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Find video protocols related to scientific articles indexed in Pubmed.
The relationship between gun ownership and stranger and nonstranger firearm homicide rates in the United States, 1981-2010.
Am J Public Health
PUBLISHED: 08-14-2014
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We examined the relationship between gun ownership and stranger versus nonstranger homicide rates.
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Cross-sectional study of the burden of vector-borne and soil-transmitted polyparasitism in rural communities of Coast Province, Kenya.
PLoS Negl Trop Dis
PUBLISHED: 07-01-2014
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In coastal Kenya, infection of human populations by a variety of parasites often results in co-infection or poly-parasitism. These parasitic infections, separately and in conjunction, are a major cause of chronic clinical and sub-clinical human disease and exert a long-term toll on economic welfare of affected populations. Risk factors for these infections are often shared and overlap in space, resulting in interrelated patterns of transmission that need to be considered at different spatial scales. Integration of novel quantitative tools and qualitative approaches is needed to analyze transmission dynamics and design effective interventions.
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Isolation, culture, and imaging of human fetal pancreatic cell clusters.
J Vis Exp
PUBLISHED: 06-05-2014
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For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation(1-9). However in vitro, genesis of insulin producing cells from human fetal ICCs is low(10); results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise as a potential therapeutic treatment for type 1 diabetes. Like ICCs, transplantation of partially differentiated hESC generate glucose responsive, insulin producing cells, but in vitro genesis of insulin producing cells from hESC is much less robust(11-17). A complete understanding of the factors that influence the growth and differentiation of endocrine precursor cells will likely require data generated from both ICCs and hESC. While a number of protocols exist to generate insulin producing cells from hESC in vitro(11-22), far fewer exist for ICCs(10,23,24). Part of that discrepancy likely comes from the difficulty of working with human fetal pancreas. Towards that end, we have continued to build upon existing methods to isolate fetal islets from human pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a monolayer or in suspension, and image for cell proliferation, pancreatic markers and human hormones including glucagon and C-peptide. ICCs generated by the protocol described below result in C-peptide release after transplantation under the kidney capsule of nude mice that are similar to C-peptide levels obtained by transplantation of fresh tissue(6). Although the examples presented here focus upon the pancreatic endoderm proliferation and ? cell genesis, the protocol can be employed to study other aspects of pancreatic development, including exocrine, ductal, and other hormone producing cells.
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HIV and schistosomiasis co-infection in African children.
Lancet Infect Dis
PUBLISHED: 04-17-2014
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HIV/AIDS and schistosomiasis both cause a substantial disease burden in sub-Saharan Africa and the two diseases often overlap in their epidemiological characteristics. Although disease-specific control interventions are continuing, potential synergies in the control efforts for these two diseases have not been investigated. With a focus on children with schistosomiasis, we assess the risk for increased HIV transmission, HIV progression, and impaired response to drugs when given alongside HIV interventions. A new research agenda tailored to children is needed to better understand the interactions of these two diseases and the potential for combined responses.
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Examining the relationship between the prevalence of guns and homicide rates in the USA using a new and improved state-level gun ownership proxy.
Inj. Prev.
PUBLISHED: 04-16-2014
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Determining the relationship between gun ownership levels and firearm homicide rates is critical to inform public health policy. Previous research has shown that state-level gun ownership, as measured by a widely used proxy, is positively associated with firearm homicide rates. A newly developed proxy measure that incorporates the hunting license rate in addition to the proportion of firearm suicides correlates more highly with state-level gun ownership. To corroborate previous research, we used this new proxy to estimate the association of state-level gun ownership with total, firearm, and non-firearm homicides. Using state-specific data for the years 1981-2010, we modelled these rates as a function of gun ownership level, controlling for potential confounding factors. We used a negative binomial regression model and accounted for clustering of observations among states. We found that state-level gun ownership as measured by the new proxy, is significantly associated with firearm and total homicides but not with non-firearm homicides.
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Human schistosomiasis.
Lancet
PUBLISHED: 04-01-2014
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Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.
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sRNA-seq analysis of human embryonic stem cells and definitive endoderm reveals differentially expressed microRNAs and novel IsomiRs with distinct targets.
Stem Cells
PUBLISHED: 03-30-2014
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MicroRNAs (miRNAs) are noncoding, regulatory RNAs expressed dynamically during differentiation of human embryonic stem cells (hESCs) into defined lineages. Mapping developmental expression of miRNAs during transition from pluripotency to definitive endoderm (DE) should help to elucidate the mechanisms underlying lineage specification and ultimately enhance differentiation protocols. In this report, next generation sequencing was used to build upon our previous analysis of miRNA expression in human hESCs and DE. From millions of sequencing reads, 747 and 734 annotated miRNAs were identified in pluripotent and DE cells, respectively, including 77 differentially expressed miRNAs. Among these, four of the top five upregulated miRNAs were previously undetected in DE. Furthermore, the stem-loop for miR-302a, an important miRNA for both hESCs self-renewal and endoderm specification, produced several highly expressed miRNA species (isomiRs). Overall, isomiRs represented >10% of sequencing reads in >40% of all detected stem-loop arms, suggesting that the impact of these abundant miRNA species may have been overlooked in previous studies. Because of their relative abundance, the role of differential isomiR targeting was studied using the miR-302 cluster as a model system. A miRNA mimetic for miR-302a-5p, but not miR-302a-5p(+3), decreased expression of orthodenticle homeobox 2 (OTX2). Conversely, isomiR 302a-5p(+3) selectively decreased expression of tuberous sclerosis protein 1, but not OTX2, indicating nonoverlapping specificity of miRNA processing variants. Taken together, our characterization of miRNA expression, which includes novel miRNAs and isomiRs, helps establish a foundation for understanding the role of miRNAs in DE formation and selective targeting by isomiRs.
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Development of a specimen-sparing multichannel bead assay to detect antiparasite IgG4 for the diagnosis of Schistosoma and Wuchereria infections on the coast of Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 02-10-2014
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To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay. For schistosomiasis, the bead assay had an estimated sensitivity of 81% and a specificity of 45%, and it was more sensitive than ELISA or urine egg counts for diagnosing infection. For filariasis, it had a sensitivity of 86% and a specificity of 39%, and it was more sensitive than ELISA or RDT. Measuring antibody by MFI is feasible and may provide more accurate epidemiological information than current parasitological tests, especially in the setting of low-intensity infections.
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Monitoring malaria vector control interventions: effectiveness of five different adult mosquito sampling methods.
J. Med. Entomol.
PUBLISHED: 11-05-2013
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Long-term success of ongoing malaria control efforts based on mosquito bed nets (long-lasting insecticidal net) and indoor residual spraying is dependent on continuous monitoring of mosquito vectors, and thus on effective mosquito sampling tools. The objective of our study was to identify the most efficient mosquito sampling tool(s) for routine vector surveillance for malaria and lymphatic filariasis transmission in coastal Kenya. We evaluated relative efficacy of five collection methods--light traps associated with a person sleeping under a net, pyrethrum spray catches, Prokopack aspirator, clay pots, and urine-baited traps--in four villages representing three ecological settings along the south coast of Kenya. Of the five methods, light traps were the most efficient for collecting female Anopheles gambiae s.l. (Giles) (Diptera: Culicidae) and Anopheles funestus (Giles) (Diptera: Culicidae) mosquitoes, whereas the Prokopack aspirator was most efficient in collecting Culex quinquefasciatus (Say) (Diptera: Culicidae) and other culicines. With the low vector densities here, and across much of sub-Saharan Africa, wherever malaria interventions, long-lasting insecticidal nets, and/or indoor residual spraying are in place, the use of a single mosquito collection method will not be sufficient to achieve a representative sample of mosquito population structure. Light traps will remain a relevant tool for host-seeking mosquitoes, especially in the absence of human landing catches. For a fair representation of the indoor mosquito population, light traps will have to be supplemented with aspirator use, which has potential for routine monitoring of indoor resting mosquitoes, and can substitute the more labor-intensive and intrusive pyrethrum spray catches. There are still no sufficiently efficient mosquito collection methods for sampling outdoor mosquitoes, particularly those that are bloodfed.
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State-specific liquor excise taxes and retail prices in 8 US states, 2012.
Subst Abus
PUBLISHED: 10-29-2013
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The authors investigated the relationship between state excise taxes and liquor prices in 8 states, using 2012 data for 45 brands. The authors made 6042 price observations among 177 liquor stores with online prices. Using a hierarchical model, the authors examined the relationship between excise taxes and product prices. State excise taxes were significantly related to liquor prices, with an estimated pass-through rate of 0.93. The proportion of price accounted for by excise taxes averaged 7.0%. The authors find that excise taxes do increase the price of alcohol, but states are not taking advantage of this opportunity to reduce alcohol-related morbidity and mortality.
