Productivity cost due to maternal ill health in sri lanka

Background

The global impact of maternal ill health on economic productivity is estimated to be over 15 billion USD per year. Global data on productivity cost associated with maternal ill health are limited to estimations based on secondary data. Purpose of our study was to determine the productivity cost due to maternal ill health during pregnancy in Sri Lanka.

Methods and Findings

We studied 466 pregnant women, aged 24 to 36 weeks, residing in Anuradhapura, Sri Lanka. A two stage cluster sampling procedure was used in a cross sectional design and all pregnant women were interviewed at clinic centers, using the culturally adapted Immpact tool kit for productivity cost assessment. Of the 466 pregnant women studied, 421 (90.3%) reported at least one ill health condition during the pregnancy period, and 353 (83.8%) of them had conditions affecting their daily life. Total incapacitation requiring another person to carry out all their routine activities was reported by 122 (26.1%) of the women. In this study sample, during the last episode of ill health, total number of days lost due to absenteeism was 3,356 (32.9% of total loss) and the days lost due to presenteeism was 6,832.8 (67.1% of the total loss). Of the 353 women with ill health conditions affecting their daily life, 280 (60%) had coping strategies to recover loss of productivity. Of the coping strategies used to recover productivity loss during maternal ill health, 76.8% (n = 215) was an intra-household adaptation, and 22.8% (n = 64) was through social networks. Loss of productivity was 28.9 days per episode of maternal ill health. The mean productivity cost due to last episode of ill health in this sample was Rs.8,444.26 (95% CI-Rs.6888.74-Rs.9999.78).

Conclusions

Maternal ill health has a major impact on household productivity and economy. The major impact is due to, generally ignored minor ailments during pregnancy.     

Discrimination of lesion removal of N-methylpurine-DNA glycosylase revealed by a potent neutralizing monoclonal antibody

N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, initiates excision repair of several N-alkylpurine adducts, induced by alkylating chemotherapeutics, and deaminated and lipid peroxidation-induced purine adducts. We have generated monoclonal antibodies (moAbs) against human MPG. Twelve independent hybridoma clones were characterized, which, except 520-16A, are identical based on epitope exclusion assay. Four moAbs, including 520-2A, 520-3A, 520-16A, and 520-26A, have high affinity (K(D) approximately 0.3-1.6nM), and their subtypes were IgG(2a), IgG(1), IgG(2a), and IgG(2b), respectively. moAb 520-3A recognizes the sequence (52)AQAPCPRERCLGPP(66)T, an epitope exclusively present in the N-terminal extension of human MPG. We found that moAb 520-3A significantly inhibited MPG's enzymatic activity towards different substrates, such as hypoxanthine, 1,N(6)ethenoadenine and methylated bases, which represent different classes of DNA damage, however, with different efficiencies. Real-time binding experiments using surface plasmon resonance (SPR) spectroscopy showed that the pronounced inhibition of activity was not in the substrate-binding step. Single turnover kinetics (STO) revealed that the inhibition was at the catalytic step. Since we found that this antibody has an epitope in the N-terminal tail, the latter appears to have an important role in substrate discrimination, however, with a differential effect on different substrates.     

Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3

Microtubule pulling forces that govern mitotic spindle movement of chromosomes are tightly regulated by G-proteins. A host of proteins, including Galpha subunits, Ric-8, AGS3, regulators of G-protein signalings, and scaffolding proteins, coordinate this vital cellular process. Ric-8A, acting as a guanine nucleotide exchange factor, catalyzes the release of GDP from various Galpha.GDP subunits and forms a stable nucleotide-free Ric-8A:Galpha complex. AGS3, a guanine nucleotide dissociation inhibitor (GDI), binds and stabilizes Galpha subunits in their GDP-bound state. Because Ric-8A and AGS3 may recognize and compete for Galpha.GDP in this pathway, we probed the interactions of a truncated AGS3 (AGS3-C; containing only the residues responsible for GDI activity), with Ric-8A:Galpha(il) and that of Ric-8A with the AGS3-C:Galpha(il).GDP complex. Pulldown assays, gel filtration, isothermal titration calorimetry, and rapid mixing stopped-flow fluorescence spectroscopy indicate that Ric-8A catalyzes the rapid release of GDP from AGS3-C:Galpha(i1).GDP. Thus, Ric-8A forms a transient ternary complex with AGS3-C:Galpha(i1).GDP. Subsequent dissociation of AGS3-C and GDP from Galpha(i1) yields a stable nucleotide free Ric-8A.Galpha(i1) complex that, in the presence of GTP, dissociates to yield Ric-8A and Galpha(i1).GTP. AGS3-C does not induce dissociation of the Ric-8A.Galpha(i1) complex, even when present at very high concentrations. The action of Ric-8A on AGS3:Galpha(i1).GDP ensures unidirectional activation of Galpha subunits that cannot be reversed by AGS3.     

Interplay of Troponin- and Myosin-Based Pathways of Calcium Activation in Skeletal and Cardiac Muscle: The Use of W7 as an Inhibitor of Thin Filament Activation

To investigate the interplay between the thin and thick filaments during calcium activation in striated muscle, we employed n-(6-aminohexyl) 5-chloro-1-napthalenesulfonamide (W7) as an inhibitor of troponin C and compared its effects with that of the myosin-specific inhibitor, 2,3-butanedione 2-monoxime (BDM). In both skeletal and cardiac fibers, W7 reversibly inhibited ATPase and tension over the full range of calcium activation between pCa 8.0 and 4.5, resulting in reduced calcium sensitivity and cooperativity of ATPase and tension activations. At maximal activation in skeletal fibers, the W7 concentrations for half-maximal inhibition (K_I) were 70–80 μM for ATPase and 20–30 μM for tension, nearly >200-fold lower than BDM (20 mM and 5–8 mM, respectively). When W7 (50 μM) and BDM (20 mM) were combined in skeletal fibers, the ATPase and tension-pCa curves exhibited lower apparent cooperativity and maxima and higher calcium sensitivity than expected from two independent activation pathways, suggesting that the interplay between the thin and thick filaments varies with the level of activation. Significantly, the inhibition of W7 increased the ATPase/tension ratio during activation in both muscle types. W7 holds much promise as a potent and reversible inhibitor of thin filament-mediated calcium activation of skeletal and cardiac muscle contraction.     

Ex vivo analysis of synergistic anion binding to FbpA in Gram-negative bacteria

Ferric binding protein, FbpA, is a member of the transferrin superfamily whose function is to move an essential nutrient, iron, across the periplasm and into the cytosol through formation of a ternary complex containing Fe (3+) and a synergistic anion, X. Here we utilize SUPREX ( stability of unpurified proteins from rates of H/D exchange) to determine the identification and distribution of the synergistic anion in FeFbpA-X species in periplasmic preparations from Gram-negative bacteria. SUPREX is a mass spectrometry-based technique uniquely suited for thermodynamic analyses of protein-ligand complexes in complex biological mixtures such as periplasmic preparations. Model binary mixtures of FeFbpA-Cit and FeFbpA-PO 4 were initially characterized by SUPREX due to the likely presence of citrate and phosphate ions in the periplasm. Ex vivo SUPREX analyses were performed on FeFbpA-X species overexpressed in an Escherichia coli cell line and on endogenous FeFbpA-X species in Neisseria gonorrheae. Detected in the E. coli periplasmic extract were two distinct populations of FbpA, including one in which the protein was unliganded (i.e., apoFbpA) and one in which the protein was bound to iron and the synergistic anion, phosphate (i.e., FeFbpA-PO 4). FeFbpA-PO 4 was the only population of FbpA molecules detected in the N. gonorrheae periplasmic extract. This work provides the first determination of the identity of the in vivo anion bound to FeFbpA-X in the periplasm and substantiates the hypothesis that the synergistic anion plays a structural and functional role in FbpA-mediated transport of iron across the periplasm and into the cytosol.     

Dibenzothiophene desulfurization in hydrocarbon environment by Staphylococcus sp. resting cells

Staphylococcus sp. strain S3/C desulfurized dibenzothiophene/n-hexadecane (3 mg ml^–1) in a hydrocarbon aqueous biphasic culture. The resting cells decreased the sulfur content of the hydrocarbon phase by 57% at 2.2 mg l^–1 h^–1 in the absence of any additional carbon and sulfur source.     

