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2.  Coding System: A Source of Variability in Reported Prevalence Rates of Atrial Septal Defect 
doi:10.5210/ojphi.v6i1.5058
PMCID: PMC4050898
coding systems: CDC, ICD9/10-CM; Atrial Septal Defects; Birth Defects Surveillance; Poisson regression
3.  Knowledge of HIV and factors associated with attitudes towards HIV among final-year medical students at Hanoi medical university in Vietnam 
BMC Public Health  2014;14:265.
Background
The success of HIV care strongly depends upon skills of the healthcare worker. Vietnam has a punitive history towards HIV and even though this has changed recently, persons living with HIV are still facing discrimination. The objective of this paper is to assess the gaps in knowledge of HIV and factors associated with discriminatory attitudes towards persons living with HIV among medical students in order to improve medical training.
Methods
In a cross-sectional quantitative study using a structured questionnaire, 200 final-year medical students at Hanoi Medical University were approached for data collection in May of 2012. Descriptive statistics (percentages) were used to present four HIV knowledge tests. Linear regression models were examined to highlight factors that are associated with general attitudes towards HIV and attitudes towards HIV in a clinical setting.
Results
Although students performed overall well in the knowledge category of HIV discrimination and stigma, there were several gaps in knowledge of HIV, including the categories of HIV-related basic sciences, prevention, and care and treatment. Knowledge of stigma and discrimination was a significant positive predictor of General non-prejudicial attitude to HIV and AIDS (β = 0.186, P < 0.01) and Non-discriminatory attitude to HIV and AIDS at work (β = 0.188, P < 0.01). Training on methadone treatment was found to be a significant positive predictor (β = 0.168, P < 0.05) while family size was negatively associated (β = -0.170, P < 0.05) with General non-prejudicial attitude to HIV and AIDS.
Conclusions
The study suggests a need for incorporating HIV training into the core curricula for medical students. As persons who inject drugs carry a proportionately high burden of HIV in Vietnam, it is also important to include methadone training for students.
doi:10.1186/1471-2458-14-265
PMCID: PMC3994540  PMID: 24649918
HIV; Vietnam; Medical students; Knowledge; Attitude
4.  Twisted Cyanines: A Non-Planar Fluorogenic Dye with Superior Photostability and its Use in a Protein-Based Fluoromodule 
The cyanine dye thiazole orange (TO) is a well-known fluorogenic stain for DNA and RNA, but this property precludes its use as an intracellular fluorescent probe for non-nucleic acid biomolecules. Further, as is the case with many cyanines, the dye suffers from low photostability. Here we report the synthesis of a bridge-substituted version of TO named α-CN-TO, where the central methine hydrogen of TO is replaced by an electron withdrawing cyano group, which was expected to decrease the susceptibility of the dye toward singlet oxygen-mediated degradation. An X-ray crystal structure shows that α-CN-TO is twisted drastically out of plane, in contrast to TO, which crystallizes in the planar conformation. α-CN-TO retains the fluorogenic behavior of the parent dye TO in viscous glycerol/water solvent, but direct irradiation and indirect bleaching studies showed that α-CN-TO is essentially inert to visible light and singlet oxygen. In addition, the twisted conformation of α-CN-TO mitigates non-specific binding and fluorescence activation by DNA and a previously selected TO-binding protein and exhibits low background fluorescence in HeLa cell culture. α-CN-TO was then used to select a new protein that binds and activates fluorescence from the dye. The new α-CN-TO/protein fluoromodule exhibits superior photostability to an analogous TO/protein fluoromodule. These properties indicate that α-CN-TO will be a useful fluorogenic dye in combination with specific RNA and protein binding partners for both in vitro and cell-based applications. More broadly, structural features that promote nonplanar conformations can provide an effective method for reducing nonspecific binding of cationic dyes to nucleic acids and other biomolecules.
doi:10.1021/ja308629w
PMCID: PMC3574795  PMID: 23252842
5.  Stigma, an important source of dissatisfaction of health workers in HIV response in Vietnam: a qualitative study 
Background
Like in many other low- and middle-income countries, the recent development of an HIV epidemic in Vietnam has led to a growing need for prevention, treatment, care, and support services for people living with HIV (PLHIV). This puts greater demands on the national HIV services, primarily on health workers, which increases the importance of their job satisfaction and working conditions. This study describes health worker perceptions and explores the factors that influence job satisfaction and dissatisfaction of health personnel working on the HIV response in Vietnam. Spector’s job satisfaction model was used as the theoretical framework for the study design and analysis.