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The relationship between gun ownership and firearm homicide rates in the United States, 1981-2010.
Am J Public Health
PUBLISHED: 09-12-2013
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We examined the relationship between levels of household firearm ownership, as measured directly and by a proxy-the percentage of suicides committed with a firearm-and age-adjusted firearm homicide rates at the state level.
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Meta-analysis of urine heme dipstick diagnosis of Schistosoma haematobium infection, including low-prevalence and previously-treated populations.
PLoS Negl Trop Dis
PUBLISHED: 09-01-2013
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Urogenital schistosomiasis remains highly endemic in Africa. Current control is based on drug administration, targeted either to school-age children or to high-risk communities at-large. Urine dipsticks for detection of microhematuria offer an inexpensive means for estimating infection prevalence. However, their diagnostic performance has not been systematically evaluated after community treatment, or in areas with continuing low prevalence. The objective of the present study was to perform meta-analysis of dipstick accuracy for S. haematobium infection in endemic regions, with special attention to performance where infection intensity or prevalence was low.
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A new proxy measure for state-level gun ownership in studies of firearm injury prevention.
Inj. Prev.
PUBLISHED: 08-16-2013
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Since many states are considering gun control laws, researchers need reliable data on rates of gun ownership at the state level. Survey measures of gun ownership in all 50 states, however, are only available for 3 years, and no state-level data have been collected since 2004. Consequently, the National Research Council has declared the development of a valid proxy that can be constructed from accessible, annual, state-level data to be a priority. While such a proxy does exist (the proportion of suicides in a state committed using a gun (FS/S), its correlation with state estimates of gun ownership in recent years is only 0.80. Using state-level data for the years 2001, 2002 and 2004, we developed an improved proxy for state-level gun ownership that uses FS/S (firearm suicides divided by all suicides) and also the per capita number of hunting licenses. We validated this measure using data from surveys of gun ownership conducted in 48 states during 1996 and 1999, and in 21 states during 1995-1998. Adding per capita hunting licenses to the proxy increased its correlation with survey-measured gun ownership from 0.80 to 0.95. The correlations of the new proxy with gun ownership in the two validation studies were 0.95 and 0.97. We conclude that the combination of FS/S and per capita hunting licenses improves substantially upon FS/S alone. This new proxy is easily computed from data that are available annually by state and may be useful for investigating the effect of gun prevalence on firearm-related morbidity and mortality.
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Potential for autoimmune pathogenesis of Rift Valley Fever virus retinitis.
Am. J. Trop. Med. Hyg.
PUBLISHED: 08-05-2013
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Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication.
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Accelerating next-generation vaccine development for global disease prevention.
Science
PUBLISHED: 06-01-2013
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Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, tuberculosis, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances toward vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively generating vaccine-induced protective immune responses.
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Choosing wisely: the American College of Rheumatologys Top 5 list of things physicians and patients should question.
Arthritis Care Res (Hoboken)
PUBLISHED: 02-26-2013
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We sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients.
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RNA helicase signaling is critical for type i interferon production and protection against Rift Valley fever virus during mucosal challenge.
J. Virol.
PUBLISHED: 02-13-2013
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Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV.
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Brand-specific consumption of alcohol among underage youth in the United States.
Alcohol. Clin. Exp. Res.
PUBLISHED: 02-07-2013
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Little is known about brand-specific alcohol consumption among underage youth, as existing information is collected at the level of alcoholic beverage type. This study identifies the alcohol brands consumed by a nationally representative sample of underage youth in the United States.
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Health metrics for helminth infections.
Acta Trop.
PUBLISHED: 02-01-2013
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Health metrics based on health-adjusted life years have become standard units for comparing the disease burden and treatment benefits of individual health conditions. The Disability-Adjusted Life Year (DALY) and the Quality-Adjusted Life Year (QALY) are the most frequently used in cost-effect analyses in national and global health policy discussions for allocation of health care resources. While sometimes useful, both the DALY and QALY metrics have limitations in their ability to capture the full health impact of helminth infections and other neglected tropical diseases (NTDs). Gaps in current knowledge of disease burden are identified, and interim approaches to disease burden assessment are discussed.
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Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study.
PLoS Negl Trop Dis
PUBLISHED: 01-29-2013
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Schistosomiasis remains a global public health challenge, with 93% of the ~237 million infections occurring in sub-Saharan Africa. Though rarely fatal, its recurring nature makes it a lifetime disorder with significant chronic health burdens. Much of its negative health impact is due to non-specific conditions such as anemia, undernutrition, pain, exercise intolerance, poor school performance, and decreased work capacity. This makes it difficult to estimate the disease burden specific to schistosomiasis using the standard DALY metric.
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Physical condition and maintenance of mosquito bed nets in Kwale County, coastal Kenya.
Malar. J.
PUBLISHED: 01-29-2013
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Despite the extensive ownership and use of insecticide-treated nets (ITNs) over the last decade, the effective lifespan of these nets, especially their physical integrity, under true operational conditions is not well-understood. Usefulness of nets declines primarily due to physical damage or loss of insecticidal activity.
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A five-country evaluation of a point-of-care circulating cathodic antigen urine assay for the prevalence of Schistosoma mansoni.
Am. J. Trop. Med. Hyg.
PUBLISHED: 01-21-2013
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We evaluated a commercial point-of-care circulating cathodic antigen (POC-CCA) test for assessing Schistosoma mansoni infection prevalence in areas at risk. Overall, 4,405 school-age children in Cameroon, Côte dIvoire, Ethiopia, Kenya, and Uganda provided urine for POC-CCA testing and stool for Kato-Katz assays. By latent class analysis, one POC-CCA test was more sensitive (86% versus 62%) but less specific (72% versus ~100%) than multiple Kato-Katz smears from one stool. However, only 1% of POC-CCA tests in a non-endemic area were false positives, suggesting the latent class analysis underestimated the POC-CCA specificity. Multivariable modeling estimated POC-CCA as significantly more sensitive than Kato-Katz at low infection intensities (< 100 eggs/gram stool). By linear regression, 72% prevalence among 9-12 year olds by POC-CCA corresponded to 50% prevalence by Kato-Katz, whereas 46% POC-CCA prevalence corresponded to 10% Kato-Katz prevalence. We conclude that one urine POC-CCA test can replace Kato-Katz testing for community-level S. mansoni prevalence mapping.
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Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area.
Am. J. Trop. Med. Hyg.
PUBLISHED: 01-16-2013
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We measured prevalence of Schistosoma haematobium, Wuchereria bancrofti, Plasmodium falciparum, hookworm, and other geohelminths among school-aged children in four endemic villages in Kwale County, Kenya and explored the relationship between multiparasite burden, undernutrition, and anemia. In 2009-2010 surveys, cross-sectional data were obtained for 2,030 children 5-18 years old. Infections were most prevalent for S. haematobium (25-62%), hookworm (11-28%), and falciparum malaria (8-24%). Over one-half of children were anemic, with high rates of acute and chronic malnutrition. Associations with infection status showed significant age and sex differences. For boys, young age, low socioeconomic standing (SES), S. haematobium, and/or malaria infections were associated with greater odds of anemia, wasting, and/or stunting; for girls, heavy S. haematobium infection and age were the significant cofactors for anemia, whereas low SES and older age were linked to stunting. The broad overlap of infection-related causes for anemia and malnutrition and the high frequency of polyparasitic infections suggest that there will be significant advantages to integrated parasite control in this area.
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A kinase interacting protein (AKIP1) is a key regulator of cardiac stress.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-14-2013
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cAMP-dependent protein kinase (PKA) regulates a myriad of functions in the heart, including cardiac contractility, myocardial metabolism,and gene expression. However, a molecular integrator of the PKA response in the heart is unknown. Here, we show that the PKA adaptor A-kinase interacting protein 1 (AKIP1) is up-regulated in cardiac myocytes in response to oxidant stress. Mice with cardiac gene transfer of AKIP1 have enhanced protection to ischemic stress. We hypothesized that this adaptation to stress was mitochondrial dependent. AKIP1 interacted with the mitochondrial localized apoptosis inducing factor (AIF) under both normal and oxidant stress. When cardiac myocytes or whole hearts are exposed to oxidant and ischemic stress, levels of both AKIP1 and AIF were enhanced. AKIP1 is preferentially localized to interfibrillary mitochondria and up-regulated in this cardiac mitochondrial subpopulation on ischemic injury. Mitochondria isolated from AKIP1 gene transferred hearts showed increased mitochondrial localization of AKIP1, decreased reactive oxygen species generation, enhanced calcium tolerance, decreased mitochondrial cytochrome C release,and enhance phosphorylation of mitochondrial PKA substrates on ischemic stress. These observations highlight AKIP1 as a critical molecular regulator and a therapeutic control point for stress adaptation in the heart.
