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Find video protocols related to scientific articles indexed in Pubmed.
Community Mobilization to Reduce Drug Use, Quang Ninh, Vietnam.
Am J Public Health
PUBLISHED: 11-14-2014
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Objectives. We implemented an intervention to reduce drug use in an urban commune in northern Vietnam. Methods. We encouraged the intervention commune to accept responsibility for developing their own intervention strategies based on a community mobilization model used in southern, rural China. We selected a comparison commune, which had demographic characteristics and a drug history similar to the intervention commune. The 2-year incidence of new drug users was estimated retrospectively in the intervention and comparison communes between baseline (2003) and follow-up (2009). Results. Increased incidence of new (noninjecting) drug users between 2003 and 2009 in the intervention commune was lower than that in the comparison commune, and these participants expressed more positive attitudes toward local authority and people with drug use and HIV/AIDS. Increased condom use during last intercourse with female sex workers and with female casual partners was observed in the intervention commune. HIV prevalence and positive opioid tests decreased more in the intervention commune. Conclusions. Our results suggested that the community mobilization had a positive influence in the intervention commune. (Am J Public Health. Published online ahead of print November 13, 2014: e1-e7. doi:10.2105/AJPH.2014.302101).
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Viral aetiology of central nervous system infections in adults admitted to a tertiary referral hospital in southern Vietnam over 12 years.
PLoS Negl Trop Dis
PUBLISHED: 08-28-2014
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Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management.
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Determinants of influenza transmission in South East Asia: insights from a household cohort study in Vietnam.
PLoS Pathog.
PUBLISHED: 08-21-2014
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To guide control policies, it is important that the determinants of influenza transmission are fully characterized. Such assessment is complex because the risk of influenza infection is multifaceted and depends both on immunity acquired naturally or via vaccination and on the individual level of exposure to influenza in the community or in the household. Here, we analyse a large household cohort study conducted in 2007-2010 in Vietnam using innovative statistical methods to ascertain in an integrative framework the relative contribution of variables that influence the transmission of seasonal (H1N1, H3N2, B) and pandemic H1N1pdm09 influenza. Influenza infection was diagnosed by haemagglutination-inhibition (HI) antibody assay of paired serum samples. We used a Bayesian data augmentation Markov chain Monte Carlo strategy based on digraphs to reconstruct unobserved chains of transmission in households and estimate transmission parameters. The probability of transmission from an infected individual to another household member was 8% (95% CI, 6%, 10%) on average, and varied with pre-season titers, age and household size. Within households of size 3, the probability of transmission from an infected member to a child with low pre-season HI antibody titers was 27% (95% CI 21%-35%). High pre-season HI titers were protective against infection, with a reduction in the hazard of infection of 59% (95% CI, 44%-71%) and 87% (95% CI, 70%-96%) for intermediate (1?20-1?40) and high (?1?80) HI titers, respectively. Even after correcting for pre-season HI titers, adults had half the infection risk of children. Twenty six percent (95% CI: 21%, 30%) of infections may be attributed to household transmission. Our results highlight the importance of integrated analysis by influenza sub-type, age and pre-season HI titers in order to infer influenza transmission risks in and outside of the household.
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Spread of artemisinin resistance in Plasmodium falciparum malaria.
N. Engl. J. Med.
PUBLISHED: 07-31-2014
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Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies.
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Three-Year Outcomes Following 1,420 ABO-Incompatible Living-Donor Kidney Transplants Performed After ABO Antibody Reduction: Results From 101 Centers.
Transplantation
PUBLISHED: 07-23-2014
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Reports from experienced centers suggest that recipients of an ABO-incompatible living-donor kidney transplant after reduction of ABO antibodies experience no penalty in graft and patient survival versus ABO-compatible transplants, but confirmation that these results can be widely replicated is lacking.
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Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator-associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam.
J. Med. Microbiol.
PUBLISHED: 07-18-2014
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Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30?% of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend; odds ratio 1.656, P?=?0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a blaOXA-23-positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single blaNDM-1-positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
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Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation.
Infect. Immun.
PUBLISHED: 06-30-2014
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Caseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (?clpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.
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Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans.
Emerging Infect. Dis.
PUBLISHED: 06-25-2014
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Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.
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Variation at HLA-DRB1 is associated with resistance to enteric fever.
Nat. Genet.
PUBLISHED: 06-23-2014
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Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10(-10)), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1*04:05 allele (OR = 0.14, P = 2.60 × 10(-11)) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.
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Qualitative study of the feasibility of HPV vaccine delivery to young adolescent girls in Vietnam: evidence from a government-implemented demonstration program.
