Clinico-social parameters of diabetes among patientsutilizing emergency medical services

Background: Diabetes mellitus (DM) is increasing in its potential in developing countries. Rise in diabetic patients calling emergency medical services (EMS) is expected. It calls for thorough assessment of patients with DM utilizing EMS. In the present study, was to assess magnitude of DM among patients utilizing EMS and its clinico-social parameters.Methods: It was hospital record based observational study of patients calling EMS delivered by a tertiary care hospital in Pune, Maharashtra, India during 1st January 2013 to 31st December 2014. Patients with incomplete records were excluded. A person with medical background was trained to extract required information from hospital records. Patients with previously diagnosed DM were considered those who were on diet, oral hypoglycemic agents or taking insulin therapy and newly diagnosed patients with DM were considered those with the value of glycemia on admission >200 mg/dl in first 24 hours. Data analysis was done using SPSS 15.0 software.Results: 45.8% (894/1951) were Patients with DM out of that 78.19% (699/894) were known to have DM while 28.81% (195/1951) were new cases of DM. 5.1% (100/1951) patients had uncontrolled DM. DM was significantly more in >60 years age group and in urban residents (p<0.001). Patients with DM were significantly more to have breathlessness, altered sensorium and dyspnoea as major purpose to call EMS (p<0.001, <0.001 and 0.045 respectively). Other co-morbidities in the form of Hypertension, other cardiovascular abnormalities, COPD, CKD and history of CVA were significantly more among Patients with DM (p<0.001, except for COPD, p=0.027).Conclusions: There was a high burden of patients with DM on EMS. EMS teams should be well trained to diagnose and manage such emergencies. Mass awareness of screening for DM and its proper management will help to decrease such burden

Characterizing the normal proteome of human ciliary body

BACKGROUND: The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body. RESULTS: In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis. CONCLUSIONS: More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia

Arrays of holes fabricated by electron-beam lithography combined with image reversal process using nickel pulse reversal plating

Abstract : A critical issue in fabricating arrays of holes is to achieve high-aspect-ratio structures. Formation of ordered arrays of nanoholes in silicon nitride was investigated by the use of ultrathin hard etch mask formed by nickel pulse reversal plating to invert the tonality of a dry e-beam resist patterned by e-beam lithography. Ni plating was carried out using a commercial plating solution based on nickel sulfamate salt without organic additives. Reactive ion etching using SF6/CH4SF6/CH4 was found to be very effective for pattern transfer to silicon nitride. Holes array of 100 nm diam, 270 nm period, and 400 nm depth was fabricated on a 5×5 mm2 area

Natural Killer Cell Degranulation Defect: A Cause for Impaired NK-Cell Cytotoxicity and Hyperinflammation in Fanconi Anemia Patients

Fanconi anemia (FA) is a rare inherited syndrome characterized by progressive bone marrow failure (BMF), abnormal skin pigmentation, short stature, and increased cancer risk. BMF in FA is multifactorial and largely results from the death of hematopoietic stem cells due to genomic instability. Also, inflammatory pathology in FA has been previously reported, however the mechanism is still not clear. In literature, decreased NK-cell count and/or impaired NK-cell activity, along with other immunological abnormalities have been described in FA-patients (1). However, to the best of our knowledge, this is the first report showing a defective degranulation mechanism leading to abnormal NK-cell cytotoxicity in FA-patients, which may explain the development of a hyperinflammatory response in these patients. This may predispose some patients to develop Hemophagocytic lymphohistiocytosis (HLH) which manifests with prolonged fever, progressive cytopenias and organomegaly. Early diagnosis and initiation of immunosuppressive therapy in these patients will help to better manage these patients. We also propose FA genes to be listed as a cause of familial HLH

What Is a Microsatellite: A Computational and Experimental Definition Based upon Repeat Mutational Behavior at A/T and GT/AC Repeats

Microsatellites are abundant in eukaryotic genomes and have high rates of strand slippage-induced repeat number alterations. They are popular genetic markers, and their mutations are associated with numerous neurological diseases. However, the minimal number of repeats required to constitute a microsatellite has been debated, and a definition of a microsatellite that considers its mutational behavior has been lacking. To define a microsatellite, we investigated slippage dynamics for a range of repeat sizes, utilizing two approaches. Computationally, we assessed length polymorphism at repeat loci in ten ENCODE regions resequenced in four human populations, assuming that the occurrence of polymorphism reflects strand slippage rates. Experimentally, we determined the in vitro DNA polymerase-mediated strand slippage error rates as a function of repeat number. In both approaches, we compared strand slippage rates at tandem repeats with the background slippage rates. We observed two distinct modes of mutational behavior. At small repeat numbers, slippage rates were low and indistinguishable from background measurements. A marked transition in mutability was observed as the repeat array lengthened, such that slippage rates at large repeat numbers were significantly higher than the background rates. For both mononucleotide and dinucleotide microsatellites studied, the transition length corresponded to a similar number of nucleotides (approximately 10). Thus, microsatellite threshold is determined not by the presence/absence of strand slippage at repeats but by an abrupt alteration in slippage rates relative to background. These findings have implications for understanding microsatellite mutagenesis, standardization of genome-wide microsatellite analyses, and predicting polymorphism levels of individual microsatellite loci

