Biomedical subjects

Burton H Singer

Publications and source records attributed to Burton H Singer.

At least 19 recordsLinked to original sources

PubMed2006

Combinations of biomarkers predictive of later life mortality.

A wide range of biomarkers, reflecting activity in a number of biological systems (e.g., neuroendocrine, immune, cardiovascular, and metabolic), have been found to prospectively predict disability, morbidity, and mortality outcomes in older adult populations. Levels of these biomarkers, singly or in combination, may serve as an early warning system of risk for future adverse health outcomes. In the current investigation, 13 biomarkers were examined as predictors of mortality occurrence over a 12-year period in a sample of men and women (n = 1,189) 70-79 years of age at enrollment into the study. Biomarkers examined in analyses included markers of neuroendocrine functioning (epinephrine, norepinephrine, cortisol, and dehydroepiandrosterone), immune activity (C-reactive protein, fibrinogen, IL-6, and albumin), cardiovascular functioning (systolic and diastolic blood pressure), and metabolic activity [high-density lipoprotein (HDL) cholesterol, total to HDL cholesterol ratio, and glycosylated hemoglobin]. Recursive partitioning techniques were used to identify a set of pathways, composed of combinations of different biomarkers, that were associated with a high-risk of mortality over the 12-year period. Of the 13 biomarkers examined, almost all entered into one or more high-risk pathways although combinations of neuroendocrine and immune markers appeared frequently in high-risk male pathways, and systolic blood pressure was present in combination with other biomarkers in all high-risk female pathways. These findings illustrate the utility of recursive partitioning techniques in identifying biomarker combinations predictive of mortal outcomes in older adults, as well as the multiplicity of biological pathways to mortality in elderly populations.

Age Factors↗

PubMed2006

Spatial patterns of malaria in the Amazon: implications for surveillance and targeted interventions.

A measure of local spatial association, G(i)*(d), is applied to test for the presence of malaria clusters in a colonization area in the Brazilian Amazon. Clusters of high and low malaria rates at different moments in time are identified. They suggest unambiguous spatial patterns of transmission, most likely linked to the social and natural habitat. Results imply that a comprehensive identification of the determinants of malaria transmission requires a spatial framework of analysis, and that control strategies must be spatially targeted and guided by a surveillance system that constantly learns the specificities of local transmission and adapts interventions to them.

Brazil↗

PubMed2006

An integrated approach for risk profiling and spatial prediction of Schistosoma mansoni-hookworm coinfection.

Multiple-species parasitic infections are pervasive in the developing world, yet resources for their control are scarce. We present an integrated approach for risk profiling and spatial prediction of coinfection with Schistosoma mansoni and hookworm for western Côte d'Ivoire. Our approach combines demographic, environmental, and socioeconomic data; incorporates them into a geographic information system; and employs spatial statistics. Demographic and socioeconomic data were obtained from education registries and from a questionnaire administered to schoolchildren. Environmental data were derived from remotely sensed satellite images and digitized ground maps. Parasitologic data, obtained from fecal examination by using two different diagnostic approaches, served as the outcome measure. Bayesian variogram models were used to assess risk factors and spatial variation of S. mansoni-hookworm coinfection in relation to demographic, environmental, and socioeconomic variables. Coinfections were found in 680 of 3,578 schoolchildren (19.0%) with complete data records. The prevalence of monoinfections with either hookworm or S. mansoni was 24.3% and 24.1%, respectively. Multinomial Bayesian spatial models showed that age, sex, socioeconomic status, and elevation were good predictors for the spatial distribution of S. mansoni-hookworm coinfection. We conclude that our integrated approach, employing a diversity of data sources, geographic information system and remote sensing technologies, and Bayesian spatial statistics, is a powerful tool for risk profiling and spatial prediction of S. mansoni-hookworm coinfection. More generally, this approach facilitates risk mapping and prediction of other parasite combinations and multiparasitism, and hence can guide integrated disease control programs in resource-constrained settings.