BMC Public Health
PUBLISHED: 05-30-2014
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Introduction of human papillomavirus (HPV) vaccine in national programs has proceeded apace since 2006, mostly in high-income countries. Recently concluded pilots of HPV vaccination in low-income countries have provided important lessons learned for these settings; however, rigorous evaluations of the feasibility of these delivery strategies that effectively reach young adolescents have been few. This paper presents results from a qualitative evaluation of a demonstration program which implemented school-based and health center-based HPV vaccinations to all girls in grade 6, or 11 years of age, for two years in four districts of Vietnam.
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CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial.
Trials
PUBLISHED: 05-16-2014
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Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It is the leading cause of death in HIV patients in Asia and Africa.No major advance has been made in the treatment of CM since the 1970s. The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest. Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM. Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested.The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality? Dexamethasone is a cheap, readily available, and practicable intervention.
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Hemagglutination inhibiting antibodies and protection against seasonal and pandemic influenza infection.
J. Infect.
PUBLISHED: 05-15-2014
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Hemagglutination inhibiting (HI) antibodies correlate with influenza vaccine protection but their association with protection induced by natural infection has received less attention and was studied here.
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The impact of obesity on the presentation of primary hyperparathyroidism.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-31-2014
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Obesity has been associated with elevated serum PTH (sPTH) in the general population. Obesity may also alter the clinical presentation in patients with primary hyperparathyroidism (PHPT).
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Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.
FASEB J.
PUBLISHED: 03-20-2014
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Endothelial dysfunction is defined as impairment of the balance between endothelium-dependent vasodilation and constriction. Despite evidence of uric acid-induced endothelial dysfunction, a relationship with insulin resistance has not been clearly established. In this study, we investigated the role of vascular insulin resistance in uric acid-induced endothelial dysfunction. Uric acid inhibited insulin-induced endothelial nitric oxide synthase (eNOS) phosphorylation and NO production more substantially than endothelin-1 expression in HUVECs, with IC50 of 51.0, 73.6, and 184.2, respectively. Suppression of eNOS phosphorylation and NO production by uric acid was PI3K/Akt-dependent, as verified by the transfection with p110. Treatment of rats with the uricase inhibitor allantoxanamide induced mild hyperuricemia and increased mean arterial pressure by 25%. While hyperuricemic rats did not show systemic insulin resistance, they showed impaired vasorelaxation induced by insulin by 56%. A compromised insulin response in terms of the Akt/eNOS pathway was observed in the aortic ring of hyperuricemic rats. Coadministration with allopurinol reduced serum uric acid levels and blood pressure and restored the effect of insulin on Akt-eNOS pathway and vasorelaxation. Taken together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin-induced NO production, potentially leading to the development of hypertension.-Choi, Y.-J., Yoon, Y., Lee, K.-Y., Hien, T. T., Kang, K. W., Kim, K.-C., Lee, J., Lee, M.-Y., Lee, S. M., Kang, D.-H., Lee, B.-H. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis.
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?-synuclein immunotherapy blocks uptake and templated propagation of misfolded ?-synuclein and neurodegeneration.
Cell Rep
PUBLISHED: 03-16-2014
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Accumulation of misfolded alpha-synuclein (?-syn) into Lewy bodies (LBs) and Lewy neurites (LNs) is a major hallmark of Parkinson's disease (PD) and dementia with LBs (DLB). Recent studies showed that synthetic preformed fibrils (pffs) recruit endogenous ?-syn and induce LB/LN pathology in vitro and in vivo, thereby implicating propagation and cell-to-cell transmission of pathological ?-syn as mechanisms for the progressive spread of LBs/LNs. Here, we demonstrate that ?-syn monoclonal antibodies (mAbs) reduce ?-syn pff-induced LB/LN formation and rescue synapse/neuron loss in primary neuronal cultures by preventing both pff uptake and subsequent cell-to-cell transmission of pathology. Moreover, intraperitoneal (i.p.) administration of mAb specific for misfolded ?-syn into nontransgenic mice injected intrastriatally with ?-syn pffs reduces LB/LN pathology, ameliorates substantia nigra dopaminergic neuron loss, and improves motor impairments. We conclude that ?-syn antibodies could exert therapeutic effects in PD/DLB by blocking entry of pathological ?-syn and/or its propagation in neurons.
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Investigation of dengue and Japanese encephalitis virus transmission in Hanam, Viet Nam.
Am. J. Trop. Med. Hyg.
PUBLISHED: 03-10-2014
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This study investigated whether a large dengue epidemic that struck Hanoi in 2009 also affected a nearby semirural area. Seroconversion (dengue virus-reactive immunoglobulin G enzyme-linked immunosorbent assay) was high during 2009 compared with 2008, but neutralization assays showed that it was caused by both dengue virus and Japanese encephalitis virus infections. The findings highlight the importance of continued Japanese encephalitis virus vaccination and dengue surveillance.
