Possible Hypoxia Signaling Induced Alteration of Glucose Homeostasis in Rats Exposed to Chronic Intermittent Hypoxia - Role of Antioxidant (Vitamin C) and Ca2+ Channel Blocker (Cilnidipine)

Background: Hyperglycemia is found to be a regulator of HIF-1α gene expression but the regulation of HIF-1α on glucose homeostasis is unclear. Objective: To determine whether chronic intermittent hypoxia (CIH) alters glucose regulation and such alterations can revert through treatments with either antioxidant (vitamin c) or calcium channel blocker (cilnidipine) in male albino rats. Methods: The rats were divided into six groups i.e. normoxia (21% oxygen), CIH (10% oxygen with cycle time 3:1.5; 8h/day), normoxia with vitamin c (50 mg /100g. b.wt, orally), CIH with vitamin c, normoxia with cilnidipine (1 mg/kg/day; ip) and CIH with cilnidipine. Serum MDA, HIF-1α, fasting plasma glucose, insulin, GTT, HOMA-IR and insulinogenic index were evaluated. Results: Serum HIF-1α and MDA concentration in rats exposed to CIH increased significantly whereas simultaneous CIH with vitamin c and CIH with cilnidipine treatment show reversion of both serum HIF- 1α and MDA concentrations towards normoxic status. CIH rats showed increased fasting glucose level with unchanged plasma insulin level but both vitamin c and cilnidipine treatment improved the status. Elevated HOMA-IR and insulinogenic index along with impaired GTT were found in CIH groups although vitamin c and cilnidipine improved the glucose homeostasis in CIH exposed rats. Conclusion: CIH induces over production of reactive oxygen species as well as hyper activities of sympathetic N-type Ca2+ channels possibly through HIF 1-α expression and influence on insulin signaling by causing hyperglycemia, glucose intolerance and insulin resistance in rats. Simultaneous treatment with vitamin c or cilnidipine improves glucose homeostasis in CIH exposed rats

A readily accessible porous organic polymer facilitates high-yielding Knoevenagel condensation at room temperature both in water and under solvent-free mechanochemical conditions

A novel nitrogen-rich amorphous porous organic polymer has been synthesized using a microwave-assisted process. Its high chemical stability, reusability and poor solubility enable the use of the porous polymer as a metal-free heterogeneous catalyst for C–C bond formation at ambient temperature under environmentally benign conditions

High concentration of childhood deaths in the low-lying areas of Chakaria HDSS, Bangladesh: findings from a spatial analysis

Background: Despite significant reduction of childhood mortality in Bangladesh, large spatial variations persist. Identification of lower level spatial units with higher concentrations of deaths can be useful for strengthening services in these areas. This paper reports findings from a spatial analysis of deaths in Chakaria, a rural subdistrict, where a Health and Demographic Surveillance System has been in place since 1999. Chakaria is an INDEPTH member site. Methods: An analysis was done of 339 deaths among nearly 24,500 children under the age of five during 2005–2008. One ward, the lowest level of administrative units, was the unit of spatial analysis. Data from 24 wards were analyzed. The Discrete Poisson Probability Model was used to identify the clustering of deaths. Results: Deaths were concentrated within 12 wards located in the low-lying deltaic flood plains of the Chakaria HDSS area. The risk of death in the low-lying areas was statistically, significantly higher, 1.5 times, than the non-low-lying areas (p<0.02). Conclusion: Spatial analysis can be a useful tool for identifying high-risk mortality areas. An understanding of the risk factors prevalent in the low-lying areas can help design effective interventions to reduce mortality in these areas

Oxidative and pre-inflammatory stress in wedge resection of pulmonary parenchyma using the radiofrequency ablation technique in a swine model

<p>Abstract</p> <p>Background</p> <p>Radiofrequency ablation (RFA) is a thermal energy delivery system used for coagulative cellular destruction of small tumors through percutaneous or intraoperative application of its needle electrode to the target area, and for assisting partial resection of liver and kidney. We tried to evaluate the regional oxidative and pre-inflammatory stress of RFA-assisted wedge lung resection, by measuring the MDA and tumor Necrosis Factor Alpha (TNF-α) concentration in the resected lung tissue of a swine model.</p> <p>Method</p> <p>Fourteen white male swines, divided in two groups, the RFA-group and the control group (C-group) underwent a small left thoracotomy and wedge lung resection of the lingula. The wedge resection in the RFA-group was performed using the RFA technique whereas in C-group the simple "cut and sew" method was performed. We measured the malondialdehyde (MDA) and TNF-α concentration in the resected lung tissue of both groups.</p> <p>Results</p> <p>In C-group the MDA mean deviation rate was 113 ± 42.6 whereas in RFA-group the MDA mean deviation rate was significantly higher 353 ± 184 (p = 0.006). A statistically significant increase in TNF-α levels was also observed in the RFA-group (5.25 ± 1.36) compared to C-group (mean ± SD = 8.48 ± 2.82) (p = 0.006).</p> <p>Conclusion</p> <p>Our data indicate that RFA-assisted wedge lung resection in a swine model increases regional MDA and TNF-a factors affecting by this oxidative and pre-inflammatory stress of the procedure. Although RFA-assisted liver resection can be well tolerated in humans, the possible use of this method to the lung has to be further investigated in terms of regional and systemic reactions and the feasibility of performing larger lung resections.</p