Adolescent↗

PubMed2006

Malaria risk on the Amazon frontier.

Frontier malaria is a biological, ecological, and sociodemographic phenomenon operating over time at three spatial scales (micro/individual, community, and state and national). We explicate these linkages by integrating data from remote sensing surveys, ground-level surveys and ethnographic appraisal, focusing on the Machadinho settlement project in Rondônia, Brazil. Spatially explicit analyses reveal that the early stages of frontier settlement are dominated by environmental risks, consequential to ecosystem transformations that promote larval habitats of Anopheles darlingi. With the advance of forest clearance and the establishment of agriculture, ranching, and urban development, malaria transmission is substantially reduced, and risks of new infection are largely driven by human behavioral factors. Malaria mitigation strategies for frontier settlements require a combination of preventive and curative methods and close collaboration between the health and agricultural sectors. Of fundamental importance is matching the agricultural potential of specific plots to the economic and technical capacities of new migrants. Equally important is providing an effective agricultural extension service.

Animals↗

PubMed2005

Social relationships, sleep quality, and interleukin-6 in aging women.

This study examined the interplay of social engagement, sleep quality, and plasma levels of interleukin-6 (IL-6) in a sample of aging women (n = 74, aged 61-90, M age = 73.4). Social engagement was assessed by questionnaire, sleep was assessed by using the NightCap in-home sleep monitoring system and the Pittsburgh Sleep Quality Index, and blood samples were obtained for analysis of plasma levels of IL-6. Regarding subjective assessment, poorer sleep (higher scores on the Pittsburgh Sleep Quality Index) was associated with lower positive social relations scores. Multivariate regression analyses showed that lower levels of plasma IL-6 were predicted by greater sleep efficiency (P < 0.001), measured objectively and by more positive social relations (P < 0.05). A significant interaction showed that women with the highest IL-6 levels were those with both poor sleep efficiency and poor social relations (P < 0.05). However, those with low sleep efficiency but compensating good relationships as well as women with poor relationships but compensating high sleep efficiency had IL-6 levels comparable to those with the protective influences of both good social ties and good sleep.

Aged↗

PubMed2005

Urinary cortisol excretion as a predictor of incident cognitive impairment.

Elevated glucocorticoid levels have been associated with cognitive impairment, including dementia. However, few longitudinal studies have examined the association between resting cortisol levels and the incidence of cognitive impairment. We measured overnight urinary excretion of cortisol in 538 high-functioning men and women, 70-79 years of age, in 1988, and assessed their cognitive functioning in 1988, 1991, and 1995 using the short portable mental status questionnaire (SPMSQ). Compared to participants in the bottom quartile of urinary cortisol at baseline, those in the top three quartiles had higher risk of incident cognitive impairment over the 7-year follow up (i.e., decline in SPMSQ score to below six out of nine). This association was not affected by adjustment for age, gender, education level, ethnicity, smoking, prevalent cardiovascular disease, and blood pressure (adjusted odds ratio for the highest quartile 2.34, 95% confidence interval, 1.07-5.14). There was no effect modification by gender; the association was equally strong in men and women. We conclude that urinary excretion of cortisol predicts incident cognitive impairment in older men and women.

Aged↗

PubMed2005

System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster.

A metabolic profiling strategy was used to investigate the metabolic responses of Syrian hamsters (SLAC) to a Schistosoma japonicum infection using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy and pattern recognition. In two independent experiments, male hamsters were each infected with 100 S. japonicum cercariae. At days 34-36 post-infection, urine was obtained from hamsters housed individually in metabolism cages. At the same time, urine was collected from age- and sex-matched infection-free control hamsters. The main biochemical effects of a S. japonicum infection in the hamster consisted of reduced levels of urinary tricarboxylic acid cycle intermediates, including citrate and succinate and increased levels of pyruvate. In addition, a range of microbial-related metabolites, such as hippurate, p-cresol glucuronide, phenylacetylglycine and trimethylamine were also associated with a S. japonicum infection. Most of the observed biochemical effects were in common with those previously characterized for a S. mansoni infection in a mouse host. The major distinguishing consequence of a S. japonicum infection in the hamster was the inhibition of manufacture or utilization of short-chain fatty acids, when compared to a S. mansoni infection in the mouse.