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Pin1 induction in the fibrotic liver and its roles in TGF-?1 expression and Smad2/3 phosphorylation.
J. Hepatol.
PUBLISHED: 02-04-2014
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Therapeutic management of liver fibrosis remains an unsolved clinical problem. Hepatic accumulation of extracellular matrix, mainly collagen, is mediated by the production of transforming growth factor-?1 (TGF-?1) in stellate cells. Pin1, a peptidyl-prolyl isomerase, plays an important pathophysiological role in several diseases, including neurodegeneration and cancer. Herein, we determined whether Pin1 regulates liver fibrogenesis and examined its mechanism of action by focusing on TGF-?1 signalling and hepatic stellate cell (HSC) activation.
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Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1.
Clin. Infect. Dis.
PUBLISHED: 01-31-2014
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Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections.
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Strengthening global health security capacity--Vietnam demonstration project, 2013.
MMWR Morb. Mortal. Wkly. Rep.
PUBLISHED: 01-31-2014
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Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication.
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Risk factors for the development of severe typhoid fever in Vietnam.
BMC Infect. Dis.
PUBLISHED: 01-30-2014
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Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever.
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Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort.
J. Infect.
PUBLISHED: 01-21-2014
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Influenza household transmission studies are required to guide prevention strategies but most passively recruit index cases that seek healthcare. We investigated A(H1N1)pdm09 transmission in a household-based cohort during 2009.
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Limited geographic distribution of the novel cyclovirus CyCV-VN.
Sci Rep
PUBLISHED: 01-17-2014
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A novel cyclovirus, CyCV-VN, was recently identified in cerebrospinal fluid (CSF) from patients with central nervous system (CNS) infections in central and southern Vietnam. To explore the geographic distribution of this novel virus, more than 600?CSF specimens from patients with suspected CNS infections in northern Vietnam, Cambodia, Nepal and The Netherlands were screened for the presence of CyCV-VN but all were negative. Sequence comparison and phylogenetic analysis between CyCV-VN and another novel cyclovirus recently identified in CSF from Malawian patients indicated that these represent distinct cycloviral species, albeit phylogenetically closely related. The data suggest that CyCV-VN has a limited geographic distribution within southern and central Vietnam. Further research is needed to determine the global distribution and diversity of cycloviruses and importantly their possible association with human disease.
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Nectandrin B suppresses the expression of adhesion molecules in endothelial cells: Role of AMP-activated protein kinase activation.
Food Chem. Toxicol.
PUBLISHED: 01-15-2014
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We have previously shown that nectandrin B, a potent natural activator of AMP-activated protein kinase (AMPK) results in endothelium-dependent relaxation via endothelial nitric oxide synthase phosphorylation. This study examined the effects of nectandrin B on monocyte adhesion and on the expression of adhesion molecules in endothelial cells, an initial event in atherogenesis. Nectandrin B inhibited tumor necrosis factor-? (TNF?)-induced monocytoid THP-1 cell adhesion to ECV 304 human endothelial cells. This lignan also suppressed TNF?-induced protein and mRNA expression of two cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). In addition, expression of cyclooxygenase-2 and inducible nitric oxide synthase were diminished by nectandrin B treatment. Reporter gene and immunoblot analyses revealed that transcription factor activities of nuclear factor-?B (NF-?B), activator protein-1 (AP-1), and cyclic AMP response element binding protein (CREB) were inhibited by nectandrin B. Moreover, nectandrin B activated AMP-activated protein kinase (AMPK) in ECV 304 cells. Transfection of a dominant-negative mutant form of AMPK (DN-AMPK) partially reversed inhibitory effects of nectandrin B on the expression of VCAM-1 and ICAM-1, and on the transcriptional activity of CREB.
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Genetic variability of Plasmodium malariae dihydropteroate synthase (dhps) in four Asian countries.
PLoS ONE
PUBLISHED: 01-01-2014
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The dihydropteroate synthase (dhps) genes of 44 P. malariae strains from four Asian countries were isolated. Only a limited number of polymorphisms were observed. Comparison with homologous mutations in other Plasmodium species showed that these polymorphisms are unlikely to be associated with sulfadoxine resistance.
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Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Most adults dying from falciparum malaria will die within 48 hours of their hospitalisation. An essential component of early supportive care is the rapid identification of patients at greatest risk. In resource-poor settings, where most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone.
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PlasmoView: A web-based resource to visualise global Plasmodium falciparum genomic variation.
J. Infect. Dis.
PUBLISHED: 12-12-2013
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Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (e.g. biological function) in a geographic setting. The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).
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Migration and persistence of human influenza A viruses, Vietnam, 2001-2008.
Emerging Infect. Dis.
PUBLISHED: 11-06-2013
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Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001-2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year.
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Adverse events associated with mohs micrographic surgery: multicenter prospective cohort study of 20?821 cases at 23 centers.