Effects of complexity of handwashing instructions on handwashing procedure replication in low-income urban slums in Bangladesh: a randomized non-inferiority field trial

Abstract Handwashing instructions vary in complexity, with some recommending multiple steps. To assess whether complex handwashing instructions changed handwashing procedure replication, we conducted a randomized non-inferiority trial in a low-income area, Dhaka. We randomly assigned mothers and children aged 5–10 years to one of three handwashing instruction sets: simple (N = 85 mothers/134 children), moderate (N = 75 mothers/148 children), or complex (84 mothers/147 children). Simple instructions had three steps: wet, lather, and rinse hands, and moderate included the simple instructions plus steps to scrub palms, backs of hands, and dry hands in the air. Complex instructions included moderate instructions plus steps to scrub between fingers, under nails, and lather for 20 s. After baseline, cue cards were used to promote handwashing instructions, and adherence after 2 weeks of interventions was evaluated. Compliance with handwashing procedure replication to all instructions in simple, moderate, and complex increased after the intervention among mothers and children. Compliance to all instructions in the simple group was higher in the simple group (100%) compared to all instructions in moderate (47%) and complex instruction groups (38%). Simple handwashing steps are easier to remember for long time periods compared to complex steps.</jats:p

Field trial of an automated batch chlorinator system at shared water points in an urban community of Dhaka, Bangladesh

Point-of-use water treatment with chlorine is underutilized in low-income households. The Zimba, an automated batch chlorinator, requires no electricity or moving parts, and can be installed at shared water points with intermittent flow. We conducted a small-scale trial to assess the acceptability and quality of Zimba-treated municipal water. Fieldworkers collected stored drinking water over a 10-week period from control (n = 24 households) and treatment (n = 30 households) compounds to assess levels of free chlorine and E. coli contamination. Overall, 80% of stored drinking water samples had a safe chlorine residual among treatment households, compared to 29% among control households (P &amp;lt; 0.001). Concentrations of E. coli were lower (mean difference = 0.4 log colony-forming units/100 mL, P = 0.004) in treatment compared to control households. Fifty-three percent of mothers (n = 17), thought the Zimba was easy to use and 76% were satisfied with the taste. The majority of mothers mentioned that collecting water from the Zimba took more time and created a long queue at the handpump. The Zimba successfully chlorinated household stored drinking water; however, further technology development is required to address user preferences. The Zimba may be a good option for point-of-collection water treatment in areas where queuing for water is uncommon.</jats:p

Robotic assisted Laparoscopic partial Nephrectomy for suspected Renal Cell Carcinoma: Retrospective review of surgical outcomes of 35 Cases

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Whole-chromosome hitchhiking driven by a male-killing endosymbiont.

Neo-sex chromosomes are found in many taxa, but the forces driving their emergence and spread are poorly understood. The female-specific neo-W chromosome of the African monarch (or queen) butterfly Danaus chrysippus presents an intriguing case study because it is restricted to a single 'contact zone' population, involves a putative colour patterning supergene, and co-occurs with infection by the male-killing endosymbiont Spiroplasma. We investigated the origin and evolution of this system using whole genome sequencing. We first identify the 'BC supergene', a broad region of suppressed recombination across nearly half a chromosome, which links two colour patterning loci. Association analysis suggests that the genes yellow and arrow in this region control the forewing colour pattern differences between D. chrysippus subspecies. We then show that the same chromosome has recently formed a neo-W that has spread through the contact zone within approximately 2,200 years. We also assembled the genome of the male-killing Spiroplasma, and find that it shows perfect genealogical congruence with the neo-W, suggesting that the neo-W has hitchhiked to high frequency as the male-killer has spread through the population. The complete absence of female crossing-over in the Lepidoptera causes whole-chromosome hitchhiking of a single neo-W haplotype, carrying a single allele of the BC supergene and dragging multiple non-synonymous mutations to high frequency. This has created a population of infected females that all carry the same recessive colour patterning allele, making the phenotypes of each successive generation highly dependent on uninfected male immigrants. Our findings show how hitchhiking can occur between the physically unlinked genomes of host and endosymbiont, with dramatic consequences

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk