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.     

What determines nasal carriage of Staphylococcus aureus?

Nasal carriage of Staphylococcus aureus is an important risk factor for infection by this organism in both community and hospital settings; this article reviews the role of host and bacterial factors in carriage. A host genetic influence appears likely but the phenotypic determinants are unknown. Possibilities include variability in host adhesins, immune response or secretion of antimicrobial molecules. Colonization resistance by S. aureus, together with the observation that persistent carriers often carry a single strain whereas intermittent carriers can be colonized with unrelated strains over time, suggests that bacterial factors could also be involved.     

Synthesis and characterizations of novel quinoline derivatives having mixed ligand activities at the κ and μ receptors: Potential therapeutic efficacy against morphine dependence

Based on an established 3D pharmacophore, a series of quinoline derivatives were synthesized. The opioidergic properties of these compounds were determined by a competitive binding assay using ¹²⁵I-Dynorphine, ³H-DAMGO and ¹²⁵I-DADLE for κ, μ, and δ receptors, respectively. Results showed varying degree of activities of the compounds to κ and μ opioid receptors with negligible interactions at the δ receptor. The compound, S4 was the most successful in inhibiting the two most prominent quantitative features of naloxone precipitated withdrawal symptoms - stereotyped jumping and body weight loss. Determination of IC₅₀ of S4 revealed a greater affinity towards μ compared to κ receptor. In conclusion, quinoline derivatives of S4 like structure offer potential tool for treatment of narcotic addictions.     

Genetic diversity and selection at the Plasmodium vivax apical membrane antigen-1 (PvAMA-1) locus in a Sri Lankan population

Plasmodium vivax apical membrane antigen 1 (PvAMA-1) is an important malaria vaccine candidate. We present the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Sri Lanka. In contrast to what has been observed at the AMA-1 locus of Plasmodium falciparum, the signature of diversifying selection is seen most strongly in Domain II of PvAMA-1, indicating that the different domains in each species may be subject to varying selective pressures and functional constraints. We also find that recombination plays an important role in generating haplotype diversity at this locus, even in a region of low endemicity such as Sri Lanka. Mapping of diversity and recombination hotspots onto a 3-dimensional structural model of the protein indicates that one surface of the molecule may be particularly likely to bear epitopes for antibody recognition. Regions of this surface that show constrained variability may prove to be promising vaccine targets.     

NR2B-NMDA receptor mediated modulation of the tyrosine phosphatase STEP regulates glutamate induced neuronal cell death

The present study examines the role of a neuron-specific tyrosine phosphatase (STEP, striatal-enriched tyrosine phosphatase) in excitotoxic cell death. Our findings demonstrate that p38 MAPK, a stress-activated kinase that is known to play a role in the etiology of excitotoxic cell death is a substrate of STEP. Glutamate-mediated NMDA receptor stimulation leads to rapid but transient activation of p38 MAPK, which is primarily dependent on NR2A-NMDA receptor activation. Conversely, activation of NR2B-NMDA receptors leads to dephosphorylation and subsequent activation of STEP, which in turn leads to inactivation of p38 MAPK. Thus, during transient NMDA receptor stimulation, increases in STEP activity appears to limit the duration of activation of p38 MAPK and improves neuronal survival. However, if NR2B-NMDA receptor stimulation is sustained, protective effects of STEP activation are lost, as these stimuli cause significant degradation of active STEP, leading to secondary activation of p38 MAPK. Consistent with this observation, a cell transducible TAT-STEP peptide that constitutively binds to p38 MAPK attenuated neuronal cell death caused by sustained NMDA receptor stimulation. The findings imply that the activation and levels of STEP are dependent on the duration and magnitude of NR2B-NMDA receptor stimulation and STEP serves as a modulator of NMDA receptor dependent neuronal injury, through its regulation of p38 MAPK.     

Missed Opportunities: Refusal to Confirm Reactive Rapid HIV Tests in the Emergency Department

Background

HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care.

Methodology

In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol.

Principal Findings

Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage.

Conclusions

These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00502944","term_id":"NCT00502944"}}NCT00502944; {"type":"clinical-trial","attrs":{"text":"NCT01258582","term_id":"NCT01258582"}}NCT01258582.     

Oxidative stress-induced oligomerization inhibits the activity of the non-receptor tyrosine phosphatase STEP61

The neuron-specific tyrosine phosphatase STriatal Enriched Phosphatase (STEP) is emerging as an important mediator of glutamatergic transmission in the brain. STEP is also thought to be involved in the etiology of neurodegenerative disorders that are linked to oxidative stress such as Alzheimer's disease and cerebral ischemia. However, the mechanism by which oxidative stress can modulate STEP activity is still unclear. In this study, we have investigated whether dimerization may play a role in regulating the activity of STEP. Our findings show that STEP(61), the membrane associated isoform, can undergo homodimerization under basal conditions in neurons. Dimerization of STEP(61) involves intermolecular disulfide bond formation between two cysteine residues (Cys 65 and Cys 76 respectively) present in the hydrophobic region at the N-terminus specific to STEP(61). Oxidative stress induced by hydrogen peroxide leads to a significant increase in the formation of dimers and higher-order oligomers of STEP(61). Using two substrates, para-nitrophenylphosphate and extracellular-regulated kinase MAPK we further demonstrate that oligomerization leads to a significant reduction in its enzymatic activity.