Animals↗

PubMed2005

Effect of irrigated rice agriculture on Japanese encephalitis, including challenges and opportunities for integrated vector management.

Japanese encephalitis (JE) is a disease caused by an arbovirus that is spread by marsh birds, amplified by pigs, and mainly transmitted by the bite of infected Culex tritaeniorhynchus mosquitoes. The estimated annual incidence and mortality rates are 30,000--50,000 and 10,000, respectively, and the estimated global burden of JE in 2002 was 709,000 disability-adjusted life years lost. Here, we discuss the contextual determinants of JE, and systematically examine studies assessing the relationship between irrigated rice agriculture and clinical parameters of JE. Estimates of the sizes of the rural population and population in irrigated areas are presented, and trends of the rural population, the rice-irrigated area, and the rice production are analyzed from 1963 to 2003. We find that approximately 1.9 billion people currently live in rural JE-prone areas of the world. Among them 220 million people live in proximity to rice-irrigation schemes. In 2003, the total rice harvested area of all JE-endemic countries (excluding the Russian Federation and Australia) was 1,345,000 km(2). This is an increase of 22% over the past 40 years. Meanwhile, the total rice production in these countries has risen from 226 millions of tonnes to 529 millions of tonnes (+134%). Finally, we evaluate the effect of different vector control interventions in rice fields, including environmental measures (i.e. alternate wet and dry irrigation (AWDI)), and biological control approaches (i.e. bacteria, nematodes, invertebrate predators, larvivorous fish, fungi and other natural products). We conclude that in JE-endemic rural settings, where vaccination rates are often low, an integrated vector management approach with AWDI and the use of larvivorous fish as its main components can reduce vector populations, and hence has the potential to reduce the transmission level and the burden of JE.

Agriculture↗

PubMed2005

Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging.

BACKGROUND: High stress hormone levels are associated with increased risk of cognitive decline in elderly individuals. However, the effect of late-life changes in stress hormone levels on cognitive decline risk has not been examined. Our objective was to investigate whether increase over time in urinary epinephrine excretion in older adults was associated with subsequent cognitive decline. METHODS: Measurements were made on 154 high-functioning men and women, 70-79 years of age, in 1988, 1991, and 1995. Twelve-hour overnight urinary excretion of epinephrine (normalized by creatinine excretion to adjust for body size) was recorded in 1988 and 1991. Cognitive functioning was assessed in 1991 and 1995 by summary scores based on standard tests of language, memory, abstraction, spatial recognition, and spatial construction. RESULTS: Compared to individuals whose epinephrine excretion decreased between 1988 and 1991, the individuals whose epinephrine excretion increased over the same period had greater subsequent declines in summary cognitive scores between 1991 and 1995. After adjusting for baseline epinephrine, baseline cognitive function, and relevant covariates, and stratifying by gender, increases in urine epinephrine were positively associated with cognitive decline only in men. CONCLUSIONS: We conclude that increase in urinary excretion of epinephrine predicts subsequent cognitive decline in older men.

Aged↗

PubMed2005

Impact of socioeconomic status on longitudinal accumulation of cardiovascular risk in young adults: the CARDIA Study (USA).