JAMA Dermatol
PUBLISHED: 10-02-2013
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IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.
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Tracking the establishment of local endemic populations of an emergent enteric pathogen.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2013
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Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population.
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An Intervention to Improve Mental Health and Family Well-Being of Injecting Drug Users and Family Members in Vietnam.
Psychol Addict Behav
PUBLISHED: 09-30-2013
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Family plays an important role in the lives of injecting drug users (IDUs) in Vietnam. This study examined the preliminary outcomes of an intervention targeting IDUs and their family members in Vietnam. Eighty-three families, including 83 IDUs and 83 family members, were recruited from 4 communes in Phú T?o Province, Vietnam. The 4 communes were randomized to either an intervention condition or a standard care condition. The IDUs and their family members in the intervention condition completed 4 group sessions, with the aims to improve their mental health and family relations and to promote positive behavioral change. The intervention effect was evaluated at baseline and 3- and 6-month follow-up assessments. A significant reduction in depressive symptoms and improvement in family functioning were reported for IDUs in the intervention group compared with those in the standard care group. The family members in the intervention group reported better coping skills at 3 months, fewer depressive symptoms at 6 months, and improved family function at both 3 and 6 months compared with those in the standard care group. However, no significant intervention effect was observed for IDUs in terms of drug-using behavior. This study demonstrates the feasibility and preliminary outcomes of an intervention that simultaneously targets IDUs and their family members in Vietnam. Study findings highlight the importance of including family members and enhancing their role in drug use intervention efforts. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination.
Vaccine
PUBLISHED: 09-25-2013
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Vietnam has high endemic hepatitis B virus infection with >8% of adults estimated to have chronic infection. Hepatitis B vaccine was first introduced in the national childhood immunization program in 1997 in high-risk areas, expanded nationwide in 2002, and included birth dose vaccination in 2003. This survey aimed to assess the impact of Vietnams vaccination programme by estimating the prevalence of hepatitis B surface antigen (HBsAg) among children born during 2000-2008.
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Genetic marker suitable for identification and genotyping of Plasmodium ovale curtisi and Plasmodium ovale wallikeri.
J. Clin. Microbiol.
PUBLISHED: 09-25-2013
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We present a seminested PCR method that specifically discriminates between Plasmodium ovale curtisi and P. ovale wallikeri with high sensitivity. The test is based on species-specific amplification of a size-polymorphic fragment of the tryptophan-rich antigen gene, potra, which also permits discrimination of intraspecific sequence variants at this locus.
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Subclinical avian influenza A(H5N1) virus infection in human, Vietnam.
Emerging Infect. Dis.
PUBLISHED: 09-20-2013
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Laboratory-confirmed cases of subclinical infection with avian influenza A(H5N1) virus in humans are rare, and the true number of these cases is unknown. We describe the identification of a laboratory-confirmed subclinical case in a woman during an influenza A(H5N1) contact investigation in northern Vietnam.
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Factors associated with dengue shock syndrome: a systematic review and meta-analysis.
PLoS Negl Trop Dis
PUBLISHED: 09-01-2013
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The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
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Malaria.
Lancet
PUBLISHED: 08-15-2013
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Although global morbidity and mortality have decreased substantially, malaria, a parasite infection of red blood cells, still kills roughly 2000 people per day, most of whom are children in Africa. Two factors largely account for these decreases; increased deployment of insecticide-treated bednets and increased availability of highly effective artemisinin combination treatments. In large trials, parenteral artesunate (an artemisinin derivative) reduced severe malaria mortality by 22·5% in Africa and 34·7% in Asia compared with quinine, whereas adjunctive interventions have been uniformly unsuccessful. Rapid tests have been an important addition to microscopy for malaria diagnosis. Chemopreventive strategies have been increasingly deployed in Africa, notably intermittent sulfadoxine-pyrimethamine treatment in pregnancy, and monthly amodiaquine-sulfadoxine-pyrimethamine during the rainy season months in children aged between 3 months and 5 years across the sub-Sahel. Enthusiasm for malaria elimination has resurfaced. This ambitious but laudable goal faces many challenges, including the worldwide economic downturn, difficulties in elimination of vivax malaria, development of pyrethroid resistance in some anopheline mosquitoes, and the emergence of artemisinin resistance in Plasmodium falciparum in southeast Asia. We review the epidemiology, clinical features, pathology, prevention, and treatment of malaria.
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Protective effect of nectandrin B, a potent AMPK activator on neointima formation: inhibition of Pin1 expression through AMPK activation.
Br. J. Pharmacol.
PUBLISHED: 07-17-2013
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Neointima is considered a critical event in the development of vascular occlusive disease. Nectandrin B from nutmeg functions as a potent AMP-activated protein kinase (AMPK) activators. The present study addressed whether nectandrin B inhibits intimal hyperplasia in guide wire-injured arteries and examined its molecular mechanism.