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Impact of drought on the spatial pattern of transmission of Schistosoma haematobium in coastal Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 12-07-2011
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We analyzed temporal changes in spatial patterns of active Schistosoma haematobium infection in different age groups and associated them with ponds infested with Bulinus snails. A major drought between 2001 and 2009 resulted in drying of ponds that were known sources of infection, and we detected very few or no snails in ponds that were infested in the past. The household-level spatial pattern of infection for children of various age groups in 2009 was contrasted with historical data from 2000. The significant local clustering of high- and low-infection levels among school-aged children that occurred in 2000 was absent in 2009. We attribute the disappearance of significant clustering around historical transmission hot spots to a decade-long drought in our study area. The implications of extreme weather and climate conditions on risk and transmission of S. haematobium and their relevance to control strategies are discussed.
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Impact of insecticide-treated bed nets on malaria transmission indices on the south coast of Kenya.
Malar. J.
PUBLISHED: 09-15-2011
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Besides significantly reducing malaria vector densities, prolonged usage of bed nets has been linked to decline of Anopheles gambiae s.s. relative to Anopheles arabiensis, changes in host feeding preference of malaria vectors, and behavioural shifts to exophagy (outdoor biting) for the two important malaria vectors in Africa, An. gambiae s.l. and Anopheles funestus. In southern coastal Kenya, bed net use was negligible in 1997-1998 when Anopheles funestus and An. gambiae s.s. were the primary malaria vectors, with An. arabiensis and Anopheles merus playing a secondary role. Since 2001, bed net use has increased progressively and reached high levels by 2009-2010 with corresponding decline in malaria transmission.
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Serologic evidence of arboviral infections among humans in Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 07-08-2011
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Outbreaks of arthropod-borne viral infections occur periodically across Kenya. However, limited surveillance takes place during interepidemic periods. Using serum samples obtained from asymptomatic persons across Kenya in 2000-2004, we assessed (by indirect immunofluorescent assay) prevalence of IgG against yellow fever virus (YFV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), dengue virus serotypes 1-4 (DENV1-4), and chikungunya virus (CHIKV). Older persons on the Indian Ocean coast were more likely to be seropositive than children inland: YFV = 42% versus 6%, WNV = 29% versus 6%, TBEV = 16% versus 6%, DENV-1 = 63% versus 9%, DENV-2 = 67% versus 7%, DENV-3 = 55% versus 6%, DENV-4 = 44% versus 8%, and CHIKV = 37% versus 20%. Among inland samples, children in lowlands were more likely to be seropositive for CHIKV (42% versus 0%) than children in highlands. In Kenya, transmission of arboviral infection continues between known epidemics and remains common across the country.
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Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.
PLoS Negl Trop Dis
PUBLISHED: 06-03-2011
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Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.
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A sub-microscopic gametocyte reservoir can sustain malaria transmission.
PLoS ONE
PUBLISHED: 05-13-2011
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Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM).
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Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.
PLoS Negl Trop Dis
PUBLISHED: 05-11-2011
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To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the bodys inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test.
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Modeling the effect of chronic schistosomiasis on childhood development and the potential for catch-up growth with different drug treatment strategies promoted for control of endemic schistosomiasis.
Am. J. Trop. Med. Hyg.
PUBLISHED: 05-05-2011
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In areas endemic for schistosomiasis having limited healthcare, targeted drug treatment of school-age children is recommended for control of Schistosoma-associated morbidity. However, optimal timing, number, and frequency of treatments are not established. Because longitudinal studies of long-term impact of treatment are few, for current policy considerations we performed quantitative simulation (based on calibrated modeling of Schistosoma-associated disease formation) to project the impact of different school-age treatment regimens. Using published efficacy data from targeted programs, combined with age-specific risk for growth retardation and reinfection, we examined the likely impact of different strategies for morbidity prevention. Results suggest the need for early, repeated treatment through primary school years to optimally prevent the disabling sequelae of stunting and undernutrition. Dynamics of infection/reinfection during childhood and adolescence, combined with early treatment effects against reversible infection-associated morbidities, create a need for aggressive retreatment of preadolescents to achieve optimal suppression of morbidity where drug-based control is used.
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Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study.
PLoS Negl Trop Dis
PUBLISHED: 04-27-2011
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In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies.
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Rift Valley fever virus infection in African buffalo (Syncerus caffer) herds in rural South Africa: evidence of interepidemic transmission.
Am. J. Trop. Med. Hyg.
PUBLISHED: 04-05-2011
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Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000-2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001-2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk.
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The rate of NF-?B nuclear translocation is regulated by PKA and A kinase interacting protein 1.
PLoS ONE
PUBLISHED: 03-16-2011
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The mechanism of PKAc-dependent NF-?B activation and subsequent translocation into the nucleus is not well defined. Previously, we showed that A kinase interacting protein 1 (AKIP1) was important for binding and retaining PKAc in the nucleus. Since then, other groups have demonstrated that AKIP1 binds the p65 subunit of NF-?B and regulates its transcriptional activity through the phosphorylation at Ser 276 by PKAc. However, little is known about the formation and activation of the PKAc/AKIP1/p65 complex and the rate at which it enters the nucleus. Initially, we found that the AKIP1 isoform (AKIP 1A) simultaneously binds PKAc and p65 in resting and serum starved cells. Using peptide arrays, we refined the region of AKIP 1A binding on PKAc and mapped the non-overlapping regions on AKIP 1A where PKAc and p65 bind. A peptide to the amino-terminus of PKAc (CAT 1-29) was generated to specifically disrupt the interaction between AKIP 1A and PKAc to study nuclear import of the complex. The rate of p65 nuclear translocation was monitored in the presence or absence of overexpressed AKIP 1A and/or (CAT 1-29). Enhanced nuclear translocation of p65 was observed in the presence of overexpressed AKIP1 and/or CAT 1-29 in cells stimulated with TNF?, and this correlated with decreased phosphorylation of serine 276. To determine whether PKAc phosphorylation of p65 in the cytosol regulated nuclear translocation, serine 276 was mutated to alanine or aspartic acid. Accelerated nuclear accumulation of p65 was observed in the alanine mutant, while the aspartic acid mutation displayed slowed nuclear translocation kinetics. In addition, enhanced nuclear translocation of p65 was observed when PKAc was knocked-down by siRNA. Taken together, these results suggest that AKIP 1A acts to scaffold PKAc to NF-?B in the cytosol by protecting the phosphorylation site and thereby regulating the rate of nuclear translocation of p65.
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Arbovirus prevalence in mosquitoes, Kenya.
Emerging Infect. Dis.
PUBLISHED: 02-05-2011
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Few studies have investigated the many mosquito species that harbor arboviruses in Kenya. During the 2006-2007 Rift Valley fever outbreak in North Eastern Province, Kenya, exophilic mosquitoes were collected from homesteads within 2 affected areas: Gumarey (rural) and Sogan-Godud (urban). Mosquitoes (n = 920) were pooled by trap location and tested for Rift Valley fever virus and West Nile virus. The most common mosquitoes trapped belonged to the genus Culex (75%). Of 105 mosquito pools tested, 22% were positive for Rift Valley fever virus, 18% were positive for West Nile virus, and 3% were positive for both. Estimated mosquito minimum infection rates did not differ between locations. Our data demonstrate the local abundance of mosquitoes that could propagate arboviral infections in Kenya and the high prevalence of vector arbovirus positivity during a Rift Valley fever outbreak.
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Quantifying quality of life and disability of patients with advanced schistosomiasis japonica.
PLoS Negl Trop Dis
PUBLISHED: 01-18-2011
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The Chinese government lists advanced schistosomiasis as a leading healthcare priority due to its serious health and economic impacts, yet it has not been included in the estimates of schistosomiasis burden in the Global Burden of Disease (GBD) study. Therefore, the quality of life and disability weight (DW) for the advanced cases of schistosomiasis japonica have to be taken into account in the re-estimation of burden of disease due to schistosomiasis.
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Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections.
Popul Health Metr
PUBLISHED: 01-10-2011
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Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.
