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Clean water is the necessity of every living being. Quality of water is linked to our cultural and economicexistence too. We human beings have however neglected this primary and the most essential resource ofours. While there have been a lot of studies on analyzing the water quality of various watersources inrelation to physical and chemical parameters, not much of importance is given to the biological parameters.The presentwork aims to analyze the variation in two of the most common biological parameters: Total Coliformand Thermotolerant (Fecal) Coliform in Himalayan and Upper Segment of Yamuna river.

3D printing and nanotechnology have been two of the most important tools in the development of personalized medical treatments. More recently, their alliance has developed in an effort to create new, flexible, multidisciplinary, and/or medical and drug-wise products. Therefore, a comprehensive review of scientific studies, including 3D printing and nanomaterials on the development of new pharmaceutical methods and medical applications for the treatment and prevention of diseases, is presented here with the help of secondary research from most recent articles. 3D printing, also known as additive manufacturing, has held the power of building a new class of active nanocomposites. With the ability to print a layer of complex 3D objects by layer, additional production of nanomaterials can be used in new ways to significantly control architectural structures of all sizes. The high efficiency of embedded nanomaterials can further extend the power of nanocomposites to structures such as gradients in thermal conductivity, converted photonic emissions, and increased energy and reduced weight. According to the survey done by annual industry, around 50% of the market of 3d printing in the industrial sectors is credited to created prototypes by means of photopolymers. While, Formlabs, Stratasys, HP, Desktop Metal, Ultimaker, Carbon, EOS, Nanoscribe and Markforged are among the top additive manufacturers. This work is hereby an effort to focus on different techniques, merits and demerits, applications, recent advances, relation with nanotechnology along with future aspects.

Nanophthalmos is characterised by shorter posterior and anterior segments of the eye, with a predisposition towards high hyperopia and primary angle-closure glaucoma. Variants in TMEM98 have been associated with autosomal dominant nanophthalmos in multiple kindreds, but definitive evidence for causation has been limited. Here we used CRISPR/Cas9 mutagenesis to recreate the human nanophthalmos-associated TMEM98 p.Ala193Pro (A193P) variant in mice. The A193P variant was associated with ocular phenotypes in both mice and humans, with dominant inheritance in humans and recessive inheritance in mice. Unlike their human counterparts, A193P homozygous mutant mice had normal axial length, normal intraocular pressure, and structurally normal scleral collagen. However, in both homozygous mice and heterozygous humans, the A193P variant was associated with discrete white spots throughout the retinal fundus, with corresponding retinal folds on histology. This direct comparison of a TMEM98 variant in mouse and human suggests that certain nanophthalmos-associated phenotypes are not only a consequence of a smaller eye, but that TMEM98 may itself play a primary role in retinal and scleral structure and integrity.

Objective An ambulance is a medically equipped vehicle which is used in case of any medical emergency for the transport of patients to treatment facilities. The ambulances help in the transportation of thousands of patients per year, and such patients may carry infectious microorganisms which pose a major threat to the treatment of such patients. In this study, we analyzed the extent of bacterial contamination in our ambulance vehicles and measured the degree of antimicrobial resistance among isolated pathogens. Material and Method This study included five ambulances of our tertiary care hospital and different random sites were swabbed in each vehicle. These were selected based on their well-known high frequency of contact by emergency personnel and patients. Swabs were inserted into sterile test tubes containing normal saline and immediately transferred to our microbiology laboratory to identify bacterial contaminants utilizing standard microbiological procedures. Result A total of 198 swab samples were collected from all the five ambulances, out of which 170 (85.8%) swabs were sterile and 28 (14.2%) swabs yielded potentially pathogenic bacterial isolates. The highest contamination rate with pathogenic bacteria was detected in the oxygen flow meter knob (60%), suction machine tubing (60%), and stethoscope (40%). Staphylococcus aureus (32%) was the most frequently detected microorganism. Conclusion Our study showed low prevalence of bacterial contamination in ambulances because of good infection control policy of our hospital, however, some areas still need improvement and require proper standard operating procedures of disinfection policies of these emergency vehicles.

Objective: Source of infection in a burn patient is from the patient’s flora, contaminated environmental surfaces and transmitted from health care workers. Insufficiently disinfected hospital environmental surface provides a niche for multidrug resistant bacteria. This study was carried out to assess the bacteriological profile of the pathogens from burn wounds and the surrounding environmental areas. Methods: During 6 months, wound swabs from burn patients were collected on admission (after 48 hours of admission), on day 5 and then weekly. Environmental samples were also collected from burn ward and studied for the bacteriological and anti-microgram profiles. Results: Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were the major bacterial isolates from the wound swabs and the environmental samples. ESBL was detected in 56.6% of our Enterobacteriaceae isolates. The environmental sites from which these bacterial isolates were found were nursing counter, sink, dressing trolley, medicine locker and patient’s bed. The percentage of MRSA decreased from 50 to 5% and there was an increased role of Enterococci species causing infections (13.63%). Conclusions: In this study, there appears that the colonizers of the environment may play a role in the causation of infection in burn patients. In burns ward, rigorous implementation of infection control program should be warranted, which includes and hygiene and use of personal protective equipment, environmental disinfection, cohort nursing care and antibiotics stewardship programme.