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Optimal sampling designs for estimation of Plasmodium falciparum clearance rates in patients treated with artemisinin derivatives.
Malar. J.
PUBLISHED: 07-10-2013
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The emergence of Plasmodium falciparum resistance to artemisinins in Southeast Asia threatens the control of malaria worldwide. The pharmacodynamic hallmark of artemisinin derivatives is rapid parasite clearance (a short parasite half-life), therefore, the in vivo phenotype of slow clearance defines the reduced susceptibility to the drug. Measurement of parasite counts every six hours during the first three days after treatment have been recommended to measure the parasite clearance half-life, but it remains unclear whether simpler sampling intervals and frequencies might also be sufficient to reliably estimate this parameter.
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Correlated outcomes of a pilot intervention for people injecting drugs and their family members in Vietnam.
Drug Alcohol Depend
PUBLISHED: 07-03-2013
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The interrelationship between the well-being of injecting drug users (IDUs) and their family environment has been widely documented. However, few intervention programs have addressed the needs of both IDUs and their family members.
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Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.
Virology
PUBLISHED: 06-21-2013
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As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.
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Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.
MBio
PUBLISHED: 06-20-2013
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Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.
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SIRT1-Mediated FoxO1 Deacetylation Is Essential for Multidrug Resistance-Associated Protein 2 Expression in Tamoxifen-Resistant Breast Cancer Cells.
Mol. Pharm.
PUBLISHED: 06-13-2013
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Our previous studies have shown that multidrug resistance protein 2 (MRP2) is overexpressed in tamoxifen-resistant MCF-7 breast cancer cells (TAMR-MCF-7 cells) and forkhead box-containing protein, O subfamily1 (FoxO1), functions as a key regulator of multidrug resistance 1 (MDR1) gene transcription. This study aimed to investigate the role of FoxO1 in regulating MRP2 gene expression in TAMR-MCF-7 cells. The proximal promoter region of the human MRP2 gene contains four putative FoxO binding sites, and MRP2 gene transcription was stimulated by FoxO1 overexpression in MCF-7 cells. Subcellular fractionation and immunoblot analyses revealed that basal MRP2 expression and nuclear levels of FoxO1 were enhanced in TAMR-MCF-7 cells compared to MCF-7 cells and the enhanced MRP2 gene transcription was suppressed by FoxO1 siRNA. Because nuclear localization of FoxO1 is regulated by SIRT1 deacetylase, we were further interested in whether SIRT1 is involved in MRP2 expression. Overexpression of SIRT1 with FoxO1 potentiated the gene transcriptional activity of MRP2, and the basal activity and expression of SIRT1 was increased in TAMR-MCF-7 cells. In addition, SIRT1 inhibition reduced both the nuclear FoxO1 levels and MRP2 expression and enhanced cytotoxic effects of paclitaxel and doxorubicin in TAMR-MCF-7 cells. These results suggest that FoxO1 activation via SIRT1-mediated deacetylation is closely related with up-regulation of MRP2 in TAMR-MCF-7 cells.
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Population-level antibody estimates to novel influenza A/H7N9.
J. Infect. Dis.
PUBLISHED: 05-17-2013
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There are no contemporary data available describing human immunity to novel influenza A/H7N9. Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to 5 avian influenza virus antigens, using a protein microarray. General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5 and lower than titers against H9. The highest titers were observed for human influenza virus subtypes. Titers to avian influenza virus antigens increased with age and with geometric mean antibody titer to human influenza virus antigens. There were no titer differences between the urban and the rural location in our study.
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Cost of dengue outbreaks: literature review and country case studies.
BMC Public Health
PUBLISHED: 05-08-2013
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Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save--through early response activities--resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks.
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Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam.
BMC Public Health
PUBLISHED: 04-19-2013
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Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance.
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Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway.
Cell
PUBLISHED: 04-12-2013
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The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patients life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohns disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGF?1 reduces production of proinflammatory cytokines, including TNF?, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.
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Combination antifungal therapy for cryptococcal meningitis.
N. Engl. J. Med.
PUBLISHED: 04-05-2013
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Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
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Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia.
Nat. Genet.
PUBLISHED: 04-04-2013
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We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
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Sharing experiences: towards an evidence based model of dengue surveillance and outbreak response in Latin America and Asia.
BMC Public Health
PUBLISHED: 01-31-2013
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The increasing frequency and intensity of dengue outbreaks in endemic and non-endemic countries requires a rational, evidence based response. To this end, we aimed to collate the experiences of a number of affected countries, identify strengths and limitations in dengue surveillance, outbreak preparedness, detection and response and contribute towards the development of a model contingency plan adaptable to country needs.
