Toxoplasma gondii specific IgG avidity assay: Role and implication in the confirmatory diagnosis of acute toxoplasmosis in seropositive pregnant women

This study was undertaken to apply Toxoplasma gondii specific IgG avidity test in seropositive pregnant women to differentiate acute and past infection. T. gondii specific IgG avidity test was conducted in 39 seropositive pregnant women and their pregnancy outcomes were observed later on. Out of 39 T. gondii seropositive pregnant women 33 (84%) were only IgG positive and 6 (15.4%) were both IgG-IgM positive. All the IgG positive cases (100%) and 2(33.3%) IgG-IgM positive cases had high avidity antibodies and they gave birth to healthy babies. Rest of the 4 (66.7%) IgG-IgM positive women had low avidity and 50% of them had abortion and 50% gave birth to unhealthy babies. This reveals that the seropositive mothers having high IgG avidity had past infection and no risk of congenital transmission. Seropositive mothers having low IgG avidity had acute infection and so congenital transmission occurred. Presence of T. gondii specific IgG and IgM antibody does not indicate acute infection always. IgG-IgM positive pregnant women should be further evaluated by IgG avidity assay to confirm acute infection.

Socioeconomic inequality in child injury in Bangladesh – implication for developing countries

<p>Abstract</p> <p>Background</p> <p>Child injury is an emerging public health issue in both developed and developing countries. It is the main cause of deaths and disabilities of children after infancy. The aim of this study was to investigate the socioeconomic inequality in injury related morbidity and mortality among 1–4 years children.</p> <p>Materials and methods</p> <p>Data used for this study derived from Bangladesh Health and Injury Survey. A multistage cluster sampling technique was conducted for this survey. In this study quintiles of socioeconomic status were calculated on the basis of assets and wealth score by using principle component analysis. The numerical measures of inequality in mortality and morbidity were assessed by the concentration index.</p> <p>Results</p> <p>The poorest-richest quintile ratio of mortality due to injury was 6.0 whereas this ratio was 5.6 and 5.5 for the infectious diseases and non-communicable diseases. The values of mortality concentration indices for child mortality due to infection, non-communicable diseases and injury causes were -0.40, -0.32 and -0.26 respectively. Among the morbidity concentration indices, injury showed significantly greater inequality. All the concentration indices revealed that there were significant inequalities among the groups. The logistic regression analysis indicated that poor children were 2.8 times more likelihood to suffer from injury mortality than rich children, taking into account all the other factors.</p> <p>Conclusion</p> <p>Despite concentration indices used in this study, the analysis reflected the family's socioeconomic position in a Bangladesh context, showing a very strong statistical association with child mortality. Due to the existing socioeconomic situation in Bangladesh, the poor children were more vulnerable to injury occurrence.</p

Health seeking behaviour of parents of burned children in Bangladesh is related to family socioeconomics

Objective: The study was design to explore the health seeking behaviour of Bangladeshi parents for their children during burn injuries. Methods: A population-based cross-sectional survey was conducted between January and December 2003 in Bangladesh. Nationally representative data were collected from 171,366 rural and urban households comprising of a total population of 819,429, including 351,651 children of 0–18 years. Mothers or heads of households were interviewed with a structured questionnaire in obtaining the information. Results: About sixty percent parents seek health care from unqualified service providers for their children during a childhood burn injury. Educated and the higher income groups parents choose qualified service provider at significantly higher rate compared to illiterate and poor. Higher proportion of parents of urban residence chooses qualified service provider compared to rural. No significant difference of health seeking behaviour of parent in choosing care provider was found in relation to sex of the children. Conclusion: Education, economic condition and place of residence were found as the contributory factors in choosing service provider. Education to the parents can contribute in changes in health seeking behaviour which ultimately contribute in reducing morbidity and mortality from childhood burn injuries. Including parent's education a national burn prevention program needs to be developed to combat the devastating child injury, burn

Viral cystatin evolution and three-dimensional structure modelling: A case of directional selection acting on a viral protein involved in a host-parasitoid interaction

<p>Abstract</p> <p>Background</p> <p>In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily.</p> <p>Results</p> <p>We show that <it>cystatins </it>are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of <it>Cotesia congregata </it>bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different <it>cystatin </it>forms which evolved under different selective constraints and are characterized by independent adaptive duplication events.</p> <p>Conclusion</p> <p>Positive selection acts to maintain <it>cystatin </it>gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence factors, as was already proposed in previous functional studies.</p

Consequences of childhood burn: Findings from the largest community-based injury survey in Bangladesh