Our objectives were to describe the trajectories of biological risk factors of cardiovascular disease in young adults, and to study the association of socioeconomic status (SES) with aggregate risk scores that summarize longitudinal risk accumulation from multiple risk factors. We used data from a prospective, bi-racial, cohort study of 18-30-year-old adults in the USA, initiated in 1985, with 10-year follow-up. SES was measured by parental education level, financial hardship during the study, and the participant's education level by the end of the study. We studied growth patterns of seven biological risk factors for cardiovascular disease using a semi-parametric, class-mixture model to identify clusters of individuals with distinct growth trajectories. Risk scores that summarize risk from all seven risk factors were created to reflect risk at baseline, longitudinal risk change over 10 years, and total accumulated risk. Multivariable regression was used to study their associations with SES within each race/gender group. We found tracking of all seven risk factors: in each case, the cluster with the highest baseline value maintained its position as the highest-risk cluster over the next 10 years. After adjustment for age, lifestyle, and healthcare access, SES was associated inversely with baseline risk score in women (black and white), with risk change score in all four race/gender groups, and with accumulated risk score in women (black and white) and in white men. Our findings suggest that individuals with high overall cardiovascular risk in midlife can be identified by their relatively higher values of risk factors in younger ages and that socioeconomic differences in cardiovascular risk start accumulating early in life.

Adolescent↗

PubMed2005

Reducing the burden of malaria in different eco-epidemiological settings with environmental management: a systematic review.

The public health and economic significance of malaria is enormous, and its control remains a great challenge. Many established malaria control methods are hampered by drug resistance and insecticide-resistant vectors. Malaria control measures built around environmental management are non-toxic, cost-effective, and sustainable. However, there has been no comprehensive review of the literature or meta-analysis examining the effect of these interventions. We therefore did a systematic literature review and identified 40 studies that emphasised environmental management interventions and reported clinical malaria variables as outcome measures. Of these 40 studies, environmental modification (measures aiming to create a permanent or long-lasting effect on land, water, or vegetation to reduce vector habitats--eg, the installation and maintenance of drains) was the central feature in 27 studies, environmental manipulation (methods creating temporary unfavourable conditions for the vector--eg, water or vegetation management) in four, and nine quantified the effect of modifications of human habitation. Most of the studies (n=34, 85%) were implemented before the Global Malaria Eradication Campaign (1955-69), which mainly relied on indoor residual spraying with dichlorodiphenyltrichloroethane (DDT). In 16 studies that applied environmental modification and in eight studies on modification of human habitation, the risk ratio of malaria was reduced by 88.0% (95% CI 81.7-92.1) and 79.5% (95% CI 67.4-87.2), respectively. We conclude that malaria control programmes that emphasise environmental management are highly effective in reducing morbidity and mortality. Lessons learned from these past successful programmes can inspire sound and sustainable malaria control approaches and strategies.

Communicable Disease Control↗

PubMed2005

Social environments and the genetics of aging: advancing knowledge of protective health mechanisms.

We selectively review the literature in behavioral and molecular genetics, including both laboratory and epidemiologic studies, with emphasis on how social environments, particularly emotion in significant social relationships, influence gene expression. Attention is given to cross-talk between human and animal studies. Environments are pivotal in understanding phenotypic outcomes, and this demands research on gene-environment interactions. Illustrative interactions, involving both behavioral and molecular genetics, are provided. Many people with susceptibility genes for diverse diseases never proceed to disease status. Substantial associational evidence implicates social environmental factors as protective agents. Mechanistic understanding of these linkages is quite advanced in some animal populations and suggests new lines of inquiry in human studies. Developing the interface between genetics, social environments, and health will require close collaboration between those well versed in molecular biology and biochemistry and persons with expertise in genetic epidemiology and social psychology. Particularly important is the identification of environmental influences that protect susceptible persons from disease incidence.

Aged↗

PubMed2005

Environmental risks in the developing world: exposure indicators for evaluating interventions, programmes, and policies.