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The collaborative transplant study registry.
Transplant Rev (Orlando)
PUBLISHED: 01-22-2013
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The Collaborative Transplant Study (CTS) was initiated in 1982. Over the last 30 years, it has collected information on over half a million kidney, liver, heart, lung, and pancreas transplant procedures. Participation is voluntary and the study has strictly scientific objectives. Analyses of the CTS database serve as an international reference source in the field of solid organ transplantation.
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Nrf2 regulates haematopoietic stem cell function.
Nat. Cell Biol.
PUBLISHED: 01-22-2013
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Coordinating the balance between haematopoietic stem cell (HSC) quiescence and self-renewal is crucial for maintaining haematopoiesis lifelong. Equally important for haematopoietic function is modulating HSC localization within the bone marrow niches, as maintenance of HSC function is tightly controlled by a complex network of intrinsic molecular mechanisms and extrinsic signalling interactions with their surrounding microenvironment. In this study we demonstrate that nuclear factor erythroid 2-related factor 2 (Nfe2l2, or Nrf2), well established as a global regulator of the oxidative stress response, plays a regulatory role in several aspects of HSC homeostasis. Nrf2 deficiency results in an expansion of the haematopoietic stem and progenitor cell compartment due to cell-intrinsic hyperproliferation, which was accomplished at the expense of HSC quiescence and self-renewal. We further show that Nrf2 modulates both migration and retention of HSCs in their niche. Moreover, we identify a previously unrecognized link between Nrf2 and CXCR4, contributing, at least partially, to the maintenance of HSC function.
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Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.
Clin Exp Vaccine Res
PUBLISHED: 01-15-2013
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A pep27 mutant may be able to elicit mucosal immunity against pneumococcal diseases, and could be employed as an inexpensive attenuated vaccine. However, this particular mutant contains an erythromycin-resistance marker. The purpose of the current study is to develop a markerless pep27 mutant and assess whether this inactivated mutant is able to induce mucosal immunity.
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A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria.
Malar. J.
PUBLISHED: 01-14-2013
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Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adults and children with falciparum malaria. However the mechanism of action of the angiopoietins in fatal malaria is unclear. This study aimed to determine whether the expression of Ang-1 and Ang-2 and their receptor Tie-2 in cerebral endothelial or parenchymal cells was specific to cerebral malaria (CM), correlated with coma or other severe clinical features, and whether plasma and CSF levels of these markers correlated with the clinical and neuropathological features of severe and fatal malaria in Vietnamese adults.
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Sequestration and microvascular congestion are associated with coma in human cerebral malaria.
J. Infect. Dis.
PUBLISHED: 12-29-2011
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The pathogenesis of coma in severe Plasmodium falciparum malaria remains poorly understood. Obstruction of the brain microvasculature because of sequestration of parasitized red blood cells (pRBCs) represents one mechanism that could contribute to coma in cerebral malaria. Quantitative postmortem microscopy of brain sections from Vietnamese adults dying of malaria confirmed that sequestration in the cerebral microvasculature was significantly higher in patients with cerebral malaria (CM; n = 21) than in patients with non-CM (n = 23). Sequestration of pRBCs and CM was also significantly associated with increased microvascular congestion by infected and uninfected erythrocytes. Clinicopathological correlation showed that sequestration and congestion were significantly associated with deeper levels of premortem coma and shorter time to death. Microvascular congestion and sequestration were highly correlated as microscopic findings but were independent predictors of a clinical diagnosis of CM. Increased microvascular congestion accompanies coma in CM, associated with parasite sequestration in the cerebral microvasculature.
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High-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections.
J. Virol.
PUBLISHED: 11-16-2011
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Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia.
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Identification of H5N1-specific T-cell responses in a high-risk cohort in vietnam indicates the existence of potential asymptomatic infections.
J. Infect. Dis.
PUBLISHED: 11-11-2011
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Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam.
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Short communication: phylogenetic characterization of HIV type 1 CRF01_AE V3 envelope sequences in pregnant women in Northern Vietnam.
AIDS Res. Hum. Retroviruses
PUBLISHED: 11-11-2011
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Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005-2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology.
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Social contexts of risk behaviors for HIV among male, unskilled, unregistered laborers in urban Vietnam.
Qual Health Res
PUBLISHED: 11-07-2011
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In Vietnam there has been relatively little success in controlling the HIV epidemic, in part because the subpopulations most exposed to the virus are often difficult to engage in prevention research and programs. In this qualitative study we explored social contexts shaping HIV risk behaviors among Vietnamese men involved in unskilled, unregistered, and low-income labor in urban settings. Based on self-disclosed behaviors, it is clear that these men were at high risk of sexually transmitted infection (STI). Evidence emerged from the interview data highlighting equivalent influences of individual psychological factors, social integration, social barriers, and accessibility regarding drug use and sexual risk behavior. Psychological influences such as tedium, distress, fatalism and revenge, and the strong effects of collective decision making and fear of social isolation appeared important for these men living on the economic and social margins of this rapidly urbanizing society. The study findings suggest directions for research and culturally appropriate HIV preventive education and services for these men.
