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Find video protocols related to scientific articles indexed in Pubmed.
Direct costs of hypertensive patients admitted to hospital in Vietnam- a bottom-up micro-costing analysis.
BMC Health Serv Res
PUBLISHED: 10-13-2014
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There is an economic burden associated with hypertension both worldwide and in Vietnam. In Vietnam, patients with uncontrolled high blood pressure are hospitalized for further diagnosis and initiation of treatment. Because there is no evidence on costs of inpatient care for hypertensive patients available yet to inform policy makers, health insurance and hospitals, this study aims to quantify direct costs of inpatient care for these patients in Vietnam.
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Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection.
Antivir. Ther. (Lond.)
PUBLISHED: 10-01-2014
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We explored the relationship between virologic response in the first year of treatment and long-term outcomes in the BENCHMRK studies.
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Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection.
Antivir. Ther. (Lond.)
PUBLISHED: 10-01-2014
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We explored the relationship between virologic response in the first year of treatment and long-term outcomes in the BENCHMRK studies.
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Photostability of Cosmetic UV Filters on Mammalian Skin Under UV Exposure.
Photochem. Photobiol.
PUBLISHED: 08-18-2014
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Previous studies showed that the common UV filter substances benzophenone-3 (BP-3), butyl methoxydibenzoylmethane (BM-DBM), octocrylene (OCR), ethylhexyl methoxycinnamate (EHMC), ethylhexyl salicylate (EHS) and ethylhexyl triazone (EHT) were able to react with amino side chains of different proteins in vitro. To transfer the results to mammalian skin conditions, sunscreen products were applied on both prepared fresh porcine skin and glass plates, followed by UV irradiation and the determination of depletion of the respective UV filters. Significantly lower recoveries of the UV filters extracted from skin samples than from glass plates indicated the additional reaction of the UV filters with skin constituents, when proteins will be the most important reactants. Among the products tested, BP-3 showed the greatest differences in recoveries between glass and skin samples of about 13% and 24% after 2 and 4 h of irradiation, respectively, followed by EHS > BM-DBM > OCR > EHMC > EHT. The obtained results raise the question, whether the common in vitro evaluations of sunscreens, using inert substrate materials like roughened quartz or polymethyl methacrylate (PMMA) plates are really suitable to fully replace in vivo methods, as they cannot include skin-typical reactions.
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Attributes and perspectives of public providers related to provision of medical abortion at public health facilities in Vietnam: a cross-sectional study in three provinces.
Int J Womens Health
PUBLISHED: 08-14-2014
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The purpose of this study was to investigate attributes of public service providers associated with the provision of medical abortion in Vietnam.
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Two cases of bacteriemia caused by nontoxigenic, non-O1, non-O139 Vibrio cholerae isolates in Ho Chi Minh City, Vietnam.
J. Clin. Microbiol.
PUBLISHED: 08-13-2014
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The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non-O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period.
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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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Palliative care development in the Asia-Pacific region: an international survey from the Asia Pacific Hospice Palliative Care Network (APHN).
BMJ Support Palliat Care
PUBLISHED: 07-12-2014
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Although palliative care is an important public healthcare issue worldwide, the current situation in the Asia-Pacific region has not been systematically evaluated.
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Hydroxylated, methoxylated, and parent polybrominated diphenyl ethers (PBDEs) in the inland environment, Korea, and potential OH- and MeO-BDE source.
Environ. Sci. Technol.
PUBLISHED: 06-18-2014
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The concentrations, congener profiles, and phase-specific distribution profiles of 27 polybrominated diphenyl ethers and 10 hydroxylated and 18 methoxylated brominated diphenyl ethers (OH- and MeO-BDEs; later called structural analogues of PBDEs) were determined in surface soil, water, air, and vegetation from the southeastern city of Busan, Korea for 2010-2011. The total PBDE concentrations were 0.18-7.7 ng/g in soil, 6.3-87 ng/L in water, 5.3-16 pg/m(3) in air, and 0.06-0.22 ng/g in vegetation. The OH- and MeO-BDE concentrations were lower than the parent PBDE concentrations in soil samples but OH-BDEs were much greater in the water samples and MeO-BDEs were much greater in the air samples. The relative concentrations of the PBDEs and their structural analogues varied depending on the type and homologue of the degradation product, the substituent position, and the characteristics of the environmental medium. In particular, the OH-BDEs were not found in air samples and the OH-penta BDEs were not detected in any of the matrices. The dominance of the ortho-substituted structural analogues found in water and vegetation suggested that they may have natural sources, but different substituent patterns were found in the air and soil samples, suggesting that the structural analogues had different formation mechanisms in these media.
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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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Blood glucose level and outcome after cardiac arrest: insights from a large registry in the hypothermia era.
Intensive Care Med
PUBLISHED: 03-13-2014
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The influence of blood glucose (BG) level during the post-resuscitation period after out-of-hospital cardiac arrest (OHCA) is still debated. To evaluate the relationship between blood glucose level and outcome, we included the median glycemia and its maximal amplitude over the first 48 h following ICU admission in an analysis of outcome predictors.
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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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Risk factors for repeat abortion and implications for addressing unintended pregnancy in Vietnam.
Int J Gynaecol Obstet
PUBLISHED: 02-25-2014
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To determine predictors of repeat abortion in 3 provinces in Vietnam.
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Service users' attributes associated with the uptake of medical versus surgical abortion at public health facilities in Vietnam.
Int J Gynaecol Obstet
PUBLISHED: 02-25-2014
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To investigate the attributes of service users associated with uptake of medical abortion (MA) versus manual vacuum aspiration (MVA) at public health facilities in Vietnam.
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Adult survivorship of the dengue mosquito Aedes aegypti varies seasonally in central Vietnam.
