Pathological bile acid concentrations in chronic cholestasis cause adipose mitochondrial defects.

Background & Aims: Although fat loss is observed in patients with cholestasis, how chronically elevated bile acids (BAs) impact white and brown fat depots remains obscure. Methods: To determine the direct effect of pathological levels of BAs on lipid accumulation and mitochondrial function, primary white and brown adipocyte cultures along with fat depots from two separate mouse models of cholestatic liver diseases, namely (i) genetic deletion of farnesoid X receptor (Fxr); small heterodimer (Shp) double knockout (DKO) and (ii) injury by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), were used. Results: As expected, cholestatic mice accumulate high systemic BA levels and exhibit fat loss. Here, we demonstrate that chronic exposure to pathological BA levels results in mitochondrial dysfunction and defective thermogenesis. Consistently, both DKO and DDC-fed mice exhibit lower body temperature. Importantly, thermoneutral (30 °C) housing of the cholestatic DKO mice rescues the decrease in brown fat mass, and the expression of genes responsible for lipogenesis and regulation of mitochondrial function. To overcome systemic effects, primary adipocyte cultures were treated with pathological BA concentrations. Mitochondrial permeability and respiration analysis revealed that BA overload is sufficient to reduce mitochondrial function in primary adipocytes, which is not as a result of cytotoxicity. Instead, we found robust reductions in uncoupling protein 1 (Ucp1), PR domain containing 16 (Prdm16), and deiodinase, iodothyronine, type II (Dio2) transcripts in brown adipocytes upon treatment with chenodeoxycholic acid, whereas taurocholic acid led to the suppression of Dio2 transcript. This BA-mediated decrease in transcripts was alleviated by pharmacological activation of UCP1. Conclusions: High concentrations of BAs cause defective thermogenesis by reducing the expression of crucial regulators of mitochondrial function, including UCP1, which may explain the clinical features of hypothermia and fat loss observed in patients with cholestatic liver diseases. Impact and Implications: We uncover a detrimental effect of chronic bile acid overload on adipose mitochondrial function. Pathological concentration of different BAs reduces the expression of distinct genes involved in energy expenditure, which can be mitigated with pharmacological UCP1 activation.

Reducing Obesogenic Eating Behaviors in Hispanic Children through a Family-Based, Culturally-Tailored RCT: Abriendo Caminos.

Family-based interventions that incorporate culturally-tailored multi-component curricula and are grounded on evidence-based information and theoretical frameworks can help reduce the prevalence of obesity among Hispanic children. Abriendo Caminos: Clearing the Path to Hispanic Health is a multi-site culturally-tailored randomized control trial that aims to reduce obesity rates in Hispanic families by delivering education on nutrition, family wellness, and physical activity. This study evaluated the effect of the Abriendo Caminos six-week intervention on dietary behaviors of Hispanic children (6-18 years). Mothers (n = 365) reported their child's eating behavior intake using the U.S. Department of Education's Early Childhood Longitudinal Study protocol (ECLS). Pre/post dietary changes were evaluated using separate generalized estimating equation models adjusted for site, child sex, and child age group. Findings indicate a reduction in the frequency of sugar-sweetened beverages (OR 0.55, 95% CI 0.35, 0.87, p = 0.01), French fries (OR 0.56, 95% CI 0.36, 0.86, p = 0.009), and fast food (OR 0.55, 95% CI 0.36, 0.84, p = 0.006) consumption among children in the intervention arm. Additionally, children in the intervention arm increased their frequency of vegetable consumption (OR 1.84, 95% CI 1.08, 3.12, p = 0.03). The Abriendo Caminos intervention effectively improved four of eight eating behaviors in a short-term intervention.

Effects of Culturally Tailored Nutrition Education on Dietary Quality of Hispanic Mothers: A Randomized Control Trial.

OBJECTIVE: To assess whether participation in a culturally tailored nutrition education program increases diet quality of Hispanic mothers. DESIGN: A randomized controlled trial. SETTING: Community centers and universities. PARTICIPANTS: Sixty-five mothers (35 in experimental group, 30 in control group) completed pre- and postworkshop surveys. Eligibility criteria included being of Mexican or Puerto Rican descent and having a child between the ages of 6 and 18 years who could participate in the workshops with the parent. INTERVENTION: Families in the experimental group participated in a 6-week workshop series that included weekly nutrition education classes. MAIN OUTCOME MEASURE: Diet quality was assessed by the Rate Your Plate questionnaire. ANALYSIS: Repeated measures ANOVA was used to compare differences between the experimental and control groups. A Wilcoxon signed rank test was conducted to test for significant shifts in categorization pre- and postprogram. RESULTS: There was a significant change in diet quality categorization after participating in the workshops (P < .001, effect size 0.39). No changes were found in the control group. CONCLUSIONS AND IMPLICATIONS: Abriendo Caminos was effective at increasing the diet quality of Hispanic mothers who participated the most in the program. More research is needed in this at-risk population to determine the relationships among nutrition knowledge, diet quality, and achievement of healthy weight.