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Planning for Rift Valley fever virus: use of geographical information systems to estimate the human health threat of white-tailed deer (Odocoileus virginianus)-related transmission.
Geospat Health
PUBLISHED: 11-17-2010
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Rift Valley fever (RVF) virus is a mosquito-borne phlebovirus of the Bunyaviridae family that causes frequent outbreaks of severe animal and human disease in sub-Saharan Africa, Egypt and the Arabian Peninsula. Based on its many known competent vectors, its potential for transmission via aerosolization, and its progressive spread from East Africa to neighbouring regions, RVF is considered a high-priority, emerging health threat for humans, livestock and wildlife in all parts of the world. Introduction of West Nile virus to North America has shown the potential for "exotic" viral pathogens to become embedded in local ecological systems. While RVF is known to infect and amplify within domestic livestock, such as taurine cattle, sheep and goats, if RVF virus is accidentally or intentionally introduced into North America, an important unknown factor will be the role of local wildlife in the maintenance or propagation of virus transmission. We examined the potential impact of RVF transmission via white-tailed deer (Odocoileus virginianus) in a typical north-eastern United States urban-suburban landscape, where livestock are rare but where these potentially susceptible, ungulate wildlife are highly abundant. Model results, based on overlap of mosquito, human and projected deer densities, indicate that a significant proportion (497/1186 km(2), i.e. 42%) of the urban and peri-urban landscape could be affected by RVF transmission during the late summer months. Deer population losses, either by intervention for herd reduction or by RVF-related mortality, would substantially reduce these likely transmission zones to 53.1 km(2), i.e. by 89%.
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Type I signal peptidase and protein secretion in Staphylococcus epidermidis.
J. Bacteriol.
PUBLISHED: 11-12-2010
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Bacterial protein secretion is a highly orchestrated process that is essential for infection and virulence. Despite extensive efforts to predict or experimentally detect proteins that are secreted, the characterization of the bacterial secretome has remained challenging. A central event in protein secretion is the type I signal peptidase (SPase)-mediated cleavage of the N-terminal signal peptide that targets a protein for secretion via the general secretory pathway, and the arylomycins are a class of natural products that inhibit SPase, suggesting that they may be useful chemical biology tools for characterizing the secretome. Here, using an arylomycin derivative, along with two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identify 11 proteins whose secretion from stationary-phase Staphylococcus epidermidis is dependent on SPase activity, 9 of which are predicted to be translated with canonical N-terminal signal peptides. In addition, we find that the presence of extracellular domains of lipoteichoic acid synthase (LtaS) and the ?-lactam response sensor BlaR1 in the medium is dependent on SPase activity, suggesting that they are cleaved at noncanonical sites within the protein. In all, the data define the proteins whose stationary-phase secretion depends on SPase and also suggest that the arylomycins should be valuable chemical biology tools for the study of protein secretion in a wide variety of different bacteria.
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Accessibility to and utilisation of schistosomiasis-related health services in a rural area of state of Minas Gerais, Brazil.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-20-2010
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The objective of the present paper was to compare accessibility and utilisation of schistosomiasis diagnostic and treatment services in a small village and the surrounding rural area in northern part of the state of Minas Gerais Brazil. The study included 1,228 individuals: 935 central village residents and 293 rural residents of São Pedro do Jequitinhonha. Schistosoma mansoni infection rates were significantly higher in the central village than in the rural area during a survey in 2007 (44.3% and 23.5%, respectively) and during the 2002 schistosomiasis case-finding campaign (33.1% and 26.5%, respectively) (p < 0.001). However, during the 2002-2006 period, only 23.7% of the villagers and 27% of the rural residents obtained tests on their own from health centres, hospitals and private clinics in various nearby towns. In 2007, 63% of the villagers and 70.5% of the rural residents reported never having received treatment for schistosomiasis. This paper reveals considerable variation in the accessibility and utilisation of schistosomiasis-related health services between the central village and the rural area. A combination of low utilisation rates between 2002-2006 and persistently high S. mansoni infection rates suggest that the schistosomiasis control program must be more rapidly incorporated into the primary health services.
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Detection of Schistosoma mansoni and Schistosoma haematobium DNA by loop-mediated isothermal amplification: identification of infected snails from early prepatency.
Am. J. Trop. Med. Hyg.
PUBLISHED: 08-05-2010
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Monitoring post-control transmission of schistosomes by examining humans becomes less effective as infection rates among humans decrease. Molecular monitoring of prepatent schistosome infection in snails by the polymerase chain reaction (PCR) has been used for studying human-to-snail transmission, and snail prepatent infection rates were found to correspond to infection prevalence and average intensity in human populations contacting the sites studied. We have now developed loop-mediated isothermal amplification (LAMP) assays for identifying Schistosoma mansoni and S. haematobium to facilitate large-scale evaluation of post-intervention transmission potential. LAMP primers were designed based on the Sm1-7 and DraI repeated sequences of the corresponding schistosomes, and amplification by LAMP of these 121-basepair highly abundant sequences provided a detection sensitivity of 0.1 fg of genomic DNA. When these LAMP assays were applied for examining infected laboratory snails, it was possible to identify infection from the first day after exposure to miracidia. The potential advantages of these assays are discussed.
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Health metrics for helminthic infections.
Adv. Parasitol.
PUBLISHED: 07-15-2010
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Over the past five decades, accurate and comparable assessment of disease burden due to different worm infections has proven problematic. Estimates of the health impact of helminths have varied significantly, depending on the assessors perspective and the approaches taken to quantifying disease effects on patient performance status. Past surveys have frequently suffered from misclassification bias due to the lack of a diagnostic gold standard. At the same time, there has been a tendency to define disease based solely on late-onset, pathognomonic outcomes that can be uniquely attributed to each pathogen. However, we are now gaining a much better understanding of the role of helminths in anaemia causation, impaired growth and development, and poor school or work performance. With a new appreciation of the link between long-term, parasite-mediated inflammation and the patients lifetime risk of disability, we recognise that the bulk of worm-associated diseases is found in the latter, non-specific categories, with relevance to individual performance status and detriment to regional levels of human capital. Appropriately, the emerging use of comprehensive disability metrics such as the quality-adjusted life year (QALY)-as opposed to the widely used disability-adjusted life year (DALY) metrics-will better capture the impact of helminthic infections on the long-term health of Asian and other developing world populations. This improved, more valid assessment is expected to provide evidence favouring preventive over curative intervention for control of these highly prevalent diseases.
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Advances in Rift Valley fever research: insights for disease prevention.
Curr. Opin. Infect. Dis.
PUBLISHED: 07-09-2010
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The purpose was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates.
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Severe Rift Valley fever may present with a characteristic clinical syndrome.
Am. J. Trop. Med. Hyg.
PUBLISHED: 03-09-2010
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Rift Valley fever (RVF) virus is an emerging pathogen that is transmitted in many regions of sub-Saharan Africa, parts of Egypt, and the Arabian peninsula. Outbreaks of RVF, like other diseases caused by hemorrhagic fever viruses, typically present in locations with very limited health resources, where initial diagnosis must be based only on history and physical examination. Although general signs and symptoms of human RVF have been documented, a specific clinical syndrome has not been described. In 2007, a Kenyan outbreak of RVF provided opportunity to assess acutely ill RVF patients and better delineate its presentation and clinical course. Our data reveal an identifiable clinical syndrome suggestive of severe RVF, characterized by fever, large-joint arthralgia, and gastrointestinal complaints and later followed by jaundice, right upper-quadrant pain, and delirium, often coinciding with hemorrhagic manifestations. Further characterization of a distinct RVF clinical syndrome will aid earlier detection of RVF outbreaks and should allow more rapid implementation of control.
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Acoustical properties of the swimbladder in the oyster toadfish Opsanus tau.
J. Exp. Biol.
PUBLISHED: 10-20-2009
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Both the swimbladder and sonic muscles of the oyster toadfish Opsanus tau (Linnaeus) increase in size with fish growth making it difficult to distinguish their relative contributions to sound production. We examined acoustics of the swimbladder independent of the sonic muscles by striking it with a piezoelectric impact hammer. Amplitude and timing characteristics of bladder sound and displacement were compared for strikes of different amplitudes. Most of the first cycle of sound occurred during swimbladder compression, indicating that the bladder rapidly contracted and expanded as force increased during the strike. Harder hits were shorter in duration and generated a 30 dB increase in amplitude for a 5-fold or 14 dB range in displacement. For an equivalent strike dominant frequency, damping, bladder displacement and sound amplitude did not change with fish size, i.e. equal input generated equal output. The frequency spectrum was broad, and dominant frequency was driven by the strike and not the natural frequency of the bladder. Bladder displacement decayed rapidly (zeta averaged 0.33, equivalent to an automobile shock absorber), and the bladder had a low Q (sharpness of tuning), averaging 1.8. Sound output of an acoustic source is determined by volume velocity (surface area x velocity), and bladder surface area, muscle dimensions and contraction amplitude increase with fish size. Therefore, larger fish will be capable of producing more intense sound. Because the bladder is a low Q resonator, its output will follow muscle contraction rates independent of its size and natural frequency.