PLoS Negl Trop Dis
PUBLISHED: 02-01-2014
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The survival characteristics of the mosquito Aedes aegypti affect transmission rates of dengue because transmission requires infected mosquitoes to survive long enough for the virus to infect the salivary glands. Mosquito survival is assumed to be high in tropical, dengue endemic, countries like Vietnam. However, the survival rates of wild populations of mosquitoes are seldom measured due the difficulty of predicting mosquito age. Hon Mieu Island in central Vietnam is the site of a pilot release of Ae. aegypti infected with a strain of Wolbachia pipientis bacteria (wMelPop) that induces virus interference and mosquito life-shortening. We used the most accurate mosquito age grading approach, transcriptional profiling, to establish the survival patterns of the mosquito population from the population age structure. Furthermore, estimations were validated on mosquitoes released into a large semi-field environment consisting of an enclosed house, garden and yard to incorporate natural environmental variability. Mosquito survival was highest during the dry/cool (January-April) and dry/hot (May-August) seasons, when 92 and 64% of Hon Mieu mosquitoes had survived to an age that they were able to transmit dengue (12 d), respectively. This was reduced to 29% during the wet/cool season from September to December. The presence of Ae. aegypti older than 12 d during each season is likely to facilitate the observed continuity of dengue transmission in the region. We provide season specific Ae. aegypti survival models for improved dengue epidemiology and evaluation of mosquito control strategies that aim to reduce mosquito survival to break the dengue transmission cycle.
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The effects of poly(3, 4-ethylenedioxythiophene) (PEDOT) coating on magnesium degradation and cytocompatibility with human embryonic stem cells for potential neural applications.
J Biomed Mater Res A
PUBLISHED: 01-29-2014
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Magnesium (Mg) is a promising conductive metallic biomaterial due to its desirable mechanical properties for load bearing and biodegradability in human body. Controlling the rapid degradation of Mg in physiological environment continues to be the key challenge toward clinical translation. In this study, we investigated the effects of conductive poly(3, 4-ethylenedioxythiophene) (PEDOT) coating on the degradation behavior of Mg substrates and their cytocompatibility. Human embryonic stem cells (hESCs) were used as the in vitro model system to study cellular responses to Mg degradation because they are sensitive and can potentially differentiate into many cell types of interest (e.g. neurons) for regenerative medicine. The PEDOT was deposited on Mg substrates using electrochemical deposition. The greater number of cyclic voltammetry cycles yielded thicker PEDOT coatings on Mg substrates. Specifically, the coatings produced by 2, 5, and 10 CV cycles (denoted as 2x-PEDOT-Mg, 5x-PEDOT-Mg, and 10x-PEDOT-Mg) had an average thickness of 31, 63, and 78 µm, respectively. Compared with non-coated Mg samples, all PEDOT coated Mg samples showed slower degradation rates, as indicated by Tafel test results and Mg ion concentrations in the post-culture media. The 5x-PEDOT-Mg showed the best coating adhesion and slowest Mg degradation among the tested samples. Moreover, hESCs survived for the longest period when cultured with the 5x-PEDOT-Mg samples compared with the non-coated Mg and 2x-PEDOT-Mg. Overall, the results of this study showed promise in using PEDOT coating on biodegradable Mg-based implants for potential neural recording, stimulation and tissue engineering applications, thus encouraging further research.
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Antibiotic sales in rural and urban pharmacies in northern Vietnam: an observational study.
BMC Pharmacol Toxicol
PUBLISHED: 01-29-2014
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The irrational overuse of antibiotics should be minimized as it drives the development of antibiotic resistance, but changing these practices is challenging. A better understanding is needed of practices and economic incentives for antibiotic dispensing in order to design effective interventions to reduce inappropriate antibiotic use. Here we report on both quantitative and qualitative aspects of antibiotic sales in private pharmacies in northern Vietnam.
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Mechanical ventilation and clinical practice heterogeneity in intensive care units: a multicenter case-vignette study.
Ann Intensive Care
PUBLISHED: 01-28-2014
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Observational studies on mechanical ventilation (MV) show practice variations across ICUs. We sought to determine, with a case-vignette study, the heterogeneity of processes of care in ICUs focusing on mechanical ventilation procedures, and whether organizational patterns or physician characteristics influence practice variations.
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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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Tuberculin Skin Tests versus Interferon-Gamma Release Assays in Tuberculosis Screening among Immigrant Visa Applicants.
Tuberc Res Treat
PUBLISHED: 01-15-2014
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Objective. Use of tuberculin skin tests (TSTs) and interferon gamma release assays (IGRAs) as part of tuberculosis (TB) screening among immigrants from high TB-burden countries has not been fully evaluated. Methods. Prevalence of Mycobacterium tuberculosis infection (MTBI) based on TST, or the QuantiFERON-TB Gold test (QFT-G), was determined among immigrant applicants in Vietnam bound for the United States (US); factors associated with test results and discordance were assessed; predictive values of TST and QFT-G for identifying chest radiographs (CXRs) consistent with TB were calculated. Results. Of 1,246 immigrant visa applicants studied, 57.9% were TST positive, 28.3% were QFT-G positive, and test agreement was 59.4%. Increasing age was associated with positive TST results, positive QFT-G results, TST-positive but QFT-G-negative discordance, and abnormal CXRs consistent with TB. Positive predictive values of TST and QFT-G for an abnormal CXR were 25.9% and 25.6%, respectively. Conclusion. The estimated prevalence of MTBI among US-bound visa applicants in Vietnam based on TST was twice that based on QFT-G, and 14 times higher than a TST-based estimate of MTBI prevalence reported for the general US population in 2000. QFT-G was not better than TST at predicting abnormal CXRs consistent with TB.
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Limited Density of an Antigen Presented by RMA-S Cells Requires B7-1/CD28 Signaling to Enhance T-Cell Immunity at the Effector Phase.
