Persistent Organic Pollutants in Sediments from Sai Gon–Dong Nai River Basin,Vietnam: Levels and Temporal Trends

Surficial sediment samples were collected from Hochiminh City canals, the Sai Gon–Dong Nai River, and its estuary, one of the most predominant industrial areas in Hochiminh City, southern Vietnam, for determination of selected persistent organic pollutants (POPs). Contamination pattern was as follows: PCBs ≥ DDTs > HCB > CHLs > HCHs. Concentrations of PCBs and DDTs ranged from 0.50–150 ng/g and 0.15–72 ng/g dry wt, respectively. On the other hand, concentrations of CHLs, HCHs, and HCB were mostly <2 ng/g dry wt. Levels of the all organochlorines (OCs) in Hochiminh City canals were significantly higher than those in the other areas, indicating the urban areas as major pollution sources to the aquatic environment. The contamination pattern was PCBs > DDTs in the city canals but PCBs < DDTs in the downstream and the estuary, suggesting particularly high contamination by PCBs in the city. Examination of DDTs composition and their ratios demonstrated continuous input of this pesticide to the city canals. However, the combination of our data and those from available literature implies a decreasing trend of PCBs and DDTs in the environment. DDTs concentrations have been reduced 50% after approximately 5 years. Composition of CHLs in the sediment from Hochiminh City canals was comparable to those of common technical mixtures, suggesting continuous input of CHLs to the environment. CHLs might be in use for purposes like termite control, wood preservation, and protection of underground cables. Hazard assessment implies high toxic potential of DDTs for sediments from Hochiminh City canals and suggests the need for better management of municipal discharges.     

Vaccinating adolescents against meningococcal disease in Canada: a cost-effectiveness analysis

BACKGROUND: One dose of serogroup C meningococcal conjugate vaccine (MCV-C) at 12 months of age is the most common immunization schedule in Canada, but immunity may wane over time. OBJECTIVES: To assess the cost-effectiveness of a booster dose at 12 years of age with either MCV-C or a quadrivalent ACYW135 meningococcal conjugate vaccine (MCV-4). METHODS: A simulation model for assessing both the direct and indirect effects of vaccination was developed. Age- and serogroup-specific incidence and fatality rates were derived from Canadian surveillance data. Vaccine efficacy was estimated from data from the U.K. and Spain, assuming an age-dependent decline of vaccine efficacy over time. Expected vaccine coverage rates were 90% at 12 months, and 70% at 12 years. Herd immunity was modeled using UK data. Vaccine purchase price per dose was $23 for MCV-C and $70 for MCV-4. Costs and health outcomes were discounted at 3% per year. Results, expressed in 2004 Canadian $ and from a societal perspective, were presented for a steady state situation and a population of 1 million. RESULTS: Under the "no vaccination" base scenario, 5.7 cases of vaccine-preventable meningococcal disease would occur each year. Vaccination at 12 months using MCV-C would reduce the burden of disease by 32%. Adding MCV-C at 12 years of age would reduce the number of cases by 55% at no marginal cost, while using MCV-4 would result in a disease reduction of 78% for a marginal cost of $31000 per QALY gained. Comparing MCV-4 with MCV-C as a booster dose, the incremental cost-effectiveness ratio would be $113000 per QALY. The efficacy of C-MCV vaccination at 12 months and the differential price between the two vaccines were the parameters having the strongest impact on the cost/QALY ratios. Any increase in the incidence of serogroup Y will improve the marginal cost-effectiveness ratio associated with MCV-4. CONCLUSION: Adolescent revaccination would be beneficial. Using C-MCV would be the most cost-effective option, while using MCV-4 would be more effective but would also require more investment.     

A DNA vaccine encoding a single-chain trimer of HLA-A2 linked to human mesothelin peptide generates anti-tumor effects against human mesothelin-expressing tumors

Mesothelin is highly expressed in a majority of ovarian cancer cells and is expressed at low levels in normal cells. Therefore, mesothelin represents a potential target antigen for ovarian cancer vaccine development. DNA vaccines employing single-chain trimers (SCT) have been shown to bypass antigen processing and presentation and result in significant enhancement of DNA vaccine potency. In the current study, we created a DNA vaccine employing an SCT targeting human mesothelin and characterized the ensuing antigen-specific CD8+ T cell-mediated immune responses and anti-tumor effects against human mesothelin-expressing tumors in HLA-A2 transgenic mice. Our results showed that vaccination with DNA employing an SCT of HLA-A2 linked to human mesothelin epitope aa540-549 (pcDNA3-Hmeso540-beta2m-A2) generated strong human mesothelin peptide (aa540-549)-specific CD8+ T cell immune responses in HLA-A2 transgenic mice. Vaccination with pcDNA3-Hmeso540-beta2m-A2 prevented the growth of HLA-A2 positive human mesothelin-expressing tumor cell lines in HLA-A2 transgenic mice in contrast to vaccination with DNA encoding SCT linked to OVA CTL epitope. Thus, the employment of SCT of HLA-A2 linked to the human mesothelin epitope aa540-549 represents a potential opportunity for the clinical translation of DNA vaccines against human mesothelin-expressing tumors, particularly ovarian cancer cells.     

Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency

Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. We have previously demonstrated that intradermal delivery of DNA vaccines encoding single-chain trimer (SCT) composed of the most immunogenic epitope of human papillomavirus type 16 (HPV-16) E6 protein (aa49-57), beta2-microglobulin, and MHC class I heavy chain (SCT-E6) can bypass antigen processing and lead to stable cell-surface presentation of E6 peptides. We also showed that co-administration of DNA vaccines with DNA encoding anti-apoptotic proteins can prolong the survival of DNA-transduced DCs, resulting in significant enhancement of antigen-specific CD8(+) T cell immune responses. In the current study, we hypothesized that combining the SCT strategy and antiapoptotic strategy may further enhance DNA vaccine potency by augmenting antigen-specific CD8(+) T cell immune responses and antitumor effects in vaccinated mice. Here, we show that C57BL/6 mice vaccinated with SCT-E6 DNA combined with antiapoptotic protein Bcl-xL DNA generated enhanced E6-specific CD8(+) T cell immune responses compared to mice vaccinated with SCT-E6 DNA and a non-functional mutant Bcl-xL (mtBcl-xL) DNA. Furthermore, we show that mice treated with SCT-E6 and Bcl-xL DNA generated enhanced anti-tumor effects against E6-expressing tumor cells (TC-1/Luciferase) compared to mice treated with SCT-E6 and mtBcl-xL DNA.     

Removal of cadmium ions during stationary growth phase by an extremely cadmium-resistant strain of Stenotrophomonas sp

Stenotrophomonas sp. CD02 was isolated from a site that previously had been contaminated with high concentrations of the heavy metals cadmium (3 mg kg(-1)) and chromium (115 mg kg(-1)). This strain was able to grow on complex (Luria Bertani) medium containing high concentrations of cadmium ion (up to 4 mM). Additionally, it could remove up to 80% of the dissolved ions but only after reaching stationary growth phase. Strain CD02 also tolerated high concentrations of other heavy metals such as chromium, zinc, copper, nickel, and lead at levels more than 2 mM. Although strain CD02 can tolerate much higher cadmium concentrations than the three Stenotrophomonas maltophilia strains tested, they all possess resistance to the same range of antibiotics. This suggests that strain CD02 possesses a mechanism that allows it to tolerate and remove cadmium differently from those conferring resistance to antibiotics. Strain CD02 can be a suitable candidate for heavy metal bioremediation in contaminated environment because it is able to tolerate high concentration of heavy metals and remove cadmium aerobically.     

Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance

BACKGROUND: Submicroscopic genomic imbalance underlies well-defined microdeletion and microduplication syndromes and contributes to general developmental disorders such as mental retardation and autism. Array comparative genomic hybridization (CGH) complements routine cytogenetic methods such as karyotyping and fluorescence in situ hybridization (FISH) for the detection of genomic imbalance. Oligonucleotide arrays in particular offer advantages in ease of manufacturing, but standard arrays for single-nucleotide polymorphism genotyping or linkage analysis offer variable coverage in clinically relevant regions. We report the design and validation of a focused oligonucleotide-array CGH assay for clinical laboratory diagnosis of genomic imbalance. METHODS: We selected >10 000 60-mer oligonucleotide features from Agilent's eArray probe library to interrogate all subtelomeric and pericentromeric regions and 95 additional clinically relevant regions for a total of 179 loci. Sensitivity and specificity were measured for 105 patient samples, including 51 with known genomic-imbalance events, as detected by bacterial artificial chromosome-based array CGH, FISH, or multiplex ligation-dependent probe amplification. RESULTS: Focused array CGH detected all known regions of genomic imbalance in 51 validation samples with 100% concordance and an excellent signal-to-noise ratio. The mean SD among log(2) ratios of all noncontrol features without copy number alteration was 0.062 (median, 0.055). Clinical testing of another 211 samples from individuals with developmental delay, unexplained mental retardation, dysmorphic features, or multiple congenital anomalies revealed genomic imbalance in 25 samples (11.9%). CONCLUSIONS: This focused oligonucleotide-array CGH assay, a flexible, robust method for clinically diagnosing genetic disorders associated with genomic imbalance, offers appreciable advantages over currently available platforms.     

Decomposing Pearson's χ2 test: A linear regression and its departure from linearity

In case–control genetic association studies, a standard practice is to perform the Cochran‐Armitage (CA) trend test under the assumption of the additive model because of its robustness. We could even identify situations in which it outperformed the analysis model consistent with the underlying inheritance mode. In this article, we analytically reveal the statistical basis that leads to the phenomenon. By elucidating the origin of the CA trend test as a linear regression model, we decompose Pearson's χ²‐test statistic into two components—one is the CA trend test statistic that measures the goodness of fit of the linear regression model, and the other measures the discrepancy between data and the linear regression model. Under this framework, we show that the additive coding scheme, as well as the multiplicative coding scheme, increases the coefficient of determination of the regression model by increasing the spread of data points. We also obtain the conditions under which the CA trend test statistic equals the MAX statistic and Pearson's χ²‐test statistic.     

Nerve conduction velocity determinations in juvenile diabetes: continuing study of 190 patients.

Few prospective studies on the concomitant finding of neuropathy in juvenile diabetics exist. An ongoing study of motor and sensory nerve conduction determinations in 190 diabetic children, with sequential studies in 108 of them over an eight-year period, is the subject of this report. The incidence of neuropathy in our sample population under five years of age is neglible. In the children over five years of age, 8% had abnormal nerve conduction velocity (NCV) of the peroneal nerve, 4.5% had abnormal median motor and sensory NCV on initial study. In the sequential studies of the children over five years of age, the percentage of abnormal NCV rose from 14% to 48% as the duration of diabetes increased from one year to more than five years. It is the older juvenile diabetics with the longest duration of diabetes who would appear to have the highest incidence of neuropathy.     

Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection

Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1β. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1β production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1β protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1β in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1β synthesis in macrophages during DENV-2 infection.