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Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 08-27-2009
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Long-term planning to prevent malaria epidemics requires in-depth understanding of immunity to Plasmodium falciparum in areas of unstable transmission. Cytokine responses to immunodominant epitope peptides from liver stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) were evaluated over a nine-month interval in adults and children in Kenya from a malaria epidemic-prone highland area after several years of low transmission. The proportion and magnitude of interferon-gamma ELISPOT responses and the proportion of interleukin-10 responders to LSA-1 and TRAP peptides tended to be higher in adults than children. Frequencies of interferon-gamma responders to these peptides were similar at the two time points, but responses were not consistently generated by the same persons. These results suggest that T cell memory to pre-erythrocytic stage malaria antigens is maintained but may be unavailable for consistent detection in peripheral blood, and that these antigens induce both pro-inflammatory and anti-inflammatory cytokine responses in this population.
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Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5.
J. Exp. Med.
PUBLISHED: 07-13-2009
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Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS beta protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.
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Parasites and poverty: the case of schistosomiasis.
Acta Trop.
PUBLISHED: 07-10-2009
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Simultaneous and sequential transmission of multiple parasites, and their resultant overlapping chronic infections, are facts of life in many underdeveloped rural areas. These represent significant but often poorly measured health and economic burdens for affected populations. For example, the chronic inflammatory process associated with long-term schistosomiasis contributes to anaemia and undernutrition, which, in turn, can lead to growth stunting, poor school performance, poor work productivity, and continued poverty. To date, most national and international programs aimed at parasite control have not considered the varied economic and ecological factors underlying multi-parasite transmission, but some are beginning to provide a coordinated approach to control. In addition, interest is emerging in new studies for the re-evaluation and recalibration of the health burden of helminthic parasite infection. Their results should highlight the strong potential of integrated parasite control in efforts for poverty reduction.
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Do antenatal parasite infections devalue childhood vaccination?
PLoS Negl Trop Dis
PUBLISHED: 05-26-2009
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On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evidence from animal and human studies suggest that neglected tropical diseases (NTDs) significantly impair response to standard childhood immunizations. A review of efficacy and effectiveness studies of vaccination among individuals with chronic parasitic infections was conducted, using PUBMED database searches and analysis of data from the authors published and unpublished studies. Both animal models and human studies suggest that chronic trematode, nematode, and protozoan infections can result in decreased vaccine efficacy. Among pregnant women, who in developing countries are often infected with multiple parasites, soluble parasite antigens have been shown to cross the placenta and prime or tolerize fetal immune responses. As a result, antenatal infections can have a significant impact on later vaccine responses. Acquired childhood parasitic infections, most commonly malaria, can also affect subsequent immune response to vaccination. Additional data suggest that antiparasite therapy can improve the effectiveness of several human vaccines. Emerging evidence demonstrates that both antenatal and childhood parasitic infections alter levels of protective immune response to routine vaccinations. Successful antiparasite treatment may prevent immunomodulation caused by parasitic antigens during pregnancy and early childhood and may improve vaccine efficacy. Future research should highlight the varied effects that different parasites (alone and in combination) can have on human vaccine-related immunity. To optimize vaccine effectiveness in developing countries, better control of chronic NTDs may prove imperative.
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Adolescent exposure to alcohol advertising in magazines: an evaluation of advertising placement in relation to underage youth readership.
J Adolesc Health
PUBLISHED: 03-18-2009
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To investigate whether alcoholic beverages popular among underage youths are more likely than those less popular among these youths to be advertised in magazines with high underage youth readerships.
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Quality of life and social support among patients receiving antiretroviral therapy in Western Uganda.
AIDS Care
PUBLISHED: 03-13-2009
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Quality of life (QOL) among patients with HIV/AIDS has been shown to improve once treatment with antiretroviral therapy (ART) has been initiated. We conducted a cross-sectional study in Western Uganda to examine the factors associated with QOL among patients who had received ART for the duration of at least six months. We interviewed 330 patients attending the HIV/AIDS clinic at two government-supported hospitals in Western Uganda. We measured QOL using a culturally adapted version of the Medical Outcomes Study (MOS-HIV) tool and calculated the physical health summary (PHS) and mental health summary (MHS) scores. In addition, data were collected on sociodemographic factors, three-day self-reported adherence, social support, sexual behavior, CD4 count and viral load. Informational social support was significantly positively correlated with PHS (p=0.001) and MHS (p=0.002). Affectionate support was also significantly positively correlated to PHS (p=0.05) and MHS (p=0.03) but tangible support was not (PHS p value=0.85 and MHS p value=0.31). In the univariate analysis, older age, rural dwelling, alcohol use, CD4 count less than 200, and ART duration of less than one year were significantly associated with lower PHS scores. Lower PHS scores were also associated with sexual inactivity. In multivariate analysis, higher scores on informational social support and CD4> or =200 were associated with higher PHS score and past or recent alcohol consumption was associated with lower scores on MHS. Optimizing ART to restore CD4 count and provision of informational and affectionate social support but not tangible support, to HIV/AIDS patients may improve their QOL.
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Adherence and treatment response among HIV-1-infected adults receiving antiretroviral therapy in a rural government hospital in Southwestern Uganda.
J Int Assoc Physicians AIDS Care (Chic)
PUBLISHED: 03-03-2009
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Large-scale, government-based antiretroviral therapy (ART) programs in rural areas of resource-poor countries remain largely unevaluated.
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A fractionation method to identify qauntitative changes in protein expression mediated by IGF-1 on the proteome of murine C2C12 myoblasts.
Proteome Sci
PUBLISHED: 01-30-2009
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Although much is known about signal transduction downstream of insulin-like growth factor-1 (IGF-1), relatively little is known about the global changes in protein expression induced by this hormone. In this study, the acute effects of IGF-1 on the proteome of murine C2C12 cells were examined. Cells were treated with IGF-1 for up to 24 hours, lysed, and fractionated into cytosolic, nuclear, and insoluble portions. Proteins from the cytosolic fraction were further separated using a new batch ion-exchange chromatography method to reduce sample complexity, followed by two-dimensional (2D) electrophoresis, and identification of selected proteins by mass spectrometry. PDQuest software was utilized to identify and catalogue temporal changes in protein expression during IGF-1 stimulation. In response to IGF-1 stimulation, expression of 23 proteins increased at least three-fold and expression of 17 proteins decreased at least three-fold compared with control un-stimulated C2C12 cells. Changes in expression of selected proteins from each group, including Rho-GDI, cofillin, RAD50, enolase, IkappaB kinase b (IkappaBKb) and Hsp70 were confirmed by Western blotting. Additionally, the position of 136 landmark proteins whose expression levels and physicochemical properties did not change appreciably or consistently during IGF-1 treatment were mapped and identified. This characterization of large-scale changes in protein expression in response to growth factor stimulation of C2C12 cells will further help to establish a comprehensive understanding of the networks and pathways involved in the action of IGF-1.
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School-based health promotion for mosquito-borne disease prevention in children.
J. Pediatr.
PUBLISHED: 01-22-2009
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We enrolled 345 fourth-grade students in a classroom-randomized, controlled trial to evaluate a school-based West Nile virus health education programs impact on knowledge, attitudes, and personal protective behavior use. Immediate and sustained improvements in West Nile virus knowledge and greater frequencies of reported personal protective behaviors resulted from the educational intervention.
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CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling.
Cell Metab.
PUBLISHED: 01-14-2009
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In type 1 and type 2 diabetes (T1/T2DM), beta cell destruction by apoptosis results in decreased beta cell mass and progression of the disease. In this study, we found that the interferon gamma-inducible protein 10 plays an important role in triggering beta cell destruction. Islets isolated from patients with T2DM secreted CXCL10 and contained 33.5-fold more CXCL10 mRNA than islets from control patients. Pancreatic sections from obese nondiabetic individuals and patients with T2DM and T1DM expressed CXCL10 in beta cells. Treatment of human islets with CXCL10 decreased beta cell viability, impaired insulin secretion, and decreased insulin mRNA. CXCL10 induced sustained activation of Akt, JNK, and cleavage of p21-activated protein kinase 2 (PAK-2), switching Akt signals from proliferation to apoptosis. These effects were not mediated by the commonly known CXCL10 receptor CXCR3 but through TLR4. Our data suggest CXCL10 as a binding partner for TLR4 and as a signal toward beta cell failure in diabetes.