PLoS ONE
PUBLISHED: 01-01-2014
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The association of B7-1/CD28 between antigen presenting cells (APCs) and T-cells provides a second signal to proliferate and activate T-cell immunity at the induction phase. Many reports indicate that tumor cells transfected with B7-1 induced augmented antitumor immunity at the induction phase by mimicking APC function; however, the function of B7-1 on antitumor immunity at the effector phase is unknown. Here, we report direct evidence of enhanced T-cell antitumor immunity at the effector phase by the B7-1 molecule. Our experiments in vivo and in vitro indicated that reactivity of antigen-specific monoclonal and polyclonal T-cell effectors against a Lass5 epitope presented by RMA-S cells is increased when the cells expressed B7-1. Use of either anti-B7-1 or anti-CD28 antibodies to block the B7-1/CD28 association reduced reactivity of the T effectors against B7-1 positive RMA-S cells. Transfection of Lass5 cDNA into or pulse of Lass5 peptide onto B7-1 positive RMA-S cells overcomes the requirement of the B7-1/CD28 signal for T effector response. To our knowledge, the data offers, for the first time, strong evidence that supports the requirement of B7-1/CD28 secondary signal at the effector phase of antitumor T-cell immunity being dependent on the density of an antigenic peptide.
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Women's perspectives on termination service delivery in Vietnam: a cross-sectional survey in three provinces.
Int J Womens Health
PUBLISHED: 01-01-2014
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To explore the perspectives of abortion service users regarding termination methods and abortion service delivery in Vietnam.
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Winter refuge for Aedes aegypti and Ae. albopictus mosquitoes in Hanoi during Winter.
PLoS ONE
PUBLISHED: 01-01-2014
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Dengue occurs throughout the year in Hanoi, Vietnam, despite winter low temperatures <10°C. During July 2010 to March 2012, we surveyed monthly for Aedes larvae and pupae in 120 houses in 8 Hanoi districts. Aedes albopictus preferred discarded containers in summer and pupal density drastically decreased in winter. Aedes aegypti preferred concrete tanks and this preference increased in winter. Even in winter, the lowest water temperature found in concrete tanks was >14°C, exceeding the developmental zero point of Ae. aegypti. Although jars, drums and concrete tanks were the dominant containers previously (1994-97) in Hanoi, currently the percentage of residences with concrete tanks was still high while jars and drums were quite low. Our study showed that concrete tanks with broken lids allowing mosquitoes access were important winter refuge for Ae. aegypti. We also indicate a concern about concrete tanks serving as foci for Ae. aegypti to expand their distribution in cooler regions.
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CAROTENOID CLEAVAGE DIOXYGENASE4 Is a Negative Regulator of ?-Carotene Content in Arabidopsis Seeds.
Plant Cell
PUBLISHED: 12-24-2013
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Experimental approaches targeting carotenoid biosynthetic enzymes have successfully increased the seed ?-carotene content of crops. However, linkage analysis of seed carotenoids in Arabidopsis thaliana recombinant inbred populations showed that only 21% of quantitative trait loci, including those for ?-carotene, encode carotenoid biosynthetic enzymes in their intervals. Thus, numerous loci remain uncharacterized and underutilized in biofortification approaches. Linkage mapping and genome-wide association studies of Arabidopsis seed carotenoids identified CAROTENOID CLEAVAGE DIOXYGENASE4 (CCD4) as a major negative regulator of seed carotenoid content, especially ?-carotene. Loss of CCD4 function did not affect carotenoid homeostasis during seed development but greatly reduced carotenoid degradation during seed desiccation, increasing ?-carotene content 8.4-fold relative to the wild type. Allelic complementation of a ccd4 null mutant demonstrated that single-nucleotide polymorphisms and insertions and deletions at the locus affect dry seed carotenoid content, due at least partly to differences in CCD4 expression. CCD4 also plays a major role in carotenoid turnover during dark-induced leaf senescence, with ?-carotene accumulation again most strongly affected in the ccd4 mutant. These results demonstrate that CCD4 plays a major role in ?-carotene degradation in drying seeds and senescing leaves and suggest that CCD4 orthologs would be promising targets for stabilizing and increasing the level of provitamin A carotenoids in seeds of major food crops.
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[Mechanisms of insulin resistance].
Duodecim
PUBLISHED: 12-18-2013
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Insulin resistance refers to an aberrant physiological response to insulin in its target tissues. Several signal transduction mechanisms sensing intracellular stress are activated in situations where energy supply exceeds the cells energy requirements. This stress interferes with insulin-induced intracellular signal transduction and leads to an inflammatory state. The activation of inflammatory responses in peripheral tissues and central nervous system weakens the bodys insulin sensitivity, glucose tolerance and predisposes to obesity. Insulin resistance is thus a crucial metabolic disorder in obesity, type 2 diabetes and cardiovascular diseases.
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p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin.
Hum. Mol. Genet.
PUBLISHED: 09-18-2013
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Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntingtons disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD. Cleavage of the caspase-6 specific substrate lamin A is significantly increased in skeletal muscle obtained from HD patients as well as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-? (pif?), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53s mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6. Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy.
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Access to urban acute care services in high- vs. middle-income countries: an analysis of seven cities.
Intensive Care Med
PUBLISHED: 08-07-2013
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Cities are expanding rapidly in middle-income countries, but their supply of acute care services is unknown. We measured acute care services supply in seven cities of diverse economic background.
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Knowledge and provision practices regarding medical abortion among public providers in Hanoi, Khanh Hoa, and Ho Chi Minh City, Vietnam.
Int J Gynaecol Obstet
PUBLISHED: 06-11-2013
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To assess public service providers knowledge of medical abortion (MA) and practices, and perspectives on expanding the use of MA to primary and secondary health facilities in Vietnam.
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National surveillance for influenza and influenza-like illness in Vietnam, 2006-2010.