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H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.
J. Virol.
PUBLISHED: 09-28-2011
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Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.
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Nectandrin B activates endothelial nitric-oxide synthase phosphorylation in endothelial cells: role of the AMP-activated protein kinase/estrogen receptor ?/phosphatidylinositol 3-kinase/Akt pathway.
Mol. Pharmacol.
PUBLISHED: 09-22-2011
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We revealed previously that nectandrin B isolated from Myristica fragrans (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK) activator and showed its antiobesity effect. In this study, we investigated whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of eNOS and nitric oxide (NO) production in a concentration-dependent manner and maximal effect was found at 10 ?g/ml. Nectandrin B activates AMPK, presumably via Ca(2+)/calmodulin kinase II activation and nectandrin B-stimulated eNOS phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent reporter gene transcription were enhanced by nectandrin B. ER? inhibition by specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B-mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed the activation of ER-dependent transcription and PI3K activation in response to nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results suggest that potent AMPK activator nectandrin B enhances NO production via eNOS phosphorylation in endothelial cells and ER?-dependent PI3K activity is required.
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Heat-shock protein ClpL/HSP100 increases penicillin tolerance in Streptococcus pneumoniae.
Adv. Otorhinolaryngol.
PUBLISHED: 08-18-2011
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Penicillin resistance and tolerance has been an increasing threat to the treatment of pneumococcal pneumoniae. However, no penicillin tolerance-related genes have been claimed. Here we show that a major heat shock protein ClpL/HSP100 could modulate the expression of a cell wall synthesis enzyme PBP2x, and subsequently increase cell wall thickness and penicillin tolerance in Streptococus pneumoniae.
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Real-time PCR for detection of Streptococcus suis serotype 2 in cerebrospinal fluid of human patients with meningitis.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 07-20-2011
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Streptococcus suis serotype 2 is an emerging zoonotic pathogen and is the main cause of acute bacterial meningitis in adult patients in Vietnam. We developed an internally controlled real-time PCR for detection of S. suis serotype 2 in cerebrospinal fluid (CSF) samples targeted at the cps2J gene. Sensitivity and specificity in culture-confirmed clinical samples were 100%. The PCR detected S. suis serotype 2 infection in 101 of 238 (42.4%) prospectively collected CSF samples, of which 55 (23%) were culture positive. Culture-negative but PCR-positive CSF samples were significantly associated with the use of antimicrobial agents before admission. S. suis serotype 2 infection was more common than infections with Streptococcus pneumoniae and Neisseria meningitidis combined. Our results strikingly illustrate the additional diagnostic value of PCR in patients who are pretreated with antimicrobial agents and demonstrate the extremely high prevalence of S. suis infections among Vietnamese adult patients with bacterial meningitis.
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Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants.
Transplantation
PUBLISHED: 07-12-2011
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Allocation of deceased donor kidneys is commonly based on matching for human leukocyte antigen (HLA)-A, -B, and -DR, whereas HLA-C is currently disregarded. We investigated the influence of HLA-C compatibility on renal allograft survival. In addition, we tested an approach of matching for HLA-C epitopes.
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Distinct temporal and anatomical distributions of amyloid-? and tau abnormalities following controlled cortical impact in transgenic mice.
PLoS ONE
PUBLISHED: 07-01-2011
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Traumatic brain injury (TBI) is a major environmental risk factor for Alzheimers disease. Intracellular accumulations of amyloid-? and tau proteins have been observed within hours following severe TBI in humans. Similar abnormalities have been recapitulated in young 3xTg-AD mice subjected to the controlled cortical impact model (CCI) of TBI and sacrificed at 24 h and 7 days post injury. This study investigated the temporal and anatomical distributions of amyloid-? and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-? accumulation in the fimbria was detected as early as 1 hour and increased monotonically over 24 hours following injury. Tau immunoreactivity in the fimbria and amygdala had a biphasic time course with peaks at 1 hour and 24 hours, while tau immunoreactivity in the contralateral CA1 rose in a delayed fashion starting at 12 hours after injury. Furthermore, rapid intra-axonal amyloid-? accumulation was similarly observed post controlled cortical injury in APP/PS1 mice, another transgenic Alzheimers disease mouse model. Acute increases in total and phospho-tau immunoreactivity were also evident in single transgenic Tau(P301L) mice subjected to controlled cortical injury. These data provide further evidence for the causal effects of moderately severe contusional TBI on acceleration of acute Alzheimer-related abnormalities and the independent relationship between amyloid-? and tau in this setting.