In terms of morbidity and disability, burn is a major public health problem throughout the world, especially in low-income countries. It causes long-term disability and remains as a health, social and economic burden. A population-based survey was conducted in Bangladesh between January and December 2003. Nationally representative data were collected from 171,366 rural and urban households comprising of a total 819,429 population, which included 351,651 children under 18 years of age. Mothers/head of households were interviewed with a structured instrument. The objective of this paper is to determine the consequences of childhood burn at social and economic levels in Bangladesh. In the survey, 1013 children were found with different degrees of burn in the preceding 1 year. Among them 20 children were permanently disabled. The rate of permanent disability was found to be 5.7 per 100,000. The average loss of school days was found to be about 21 days. More than two-thirds of the burn victims required assistance in their daily activities for different durations of time. More than 7% of the children required hospitalisation for their burns. The rate of hospitalisation was 21.9 per 100,000; the average duration of hospital stay was 13.4 days. The highest duration (40 days) of hospital stay was found among girls 10– 14 years old. The highest expenditure for the treatment was also found in this age group. The average direct expenditure incurred by a family for treatment of severe burn was determined to be $462. In this study it was found that more than 61$50 a month. Burn is a devastating injury among all childhood injuries with significant additional economic consequences beyond the medical, pain, and suffering issues. Developing a national prevention program should be an immediate public health priority

The S2 subsites of cathepsins K and L and their contribution to collagen degradation

The exchange of residues 67 and 205 of the S2 pocket of human cysteine cathepsins K and L induces a permutation of their substrate specificity toward fluorogenic peptide substrates. While the cathepsin L-like cathepsin K (Tyr67Leu/Leu205Ala) mutant has a marked preference for Phe, the Leu67Tyr/Ala205Leu cathepsin L variant shows an effective cathepsin K-like preference for Leu and Pro. A similar turnaround of inhibition was observed by using specific inhibitors of cathepsin K [1-(N-Benzyloxycarbonyl-leucyl)-5-(N-Boc-phenylalanyl-leucyl)carbohydrazid e] and cathepsin L [N-(4-biphenylacetyl)-S-methylcysteine-(D)-Arg-Phe-beta-phenethylamide]. Molecular modeling studies indicated that mutations alter the character of both S2 and S3 subsites, while docking calculations were consistent with kinetics data. The cathepsin K-like cathepsin L was unable to mimic the collagen-degrading activity of cathepsin K against collagens I and II, DQ-collagens I and IV, and elastin-Congo Red. In summary, double mutations of the S2 pocket of cathepsins K (Y67L/L205A) and L (L67Y/A205L) induce a switch of their enzymatic specificity toward small selective inhibitors and peptidyl substrates, confirming the key role of residues 67 and 205. However, mutations in the S2 subsite pocket of cathepsin L alone without engineering of binding sites to chondroitin sulfate are not sufficient to generate a cathepsin K-like collagenase, emphasizing the pivotal role of the complex formation between glycosaminoglycans and cathepsin K for its unique collagenolytic activityNRC publication: Ye

A mammalian genetic system to screen for small molecules capable of disrupting protein-protein interactions

A mammalian two-hybrid system was developed for high-throughput screening of compounds that disrupt specific protein-protein interactions. The existing mammalian systems are unsatisfactory for drug screening due to nonregulated expression of interacting proteins. To construct a tightly regulated system, the tetracycline repressor was fused with the inhibitory KRAB domain as a suppressor. The binding of the suppressor to the tet operator entirely blocked expression of two interacting proteins. When both the inducer doxycycline and drugs were added to the culture, the reporter gene was either activated by interaction of the paired proteins with ineffective drugs or remained silent due to disruption of the protein interactions by the effective drugs. We demonstrate that interactions of the type I receptor for TGFbeta with FKBP12 and the epidermal growth factor receptor (EGFR) with p85 are effectively disrupted by FK506 and EGFR kinase inhibitor AG1478, respectively. The power of this system for drug screening was further demonstrated by rapid identification of inhibitors from a druglike library for the receptor kinasesEnglish15144206NRC publication: Ye

A mammalian genetic system to screen for small molecules capable of disrupting protein-protein interactions

A mammalian two-hybrid system was developed for high-throughput screening of compounds that disrupt specific protein-protein interactions. The existing mammalian systems are unsatisfactory for drug screening due to nonregulated expression of interacting proteins. To construct a tightly regulated system, the tetracycline repressor was fused with the inhibitory KRAB domain as a suppressor. The binding of the suppressor to the tet operator entirely blocked expression of two interacting proteins. When both the inducer doxycycline and drugs were added to the culture, the reporter gene was either activated by interaction of the paired proteins with ineffective drugs or remained silent due to disruption of the protein interactions by the effective drugs. We demonstrate that interactions of the type I receptor for TGFbeta with FKBP12 and the epidermal growth factor receptor (EGFR) with p85 are effectively disrupted by FK506 and EGFR kinase inhibitor AG1478, respectively. The power of this system for drug screening was further demonstrated by rapid identification of inhibitors from a druglike library for the receptor kinasesEnglish15144206NRC publication: Ye