Vaccine
PUBLISHED: 05-20-2013
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Influenza virus infections result in considerable morbidity and mortality both in the temperate and tropical world. Influenza surveillance over multiple years is important to determine the impact and epidemiology of influenza and to develop a national vaccine policy, especially in countries developing influenza vaccine manufacturing capacity, such as Vietnam. We conducted surveillance of influenza and influenza-like illness in Vietnam through the National Influenza Surveillance System during 2006-2010. At 15 sentinel sites, the first two patients presenting each weekday with influenza-like illness (ILI), defined as fever and cough and/or sore throat with illness onset within 3 days, were enrolled and throat specimens were collected and tested for influenza virus type and influenza A subtype by RT-PCR. De-identified demographic and provider reported subsequent hospitalization information was collected on each patient. Each site also collected information on the total number of patients with influenza-like illness evaluated per week. Of 29,804 enrolled patients presenting with influenza-like illness, 6516 (22%) were influenza positive. Of enrolled patients, 2737 (9.3%) were reported as subsequently hospitalized; of the 2737, 527 (19%) were influenza positive. Across all age groups with ILI, school-aged children had the highest percent of influenza infection (29%) and the highest percent of subsequent hospitalizations associated with influenza infection (28%). Influenza viruses co-circulated throughout most years in Vietnam during 2006-2010 and often reached peak levels multiple times during a year, when >20% of tests were influenza positive. Influenza is an important cause of all influenza-like illness and provider reported subsequent hospitalization among outpatients in Vietnam, especially among school-aged children. These findings may have important implications for influenza vaccine policy in Vietnam.
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Assessing the quality of VA Human Research Protection Programs: VA vs. affiliated University Institutional Review Board.
J Empir Res Hum Res Ethics
PUBLISHED: 05-09-2013
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We compared the Human Research Protection Program (HRPP) quality indicator data of the Department of Veterans Affairs (VA) facilities using their own VA institutional review boards (IRBs) with those using affiliated university IRBs. From a total of 25 performance metrics, 13 did not demonstrate statistically significant differences, while 12 reached statistically significance differences. Among the 12 with statistically significant differences, facilities using their own VA IRBs performed better on four of the metrics, while facilities using affiliate IRBs performed better on eight. However, the absolute difference was small (0.2-2.7%) in all instances, suggesting that they were of no practical significance. We conclude that it is acceptable for facilities to use their own VA IRBs or affiliated university IRBs as their IRBs of record.
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Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials.
Lancet Infect Dis
PUBLISHED: 05-07-2013
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Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study).
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Characterization of Dak Nong virus, an insect nidovirus isolated from Culex mosquitoes in Vietnam.
Arch. Virol.
PUBLISHED: 04-19-2013
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In this study, we isolated and characterized an insect nidovirus from the mosquito Culex tritaeniorhynchus Giles (Diptera: Culicidae) in Vietnam, as an additional member of the new family Mesoniviridae in the order Nidovirales. The virus, designated "Dak Nong virus (DKNV)," shared many characteristics with Cavally virus and Nam Dinh virus, which have also been discovered recently in mosquitoes, and these viruses should be considered members of a single virus species, Alphamesonivirus 1. DKNV grew in cultured mosquito cells but could not replicate in the cultured vertebrate cells tested. N-terminal sequencing of the DKNV structural proteins revealed two posttranslational cleavage sites in the spike glycoprotein precursor. DKNV is assumed to be a new member of the species Alphamesonivirus 1, and the current study provides further understanding of viruses belonging to the new family Mesoniviridae.
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Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties.
J. Inorg. Biochem.
PUBLISHED: 04-18-2013
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Indolone-N-oxides (INODs) are bioreducible and possess remarkable anti-malarial activities in the low nanomolar range in vitro against different Plasmodium falciparum (P. falciparum) strains and in vivo. INODs have an original mechanism of action: they damage the host cell membrane without affecting non-parasitized erythrocytes. These molecules produce a redox signal which activates SYK tyrosine kinases and induces a hyperphosphorylation of AE1 (band 3, erythrocyte membrane protein). The present work aimed to understand the early stages of the biochemical interactions of these compounds with some erythrocyte components from which the redox signal could originate. The interactions were studied in a biomimetic model and compared with those of chloroquine and artemisinin. The results showed that INODs i) do not enter the coordination sphere of the metal in the heme iron complex as does chloroquine; ii) do not generate iron-dependent radicals as does artemisinin; iii) generate stable free radical adducts after reduction at one electron; iv) cannot trap free radicals after reduction. These results confirm that the bioactivity of INODs does not lie in their spin-trapping properties but rather in their pro-oxidant character. This property may be the initiator of the redox signal which activates SYK tyrosine kinases.
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Studying cancer stem cell dynamics on PDMS surfaces for microfluidics device design.
Sci Rep
PUBLISHED: 03-27-2013
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This systematic study clarified a few interfacial aspects of cancer cell phenotypes on polydimethylsiloxane (PDMS) substrates and indicated that the cell phenotypic equilibrium greatly responds to cell-to-surface interactions. We demonstrated that coatings of fibronectin, bovine serum albumin (BSA), or collagen with or without oxygen-plasma treatments of the PDMS surfaces dramatically impacted the phenotypic equilibrium of breast cancer stem cells, while the variations of the PDMS elastic stiffness had much less such effects. Our results showed that the surface coatings of collagen and fibronectin on PDMS maintained breast cancer cell phenotypes to be nearly identical to the cultures on commercial polystyrene Petri dishes. The surface coating of BSA provided a weak cell-substrate adhesion that stimulated the increase in stem-cell-like subpopulation. Our observations may potentially guide surface modification approaches to obtain specific cell phenotypes.
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Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.
Cell Metab.
PUBLISHED: 03-14-2013
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Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in the elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism by which the Nlrp3 inflammasome controls systemic low-grade age-related "sterile" inflammation in both periphery and brain independently of the noncanonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome, and astrogliosis. Consistent with the hypothesis that systemic low-grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome-mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome-dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer an innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.
