thermodynamically, formate and hydrogen are oxidized at similar potentials, so formate is a viable energy source in its own right as well as an industrially important feedstock and a stable intermediate in the conversion of CO₂ to methanol and methane. FDH1 demonstrates the feasibility of interconverting CO₂ and formate electrochemically, and it is a template for the development of robust synthetic catalysts suitable for practical applications.     

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome

Objective: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients.Methods: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue.Results: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P=0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas.Conclusions: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.     

Relationship between subjective social status and measures of health in older Taiwanese persons

OBJECTIVES: To compare the association between subjective ladder ranking and health measures with the association between objective indices and health measures in older Taiwanese men and women. DESIGN: Cross-sectional study. SETTING: A population-representative sample of elderly and nearly elderly men and women in Taiwan. PARTICIPANTS: The study included 991 participants from the Social Environment and Biomarkers of Aging Study in Taiwan. MEASUREMENTS: The information collected included demographic characteristics; subjective ladder score of SES; objective measures of SES, including education, income, and occupation; health behaviors; health-related variables such as self-rated health, basic activity of daily living difficulties, instrumental activity of daily living (IADL) difficulties, and physical activity difficulties; and depression score. RESULTS: Low ladder score was associated with poorer self-rated health and more reported IADL and physical activity difficulties, even after adjustment for objective measures of SES and other covariates. The multiply adjusted odds ratio for a one-quartile difference in ladder score and worse self-rated health was 1.19 (95% confidence interval=1.06-1.33). The associations between subjective ladder ranking and health status were generally stronger in those who had 6 years or less of education than in those who received more education. CONCLUSION: A simple subjective assessment of one's ranking on the social hierarchy was associated with self-rated health and physical functional status in an older ethnic Chinese population. The associations were independent of the effects of traditional objective measures of SES, such as education, income, and occupation.     

Decreased ATP-sensitive K(+) current density during chronic human atrial fibrillation

Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However, little is known about the activity of ATP-sensitive K(+) channels (I(K,ATP)) during chronic AF. An AF-related increase in the activity of I(K,ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of I(K,ATP) in atrial myocytes from patients with sinus rhythm (SR) and chronic AF. Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I(K,ATP) was activated with the I(K,ATP) channel opener rilmakalim. The inward rectifier I(K1) and I(K,ATP) were identified by their sensitivity to 1 mM Ba(2+). Density of I(K1) did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I(K,ATP) (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 microM). However, maximum activation of I(K,ATP) with 10 microM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF, n = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I(K,ATP) current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K(+) currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF.     

Examining Mediators of the Relationship Between Community Mobilization and HIV Incidence Among Young South African Women Participating in the HPTN 068 Study Cohort

AIDS and Behavior - We previously demonstrated that village community mobilization (CM) was associated with reduced HIV incidence among adolescent girls and young women (AGYW) in South Africa....     

Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats

BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.