Evolution of covered stents in the contemporary era: clinical application,materials and manufacturing strategies using nanotechnology

Endovascular stents have revolutionised the field of interventional cardiology. Despite their excellent clinical outcome complications associated with percutaneous stent implantation following the procedure have remained a major drawback in their widespread use. To overcome such limitations, a number of novel endovascular stents have emerged including a covered stent wrapped in a thin membrane sleeve. As well as prevention of complications associated with stenting, covered stents owing to their physical barrier are used as the treatment option of choice for trauma devices during emergency situations and to treat a number of pathological disease states. The aim of this review is to provide the reader with an overall objective outlook in the use of covered stents as a treatment option in a number of vascular complications and addresses their design and materials used in the manufacturing process. In addition, new strategies are highlighted and future prospects with the emergence of novel smart alloys for 3D scaffolds and the use of nanotechnology in the development of nanocomposite materials.     

A draft genome sequence of the pulse crop chickpea (Cicer arietinum L.)

Cicer arietinum L. (chickpea) is the third most important food legume crop. We have generated the draft sequence of a desi‐type chickpea genome using next‐generation sequencing platforms, bacterial artificial chromosome end sequences and a genetic map. The 520‐Mb assembly covers 70% of the predicted 740‐Mb genome length, and more than 80% of the gene space. Genome analysis predicts the presence of 27 571 genes and 210 Mb as repeat elements. The gene expression analysis performed using 274 million RNA‐Seq reads identified several tissue‐specific and stress‐responsive genes. Although segmental duplicated blocks are observed, the chickpea genome does not exhibit any indication of recent whole‐genome duplication. Nucleotide diversity analysis provides an assessment of a narrow genetic base within the chickpea cultivars. We have developed a resource for genetic markers by comparing the genome sequences of one wild and three cultivated chickpea genotypes. The draft genome sequence is expected to facilitate genetic enhancement and breeding to develop improved chickpea varieties.     

The Immune System GTPase GIMAP6 Interacts with the Atg8 Homologue GABARAPL2 and Is Recruited to Autophagosomes

The GIMAPs (GTPases of the immunity-associated proteins) are a family of small GTPases expressed prominently in the immune systems of mammals and other vertebrates. In mammals, studies of mutant or genetically-modified rodents have indicated important roles for the GIMAP GTPases in the development and survival of lymphocytes. No clear picture has yet emerged, however, of the molecular mechanisms by which they perform their function(s). Using biotin tag-affinity purification we identified a major, and highly specific, interaction between the human cytosolic family member GIMAP6 and GABARAPL2, one of the mammalian homologues of the yeast autophagy protein Atg8. Chemical cross-linking studies performed on Jurkat T cells, which express both GIMAP6 and GABARAPL2 endogenously, indicated that the two proteins in these cells readily associate with one another in the cytosol under normal conditions. The GIMAP6-GABARAPL2 interaction was disrupted by deletion of the last 10 amino acids of GIMAP6. The N-terminal region of GIMAP6, however, which includes a putative Atg8-family interacting motif, was not required. Over-expression of GIMAP6 resulted in increased levels of endogenous GABARAPL2 in cells. After culture of cells in starvation medium, GIMAP6 was found to localise in punctate structures with both GABARAPL2 and the autophagosomal marker MAP1LC3B, indicating that GIMAP6 re-locates to autophagosomes on starvation. Consistent with this finding, we have demonstrated that starvation of Jurkat T cells results in the degradation of GIMAP6. Whilst these findings raise the possibility that the GIMAPs play roles in the regulation of autophagy, we have been unable to demonstrate an effect of GIMAP6 over-expression on autophagic flux.     

Frequent Periodic Leg Movement During Sleep Is an Unrecognized Risk Factor for Progression of Atrial Fibrillation

Sleep apnea has been recognized as a factor predisposing to atrial fibrillation recurrence and progression. The effect of other sleep-disturbing conditions on atrial fibrillation progression is not known. We sought to determine whether frequent periodic leg movement during sleep is a risk factor for progression of atrial fibrillation. In this retrospective study, patients with atrial fibrillation and a clinical suspicion of restless legs syndrome who were referred for polysomnography were divided into two groups based on severity of periodic leg movement during sleep: frequent (periodic movement index >35/h) and infrequent (≤35/h). Progression of atrial fibrillation to persistent or permanent forms between the two groups was compared using Wilcoxon rank-sum test, chi-square tests and logistic regression analysis. Of 373 patients with atrial fibrillation (77% paroxysmal, 23% persistent), 108 (29%) progressed to persistent or permanent atrial fibrillation during follow-up (median, 33 months; interquartile range, 16-50). Compared to patients with infrequent periodic leg movement during sleep (n=168), patients with frequent periodic leg movement during sleep (n=205) had a higher rate of atrial fibrillation progression (23% vs. 34%; p=0.01). Patients with frequent periodic leg movement during sleep were older and predominantly male; however, there were no significant differences at baseline in clinical factors that promote atrial fibrillation progression between both groups. On multivariate analysis, independent predictors of atrial fibrillation progression were persistent atrial fibrillation at baseline, female gender, hypertension and frequent periodic leg movement during sleep. In patients with frequent periodic leg movement during sleep, dopaminergic therapy for control of leg movements in patients with restless legs syndrome reduced risk of atrial fibrillation progression. Frequent leg movement during sleep in patients with restless legs syndrome is associated with progression of atrial fibrillation to persistent and permanent forms.     