In-vitro evaluation of the antimicrobial activity of Bauhinia variegata,locally known as koiralo

Bauhinia variegata, commonly known as Koiralo is considered as medicinal plant in Nepal and India. The alcoholic extract of this plant was found to have antimicrobial activity against Bacillus subtilis (ATCC 6635) Pseudomonas aeruginosa (ATCC 27853), Salmonella typhi, Shigella dysenteriae, Staphylococcus aureus (ATCC 29213) and Vibrio cholerae. The largest zone of inhibition (18 mm) was found to be exhibited against B. subtilis. For this organism the minimum bactericidal concentration (MBC) of the crude extract was 0.39 mg/ml. The extract was found to be more effective against gram-positive than gram-negative bacteria. The antimicrobial activity of the extract was found to be decreased during purification.     

Reliable structural information for rational design of benzoxazole type potential cholesteryl ester transfer protein (CETP) inhibitors through multiple validated modeling techniques

Abstract

The drug design and discovery of lipid modulators is very demanding as no new molecule has entered into the market in the last 35 years. Cholesteryl ester transfer protein (CETP) is a promising target as lipid modulators. Inhibition of the CETP enzyme reduces the risk of cardiovascular events. The first CETP inhibitor torcetrapib and related drug candidates failed in the clinical trial due to the off-target effects leading to high toxicity. Thus, newer CETP inhibitors have now paramount importance to accelerate the drug discovery efforts in the field of cardiovascular disease (CVD). In the present study, 140 benzoxazole compounds were studied by using different chemometric techniques, for example, pharmacophore mapping, molecular docking, three-dimensional quantitative structure–activity relationship comparative molecular field analysis (3D-QSAR CoMFA), topomer CoMFA and Bayesian classification, in order to generate complete and reliable information regarding the structural requirements for the CETP inhibition. The best pharmacophore hypothesis was statistically significant (regression coefficient of 0.957 and a lower root mean square of 0.890). Molecular docking study revealed that cyano-substituted compounds form hydrogen bond with targeted macromolecule. The 3D-QSAR CoMFA model also produced a leave-one-out (LOO) cross-validated Q² of 0.527, an R² of 0.853 and an R²_Pred of 0.603. Similarly, two topomer CoMFA models were also statistically significant and reliable in terms of their Q², R² and R²_Pred values. The Bayesian classification study also provided the excellent ROC values of 0.919 and 0.939 for training and test sets, respectively. Overall, this study may help in the rational design of newer benzoxazole type compounds with higher CETP inhibition.

Communicated by Ramaswamy H. Sarma     

Rapid ecosystem service assessment of the impact of Koshi Tappu Wildlife Reserve on wetland benefits to local communities

Wetlands are important for biodiversity and are critical for human livelihoods, providing ecosystem services such as clean water, food and global climate regulation. Many wetlands are threatened by land-use conversion, but creating protected areas to conserve them can benefit both biodiversity and people. However, protected areas can also have socio-economic costs for local communities. At Koshi Tappu Wildlife Reserve in Nepal, there has been historical conflict over the creation of the reserve. In light of a recent proposal to expand the protected area, we explored the use of a rapid ecosystem service assessment tool (TESSA) to assess the impact of the reserve on some of the key ecosystem services the site provides. Based on the ecosystem services assessed we estimated that the economic value of KTWR as a protected area is $350,000 y^?1 ($20 ha^?1y^?1) less than the value of the wetland in an unprotected state. However, this difference is relatively small and is affected by the limitations of the approach and sensitivity of the values to market prices and the assumptions made, so we cannot draw clear conclusions on the overall impact of the reserve in relation to local livelihoods. However, we found TESSA to be a useful tool for engaging with the stakeholder community and for highlighting the potential impacts that land use decisions can have on key ecosystem services. In the context of informing the potential expansion of the reserve, it is clear that further intensive socio-economic assessment of the potential costs and benefits is necessary.