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Surviving the aftershock: postearthquake access and adherence to HIV treatment among Haitis tent residents.
Qual Health Res
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In this research we examined how the conditions of Haitis tent communities, inhabited by those displaced by the January 10, 2010, earthquake, shaped access and adherence to highly active antiretroviral treatment (HAART) for Haitians with HIV. Conditions in the encampments were marked by unhygienic and cramped living spaces, exposure to the elements, a lack of privacy, unavailability of food and clean water, and a dependence on poorly functioning aid agencies. These conditions shaped access and adherence to HAART by (a) exacerbating the stigma of being HIV positive and undermining mental health; (b) presenting logistical challenges to accessing medical care, storing pills, and ingesting them safely and privately; and (c) sustaining a political economy of aid characterized by unequal treatment in major HAART-dispensing centers, unequal circulation of international funds, and the emergence of alternative medical institutions within encampments that could improve future treatment. Policy and intervention implications are discussed.
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Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
Christopher J L Murray, Theo Vos, Rafael Lozano, Mohsen Naghavi, Abraham D Flaxman, Catherine Michaud, Majid Ezzati, Kenji Shibuya, Joshua A Salomon, Safa Abdalla, Victor Aboyans, Jerry Abraham, Ilana Ackerman, Rakesh Aggarwal, Stephanie Y Ahn, Mohammed K Ali, Miriam Alvarado, H Ross Anderson, Laurie M Anderson, Kathryn G Andrews, Charles Atkinson, Larry M Baddour, Adil N Bahalim, Suzanne Barker-Collo, Lope H Barrero, David H Bartels, María-Gloria Basáñez, Amanda Baxter, Michelle L Bell, Emelia J Benjamin, Derrick Bennett, Eduardo Bernabé, Kavi Bhalla, Bishal Bhandari, Boris Bikbov, Aref Bin Abdulhak, Gretchen Birbeck, James A Black, Hannah Blencowe, Jed D Blore, Fiona Blyth, Ian Bolliger, Audrey Bonaventure, Soufiane Boufous, Rupert Bourne, Michel Boussinesq, Tasanee Braithwaite, Carol Brayne, Lisa Bridgett, Simon Brooker, Peter Brooks, Traolach S Brugha, Claire Bryan-Hancock, Chiara Bucello, Rachelle Buchbinder, Geoffrey Buckle, Christine M Budke, Michael Burch, Peter Burney, Roy Burstein, Bianca Calabria, Benjamin Campbell, Charles E Canter, Hélène Carabin, Jonathan Carapetis, Loreto Carmona, Claudia Cella, Fiona Charlson, Honglei Chen, Andrew Tai-Ann Cheng, David Chou, Sumeet S Chugh, Luc E Coffeng, Steven D Colan, Samantha Colquhoun, K Ellicott Colson, John Condon, Myles D Connor, Leslie T Cooper, Matthew Corriere, Monica Cortinovis, Karen Courville de Vaccaro, William Couser, Benjamin C Cowie, Michael H Criqui, Marita Cross, Kaustubh C Dabhadkar, Manu Dahiya, Nabila Dahodwala, James Damsere-Derry, Goodarz Danaei, Adrian Davis, Diego De Leo, Louisa Degenhardt, Robert Dellavalle, Allyne Delossantos, Julie Denenberg, Sarah Derrett, Don C Des Jarlais, Samath D Dharmaratne, Mukesh Dherani, César Diaz-Torné, Helen Dolk, E Ray Dorsey, Tim Driscoll, Herbert Duber, Beth Ebel, Karen Edmond, Alexis Elbaz, Suad Eltahir Ali, Holly Erskine, Patricia J Erwin, Patricia Espindola, Stalin E Ewoigbokhan, Farshad Farzadfar, Valery Feigin, David T Felson, Alize Ferrari, Cleusa P Ferri, Eric M Fèvre, Mariel M Finucane, Seth Flaxman, Louise Flood, Kyle Foreman, Mohammad H Forouzanfar, Francis Gerry R Fowkes, Marlene Fransen, Michael K Freeman, Belinda J Gabbe, Sherine E Gabriel, Emmanuela Gakidou, Hammad A Ganatra, Bianca Garcia, Flavio Gaspari, Richard F Gillum, Gerhard Gmel, Diego Gonzalez-Medina, Richard Gosselin, Rebecca Grainger, Bridget Grant, Justina Groeger, Francis Guillemin, David Gunnell, Ramyani Gupta, Juanita Haagsma, Holly Hagan, Yara A Halasa, Wayne Hall, Diana Haring, Josep Maria Haro, James E Harrison, Rasmus Havmoeller, Roderick J Hay, Hideki Higashi, Catherine Hill, Bruno Hoen, Howard Hoffman, Peter J Hotez, Damian Hoy, John J Huang, Sydney E Ibeanusi, Kathryn H Jacobsen, Spencer L James, Deborah Jarvis, Rashmi Jasrasaria, Sudha Jayaraman, Nicole Johns, Jost B Jonas, Ganesan Karthikeyan, Nicholas Kassebaum, Norito Kawakami, Andre Keren, Jon-Paul Khoo, Charles H King, Lisa Marie Knowlton, Olive Kobusingye, Adofo Koranteng, Rita Krishnamurthi, Francine Laden, Ratilal Lalloo, Laura L Laslett, Tim Lathlean, Janet L Leasher, Yong Yi Lee, James Leigh, Daphna Levinson, Stephen S Lim, Elizabeth Limb, John Kent Lin, Michael Lipnick, Steven E Lipshultz, Wei Liu, Maria Loane, Summer Lockett Ohno, Ronan Lyons, Jacqueline Mabweijano, Michael F MacIntyre, Reza Malekzadeh, Leslie Mallinger, Sivabalan Manivannan, Wagner Marcenes, Lyn March, David J Margolis, Guy B Marks, Robin Marks, Akira Matsumori, Richard Matzopoulos, Bongani M Mayosi, John H McAnulty, Mary M McDermott, Neil McGill, John McGrath, Maria Elena Medina-Mora, Michele Meltzer, George A Mensah, Tony R Merriman, Ana-Claire Meyer, Valeria Miglioli, Matthew Miller, Ted R Miller, Philip B Mitchell, Charles Mock, Ana Olga Mocumbi, Terrie E Moffitt, Ali A Mokdad, Lorenzo Monasta, Marcella Montico, Maziar Moradi-Lakeh, Andrew Moran, Lidia Morawska, Rintaro Mori, Michele E Murdoch, Michael K Mwaniki, Kovin Naidoo, M Nathan Nair, Luigi Naldi, K M Venkat Narayan, Paul K Nelson, Robert G Nelson, Michael C Nevitt, Charles R Newton, Sandra Nolte, Paul Norman, Rosana Norman, Martin O'Donnell, Simon O'Hanlon, Casey Olives, Saad B Omer, Katrina Ortblad, Richard Osborne, Doruk Ozgediz, Andrew Page, Bishnu Pahari, Jeyaraj Durai Pandian, Andrea Panozo Rivero, Scott B Patten, Neil Pearce, Rogelio Pérez Padilla, Fernando Perez-Ruiz, Norberto Perico, Konrad Pesudovs, David Phillips, Michael R Phillips, Kelsey Pierce, Sébastien Pion, Guilherme V Polanczyk, Suzanne Polinder, C Arden Pope, Svetlana Popova, Esteban Porrini, Farshad Pourmalek, Martin Prince, Rachel L Pullan, Kapa D Ramaiah, Dharani Ranganathan, Homie Razavi, Mathilda Regan, Jürgen T Rehm, David B Rein, Guiseppe Remuzzi, Kathryn Richardson, Frederick P Rivara, Thomas Roberts, Carolyn Robinson, Felipe Rodriguez De Leòn, Luca Ronfani, Robin Room, Lisa C Rosenfeld, Lesley Rushton, Ralph L Sacco, Sukanta Saha, Uchechukwu Sampson, Lidia Sanchez-Riera, Ella Sanman, David C Schwebel, James Graham Scott, Maria Segui-Gomez, Saeid Shahraz, Donald S Shepard, Hwashin Shin, Rupak Shivakoti, David Singh, Gitanjali M Singh, Jasvinder A Singh, Jessica Singleton, David A Sleet, Karen Sliwa, Emma Smith, Jennifer L Smith, Nicolas J C Stapelberg, Andrew Steer, Timothy Steiner, Wilma A Stolk, Lars Jacob Stovner, Christopher Sudfeld, Sana Syed, Giorgio Tamburlini, Mohammad Tavakkoli, Hugh R Taylor, Jennifer A Taylor, William J Taylor, Bernadette Thomas, W Murray Thomson, George D Thurston, Imad M Tleyjeh, Marcello Tonelli, Jeffrey A Towbin, Thomas Truelsen, Miltiadis K Tsilimbaris, Clotilde Ubeda, Eduardo A Undurraga, Marieke J van der Werf, Jim van Os, Monica S Vavilala, N Venketasubramanian, Mengru Wang, Wenzhi Wang, Kerrianne Watt, David J Weatherall, Martin A Weinstock, Robert Weintraub, Marc G Weisskopf, Myrna M Weissman, Richard A White, Harvey Whiteford, Natasha Wiebe, Steven T Wiersma, James D Wilkinson, Hywel C Williams, Sean R M Williams, Emma Witt, Frederick Wolfe, Anthony D Woolf, Sarah Wulf, Pon-Hsiu Yeh, Anita K M Zaidi, Zhi-Jie Zheng, David Zonies, Alan D Lopez, Mohammad A AlMazroa, Ziad A Memish.
