Analysis of CCR5 and CX3CR1 gene polymorphisms in association with unexplained recurrent miscarriages among north Indian women

Context

Recurrent miscarriage (RM), defined as three or more consecutive losses before the 20th week of gestation, affects 0.5–2% of pregnant women. In over 80% of cases, RM remains unexplained after investigations, suggesting the involvement of genetic factors.

Objectives

The present study investigates the common polymorphisms of chemokine receptors CCR5 (NG_012637.1:g.5303A>G) and CX₃CR1 (NG_016362.1:g.21065C>T, Thr280Met and NG_016362.1:g.20971G>A, Val249Ile) and their association with recurrent miscarriages (RM) among north Indian women.

Participants and Methods

In a retrospective case-control study 200 well characterized patients with unexplained RM and 300 controls were genotyped for three polymorphic markers of CCR5 and CX₃CR1 by restriction digestion of PCR amplified fragments.

Results

Alleles and genotypes of CX₃CR1 Val249Ile revealed statistically significant associations with RM cases when compared with the controls. The homozygous variant genotype Ile/Ile was found to be significantly higher among patients (p = 0.0002) when compared with the homozygous wild type Val/Val genotype. The haplotype of CX₃CR1 that carried major alleles of Thr280Met and Val249Ile (T-V) showed statistically significant protective association (p < 0.0001, OR = 0.41, 95% CI = 0.31–0.54). The haplotype A-T-V (all wild type alleles) revealed a statistically significant protective association (p < 0.0001, OR = 0.41, 95% CI = 0.34–0.62), whereas the haplotypes G-T-I, A-T-I and A-M-V modified the risk of RM 1.9-fold, 5.5-fold and 5.1-fold respectively.

Conclusions

A common polymorphism of CX₃CR1 gene, Val240Ile is associated with the risk of RM in north Indian women. Risk of RM may also be modified by the presence of haplotypes T-I, M-V, G-T-I, A-T-I and A-M-V.     

Health and human rights in Chin State, Western Burma: a population-based assessment using multistaged household cluster sampling

Background

The Chin State of Burma (also known as Myanmar) is an isolated ethnic minority area with poor health outcomes and reports of food insecurity and human rights violations. We report on a population-based assessment of health and human rights in Chin State. We sought to quantify reported human rights violations in Chin State and associations between these reported violations and health status at the household level.

Methods and Findings

Multistaged household cluster sampling was done. Heads of household were interviewed on demographics, access to health care, health status, food insecurity, forced displacement, forced labor, and other human rights violations during the preceding 12 months. Ratios of the prevalence of household hunger comparing exposed and unexposed to each reported violation were estimated using binomial regression, and 95% confidence intervals (CIs) were constructed. Multivariate models were done to adjust for possible confounders. Overall, 91.9% of households (95% CI 89.7%–94.1%) reported forced labor in the past 12 months. Forty-three percent of households met FANTA-2 (Food and Nutrition Technical Assistance II project) definitions for moderate to severe household hunger. Common violations reported were food theft, livestock theft or killing, forced displacement, beatings and torture, detentions, disappearances, and religious and ethnic persecution. Self reporting of multiple rights abuses was independently associated with household hunger.

Conclusions

Our findings indicate widespread self-reports of human rights violations. The nature and extent of these violations may warrant investigation by the United Nations or International Criminal Court. Please see later in the article for the Editors'' Summary     

Protein intake and stress levels in nurses and housewives of Pakistan

Stress has many biological effects on human daily life. In the present study, dietary protein intake was correlated with the investigated stress levels of nurses and housewives of the targeted urban population. Age group ranged from 30 to 45 years and both the groups belonged to middle socioeconomic status. After calculations of environmental, psychological and physiological stresses, it was observed that the levels of stress in housewives were significantly higher than those of nurses. Recommended dietary allowances, RDA and actual protein intakes, API were also compared in both the groups. The found protein intake was less in housewives as compared to that of nurses.     

Biotransformation of withanolides by cell suspension cultures of Withania somnifera (Dunal)

The biotransformation potential of cell suspension cultures generated from Withania somnifera leaf was investigated, using withanolides, i.e. withanolide A, withaferin A, and withanone as precursor substrates. Interestingly, the cell suspension cultures showed inter-conversion of withanolides, as well converted to some unknown compounds, released to the culture media. The bio-catalyzed withanolide was detected and quantified by TLC and HPLC, respectively. There is noticeable conversion of withanolide A to withanone, and vice versa though at a lower level. The type of reaction of this biotransformation appears to be substitution of 20-OH group to 17-OH in withanolide A. In this paper, we present for the first time the possibility of biotransformation by inter-conversion of withanolides of pharmacological importance through cell suspension culture of W. somnifera. The possible role of putative cytochrome P₄₅₀ hydroxylases is implicated in the conversion.     