High mortality among patients with positive blood cultures at a children's hospital in Tbilisi, Georgia.

BACKGROUND: The etiology and outcomes of blood-stream infections (BSI) among paediatric patients is not well described in resource-limited countries including Georgia. METHODOLOGY: Patients with positive blood cultures at the largest paediatric hospital in the country of Georgia were identified by review of the medical and laboratory records of patients who had blood for cultures drawn between January 2004 and June 2006. RESULTS: Of 1,693 blood cultures obtained during the study period, 338 (20%) were positive; of these, 299 were included in our analysis. The median age was 14 days from a range of 2 days to 14 years of which 178 (60%) were male; 53% of the patients with a positive culture were admitted to the Neonatal Intensive Care Unit (NICU). Gram-negative bacilli (GNB) represented 165 (55%) of 299 cultures. Further speciation of 135 (82%) of 165 Gram-negative rod (GNR) was not possible because of lack of laboratory capacity. Overall, mortality was 30% (90 of 299). Among the 90 children who died, 80 (89%) were neonates and 68 (76%) had BSI caused by Gram-negative organisms. In multivariate analysis, independent risk factors for in-hospital mortality included an age of less than 30 days (OR=4.00, 95% CI 1.89-8.46) and having a positive blood culture for a Gram-negative BSI (OR = 2.38, 95% CI 1.32-4.29). CONCLUSIONS: A high mortality rate was seen among children, particularly neonates, with positive blood cultures at the largest paediatric hospital in Georgia. Because of limited laboratory capacity, microbiological identification of common organisms known to cause BSI in children was not possible and susceptibility testing was not performed. Improving the infrastructure of diagnostic microbiology laboratories in countries with limited resources is critical in order to improve patient care and clinical outcomes, and from a public health standpoint, to improve surveillance activities.

Pneumocystis jiroveci pneumonia in patients with AIDS in the inner city: a persistent and deadly opportunistic infection.

Highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality of opportunistic infections including Pneumocystis jiroveci pneumonia (PCP) among HIV-infected individuals. We performed a hospital-based retrospective cohort study among a population of medically underserved inner city persons living in Atlanta, Georgia, diagnosed with confirmed PCP to compare the epidemiology and outcomes of PCP during 2 defined periods: 1990 to 1995, or pre-HAART period, and 1996 to 2001, or HAART period. A total of 488 patients were available for analysis. The overall mortality rate was 47% during the pre-HAART era compared with 37% during the HAART era (P = 0.02). However, among those patients that required medical intensive care unit admission and mechanical ventilation, the mortality rate was particularly high, with over 80% of patients dying as a result of their episode of PCP during both periods. PCP was the initial presentation of HIV infection in 39.3% in the pre-HAART period with a mortality rate of 52%, in contrast with 37% in the HAART period, with a mortality rate of 45%, respectively (P = NS). Only 30.7% in the pre-HAART period and 31.1% of patients in the HAART period were receiving PCP prophylaxis. The overall risk of death, when we combined both groups in the analysis, was higher for those patients who did not take PCP prophylaxis, those who smoked tobacco, and those who were admitted to the medical intensive care unit and required mechanical ventilatory support. Our findings suggest that despite the availability of HAART, PCP continues to cause a significant burden of disease among inner-city HIV-infected populations.

Chagas disease: an impediment in achieving the Millennium Development Goals in Latin American

It presents informations about chagas disease and how this disease is impending the goals of Millennium Development Goals in Latin American. Document in PDF format, required Acrobat Reader.

Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America.

BACKGROUND: Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals. DISCUSSION: Health-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with Trypanosoma cruzi, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America. SUMMARY: Addressing the cycle of destitution and suffering associated with T. cruzi infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential.

Health literacy is a predictor of HIV/AIDS knowledge.

