Developmental Lead and/or Prenatal Stress Exposures Followed by Different Types of Behavioral Experience Result in the Divergence of Brain Epigenetic Profiles in a Sex, Brain Region, and Time-Dependent Manner: Implications for Neurotoxicology.

Over a lifetime, early developmental exposures to neurocognitive risk factors, such as lead (Pb) exposures and prenatal stress (PS), will be followed by multiple varied behavioral experiences. Pb, PS and behavioral experience can each influence brain epigenetic profiles. Our recent studies show a greater level of complexity, however, as all three factors interact within each sex to generate differential adult variation in global post-translational histone modifications (PTHMs), which may result in fundamentally different consequences for life-long learning and behavioral function. We have reported that PTHM profiles differ by sex, brain region and time point of measurement following developmental exposures to Pb±PS, resulting in different profiles for each unique combination of these parameters. Imposing differing behavioral experience following developmental Pb±PS results in additional divergence of PTHM profiles, again in a sex, brain region and time-dependent manner, further increasing complexity. Such findings underscore the need to link highly localized and variable epigenetic changes along single genes to the highly-integrated brain functional connectome that is ultimately responsible for governing behavioral function. Here we advance the idea that increased understanding may be achieved through iterative reductionist and holistic approaches. Implications for experimental design of animal studies of developmental exposures to neurotoxicants include the necessity of a \u27no behavioral experience\u27 group, given that epigenetic changes in response to behavioral testing can confound effects of the neurotoxicant itself. They also suggest the potential utility of the inclusion of salient behavioral experiences as a potential effect modifier in epidemiological studies

Validation of the GenoType® MTBDRplus assay for detection of MDR-TB in a public health laboratory in Thailand

<p>Abstract</p> <p>Background</p> <p>Over the past several years, new diagnostic techniques have been developed to allow for the rapid detection of multidrug resistant tuberculosis. The GenoType^®MTBDR<it>plus </it>test is a deoxyribonucleic acid (DNA) strip assay which uses polymerase chain reaction (PCR) and hybridization to detect genetic mutations in the genes that confer isoniazid (INH) and rifampn (RIF) resistance. This assay has demonstrated good performance and a rapid time to results, making this a promising tool to accelerate MDR-TB diagnosis and improve MDR-TB control. Validation of rapid tests for MDR-TB detection in different settings is needed to ensure acceptable performance, particularly in Asia, which has the largest number of MDR-TB cases in the world but only one previous report, in Vietnam, about the performance of the GenoType^®MDR<it>plus </it>assay. Thailand is ranked 18^thof 22 "high-burden" TB countries in the world, and there is evidence to suggest that rates of MDR-TB are increasing in Thailand. We compared the performance of the GenoType^®MTBDR<it>plus </it>assay to Mycobacterial Growth Indicator Tube for Antimycobacterial Susceptibility Testing (MGIT AST) for detection INH resistance, RIF resistance, and MDR-TB in stored acid-fast bacilli (AFB)-positive sputum specimens and isolates at a Public TB laboratory in Bangkok, Thailand.</p> <p>Methods</p> <p>50 stored isolates and 164 stored AFB-positive sputum specimens were tested using both the MGIT AST and the GenoType^®MTBDR<it>plus </it>assay.</p> <p>Results</p> <p>The GenoType^®MTBDR<it>plus </it>assay had a sensitivity of 95.3%, 100%, and 94.4% for INH resistance, RIF resistance, and MDR-TB, respectively. The difference in sensitivity between sputum specimens (93%) and isolates (100%) for INH resistance was not statistically significant (p = 0.08). Specificity was 100% for all resistance patterns and for both specimens and isolates. The laboratory processing time was a median of 25 days for MGIT AST and 5 days for the GenoType^®MTBDR<it>plus </it>(p < 0.01).</p> <p>Conclusion</p> <p>The GenoType^®MTBDR<it>plus </it>assay has been validated as a rapid and reliable first-line diagnostic test on AFB-positive sputum or MTB isolates for INH resistance, RIF resistance, and MDR-TB in Bangkok, Thailand. Further studies are needed to evaluate its impact on treatment outcome and the feasibility and cost associated with widespread implementation.</p