Lancet
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Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time.
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Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
Theo Vos, Abraham D Flaxman, Mohsen Naghavi, Rafael Lozano, Catherine Michaud, Majid Ezzati, Kenji Shibuya, Joshua A Salomon, Safa Abdalla, Victor Aboyans, Jerry Abraham, Ilana Ackerman, Rakesh Aggarwal, Stephanie Y Ahn, Mohammed K Ali, Miriam Alvarado, H Ross Anderson, Laurie M Anderson, Kathryn G Andrews, Charles Atkinson, Larry M Baddour, Adil N Bahalim, Suzanne Barker-Collo, Lope H Barrero, David H Bartels, María-Gloria Basáñez, Amanda Baxter, Michelle L Bell, Emelia J Benjamin, Derrick Bennett, Eduardo Bernabé, Kavi Bhalla, Bishal Bhandari, Boris Bikbov, Aref Bin Abdulhak, Gretchen Birbeck, James A Black, Hannah Blencowe, Jed D Blore, Fiona Blyth, Ian Bolliger, Audrey Bonaventure, Soufiane Boufous, Rupert Bourne, Michel Boussinesq, Tasanee Braithwaite, Carol Brayne, Lisa Bridgett, Simon Brooker, Peter Brooks, Traolach S Brugha, Claire Bryan-Hancock, Chiara Bucello, Rachelle Buchbinder, Geoffrey Buckle, Christine M Budke, Michael Burch, Peter Burney, Roy Burstein, Bianca Calabria, Benjamin Campbell, Charles E Canter, Hélène Carabin, Jonathan Carapetis, Loreto Carmona, Claudia Cella, Fiona Charlson, Honglei Chen, Andrew Tai-Ann Cheng, David Chou, Sumeet S Chugh, Luc E Coffeng, Steven D Colan, Samantha Colquhoun, K Ellicott Colson, John Condon, Myles D Connor, Leslie T Cooper, Matthew Corriere, Monica Cortinovis, Karen Courville de Vaccaro, William Couser, Benjamin C Cowie, Michael H Criqui, Marita Cross, Kaustubh C Dabhadkar, Manu Dahiya, Nabila Dahodwala, James Damsere-Derry, Goodarz Danaei, Adrian Davis, Diego De Leo, Louisa Degenhardt, Robert Dellavalle, Allyne Delossantos, Julie Denenberg, Sarah Derrett, Don C Des Jarlais, Samath D Dharmaratne, Mukesh Dherani, César Diaz-Torné, Helen Dolk, E Ray Dorsey, Tim Driscoll, Herbert Duber, Beth Ebel, Karen Edmond, Alexis Elbaz, Suad Eltahir Ali, Holly Erskine, Patricia J Erwin, Patricia Espindola, Stalin E Ewoigbokhan, Farshad Farzadfar, Valery Feigin, David T Felson, Alize Ferrari, Cleusa P Ferri, Eric M Fèvre, Mariel M Finucane, Seth Flaxman, Louise Flood, Kyle Foreman, Mohammad H Forouzanfar, Francis Gerry R Fowkes, Richard Franklin, Marlene Fransen, Michael K Freeman, Belinda J Gabbe, Sherine E Gabriel, Emmanuela Gakidou, Hammad A Ganatra, Bianca Garcia, Flavio Gaspari, Richard F Gillum, Gerhard Gmel, Richard Gosselin, Rebecca Grainger, Justina Groeger, Francis Guillemin, David Gunnell, Ramyani Gupta, Juanita Haagsma, Holly Hagan, Yara A Halasa, Wayne Hall, Diana Haring, Josep Maria Haro, James E Harrison, Rasmus Havmoeller, Roderick J Hay, Hideki Higashi, Catherine Hill, Bruno Hoen, Howard Hoffman, Peter J Hotez, Damian Hoy, John J Huang, Sydney E Ibeanusi, Kathryn H Jacobsen, Spencer L James, Deborah Jarvis, Rashmi Jasrasaria, Sudha Jayaraman, Nicole Johns, Jost B Jonas, Ganesan Karthikeyan, Nicholas Kassebaum, Norito Kawakami, Andre Keren, Jon-Paul Khoo, Charles H King, Lisa Marie Knowlton, Olive Kobusingye, Adofo Koranteng, Rita Krishnamurthi, Ratilal Lalloo, Laura L Laslett, Tim Lathlean, Janet L Leasher, Yong Yi Lee, James Leigh, Stephen S Lim, Elizabeth Limb, John Kent Lin, Michael Lipnick, Steven E Lipshultz, Wei Liu, Maria Loane, Summer Lockett Ohno, Ronan Lyons, Jixiang Ma, Jacqueline Mabweijano, Michael F MacIntyre, Reza Malekzadeh, Leslie Mallinger, Sivabalan Manivannan, Wagner Marcenes, Lyn March, David J Margolis, Guy B Marks, Robin Marks, Akira Matsumori, Richard Matzopoulos, Bongani M Mayosi, John H McAnulty, Mary M McDermott, Neil McGill, John McGrath, Maria Elena Medina-Mora, Michele Meltzer, George A Mensah, Tony R Merriman, Ana-Claire Meyer, Valeria Miglioli, Matthew Miller, Ted R Miller, Philip B Mitchell, Ana Olga Mocumbi, Terrie E Moffitt, Ali A Mokdad, Lorenzo Monasta, Marcella Montico, Maziar Moradi-Lakeh, Andrew Moran, Lidia Morawska, Rintaro Mori, Michele E Murdoch, Michael K Mwaniki, Kovin Naidoo, M Nathan Nair, Luigi Naldi, K M Venkat Narayan, Paul K Nelson, Robert G Nelson, Michael C Nevitt, Charles R Newton, Sandra Nolte, Paul Norman, Rosana Norman, Martin O'Donnell, Simon O'Hanlon, Casey Olives, Saad B Omer, Katrina Ortblad, Richard Osborne, Doruk Ozgediz, Andrew Page, Bishnu Pahari, Jeyaraj Durai Pandian, Andrea Panozo Rivero, Scott B Patten, Neil Pearce, Rogelio Pérez Padilla, Fernando Perez-Ruiz, Norberto Perico, Konrad Pesudovs, David Phillips, Michael R Phillips, Kelsey Pierce, Sébastien Pion, Guilherme V Polanczyk, Suzanne Polinder, C Arden Pope, Svetlana Popova, Esteban Porrini, Farshad Pourmalek, Martin Prince, Rachel L Pullan, Kapa D Ramaiah, Dharani Ranganathan, Homie Razavi, Mathilda Regan, Jürgen T Rehm, David B Rein, Guiseppe Remuzzi, Kathryn Richardson, Frederick P Rivara, Thomas Roberts, Carolyn Robinson, Felipe Rodriguez De Leòn, Luca Ronfani, Robin Room, Lisa C Rosenfeld, Lesley Rushton, Ralph L Sacco, Sukanta Saha, Uchechukwu Sampson, Lidia Sanchez-Riera, Ella Sanman, David C Schwebel, James Graham Scott, Maria Segui-Gomez, Saeid Shahraz, Donald S Shepard, Hwashin Shin, Rupak Shivakoti, David Singh, Gitanjali M Singh, Jasvinder A Singh, Jessica Singleton, David A Sleet, Karen Sliwa, Emma Smith, Jennifer L Smith, Nicolas J C Stapelberg, Andrew Steer, Timothy Steiner, Wilma A Stolk, Lars Jacob Stovner, Christopher Sudfeld, Sana Syed, Giorgio Tamburlini, Mohammad Tavakkoli, Hugh R Taylor, Jennifer A Taylor, William J Taylor, Bernadette Thomas, W Murray Thomson, George D Thurston, Imad M Tleyjeh, Marcello Tonelli, Jeffrey A Towbin, Thomas Truelsen, Miltiadis K Tsilimbaris, Clotilde Ubeda, Eduardo A Undurraga, Marieke J van der Werf, Jim van Os, Monica S Vavilala, N Venketasubramanian, Mengru Wang, Wenzhi Wang, Kerrianne Watt, David J Weatherall, Martin A Weinstock, Robert Weintraub, Marc G Weisskopf, Myrna M Weissman, Richard A White, Harvey Whiteford, Steven T Wiersma, James D Wilkinson, Hywel C Williams, Sean R M Williams, Emma Witt, Frederick Wolfe, Anthony D Woolf, Sarah Wulf, Pon-Hsiu Yeh, Anita K M Zaidi, Zhi-Jie Zheng, David Zonies, Alan D Lopez, Christopher J L Murray, Mohammad A AlMazroa, Ziad A Memish.