Methods
The study employed a qualitative design with 7 focus group discussions and 15 semi-structured interviews with health workers, purposively selected from national and provincial organizations responsible for HIV services in 5 cities and provinces in Vietnam. Data were analyzed using a hybrid approach of theory-driven and data-driven coding and theme development using qualitative analysis software.
Results
HIV services are perceived by Vietnamese health workers as having both positive and negative aspects. Factors related to job satisfaction included training opportunities, social recognition, and meaningful tasks. Factors related to job dissatisfaction included unsatisfactory compensation, lack of positive feedback and support from supervisors, work-related stress from a heavy workload, fear of infection, and HIV-related stigma because of association with PLHIV. An adjusted Spector’s model of job satisfaction for HIV service health workers was developed from these results.
Conclusion
This study confirmed the relationship between stigmatization of PLHIV and stigma experienced by staff because of association with PLHIV from families, colleagues, and society. The experiencing stigma results in additional work-related stress, low self-esteem, poor views of their profession, and lower income. The study shows the importance of actions to improve staff job satisfaction such as pay raises, supportive supervision, stress management, stigma reduction and workplace safety. Immediate actions could be the provision of more information; education and communication in mass media to improve the public image of HIV services, as well as improvement of workplace safety, therefore making health workers feel that their work is valued and safe.
doi:10.1186/1472-6963-12-474
PMCID: PMC3548727  PMID: 23259923
6.  INHIBITION OF MYCOLIC ACID TRANSPORT ACROSS THE MYCOBACTERIUM TUBERCULOSIS PLASMA MEMBRANE 
Nature chemical biology  2012;8(4):334-341.
New chemotherapeutics active against multidrug-resistant Mycobacterium tuberculosis (M. tb) are urgently needed. We report on the identification of an adamantyl urea compound displaying potent bactericidal activity against M. tb and a unique mode of action, namely the abolition of the translocation of mycolic acids from the cytoplasm where they are synthesized to the periplasmic side of the plasma membrane where they are transferred onto cell wall arabinogalactan or used in the formation of virulence-associated outer membrane trehalose-containing glycolipids. Whole genome sequencing of spontaneous resistant mutants of M. tb selected in vitro followed by genetic validation experiments revealed that our prototype inhibitor targets the inner membrane transporter, MmpL3. Conditional gene expression of mmpL3 in mycobacteria and analysis of inhibitor-treated cells validate MmpL3 as essential for mycobacterial growth and support the involvement of this transporter in the translocation of trehalose monomycolate across the plasma membrane.
doi:10.1038/nchembio.794
PMCID: PMC3307863  PMID: 22344175
7.  Identification of a Polyprenylphosphomannosyl Synthase Involved in the Synthesis of Mycobacterial Mannosides▿ † 
Journal of Bacteriology  2009;191(21):6769-6772.
We report on the identification of a glycosyltransferase (GT) from Mycobacterium tuberculosis H37Rv, Rv3779, of the membranous GT-C superfamily responsible for the direct synthesis of polyprenyl-phospho-mannopyranose and thus indirectly for lipoarabinomannan, lipomannan, and the higher-order phosphatidyl-myo-inositol mannosides.
doi:10.1128/JB.00431-09
PMCID: PMC2795309  PMID: 19717608
8.  Preliminary crystallographic analysis of GpgS, a key glucosyltransferase involved in methylglucose lipopolysaccharide biosynthesis in Mycobacterium tuberculosis  
Glucosyl-3-phosphoglycerate synthase (GpgS) is a key enzyme that catalyses the first glucosylation step in methylglucose lipopolysaccharide biosynthesis in Mycobacterium spp. Here, the crystallization and preliminary crystallographic analysis of GpgS from M. tuberculosis and of its complex with UDP are reported.
Glucosyl-3-phosphoglycerate synthase (GpgS) is a key enzyme that catalyses the first glucosylation step in methylglucose lipopolysaccharide biosynthesis in mycobacteria. These important molecules are believed to be involved in the regulation of fatty-acid and mycolic acid synthesis. The enzyme belongs to the recently defined GT81 family of retaining glycosyltransferases (CAZy, Carbohydrate-Active Enzymes Database; see http://www.cazy.org). Here, the purification, crystallization and preliminary crystallographic analysis are reported of GpgS from Mycobacterium tuberculosis and of its complex with UDP. GpgS crystals belonged to space group I4, with unit-cell parameters a = 98.85, b = 98.85, c = 127.64 Å, and diffracted to 2.6 Å resolution. GpgS–UDP complex crystals belonged to space group I4, with unit-cell parameters a = 98.32, b = 98.32, c = 127.96 Å, and diffracted to 3.0 Å resolution.
doi:10.1107/S1744309108032892
PMCID: PMC2593697  PMID: 19052364
glycosyltransferases; methylglucose lipopolysaccharides; Mycobacterium tuberculosis
9.  Preliminary crystallographic analysis of GpgS, a key glucosyltransferase involved in methylglucose lipopolysaccharides biosynthesis in Mycobacterium tuberculosis 
Synopsis Glucosyl-3-phosphoglycerate synthase (GpgS) is a key enzyme that catalyses the first glucosylation step in methylglucose lipopolysaccharides (MGLP) biosynthesis in Mycobacterium spp. Here we report the crystallization and preliminary crystallographic analysis of GpgS from Mycobacterium tuberculosis and its complex with UDP at 2.6 Å and 3.0 Å resolution, respectively.