BACKGROUND AND OBJECTIVES: This study's objective was to evaluate the association between health literacy and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) knowledge among patients seen at an inner-city, public hospital urgent care center (UCC). METHODS: We used a prospective survey of patients offered an HIV test by their providers during a UCC visit. We measured patients' health literacy level using the Rapid Estimate of Adult Literacy in Medicine (REALM) scale and assessed their HIV/AIDS knowledge using a 22-item questionnaire. RESULTS: A total of 372 patients were enrolled. Among participants in this relatively young sample (55% were under the age of 40), 92 (25%) had a REALM score at or below a sixth-grade level, and 122 (33%) did not have a high school diploma. Patients' mean HIV/AIDS knowledge scores differed significantly between patients with inadequate health literacy and those with marginal or adequate health literacy. In multivariate analyses, patients' REALM scores were positively associated with patients' HIV/AIDS knowledge even after adjusting for income, education, and risk perception. CONCLUSIONS: These findings demonstrate that HIV/AIDS knowledge is strongly associated with patients' health literacy in this inner-city population. These findings reiterate the need to target HIV prevention strategies toward populations with inadequate health literacy levels and to dispel misconceptions regarding HIV/AIDS that directly influence risk-taking behaviors and health care utilization.

Low health literacy is associated with HIV test acceptance.

BACKGROUND: The Centers for Disease Control and Prevention has proposed increasing the proportion of people who learn their HIV serostatus. The health care setting represents a logical site to accomplish this goal. However, little is known about factors that determine acceptability of HIV testing in health care settings, particularly patients' health literacy. OBJECTIVE: To evaluate the association between patients' health literacy and acceptance of HIV testing among individuals at an urgent care center (UCC). METHODS: As part of a prospective study that sought to increase HIV testing at a UCC located in an inner-city hospital serving an indigent population, we surveyed patients who had been offered an HIV test by their providers and had accepted or refused testing. Pretest counseling was provided using a low-literacy brochure given to patients upon registration into the clinic. We measured health literacy level using the Rapid Estimate of Adult Literacy in Medicine (REALM) scale. RESULTS: Three hundred seventy-two patients were enrolled in the study. In univariate analysis, no statistically significant difference between HIV test acceptors or refusers was found for gender, race/ethnicity, marital status, income, type of health insurance, educational level, or type of test offered. Acceptors were more likely to have a low literacy level (odds ratio [OR], 1.763; 95% confidence interval [CI], 1.084 to 2.866) and be less than 40 years old (OR, 1.639; 95% CI, 1.085 to 2.475). In multivariate analysis, low health literacy was shown to be a predictor of HIV test acceptance controlling for age and education (OR, 2.017; 95% CI, 1.190 to 3.418). CONCLUSIONS: Low health literacy was shown to be a predictor of HIV test acceptance. Patients presenting to a UCC with poorer health literacy appear more willing to comply with health care providers' recommendations to undergo HIV testing than those with adequate health literacy when an "opt-out" strategy combined with a low-literacy brochure is used.

Infectious diseases, non-zero-sum thinking, and the developing world.

Despite some improvements in the health status of the world during the last few decades, major obstacles remain. Improvements in health outcomes have not been shared equally among countries and poverty is clearly the main reason. Infectious diseases, which remain the major cause of death worldwide, are an incalculable source of human misery and economic loss. In fact, 25% of all deaths and 30% of the global burden of disease are attributed to infectious diseases. Unfortunately, more than 95% of these deaths, most of which are preventable, occur in the developing world, where poverty is widespread. The 3 major infectious disease killers in these countries are HIV/AIDS, tuberculosis, and malaria. The principles of social justice and health as a human right in the developing world have been advocated as the main justification for health assistance from rich to poor countries. Although we do not disagree with this, we argue that a strategy that emphasizes the shared benefit to rich and poor countries would facilitate this process. We propose that the accomplishment of these challenging tasks should be viewed from the perspective of game theory, where the interests of the parties (in this case rich and poor countries) overlap. As the world becomes increasingly integrated, economic development in resource-poor countries will increase the opportunities for richer countries to profit from investment in the developing world. Global health has political and international security implications for the developed world, as well. In view of the current health status of the developing world, we are not playing a game but facing a matter of life and death. "When health is absent, wisdom cannot reveal itself, art cannot become manifest, strength cannot fight, wealth becomes useless, and intelligence cannot be applied" --Herophilus, 325 BCE (Physician to Alexander the Great). The purpose of this article is to address the relationship between health, poverty, and development in the context of game theory. We will focus on the link between economic inequalities and health outcomes, exclusively concentrating our analysis on the impact of infectious diseases. Subsequently, we will outline the game, the players, and the potential win-win outcomes that may potentially result.