Effect of ultraviolet B (302 nm) irradiation on viability, metabolic and detoxification functions of goat hepatocytes – in vitro study

The object of the present study was to investigate the effect(s) of UV-B irradiation on the functional integrity, metabolic and detoxifying capacity of the isolated goat hepatocytes. Isolated goat hepatocytes were subjected to UV-B irradiation invitro for 0, 250, 500, 1250, 2500 and 7500 Joules/m² which correspond to the irradiation time of 0, 1, 2, 5, 10 and 30 min. Cells were then analysed for Viability (Trypan blue exclusion test [TBE], 3-[4,5-dimethylthiozol-2yl]-2,5-diphenyltetrazolium bromide [MTT] assay, Membrane integrity (Lactate dehydrogenase [LDH] leakage, Lipid peroxidation) Detoxification (Ureagenesis, Cytochrome P450 activity [CYP450, Diazepam metabolism] and Glutathione-S-Transferase [GST] activity. The results show that there was no difference in functional, metabolic as well as detoxifying parameters of the hepatocytes when irradiated from 0–1250 Joules/m², whereas a significant alteration was appreciable in the parameters such as LDH leakage, lipid peroxidation, and CYP450 activity when irradiated beyond 1250 Joules/m². Our present findings suggest that the biologically compatible and feasible dose of UV-B irradiation for xenotransplantation appears to be 1250 Joules/m².     

Development of a simple and rapid fluorogenic procedure for identification of vibrionaceae family members

We describe a simple colony overlay procedure for peptidases (COPP) for the rapid fluorogenic detection and quantification of Vibrionaceae from seawater, shellfish, sewage, and clinical samples. The assay detects phosphoglucose isomerase with a lysyl aminopeptidase activity that is produced by Vibrionaceae family members. Overnight cultures are overlaid for 10 min with membranes containing a synthetic substrate, and the membranes are examined for fluorescent foci under UV illumination. Fluorescent foci were produced by all the Vibrionaceae tested, including Vibrio spp., Aeromonas spp., and Plesiomonas spp. Fluorescence was not produced by non-Vibrionaceae pathogens. Vibrio cholerae strains O1, O139, O22, and O155 were strongly positive. Seawater and oysters were assayed, and 87 of 93 (93.5%) of the positive isolates were identified biochemically as Vibrionaceae, principally Vibrio vulnificus, Vibrio parahaemolyticus, Aeromonas hydrophila, Photobacterium damselae, and Shewanella putrefaciens. None of 50 nonfluorescent isolates were Vibrionaceae. No Vibrionaceae were detected in soil, and only A. hydrophila was detected in sewage. The COPP technique may be particularly valuable in environmental and food-testing laboratories and for monitoring water quality in the aquaculture industry.     

Syntheses and biological activities of chalcone and 1,5-benzothiazepine derivatives: promising new free-radical scavengers, and esterase, urease, and alpha-glucosidase inhibitors

A series of 2,4-diaryl-2,3,4,5-tetrahydro- (36-40) and 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines (25-35) have been synthesized from the corresponding chalcones 1-24. Both the benzothiazepines and chalcones were evaluated as DPPH free-radical scavengers and as inhibitors of cholinesterases, urease, and alpha-glucosidase. Compounds 2, 5, 6, 7, 10, 13, 18, 21, 36a, 37a, 37b, and 39a showed significant cholinesterase inhibiting activities. Among the 15 dihydro-1,5-benzothiazepines, 26, 32, and 35 exhibited significant radical-scavenging activities; and six tetrahydro-1,5-benzothiazepines (35, 36a, 36b, 37a, 37b, and 39a) were found to be inhibitors of AChE and BChE. Compounds 22, 25, 26, 33, 35, 36a, 37b, and 39a inhibited urease, and 25 and 27-31 were found to be potent inhibitors of alpha-glucosidase.     

Oxidation of gum arabic by soluble colloidal MnO2

In the present work, the oxidative degradation of gum arabic by colloidal manganese dioxide (MnO2) was carried out. Monitoring the disappearance of the MnO2 spectrophotometrically at 375 nm was used to follow the kinetics. The oxidation obeyed fractional-order kinetics with respect to the [gum arabic]. Effect of various experimental parameters such as the initial colloidal [MnO2], [HClO4], temperature, and complexing agents (P2O7(4-), F-, and Mn2+) for the oxidation of gum arabic was studied. The reaction was acid catalyzed. Addition of P2O(7)4-, F-, and Mn2+ ions enhances the rate of oxidation significantly. Gum arabic adsorbs onto the surface of the colloidal MnO2 through the equatorial -OH groups of the rhamnose moiety, and the complex breaks down into products. The Arrhenius equation was valid for the oxidation kinetics between 40 and 60 degrees C. To explain the observed kinetic results, a suitable mechanism and rate law for the reaction taking place at the surface of the colloidal particle has been proposed. The reducing nature of gum arabic is found be due to the presence of -OH group in the skeleton.     

EXPERIMENTAL STUDIES IN PONDEROSA PINE. I. RELATIONSHIP BETWEEN VARIATION IN PROTEINS AND MORPHOLOGY

Ponderosa pine from California (Pinus ponderosa var. ponderosa) were crossed to one another and also to individuals from the Rocky Mountains (P. p. var. scopulorum). All crosses involved a single mother and a single pollen donor. Patterns of inheritance of electrophoretically-detectable loci followed Mendelian expectations with one exception. Shikimate dehydrogenase showed unpredictable banding patterns in intervarietal crosses. Variability at these biochemical loci was compared to variability at 14 morphometric characters. The relationship between these two levels of variation is complex and permits only one generalization: variability at one level is not a good predictor of variability at the other level.