Drug utilization study in ischaemic heart disease in a tertiary care hospital, Mangalore, India

Background: The study of drug utilization is a component of a medical audit and periodic evaluation need to be done to enable suitable modifications in prescription of drugs to increase the therapeutic benefit and decrease the adverse effects. When new drugs are used additional information on safety and efficacy may be generated. Ischaemic heart disease (IHD) is a condition in which there is an inadequate supply of blood and oxygen to a portion of the myocardium. Medications for IHD include anti-platelet therapy, nitrates, statins, ACE inhibitors, beta blockers, CCB’s, diuretics.Methods: The study was carried out at cardiology department of K. S. Hegde Charitable Hospital for a period of one year from January 2015, and relevant retrospective data were also collected from hospital records for period pertaining to one year from 1/1/2013.Results: We assessed discharge summaries of 950 patients and found that majority of patients were males than females. The highest number of patients were in the age group of 51-60 years. Polypharmacy has been observed in our study. The average number of days spent by the patients in the hospital was 3.5 days. None of the drugs were prescribed using generic names, all the drugs (100%) were prescribed in brand names only. Common co-morbidities associated with IHD were hypertension and diabetes. Most commonly prescribed drugs for IHD were Aspirin, followed by Atorvastatin, Clopidogrel, and Nitrates.Conclusions: In our study, on analysing the drug prescription data it was observed that there was no statistically significant change in drug utilization between the two years

Amoxicillin induced toxic epidermal necrolysis: a case report

Adverse reactions are the recognized hazards of drug therapy and they can occur with any class of drugs and many studies revealed that the incidence is more in case of antibiotics. Amoxicillin is a broad spectrum, bactericidal, beta lactam antibiotic, commonly used to combat various infections. Penicillin group of drugs are known to cause cutaneous drug eruptions especially in paediatric population. Most of the time, these eruptions are mild in nature, however, sometimes they represent the early manifestation of rare, severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Toxic epidermal necrolysis (TEN) is a rare, life threatening dermatological disorder that is usually induced by medications. Seventy percent of the cases of TEN are drug induced, most commonly implicated drugs being anticonvulsants, antibiotics and non-steroidalanti-inflammatory drugs (NSAIDS). Here, we report a case of toxic epidermal necrolysis induced by amoxicillin in a 12 year old male patient. Treatment with strong antibiotics, immunosuppressant and other supportive measures helped in recovery of the patient. The case is being reported to emphasize the need for efficient pharmacovigilance in order to motivate adverse drug reaction reporting so as to gather more and more data regarding adverse drug reactions. Through this report, we also seek the support of every-one concerned, to detect and, if possible, prevent adverse reactions to drugs

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200

Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd

Treatment of multiple input uncertainties using the scaled boundary finite element method

This paper presents a non-intrusive scaled boundary finite element method to consider multiple input uncertainties, viz., material and geometry. The types of geometric uncertainties considered include the shape and size of inclusions. The inclusions are implicitly defined, and a robust framework is presented to treat the interfaces, which does not require explicit generation of a conforming mesh or special enrichment techniques. A polynomial chaos expansion is used to represent the input and the output uncertainties. The efficiency and the accuracy of the proposed framework are elucidated in detail with a few problems by comparing the results with the conventional Monte Carlo method. A sensitivity analysis based on Sobol’ indices using the developed framework is presented to identify the critical input parameter that has a higher influence on the output response

A Non-Intrusive Stochastic Isogeometric Analysis of Functionally Graded Plates with Material Uncertainty

A non-intrusive approach coupled with non-uniform rational B-splines based isogeometric finite element method is proposed here. The developed methodology was employed to study the stochastic static bending and free vibration characteristics of functionally graded material plates with inhered material randomness. A first order shear deformation theory with an artificial shear correction factor was used for spatial discretization. The output randomness is represented by polynomial chaos expansion. The robustness and accuracy of the framework were demonstrated by comparing the results with Monte Carlo simulations. A systematic parametric study was carried out to bring out the sensitivity of the input randomness on the stochastic output response using Sobol’ indices. Functionally graded plates made up of Aluminium (Al) and Zirconium Oxide (ZrO2) were considered in all the numerical examples

Amoxicillin induced toxic epidermal necrolysis: a case report

Adverse reactions are the recognized hazards of drug therapy and they can occur with any class of drugs and many studies revealed that the incidence is more in case of antibiotics. Amoxicillin is a broad spectrum, bactericidal, beta lactam antibiotic, commonly used to combat various infections. Penicillin group of drugs are known to cause cutaneous drug eruptions especially in paediatric population. Most of the time, these eruptions are mild in nature, however, sometimes they represent the early manifestation of rare, severe drug-induced cutaneous reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Toxic epidermal necrolysis (TEN) is a rare, life threatening dermatological disorder that is usually induced by medications. Seventy percent of the cases of TEN are drug induced, most commonly implicated drugs being anticonvulsants, antibiotics and non-steroidalanti-inflammatory drugs (NSAIDS). Here, we report a case of toxic epidermal necrolysis induced by amoxicillin in a 12 year old male patient. Treatment with strong antibiotics, immunosuppressant and other supportive measures helped in recovery of the patient. The case is being reported to emphasize the need for efficient pharmacovigilance in order to motivate adverse drug reaction reporting so as to gather more and more data regarding adverse drug reactions. Through this report, we also seek the support of every-one concerned, to detect and, if possible, prevent adverse reactions to drugs

The transcriptional response to tumorigenic polarity loss in Drosophila.

Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA profiling of Scrib mutant tumors reveals multiple signatures of neoplasia, including altered metabolism and dedifferentiation. Prominent among these is upregulation of cytokine-like Unpaired (Upd) ligands, which drive tumor overgrowth. We identified a polarity-responsive enhancer in upd3, which is activated in a coincident manner by both JNK-dependent Fos and aPKC-mediated Yki transcription. This enhancer, and Scrib mutant overgrowth in general, are also sensitive to activity of the Polycomb Group (PcG), suggesting that PcG attenuation upon polarity loss potentiates select targets for activation by JNK and Yki. Our results link epithelial organization to signaling and epigenetic regulators that control tissue repair programs, and provide insight into why epithelial polarity is tumor-suppressive