BACKGROUND: Monitoring and empirical evaluation are essential components of evidence based public health policies and programmes. Consequently, there is a growing interest in monitoring of, and indicators for, major environmental health risks, particularly in the developing world. Current large scale data collection efforts are generally disconnected from micro-scale studies in health sciences, which in turn have insufficiently investigated the behavioural and socioeconomic factors that influence exposure. STUDY DESIGN: A basic framework is proposed for development of indicators of exposure to environmental health risks that would facilitate the (a) assessment of the health effects of risk factors, (b) design and evaluation of interventions and programmes to deliver the interventions, and (c) appraisal and quantification of inequalities in health effects of risk factors, and benefits of intervention programmes and policies. Specific emphasis is put on the features of environmental risks that should guide the choice of indicators, in particular the interactions of technology, the environment, and human behaviour in determining exposure. The indicators are divided into four categories: (a) access and infrastructure, (b) technology, (c) agents and vectors, and (d) behaviour. The study used water and sanitation, indoor air pollution from solid fuels, urban ambient air pollution, and malaria as illustrative examples for this framework. CONCLUSIONS: Organised and systematic indicator selection and monitoring can provide an evidence base for design and implementation of more effective and equitable technological interventions, delivery programmes, and policies for environmental health risks in resource poor settings.

Air Pollution↗

PubMed2005

Effect of irrigation and large dams on the burden of malaria on a global and regional scale.

Human-made ecologic transformations have occurred at an unprecedented rate over the past 50 years. Prominent among them are water resource development projects. An estimated 40,000 large dams and 800,000 small dams have been built, and 272 million hectares of land are currently under irrigation worldwide. The establishment and operation of water projects has had a history of facilitating a change in the frequency and transmission dynamics of malaria, but analyses of these environmental risk factors are sparse. Here, we present a comprehensive review of studies that assessed the impact of irrigation and dam building on malaria prevalence or incidence, stratified by the World Health Organization's (WHO) sub-regions of the world, and link these studies with the latest statistics on disability adjusted life years, irrigated agriculture, and large dams. We also present estimates of the population at risk due to proximity to irrigation schemes and large dam reservoirs. In WHO sub-regions 1 and 2, which have 87.9% of the current global malaria burden, only 9.4 million people are estimated to live near large dams and irrigation schemes. In contrast, the remaining sub-regions concentrate an estimated 15.3 million people near large dams and up to 845 million near irrigation sites, while here only 12.1% of the global malaria burden is concentrated. Whether an individual water project triggers an increase in malaria transmission depends on the contextual determinants of malaria, including the epidemiologic setting, socioeconomic factors, vector management, and health seeking behavior. We conclude that in unstable malaria endemic areas, integrated malaria control measures, coupled with sound water management, are mandatory to mitigate the current burden of malaria in locations near irrigation or dam sites.

Endemic Diseases↗

PubMed2005

Effect of water resource development and management on lymphatic filariasis, and estimates of populations at risk.

Lymphatic filariasis (LF) is a debilitating disease overwhelmingly caused by Wuchereria bancrofti, which is transmitted by various mosquito species. Here, we present a systematic literature review with the following objectives: (i) to establish global and regional estimates of populations at risk of LF with particular consideration of water resource development projects, and (ii) to assess the effects of water resource development and management on the frequency and transmission dynamics of the disease. We estimate that globally, 2 billion people are at risk of LF. Among them, there are 394.5 million urban dwellers without access to improved sanitation and 213 million rural dwellers living in close proximity to irrigation. Environmental changes due to water resource development and management consistently led to a shift in vector species composition and generally to a strong proliferation of vector populations. For example, in World Health Organization (WHO) subregions 1 and 2, mosquito densities of the Anopheles gambiae complex and Anopheles funestus were up to 25-fold higher in irrigated areas when compared with irrigation-free sites. Although the infection prevalence of LF often increased after the implementation of a water project, there was no clear association with clinical symptoms. Concluding, there is a need to assess and quantify changes of LF transmission parameters and clinical manifestations over the entire course of water resource developments. Where resources allow, integrated vector management should complement mass drug administration, and broad-based monitoring and surveillance of the disease should become an integral part of large-scale waste management and sanitation programs, whose basic rationale lies in a systemic approach to city, district, and regional level health services and disease prevention.