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Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.
J Ethnopharmacol
PUBLISHED: 03-11-2013
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Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear.
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Safety, tolerability, and efficacy of raltegravir in a diverse cohort of HIV-infected patients: 48-week results from the REALMRK Study.
AIDS Res. Hum. Retroviruses
PUBLISHED: 02-26-2013
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The racial diversity and gender distribution of HIV-infected patients make it essential to confirm the safety and efficacy of raltegravir in these populations. A multicenter, open-label, single-arm observational study was conducted in a diverse cohort of HIV-infected patients (goals: ?25% women; ?50% blacks in the United States), enrolling treatment-experienced patients failing or intolerant to current antiretroviral therapy (ART) and treatment-naive patients (limited to ?20%). All patients received raltegravir 400 mg b.i.d. in a combination antiretroviral regimen for up to 48 weeks. A total of 206 patients received study treatment at 34 sites in the United States, Brazil, Dominican Republic, Jamaica, and South Africa: 97 (47%) were female and 153 (74%) were black [116 (56%) in the United States]. Of these, 185 patients were treatment experienced: 97 (47%) were failing and 88 (43%) were intolerant to current therapy; 21 patients (10%) were treatment naive. Among treatment-intolerant patients, 55 (63%) had HIV-1 RNA<50 copies/ml at baseline. Overall, 15% of patients discontinued: 13% of men, 18% of women, 14% of blacks, and 17% of nonblacks. At week 48, HIV RNA was <50 copies/ml in 60/94 (64%) patients failing prior therapy, 61/80 (76%) patients intolerant to prior therapy, and 16/21 (76%) treatment-naive patients. Response rates were similar for men vs. women and black vs. nonblack patients. Drug-related clinical adverse events were reported by 8% of men, 18% of women, 14% of blacks, and 9% of nonblacks. After 48 weeks of treatment in a diverse cohort of HIV-infected patients, raltegravir was generally safe and well tolerated with potent efficacy regardless of gender or race.
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Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-16-2013
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STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results.
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Surveillance of Japanese encephalitis virus infection in mosquitoes in Vietnam from 2006 to 2008.
Am. J. Trop. Med. Hyg.
PUBLISHED: 01-28-2013
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Japanese encephalitis virus (JEV) infection in mosquitoes was monitored in Vietnam from 2006 to 2008. A total of 15,225 mosquitoes, identified as 26 species in five genera were collected and 12,621 were grouped into 447 pools for examination of JEV infection by assays for cytopathic effects in C6/36 cells and by RT-PCR to detect flavivirus RNA. Three JEV strains were isolated from Culex tritaeniorhynchus Giles collected in northern and southern Vietnam and two JEV strains were isolated from Culex vishnui Theobald collected in the highlands of Vietnam. Genetic and phylogenetic analyses, based on complete E gene nucleotide sequences, revealed that the five JEV strains were classified into the genotype I group and six amino acid differences were found in these five strains. These results indicated that multiple JEV genotype I populations are circulating countrywide in Vietnam, transmitted by bites of their Cx. tritaeniorhynchus and Cx. vishnui.
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An in vitro mechanism study on the proliferation and pluripotency of human embryonic stems cells in response to magnesium degradation.
PLoS ONE
PUBLISHED: 01-01-2013
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Magnesium (Mg) is a promising biodegradable metallic material for applications in cellular/tissue engineering and biomedical implants/devices. To advance clinical translation of Mg-based biomaterials, we investigated the effects and mechanisms of Mg degradation on the proliferation and pluripotency of human embryonic stem cells (hESCs). We used hESCs as the in vitro model system to study cellular responses to Mg degradation because they are sensitive to toxicants and capable of differentiating into any cell types of interest for regenerative medicine. In a previous study when hESCs were cultured in vitro with either polished metallic Mg (99.9% purity) or pre-degraded Mg, cell death was observed within the first 30 hours of culture. Excess Mg ions and hydroxide ions induced by Mg degradation may have been the causes for the observed cell death; hence, their respective effects on hESCs were investigated for the first time to reveal the potential mechanisms. For this purpose, the mTeSR®1 hESC culture media was either modified to an alkaline pH of 8.1 or supplemented with 0.4-40 mM of Mg ions. We showed that the initial increase of media pH to 8.1 had no adverse effect on hESC proliferation. At all tested Mg ion dosages, the hESCs grew to confluency and retained pluripotency as indicated by the expression of OCT4, SSEA3, and SOX2. When the supplemental Mg ion dosages increased to greater than 10 mM, however, hESC colony morphology changed and cell counts decreased. These results suggest that Mg-based implants or scaffolds are promising in combination with hESCs for regenerative medicine applications, providing their degradation rate is moderate. Additionally, the hESC culture system could serve as a standard model for cytocompatibility studies of Mg in vitro, and an identified 10 mM critical dosage of Mg ions could serve as a design guideline for safe degradation of Mg-based implants/scaffolds.
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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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Light-initiated hydroxylation of lauric acid using hybrid P450 BM3 enzymes.
Chem. Commun. (Camb.)
PUBLISHED: 10-05-2011
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We have developed hybrid P450 BM3 enzymes consisting of a Ru(II)-diimine photosensitizer covalently attached to non-native single cysteine residues of P450 BM3 heme domain mutants. These enzymes are capable, upon light activation, of selectively hydroxylating lauric acid with 40 times higher total turnover numbers compared to the peroxide shunt.
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Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.
Lancet Infect Dis
PUBLISHED: 09-18-2011
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Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to compare these dosing schedules.
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Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK.
Clin. Infect. Dis.
PUBLISHED: 09-17-2011
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We compared 3 years of antiretroviral therapy with raltegravir or efavirenz as part of a combination regimen in the ongoing STARTMRK study of treatment-naive patients infected with human immunodeficiency virus (HIV).