Hospitalization and Antimicrobial Resistance in Salmonella Outbreaks, 1984–2002

Few studies have evaluated the health consequences of antimicrobial-resistant Salmonella strains associated with outbreaks. Among 32 outbreaks occurring in the United States from 1984 to 2002, 22% of 13,286 persons in 10 Salmonella-resistant outbreaks were hospitalized, compared with 8% of 2,194 persons in 22 outbreaks caused by pansusceptible Salmonella strains (p<0.01)

HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death

SummaryBackgroundWe conducted a prospective, multicenter observational cohort study in Thailand to characterize the epidemiology of extrapulmonary tuberculosis (TB) in HIV-infected persons and to identify risk factors for death.MethodsFrom May 2005 to September 2006, we enrolled, interviewed, examined, and performed laboratory tests on HIV-infected adult TB patients and followed them from TB treatment initiation until the end of TB treatment. We conducted multivariate proportional hazards analysis to identify factors associated with death.ResultsOf the 769 patients, pulmonary TB only was diagnosed in 461 (60%), both pulmonary and extrapulmonary TB in 78 (10%), extrapulmonary TB at one site in 223 (29%), and extrapulmonary TB at more than one site in seven (1%) patients. Death during TB treatment occurred in 59 of 308 patients (19%) with any extrapulmonary involvement. In a proportional hazards model, patients with extrapulmonary TB had an increased risk of death if they had meningitis, and a CD4+ T-lymphocyte count <200 cells/μl. Patients who received co-trimoxazole, fluconazole, and antiretroviral therapy during TB treatment had a lower risk of death.ConclusionsAmong HIV-infected patients with TB, extrapulmonary disease occurred in 40% of the patients, particularly in those with advanced immune suppression. Death during TB treatment was common, but the risk of death was reduced in patients who took co-trimoxazole, fluconazole, and antiretroviral therapy

Heteroacene-Based Amphiphile as a Molecular Scaffold for Bioimaging Probes

The challenges faced with current fluorescence imaging agents have motivated us to study two nanostructures based on a hydrophobic dye, 6H-pyrrolo[3,2-b:4,5-b’]bis [1,4]benzothiazine (TRPZ). TRPZ is a heteroacene with a rigid, pi-conjugated structure, multiple reactive sites, and unique spectroscopic properties. Here we coupled TRPZ to a tert-butyl carbamate (BOC) protected 2,2-bis(hydroxymethyl)propanoic acid (bisMPA) dendron via azide-alkyne Huisgen cycloaddition. Deprotection of the protected amine groups on the dendron afforded a cationic terminated amphiphile, TRPZ-bisMPA. TRPZ-bisMPA was nanoprecipitated into water to obtain nanoparticles (NPs) with a hydrodynamic radius that was \u3c150 nm. For comparison, TRPZ-PG was encapsulated in pluronic-F127 (Mw = 12 kD), a polymer surfactant to afford NPs almost twice as large as those formed by TRPZ-bisMPA. Size and stability studies confirm the suitability of the TRPZ-bisMPA NPs for biomedical applications. The photophysical properties of the TRPZ-bisMPA NPs show a quantum yield of 49%, a Stokes shift of 201 nm (0.72 eV) and a lifetime of 6.3 ns in water. Further evidence was provided by cell viability and cellular uptake studies confirming the low cytotoxicity of TRPZ-bisMPA NPs and their potential in bioimaging

Foodborne Botulism in the Republic of Georgia

In the Republic of Georgia, high rates of foodborne botulism are largely caused by home-preserved vegetables

Causes of Death in HIV-infected Persons Who Have Tuberculosis, Thailand

Many of these patients die of a cause other than tuberculosis; expanded use of antiretroviral therapy and modern diagnostic technologies may reduce case-fatality rates

Multidrug-Resistant Tuberculosis, People’s Republic of China, 2007–2009

Early detection, effective treatment, and infection control measures are needed to reduce transmission