Geographic Variation in Access to Dog-Bite Care in Pakistan and Risk of Dog-Bite Exposure in Karachi: Prospective Surveillance Using a Low-Cost Mobile Phone System

Background

Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden. We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms (ER) in Pakistan, recording patient health-seeking behaviors, access to care and analyzed spatial distribution of cases from Karachi.

Methodology and Principal Findings

A total of 6212 dog-bite cases were identified over two years starting in February 2009 with largest number reported from Karachi (59.7%), followed by Peshawar (13.1%) and Hyderabad (11.4%). Severity of dog-bites was assessed using the WHO classification. Forty percent of patients had Category I (least severe) bites, 28.1% had Category II bites and 31.9% had Category III (most severe bites). Patients visiting a large public hospital ER in Karachi were least likely to seek immediate healthcare at non-medical facilities (Odds Ratio = 0.20, 95% CI 0.17–0.23, p-value<0.01), and had shorter mean travel time to emergency rooms, adjusted for age and gender (32.78 min, 95% CI 31.82–33.78, p-value<0.01) than patients visiting hospitals in smaller cities. Spatial analysis of dog-bites in Karachi suggested clustering of cases (Moran''s I = 0.02, p value<0.01), and increased risk of exposure in particular around Korangi and Malir that are adjacent to the city''s largest abattoir in Landhi. The direct cost of operating the mHealth surveillance system was USD 7.15 per dog-bite case reported, or approximately USD 44,408 over two years.

Conclusions

Our findings suggest significant differences in access to care and health-seeking behaviors in Pakistan following dog-bites. The distribution of cases in Karachi was suggestive of clustering of cases that could guide targeted disease-control efforts in the city. Mobile phone technologies for health (mHealth) allowed for the operation of a national-level disease reporting and surveillance system at a low cost.     

Drought Tolerance Strategies in Plants: A Mechanistic Approach

Journal of Plant Growth Regulation - Anthropogenic activities in the past and present eras have created global warming and consequently a storm of drought stress, affecting both plants and animals....     

Fluorinated 2′-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities

Chalcones are involved in the synthesis of flavonoids and are themselves known to exhibit multiple pharmacological properties. However, compared to other structurally similar phytochemicals like garcinol and curcumin, the therapeutic use of chalcones is limited because of their lower bioavailability and rapid metabolic clearance from biological system. In the present work, we have attempted to overcome these limitations in case of 2′-hydroxychalcones through bioisosteric substitution of fluoro groups in place of phenolic hydroxyls. The fluorinated chalcones were found to be more potent antioxidant and anti-proliferative compounds than their hydroxyl counterparts indicating the influence of metabolically stable C–F bonds towards bioavailability. The difluoro derivatives were found to be most effective against human pancreatic BxPC-3 cancer cells which possess up-regulated COX-2 expression and also showed activity against human breast cancer BT-20 cells with triple negative phenotype, suggesting that these compounds will have broader application in the future.     

The human obesity gene map: the 2005 update

This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTL) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2005, 176 human obesity cases due to single-gene mutations in 11 different genes have been reported, 50 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 244 genes that, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 408. The number of human obesity QTLs derived from genome scans continues to grow, and we now have 253 QTLs for obesity-related phenotypes from 61 genome-wide scans. A total of 52 genomic regions harbor QTLs supported by two or more studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably, with 426 findings of positive associations with 127 candidate genes. A promising observation is that 22 genes are each supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. The electronic version of the map with links to useful publications and relevant sites can be found at http://obesitygene.pbrc.edu.     

Endophyte bioprospecting in South Asian medicinal plants: an attractive resource for biopharmaceuticals

From the last several years, there has been an increasing interest in plant-associated bacteria commonly referred to as endophytes that reside asymptomatically in the internal plant tissues. This interest peaked since the last two decades due to the recognition that endophytes within medicinal plants have the capability to mimic and produce the bioactive metabolites of the host plant. A number of medicinal plants have been used for centuries by the people of South Asia to cure various diseases and this has led to abundant usage experience. Relating to prior ethanopharmacological experiences, scientists have searched for medicinal plants that could be valued sources for endophytes yielding novel metabolites of pharmaceutical importance. This review is therefore an effort to encompass the most recent efforts in the exploration of medicinal plants of South Asia and their endophytes.