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Intensive care unit renal support therapy volume is not associated with patient outcome.
Crit. Care Med.
PUBLISHED: 06-28-2011
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Evidence suggests that patients requiring high-risk procedures benefit from care at institutions providing a large volume of these procedures. Our objective was to determine whether there is a volume-outcome relationship among intensive care unit patients receiving renal support therapy in two different healthcare systems (France and the United States).
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A quantitative method for the specific assessment of caspase-6 activity in cell culture.
PLoS ONE
PUBLISHED: 06-10-2011
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Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimers and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples. Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly specific for caspase-6 cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts. The method is more sensitive than VEID-based assays and can be adapted to a high-content imaging platform for high-throughput screening. This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders.
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The challenge of admitting the very elderly to intensive care.
Ann Intensive Care
PUBLISHED: 06-08-2011
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The aging of the population has increased the demand for healthcare resources. The number of patients aged 80 years and older admitted to the intensive care unit (ICU) increased during the past decade, as has the intensity of care for such patients. Yet, many physicians remain reluctant to admit the oldest, arguing a "squandering" of societal resources, that ICU care could be deleterious, or that ICU care may not actually be what the patient or family wants in this instance. Other ICU physicians are strong advocates for admission of a selected elderly population. These discrepant opinions may partly be explained by the current lack of validated criteria to select accurately the patients (of any age) who will benefit most from ICU hospitalization. This review describes the epidemiology of the elderly aged 80 years and older admitted in the ICU, their long-term outcomes, and to discuss some of the solutions to cope with the burden of an aging population receiving acute care hospitalization.
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Abundance and prevalence of Aedes aegypti immatures and relationships with household water storage in rural areas in southern Viet Nam.
Int Health
PUBLISHED: 06-01-2011
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Since 2000, the Government of Viet Nam has committed to provide rural communities with increased access to safe water through a variety of household water supply schemes (wells, ferrocement tanks and jars) and piped water schemes. One possible, unintended consequence of these schemes is the concomitant increase in water containers that may serve as habitats for dengue mosquito immatures, principally Aedes aegypti. To assess these possible impacts we undertook detailed household surveys of Ae. aegypti immatures, water storage containers and various socioeconomic factors in three rural communes in southern Viet Nam. Positive relationships between the numbers of household water storage containers and the prevalence and abundance of Ae. aegypti immatures were found. Overall, water storage containers accounted for 92-97% and 93-96% of the standing crops of III/IV instars and pupae, respectively. Interestingly, households with higher socioeconomic levels had significantly higher numbers of water storage containers and therefore greater risk of Ae. aegypti infestation. Even after provision of piped water to houses, householders continued to store water in containers and there was no observed decrease in water storage container abundance in these houses, compared to those that relied entirely on stored water. These findings highlight the householders concerns about the limited availability of water and their strong behavoural patterns associated with storage of water. We conclude that household water storage container availability is a major risk factor for infestation with Ae. aegypti immatures, and that recent investment in rural water supply infrastructure are unlikely to mitigate this risk, at least in the short term.
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CD40 Co-stimulation Inhibits Sustained BCR-induced Ca Signaling in Response to Long-term Antigenic Stimulation of Immature B Cells.
Korean J. Physiol. Pharmacol.
PUBLISHED: 05-17-2011
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Regulation of B cell receptor (BCR)-induced Ca(2+) signaling by CD40 co-stimulation was compared in long-term BCR-stimulated immature (WEHI-231) and mature (Bal-17) B cells. In response to long-term pre-stimulation of immature WEHI-231 cells to ?-IgM antibody (0.5~48 hr), the initial transient decrease in BCR-induced [Ca(2+)](i) was followed by spontaneous recovery to control level within 24 hr. The recovery of Ca(2+) signaling in WEHI-231 cells was not due to restoration of internalized receptor but instead to an increase in the levels of PLC?2 and IP(3)R-3. CD40 co-stimulation of WEHI-231 cells prevented BCR-induced cell cycle arrest and apoptosis, and it strongly inhibited the recovery of BCR-induced Ca(2+) signaling. CD40 co-stimulation also enhanced BCR internalization and reduced expression of PLC?2 and IP(3)R-3. Pre-treatment of WEHI-231 cells with the antioxidant N-acetyl-L-cysteine (NAC) strongly inhibited CD40-mediated prevention of the recovery of Ca(2+) signaling. In contrast to immature WEHI-231 cells, identical long-term ?-IgM pre-stimulation of mature Bal-17 cells abolished the increase in BCR-induced [Ca(2+)](i), regardless of CD40 co-stimulation. These results suggest that CD40-mediated signaling prevents antigen-induced cell cycle arrest and apoptosis of immature B cells through inhibition of sustained BCR-induced Ca(2+) signaling.
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Decreasing temperature shifts hippocampal function from memory formation to modulation of hibernation bout duration in Syrian hamsters.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 05-11-2011
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Previous studies in hibernating species have characterized two forms of neural plasticity in the hippocampus, long-term potentiation (LTP) and its reversal, depotentiation, but not de novo long-term depression (LTD), which is also associated with memory formation. Studies have also shown that histamine injected into the hippocampus prolonged hibernation bout duration. However, spillover into the ventricles may have affected brain stem regions, not the hippocampus. Here, we tested the hypothesis that decreased brain temperature shifts the major function of the hippocampus in the Syrian hamster (Mesocricetus auratus) from one of memory formation (via LTP, depotentiation, and de novo LTD) to increasing hibernation bout duration. We found reduced evoked responses in hippocampal CA1 pyramidal neurons following low-frequency stimulation in young (<30 days old) and adult (>60 days old) hamsters, indicating that de novo LTD was generated in hippocampal slices from both pups and adults at temperatures >20°C. However, at temperatures below 20°C, synchronization of neural assemblies (a requirement for LTD generation) was markedly degraded, implying that de novo LTD cannot be generated in hibernating hamsters. Nonetheless, even at temperatures below 16°C, pyramidal neurons could still generate action potentials that may traverse a neural pathway, suppressing the ascending arousal system (ARS). In addition, histamine increased the excitability of these pyramidal cells. Taken together, these findings are consistent with the hypothesis that hippocampal circuits remain operational at low brain temperatures in Syrian hamsters and suppress the ARS to prolong bout duration, even though memory formation is muted at these low temperatures.
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Energy dissipating structures produced by walls in two-dimensional flows at vanishing viscosity.
Phys. Rev. Lett.
PUBLISHED: 05-03-2011
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We perform numerical experiments of a dipole crashing into a wall, a generic event in two-dimensional incompressible flows with solid boundaries. The Reynolds number (Re) is varied from 985 to 7880, and no-slip boundary conditions are approximated by Navier boundary conditions with a slip length proportional to Re(-1). Energy dissipation is shown to first set up within a vorticity sheet of thickness proportional to Re(-1) in the neighborhood of the wall, and to continue as this sheet rolls up into a spiral and detaches from the wall. The energy dissipation rate integrated over these regions appears to converge towards Re-independent values, indicating the existence of energy dissipating structures that persist in the vanishing viscosity limit.
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Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies.
AIDS
PUBLISHED: 04-28-2011
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We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients.
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Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents.
PLoS ONE
PUBLISHED: 04-01-2011
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Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.
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Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium.
Ann. N. Y. Acad. Sci.
PUBLISHED: 03-26-2011
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Raltegravir is the first integrase strand transfer inhibitor approved for the treatment of HIV-1 infection. As the first agent in this new class of antiretroviral therapies, raltegravir has demonstrated safety and efficacy in treatment-naive as well as heavily pretreated HIV-infected patients failing therapy with multidrug-resistant virus. Raltegravir has a favorable drug interaction profile that permits both administration to a wide, demographically diverse patient population and coadministration with many other therapeutic agents, including antiretroviral agents and supportive medications, without restrictions or dose adjustment. Data through 96 weeks of follow-up in three phase III studies, protocol 021 (STARTMRK) in treatment-naive patients, and protocols 018 (BENCHMRK-1) and 019 (BENCHMRK-2) in treatment-experienced patients, demonstrated the potent and durable antiretroviral and immunologic effects and the favorable long-term safety profile of raltegravir in both treatment-naive and treatment-experienced patients. Raltegravir represents an important addition to the current armamentarium for the treatment of HIV infection.
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Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.
Trials
PUBLISHED: 02-02-2011
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In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design.
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Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial.
Trials
PUBLISHED: 02-02-2011
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Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin.
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Social contact patterns in Vietnam and implications for the control of infectious diseases.
PLoS ONE
PUBLISHED: 01-10-2011
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The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam.
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Structural and enzyme activity studies demonstrate that aryl substituted 2,3-butadienamine analogs inactivate Arthrobacter globiformis amine oxidase (AGAO) by chemical derivatization of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor.
Biochim. Biophys. Acta
PUBLISHED: 01-06-2011
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Copper amine oxidases (CAOs) are a family of redox active enzymes containing a 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor generated from post translational modification of an active site tyrosine residue. The Arthrobacter globiformis amine oxidase (AGAO) has been widely used as a model to guide the design and development of selective inhibitors of CAOs. In this study, two aryl 2,3-butadienamine analogs, racemic 5-phenoxy-2,3-pentadienylamine (POPDA) and racemic 6-phenyl-2,3-hexadienylamine (PHDA), were synthesized and evaluated as mechanism-based inactivators of AGAO. Crystal structures show that both compounds form a covalent adduct with the amino group of the substrate-reduced TPQ, and that the chemical structures of the rac-PHDA and rac-POPDA modified TPQ differ by the allenic carbon that is attached to the cofactor. A chemical mechanism accounting for the formation of the respective TPQ derivative is proposed. Under steady-state conditions, no recovery of enzyme activity is detected when AGAO pre-treated with rac-PHDA or rac-POPDA is diluted with excess amount of the benzylamine substrate (100-fold K(m)). Comparing the IC(50) values further reveals that the phenoxy substituent in POPDA offers an approximately 4-fold increase in inhibition potency, which can be attributed to a favourable binding interaction between the oxygen atom in the phenoxy group and the active site of AGAO as revealed by crystallographic studies. This hypothesis is corroborated by the observed >3-fold higher partition ratio of PHDA compared to POPDA. Taken together, the results presented in this study reveal the mechanism by which aryl 2,3-butadienamines act as mechanism-based inhibitors of AGAO, and the potency of enzyme inactivation could be fine-tuned by optimizing binding interaction between the aryl substituent and the enzyme active site.
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Long-term safety from the raltegravir clinical development program.
Curr. HIV Res.
PUBLISHED: 01-05-2011
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Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naïve and treatment-experienced patients with HIV-1 infection. This manuscript provides a review of the raltegravir safety profile using data from these and other studies in the clinical development program.
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Serological investigations of flavivirus prevalence in Khammouane Province, Lao Peoples Democratic Republic, 2007-2008.
Am. J. Trop. Med. Hyg.
PUBLISHED: 11-02-2010
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A large-scale cross-sectional seroprevalence study of dengue (DEN) and Japanese encephalitis (JE) was conducted in Khammouane province, Lao PDR, as part of the initial baseline health impact assessment of the Nam Theun 2 hydroelectric dam construction project. Health surveys were performed between May 2007 and February 2008 with serum samples collected from healthy individuals involved in the resettlement program of 16 villages (total surveyed population 4,369). Hemagglutination inhibition assay using flavivirus antigens (DENV1, DENV3, and JEV) performed on 1,708 plasma specimens revealed 30.4% (519) cross-reactive positives, and 10% (172) and 1.3% (22) positives to JEV or DENV, respectively. Entomological surveys conducted during the rainy season of 2008 indicated the presence of competent flavivirus vectors (Culex vishnui group and Aedes albopictus), although Aedes aegypti was not found. Continued surveillance and investigation is warranted to assess the clinical disease burden of flaviviruses in this area that is undergoing rapid ecological and demographic change.
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Quantitative relationships between immature and emergent adult Aedes aegypti (Diptera: Culicidae) populations in water storage container habitats.
J. Med. Entomol.
PUBLISHED: 10-14-2010
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Although quantitative surveillance data for immature stages of Aedes aegypti are often used to prioritize containers or specific types of containers for control, the relationship between immature and emergent adult populations under field conditions is largely unknown. We examined the relationships between abundance of III/IV instars and pupae, and emerging adult population for a series of water storage containers in southern Vietnam. A large proportion of III/IV instars failed to progress to adulthood, and the relationships between III/IV instars and adults were poor. Collected IV instars appeared to be nutritionally deprived, although their size and nutrient levels were not reliable indicators of emergence success. Conversely, pupal abundance was a good indicator of emerging adult populations, especially over the ensuing 48-h period. Although there were clear advantages of pupal surveillance over surveillance of III/IV instars for the estimation of adult mosquito productivity, there were practical limitations associated with the enumeration of pupae, and their comparatively low densities may preclude the identification of potentially productive containers.
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Surveillance for Japanese encephalitis in Vietnam, 1998-2007.
Am. J. Trop. Med. Hyg.
PUBLISHED: 10-05-2010
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Japanese encephalitis (JE) is recognized as an important public health problem in Vietnam. A JE immunization program was introduced in 1997 in high-risk districts and expanded to additional districts over subsequent years. We reviewed national acute encephalitis syndrome (AES) surveillance data for 1998-2007 and analyzed more detailed data regarding JE from five northern provinces in 2004 and 2005. The annual reported incidence of AES in Vietnam ranged from 3.0 to 1.4 cases per 100,000 population with a decreasing trend over the 10-year period. The mean annual incidence of AES was highest in the northern region of the country. Of 421 AES cases from five northern provinces with laboratory results reported, 217 (52%) had laboratory evidence of recent JEV infection. As Vietnam moves closer to control of JE through immunization, accurate JE surveillance data will be important to evaluate and guide the program.
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Bloodstream infections among HIV-infected outpatients, Southeast Asia.
Emerging Infect. Dis.
PUBLISHED: 09-30-2010
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Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single Myco/F Lytic blood culture. Fifty-eight (2.9%) had a clinically significant BSI (i.e., a blood culture positive for an organism known to be a pathogen). Mycobacterium tuberculosis accounted for 31 (54%) of all BSIs, followed by fungi (13 [22%]) and bacteria (9 [16%]). Of patients for whom data were recorded about antiretroviral therapy, 0 of 119 who had received antiretroviral therapy for ?14 days had a BSI, compared with 3% of 1,801 patients who had not. In multivariate analysis, factors consistently associated with BSI were fever, low CD4+ T-lymphocyte count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness. For HIV-infected outpatients with these risk factors, clinicians should place their highest priority on diagnosing tuberculosis.
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An evidence-based systematic review of umckaloabo (Pelargonium sidoides) by the Natural Standard Research Collaboration.
J Diet Suppl
PUBLISHED: 09-01-2010
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An evidence-based systematic review, including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
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Critical care: the impact of organization and management on outcomes.
Curr Opin Crit Care
PUBLISHED: 08-07-2010
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The organization and management of ICUs are key components that can affect delivery and outcome of critical care.
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Householder perspectives and preferences on water storage and use, with reference to dengue, in the Mekong Delta, southern Vietnam.
Int Health
PUBLISHED: 06-01-2010
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Community-based perceptions and behaviour around water source preference, household water storage patterns and water use, and householders knowledge and behaviour with respect to dengue etiology and transmission, were examined in three communes located in the Mekong Delta area in southern Vietnam. Through focus group discussions, most participants identified poorly screened or uncovered water containers (including household water storage containers and other types of artificial containers) as habitats for mosquitoes that transmit dengue viruses, and thereby demonstrated a clear understanding of the links between household water storage practices and the threat of dengue. Our qualitative analyses also revealed broader community-based concerns about the limited availability of water and strong preferences for storage of rainwater based upon perceptions of cost, quality and security of supply. These perceptions are central to shaping householders responses to water infrastructure projects. The limited availability of water during the dry season and insufficient numbers of water storage containers are over-riding community concerns which provide an important context to understanding community behaviours and responses to public health interventions against dengue. Such concerns are important precursors to selecting the type of intervention.
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Sustainability and cost of a community-based strategy against Aedes aegypti in northern and central Vietnam.
Am. J. Trop. Med. Hyg.
PUBLISHED: 05-05-2010
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We previously reported a new community-based mosquito control that resulted in the elimination of Aedes aegypti in 40 of 46 communes in northern and central Vietnam. During 2007 and 2008, we revisited Nam Dinh and Khanh Hoa provinces in northern and central Vietnam, respectively, to evaluate whether or not these programs were still being maintained 7 years and 4.5 years after formal project activities had ceased, respectively. Using a previously published sustainability framework, we compared 13 criteria from Tho Nghiep commune in Nam Dinh where the local community had adopted our community-based project model using Mesocyclops from 2001. These data were compared against a formal project commune, Xuan Phong, where our successful intervention activities had ceased in 2000 and four communes operating under the National Dengue Control Program with data available. In Khanh Hoa province, we compared 2008 data at Ninh Xuan commune with data at project completion in 2003 and benchmarked these, where possible, against an untreated control commune, Ninh Binh, where few control activities had been undertaken. The three communes where the above community-based strategy had been adopted were rated as well-sustained with annual recurrent total costs (direct and indirect) of $0.28-0.89 international dollars per person.
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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.