Integrating transcriptomic and proteomic data for accurate assembly and annotation of genomes

© 2017 Wong et al.; Published by Cold Spring Harbor Laboratory Press. Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites. Based on transcriptomic data alone, we identified and corrected 535 events of incomplete genome assembly involving 1196 scaffolds and 868 protein-coding gene models. This proteogenomic approach enabled us to add 365 genes that were missed during genome annotation and identify 917 gene correction events through discovery of 151 novel exons, 297 protein extensions, 231 exon extensions, 192 novel protein start sites, 19 novel translational frames, 28 events of joining of exons, and 76 events of joining of adjacent genes as a single gene. Incorporation of proteomic evidence allowed us to change the designation of more than 87 predicted noncoding RNAs to conventional mRNAs coded by protein-coding genes. Importantly, extension of the newly corrected genome assemblies and gene models to 15 other newly assembled Anopheline genomes led to the discovery of a large number of apparent discrepancies in assembly and annotation of these genomes. Our data provide a framework for how future genome sequencing efforts should incorporate transcriptomic and proteomic analysis in combination with simultaneous manual curation to achieve near complete assembly and accurate annotation of genomes

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Development of a high resolution nanolithography technique on non-planar surfaces using an evaporated electron beam resist

Electron beam lithography systems used for patterning of extremely small structures are a very important tool for nanofabrication technologies. The on going miniaturization of electronic and photonic device, leads to a constant shrinking and increasing pattern density. Fundamental physical effects such as shot noise, which in lithography corresponds to the statistical fluctuations in the number of electrons contained in a beam, have a major impact on the achievable feature sizes as well as their roughness. Many different parameters in the lithography process must be taken into account in determining these fundamental limits, including exposure dose of the resist, resist thickness, beam energy, etc. A shot noise model has been developed in order to calculate the minimum exposure doses required for patterning electron beam resists at technology nodes of 50 nm and below while maintaining reasonable quality of the patterns. The doses must increase rapidly with reducing linewidth, thus imposing constraints on a variety of next generation lithography systems, such as massively parallel electron beam (MPEB) systems. The model results are applied to the particular case of MPEB systems for the patterning of integrated circuits on semiconductor wafers. An overall set of results is obtained indicating the minimum number of electron beams and electron beam current that will be required to meet industry standards. High resolution electron beam lithography poses severe constraints on the resist used for patterning, namely the need to work with very thin layers in order to achieve the highest resolutions. A new and interesting conformal resist is studied in this work, the sterol based QSR-5(TM) resist. The results of optimizing the resist properties and the development process are presented along with results for optimizing the sensitivity and contrast of this resist. Preserving and developing versatility in the applications has been one of the most important criteria in optimizing the QSR-5(TM) resist. Demonstrations include patterning a zone plate on the tip of an optical fiber for potential application in integrated optics. A very unusual application of patterning both sides of a silicon and a silicon nitride membrane in a single step are described which might be useful for the fabrication of high speed field effect devices such as double gate transistors (DGT). The Monte-Carlo simulation results for the case of the achievable gate length with silicon and silicon nitride membranes are also discussed. The results of conformability and patterning on V-grooves are also presented. The processes of fabrication of the high resolution metamaterial structures are discussed along with the initial measurement results via ellipsometry

Development of a high resolution nanolithography technique on non-planar surfaces using an evaporated electron beam resist

Electron beam lithography systems used for patterning of extremely small structures are a very important tool for nanofabrication technologies. The on going miniaturization of electronic and photonic device, leads to a constant shrinking and increasing pattern density. Fundamental physical effects such as shot noise, which in lithography corresponds to the statistical fluctuations in the number of electrons contained in a beam, have a major impact on the achievable feature sizes as well as their roughness. Many different parameters in the lithography process must be taken into account in determining these fundamental limits, including exposure dose of the resist, resist thickness, beam energy, etc. A shot noise model has been developed in order to calculate the minimum exposure doses required for patterning electron beam resists at technology nodes of 50 nm and below while maintaining reasonable quality of the patterns. The doses must increase rapidly with reducing linewidth, thus imposing constraints on a variety of next generation lithography systems, such as massively parallel electron beam (MPEB) systems. The model results are applied to the particular case of MPEB systems for the patterning of integrated circuits on semiconductor wafers. An overall set of results is obtained indicating the minimum number of electron beams and electron beam current that will be required to meet industry standards. High resolution electron beam lithography poses severe constraints on the resist used for patterning, namely the need to work with very thin layers in order to achieve the highest resolutions. A new and interesting conformal resist is studied in this work, the sterol based QSR-5(TM) resist. The results of optimizing the resist properties and the development process are presented along with results for optimizing the sensitivity and contrast of this resist. Preserving and developing versatility in the applications has been one of the most important criteria in optimizing the QSR-5(TM) resist. Demonstrations include patterning a zone plate on the tip of an optical fiber for potential application in integrated optics. A very unusual application of patterning both sides of a silicon and a silicon nitride membrane in a single step are described which might be useful for the fabrication of high speed field effect devices such as double gate transistors (DGT). The Monte-Carlo simulation results for the case of the achievable gate length with silicon and silicon nitride membranes are also discussed. The results of conformability and patterning on V-grooves are also presented. The processes of fabrication of the high resolution metamaterial structures are discussed along with the initial measurement results via ellipsometry