Glucosyl-3-phosphoglycerate synthase (GpgS) is a key enzyme that catalyses the first glucosylation step in methylglucose lipopolysaccharides (MGLP) biosynthesis in mycobacteria. These important molecules are believed to be involved in the regulation of fatty acid and mycolic acid synthesis. The enzyme belongs to the recently defined GT81 family of retaining glycosyltransferases (CAZy, Carbohydrate-Active enZymes data base; see www.cazy.org). Here we report the purification, crystallization and preliminary crystallographic analysis of GpgS from Mycobacterium tuberculosis and its complex with UDP. GpgS crystals belong to space group I4, with unit-cell parameters a = 98.85, b = 98.85, c= 127.64 Å, and diffract to 2.6 Å resolution. GpgS-UDP complex crystals belong to space group I4 with unit-cell parameters a= 98.32, b= 98.32, c= 127.96 Å, and diffract to 3.0 Å resolution.
doi:10.1107/S1744309108032892
PMCID: PMC2593697  PMID: 19052364
glycosyltransferase; methylglucose lipopolysaccharides; Mycobacterium; X ray structure
10.  High Content Screening Identifies Decaprenyl-Phosphoribose 2′ Epimerase as a Target for Intracellular Antimycobacterial Inhibitors 
PLoS Pathogens  2009;5(10):e1000645.
A critical feature of Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of M. tuberculosis within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against M. tuberculosis, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of M. tuberculosis with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2′ epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials.
Author Summary
Tuberculosis is still a major threat to global health. The disease in humans is caused by a bacterium, Mycobacterium tuberculosis, and treatment of an infected individual requires more than six months of chemotherapy. Because such a long course of treatment is required, compliance is low, which can result in the development of multidrug resistant strains (MDR-TB) and even extremely resistant strains (XDR-TB). Identifying new drug targets and potential lead therapeutic compounds are needed to combat MDR-XDR-TB. We developed a new type of assay based on the visualization of mycobacterium replication within host cells and applied it for the search of compounds that are able to chase the pathogen from its hideout. As a result, we found 20 new series of drug candidates that are effective against the bacilli in its hiding place, potentially addressing a crucial aspect in the resilience of the disease. We also showed that one series of compounds acts by inhibiting a key enzyme required for the synthesis of an essential component from the mycobacterial cell wall that is not targeted by any of the commercially available antituberculosis drugs. Altogether, our results pave the way for development of the next generation of antibacterial agents.
doi:10.1371/journal.ppat.1000645
PMCID: PMC2763345  PMID: 19876393
11.  Initiation of Methylglucose Lipopolysaccharide Biosynthesis in Mycobacteria 
PLoS ONE  2009;4(5):e5447.
Background
Mycobacteria produce two unique families of cytoplasmic polymethylated polysaccharides - the methylglucose lipopolysaccharides (MGLPs) and the methylmannose polysaccharides (MMPs) - the physiological functions of which are still poorly defined. Towards defining the roles of these polysaccharides in mycobacterial physiology, we generated knock-out mutations of genes in their putative biosynthetic pathways.
Methodology/Principal Findings
We report here on the characterization of the Rv1208 protein of Mycobacterium tuberculosis and its ortholog in Mycobacterium smegmatis (MSMEG_5084) as the enzymes responsible for the transfer of the first glucose residue of MGLPs. Disruption of MSMEG_5084 in M. smegmatis resulted in a dramatic decrease in MGLP synthesis directly attributable to the almost complete abolition of glucosyl-3-phosphoglycerate synthase activity in this strain. Synthesis of MGLPs in the mutant was restored upon complementation with wild-type copies of the Rv1208 gene from M. tuberculosis or MSMEG_5084 from M. smegmatis.
Conclusions/Significance
This is the first evidence linking Rv1208 to MGLP biosynthesis. Thus, the first step in the initiation of MGLP biosynthesis in mycobacteria has been defined, and subsequent steps can be inferred.
doi:10.1371/journal.pone.0005447
PMCID: PMC2674218  PMID: 19421329

Results 1-11 (11)