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Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-? accumulation and independently accelerates the development of tau abnormalities.
J. Neurosci.
PUBLISHED: 07-01-2011
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Alzheimers disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-? (A?) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. A? is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal A? and diffuse extracellular plaques occur in ?30% of human subjects after severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between A? and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal A? accumulations and increased phospho-tau immunoreactivity at 24 h and up to 7 d after TBI. Given these findings, we investigated the relationship between A? and tau pathologies after trauma in this model by systemic treatment of Compound E to inhibit ?-secretase activity, a proteolytic process required for A? production. Compound E treatment successfully blocked posttraumatic A? accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies and suggest that TBI may independently affect A? and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies.
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Signal transduction through CsrRS confers an invasive phenotype in group A Streptococcus.
PLoS Pathog.
PUBLISHED: 06-28-2011
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The CsrRS (or CovRS) two component system controls expression of up to 15% of the genome of group A Streptococcus (GAS). While some studies have suggested that the sensor histidine kinase CsrS responds to membrane perturbations as a result of various environmental stresses, other data have implicated the human antimicrobial peptide LL-37 and extracellular Mg(2+) as specific signals. We now report that Mg(2+) and LL-37 have opposite effects on expression of multiple genes that are activated or repressed by the transcriptional regulator CsrR. Using a GAS isolate representative of the recently emerged and widely disseminated M1T1 clone implicated in severe invasive disease, we found marked up-regulation by CsrRS of multiple virulence factors including pyrogenic exotoxin A, DNase Sda1, streptolysin O, and the hyaluronic acid capsular polysaccharide, among others. Topology and surface protein labeling studies indicated that CsrS is associated with the bacterial cell membrane and has a surface-exposed extracellular domain accessible to environmental ligands. Replacement of a cluster of three acidic amino acids with uncharged residues in the extracellular domain of CsrS abrogated LL-37 signaling and conferred a hyporesponsive phenotype consistent with tonic activation of CsrS autokinase activity, an effect that could be overridden by mutation of the CsrS active site histidine. Both loss- and gain-of-function mutations of a conserved site in the receiver domain of CsrR established an essential role for lysine 102 in CsrS-to-CsrR signal transduction. These results provide strong evidence that Mg(2+) and LL-37 are specific signals that function by altering CsrS autokinase activity and downstream phosphotransfer to CsrR to modulate its activity as a transcriptional regulator. The representation of multiple antiphagocytic and cytotoxic factors in the CsrRS regulon together with results of in vitro phagocytic killing assays support the hypothesis that CsrRS mediates conversion of GAS from a colonizing to an invasive phenotype in response to signaling by host LL-37.
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Epidemiology of a measles epidemic in Vietnam 2008-2010.
J. Infect. Dis.
PUBLISHED: 06-14-2011
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Vietnam conducted a measles catch-up supplementary immunization activity (SIA) during 2002-2003 that targeted children 9 months-10 years of age, followed by subnational SIAs targeting persons up to 20 years of age during 2004 and 2007-2008. A measles epidemic began among young adults in October 2008 in the northern region, spread nationwide during early 2009, and continued during 2010.
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Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 06-14-2011
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Repetitive mild or "concussive" traumatic brain injury (TBI) can cause substantial neurologic impairment, but the pathological features of this type of injury are not fully understood. We report an experimental model of TBI in which the closed skulls of anesthetized male C57BL/6J mice are struck with an electromagnetically controlled rubber impactor twice with an interval of 24 hours between impacts. The mice had deficits in Morris water maze performance in the first week after injury that only partially resolved 7 weeks later. By routine histology, there was no apparent bleeding, neuronal cell loss, or tissue disruption, and amyloid precursor protein immunohistochemistry demonstrated very few immunoreactive axonal varicosities. In contrast, silver staining revealed extensive abnormalities in the corpus callosum and bilateral external capsule, the ipsilateral cortex and thalamus, and the contralateral hippocampal CA1 stratum radiatum and stratum oriens. Electron microscopy of white matter regions demonstrated axonal cytoskeletal disruption, intra-axonal organelle compaction, and irregularities in axon caliber. Reactive microglia were observed in the same areas as the injured axons by both electron microscopy and Iba1 immunohistochemistry. Quantitative analyses of silver staining and Iba1 immunohistochemistry at multiple time points demonstrated transient cortical and thalamic abnormalities but persistent white matter pathology as late as 7 weeks after injury.Thus, prominent and long-lasting abnormalities in this TBI model were underestimated using conventional approaches. The model may be useful for mechanistic investigations and preclinical assessment of candidate therapeutics.
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Coma in fatal adult human malaria is not caused by cerebral oedema.
Malar. J.
PUBLISHED: 06-10-2011
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The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.