Lancet
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Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs).
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Evaluation of loop-mediated isothermal amplification suitable for molecular monitoring of schistosome-infected snails in field laboratories.
Am. J. Trop. Med. Hyg.
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We previously described loop-mediated isothermal amplification (LAMP) for detection of Schistosoma haematobium and S. mansoni DNA in infected snails. In the present study, we adapted the LAMP assay for application in field laboratories in schistosomiasis-endemic areas. Isolation of DNA was simplified by blotting snail tissue (extracted in NaOH/sodium dodecyl sulfate) onto treated membranes, which enabled preservation at ambient temperatures. A ready-mix of LAMP reagents, suitable for shipment at ambient temperature and storage in minimal refrigeration, was used. Local survey teams without experience in molecular biology acquired operational expertise with this test within a few hours. Fifty-four field-caught snails were tested locally by LAMP and 59 were tested at similar conditions in Jerusalem. The LAMP results were consistent with those of a polymerase chain reaction; only four samples showed false-negative results. Results indicate that LAMP assays are suitable for detection of S. haematobium and S. mansoni in low-technology parasitology laboratories in which schistosomiasis elimination activities are undertaken.
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Projecting the long-term impact of school- or community-based mass-treatment interventions for control of Schistosoma infection.
PLoS Negl Trop Dis
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Schistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006) for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown.
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Birthweight in offspring of mothers with high prevalence of helminth and malaria infection in coastal Kenya.
Am. J. Trop. Med. Hyg.
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Results of studies on the associations of maternal helminth infection and malaria-helminth co-infection on birth outcomes have been mixed. A group of 696 pregnant women from the Kwale district in Kenya were recruited and tested for malaria and helminth infection at delivery. Birthweight was documented for 664 infants. A total of 42.7% of the mothers were infected with Plasmodium falciparum, 30.6% with Schistosoma haematobium, 36.2% with filariasis, 31.5% with hookworm, and 5.9% with Trichuris trichiura; co-infection was present in 46.7%. Low birthweight (LBW) (weight < 2,500 grams) was present in 15.4% of the offspring, and 8.3% had a weight z-score ? 2 SD below the World Health Organization mean. Only gravida, age, and locale had a significant association with LBW. The high prevalence of maternal infection coupled with a higher than expected percentage of LBW highlight a need for further investigation of the association of maternal co-infection with LBW.
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Differentiating Schistosoma haematobium from related animal schistosomes by PCR amplifying inter-repeat sequences flanking newly selected repeated sequences.
Am. J. Trop. Med. Hyg.
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In schistosomiasis elimination programs, successful discrimination of Schistosoma haematobium from the related animal Schistosoma parasites will be essential for accurate detection of human parasite transmission. Polymerase chain reaction assays employing primers from two newly selected repeated sequences, named Sh73 and Sh77, did not discriminate S. haematobium when amplifying Sh73-77 intra- or inter-repeats. However, amplification between Sh73 and the previously described DraI repeat exhibited discriminative banding patterns for S. haematobium and Schistosoma bovis (sensitivity 1 pg and 10 pg, respectively). It also enabled banding pattern discrimination of Schistosoma curassoni and Schistosoma intercalatum, but Schistosoma mattheei and Schistosoma margrebowiei did not yield amplicons. Similar inter-repeat amplification between Sh77 and DraI yielded amplicons with discriminative banding for S. haematobium, and S. bovis; however, S. mattheei was detected only at low sensitivity (1 ng). The Sh73/DraI assay detected snails infected with S. haematobium, S. bovis, or both, and should prove useful for screening snails where discrimination of S. haematobium from related schistosomes is required.
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From pluripotency to islets: miRNAs as critical regulators of human cellular differentiation.
Adv. Genet.
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MicroRNAs (miRNAs) actively regulate differentiation as pluripotent cells become cells of pancreatic endocrine lineage, including insulin-producing ? cells. The process is dynamic; some miRNAs help maintain pluripotency, while others drive cell fate decisions. Here, we survey the current literature and describe the biological role of selected miRNAs in maintenance of both mouse and human embryonic stem cell (ESC) pluripotency. Subsequently, we review the increasing evidence that miRNAs act at selected points in differentiation to regulate decisions about early cell fate (definitive endoderm and mesoderm), formation of pancreatic precursor cells, endocrine cell function, as well as epithelial to mesenchymal transition.
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Partnering parasites: evidence of synergism between heavy Schistosoma haematobium and Plasmodium species infections in Kenyan children.
PLoS Negl Trop Dis
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Residents of resource-poor tropical countries carry heavy burdens of concurrent parasitic infections, leading to high rates of morbidity and mortality. This study was undertaken to help identify the social and environmental determinants of multiple parasite infection in one such community.
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The SDF-1?/CXCR4 axis is required for proliferation and maturation of human fetal pancreatic endocrine progenitor cells.
PLoS ONE
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The chemokine receptor CXCR4 and ligand SDF-1? are expressed in fetal and adult mouse islets. Neutralization of CXCR4 has previously been shown to diminish ductal cell proliferation and increase apoptosis in the IFN? transgenic mouse model in which the adult mouse pancreas displays islet regeneration. Here, we demonstrate that CXCR4 and SDF-1? are expressed in the human fetal pancreas and that during early gestation, CXCR4 colocalizes with neurogenin 3 (ngn3), a key transcription factor for endocrine specification in the pancreas. Treatment of islet like clusters (ICCs) derived from human fetal pancreas with SDF-1? resulted in increased proliferation of epithelial cells in ICCs without a concomitant increase in total insulin expression. Exposure of ICCs in vitro to AMD3100, a pharmacological inhibitor of CXCR4, did not alter expression of endocrine hormones insulin and glucagon, or the pancreatic endocrine transcription factors PDX1, Nkx6.1, Ngn3 and PAX4. However, a strong inhibition of ? cell genesis was observed when in vitro AMD3100 treatment of ICCs was followed by two weeks of in vivo treatment with AMD3100 after ICC transplantation into mice. Analysis of the grafts for human C-peptide found that inhibition of CXCR4 activity profoundly inhibits islet development. Subsequently, a model pancreatic epithelial cell system (CFPAC-1) was employed to study the signals that regulate proliferation and apoptosis by the SDF-1?/CXCR4 axis. From a selected panel of inhibitors tested, both the PI 3-kinase and MAPK pathways were identified as critical regulators of CFPAC-1 proliferation. SDF-1? stimulated Akt phosphorylation, but failed to increase phosphorylation of Erk above the high basal levels observed. Taken together, these results indicate that SDF-1?/CXCR4 axis plays a critical regulatory role in the genesis of human islets.
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Soil-transmitted helminth reinfection after drug treatment: a systematic review and meta-analysis.
PLoS Negl Trop Dis
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Soil-transmitted helminth (STH) infections (i.e., Ascaris lumbricoides, hookworm, and Trichuris trichiura) affect more than a billion people. Preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations), is the mainstay of control. This strategy, however, does not prevent reinfection. We performed a systematic review and meta-analysis to assess patterns and dynamics of STH reinfection after drug treatment.
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Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.
PLoS ONE
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Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns).
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