Elephantiasis, Filarial↗

PubMed2004

Positive health: connecting well-being with biology.

Two key types of well-being, eudaimonic and hedonic, are reviewed. The first addresses ideas of self-development, personal growth and purposeful engagement, while the second is concerned with positive feelings such as happiness and contentment. How well-being varies by age and socio-economic standing is briefly summarized, followed by examination of its biological correlates (neuroendocrine, immune, cardiovascular, rapid eye movement (REM) sleep). Preliminary findings on a sample of ageing women showed that those with higher levels of eudaimonic well-being had lower levels of daily salivary cortisol, pro-inflammatory cytokines, cardiovascular risk, and longer duration REM sleep compared with those showing lower levels of eudaimonic well-being. Hedonic well-being, however, showed minimal linkage to biomarker assessments. Future research directions building on these initial findings are discussed.

Age Factors↗

PubMed2004

Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification.

Schistosomiasis, a chronic and debilitating parasitic disease, affects approximately 200 million people in the developing world and imposes a substantial public health and economic impact. Accurately diagnosing at the individual level, monitoring disease progression, and assessing the impact of pharmacological interventions at the population level are of prime importance for controlling schistosomiasis. Using a Schistosoma mansoni-mouse model, we present a characterization of a parasitic infection by metabolic profiling, employing (1)H NMR spectroscopy and multivariate pattern recognition techniques. We infected 10 mice with 80 S. mansoni cercariae each and collected urine samples 49 and 56 days postinfection. Urine samples were also obtained from 10 uninfected control mice at the same time. The metabolic signature of an S. mansoni infection consists of reduced levels of the tricarboxylic acid cycle intermediates, including citrate, succinate, and 2-oxoglutarate, and increased levels of pyruvate, suggesting stimulated glycolysis. A disturbance of amino acid metabolism was also associated with an S. mansoni infection, as indicated by depletion of taurine, 2-oxoisocaproate, and 2-oxoisovalerate and elevation of tryptophan in the urine. A range of microbial-related metabolites, i.e., trimethylamine, phenylacetylglycine, acetate, p-cresol glucuronide, butyrate, propionate, and hippurate, were also coupled with an S. mansoni infection, indicating disturbances in the gut microbiota. Our work highlights the potential of metabolic profiling to enhance our understanding of biological responses to parasitic infections. It also holds promise as a basis for novel diagnostic tests with high sensitivity and specificity and for improved disease surveillance and control.

Animals↗

PubMed2004

Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d'Ivoire.

BACKGROUND: Concomitant parasitic infections are common in the developing world, yet most studies focus on a single parasite in a narrow age group. We investigated the extent of polyparasitism and parasite associations, and related these findings to self-reported morbidity. METHODS: Inhabitants of 75 randomly selected households from a single village in western Côte d'Ivoire provided multiple faecal specimens and a single finger prick blood sample. The Kato-Katz technique and a formol-ether concentration method were employed to screen faecal samples for Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa. Giemsa-stained blood smears were analysed for malaria parasites. A questionnaire was administered for collection of demographic information and self-reported morbidity indicators. RESULTS: Complete parasitological data were obtained for 500/561 (89.1%) participants, similarly distributed among sex, with an age range from 5 days to 91 years. The prevalences of Plasmodium falciparum, hookworms, Entamoeba histolytica/E. dispar, and S. mansoni were 76.4%, 45.0%, 42.2%, and 39.8%, respectively. Three-quarters of the population harboured three or more parasites concurrently. Multivariate analysis revealed significant associations between several pairs of parasites. Some parasitic infections and the total number of parasites were significantly associated with self-reported morbidity indicators. CONCLUSIONS: Our data confirm that polyparasitism is very common in rural Côte d'Ivoire and that people have clear perceptions about the morbidity caused by some of these parasitic infections. Our findings can be used for the design and implementation of sound intervention strategies to mitigate morbidity and co-morbidity.

Adolescent↗