Introduction: The members of the tribe Proteeae, Morganella and Providencia are being increasingly recognized as important pathogens. The spectrum of disease caused by them is wide and in reported cases, the mortality is high. Previously both of these pathogens were considered to be rare pathogens as the potential to cause nosocomial transmission and infection was not much studied. But their phenomenal evolution and increase in multidrug-resistance (MDR) strains of these pathogens are posing a major threat toward public health throughout the world. Methods: This present study was carried out from July 2018 to December 2018 on all the pus and body fluid samples that were received in the Department of Microbiology. Samples were processed as per the standard Microbiological guidelines and also were analyzed for their antimicrobial susceptibility profile as per Clinical Laboratory Standards Institute. Results: Out of 8425 samples received, 2140 were culture positive, amongst which 19 samples (0.89%) were positive for Providencia species (9) and Morganella morganii(10). The male : female ratio of these 19 patients was 2.8 : 1 and maximum patients (13) belonged to 20-60 years. As far as risk factors are concerned, maximum patients were diabetics (7) followed by abnormal liver function tests (6), concomitant UTI (6), history of invasive procedure (5), prior exposure to antibiotics (5) and urinary catheterization (4). About 6 were polymicrobial infections. Antibiotic susceptibility patterns revealed that Providencia strains were sensitive to ampicillin- sulbactum (77.7%) and amikacin (77.7%), while all Morganella strains were 100% sensitive to tobramycin and piperacillintazobactam. Conclusion: This study heralds in need for more research in this area as infections caused by these two pathogens are on the rise. Moreover, resistance to antimicrobials is also an increasingly common problem thus delaying the treatment and prognosis of the disease.

Background: Coagulase negative Staphylococci (CoNS) are important. The common antibiotics used for the treatment of the infections caused by CoNS are penicillin, oxacillin, ciprofloxacin, clindamycin, erythromycin, gentamicin, and vancomycin. Linezolid is an oxazolidinone group of antibiotic with activity against Gram-positive bacteria. It is used for the treatment of serious infections caused by Gram-positive bacteria resistant to other antibiotics, including streptococci, vancomycin-resistant enterococci (VRE). Aim and Objective: This study emphasizes on the judicious use of newer antibiotics to contain the spread of resistance. Methods: We are discussing five cases of Linezolid resistant Staphylococcus Haemolyticus which were reported in our laboratory during one year from patients with device related infections and also review of literature is being presented for an update. Results: In our study, the isolates were resistant to other groups of antimicrobials but susceptible to glycopeptides. All the isolates were methicillin-resistant. Conclusion: Linezolid is approved as an alternative drug to be given for catheter-related bloodstream infections. In earlier studies, linezolid-resistant staphylococci have been reported increasingly all over the world. This study is to create awareness amongst clinicians that improper and excessive use of linezolid will make this antibiotic-resistant and thus will be of no help in future, so judicious and relevant use of antibiotics needs to be emphasized.

Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research.Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets.Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated.This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.

The present paper deals with the problem of estimating the product of two population means using the information of auxiliary character under double sampling the non-respondents. Two different cases are considered for suggesting the estimators to estimate the product of two population means. The bias and mean square errors are obtained up to the first order of approximation, and the conditions for obtaining the minimum mean square errors of suggested estimators are derived. Theoretical and empirical studies with real data sets published by the Government of India are carried out to demonstrate the efficiency of the proposed estimators over the relevant estimators used in practice.

Background: Serratia spp. is a common enteric bacterium generally thought not to be pathogenic in the gastrointestinal tract. Serratia marcescens is a member of the genus Serratia, which is a part of the family Enterobacteriales. Of all Serratia species, S. marcescens is the most common clinical isolate and the most important human pathogen. Objective: We discuss here four cases of Serratia marcescens which were reported in our laboratory at the Department of Microbiology Government Medical College and Hospital Chandigarh within six months of duration. Method: All the samples were processed and identified using standard microbiological techniques. The isolates of Serratia marcescens were identified, depending upon their biochemical and morphological characteristics, and further confirmed by MALDI-TOF-MS, PGIMER Chandigarh. Result: In one of the four cases, polymicrobial infection was observed, and among the cases, one patient was diabetic and the rest three patients were immunocompetent. The importance of detection of Serratia marcescens is related to the concern regarding its increased spread in hospital settings as nosocomial infection. Conclusion: We need to identify and isolate this pathogen not thinking of it only as a contaminant and opportunistic pathogen but as a pathogen which can lead to serious infections in hospital settings.

Rivers are the lifeline of every living being, be it humans or animals. Clean water is essential for everyone. However, increased urbanization and rapid industrialization have led to rising pollution level in rivers. COVID-19 on the contrary has changed the entire ecosystem. Limited industrial activities, reduced people movement during COVID times has led to improvement in environment, be it atmosphere or hydrosphere. Present work aims to study the impact of COVID-19 on water quality index of river Yamuna as it traverses from Himalayan segment to Upper segment. Five sites are chosen between a stretch of 60+ km, and samples are collected during monsoon and post-monsoon seasons. Physico-chemical parameters (pH, Turbidity, Sulphate, Phosphate, Fluoride, Chloride, Total Hardness, Calcium, Magnesium, Dissolved Oxygen, BOD, COD, Alkalinity), water quality index and Pearson correlation coefficient were calculated for all chosen sites. Since the study was initiated during COVID, initial results show the impact of reduced industrial and urban activities in improving the overall water quality.

Reverse Logistics (RL) has become an important factor for manufacturing industries to gain competitive edge, address environmental concerns and enhance supply chain sustainability. Due to lack of expertise, financial support and resources, manufacturers prefer outsourcing all activities related to the return flow of products to Third Party Reverse Logistics Providers (3PRLPs). However, in the current scenario, with regard to being truly sustainable, manufacturers are considering possibilities of collaboration with the 3PRLPs in order to reap benefits of better customer satisfaction, reduced environmental impact and generation of additional revenue. Thus, it becomes essential to analyze plausible Critical Success Factors (CSFs) which can aid in realizing sustainable collaboration with 3PRLPs. With this perspective, the present study seeks to recognize and examine CSFs related to the implementation of RL under sustainable collaboration with 3PRLPs. Further it attempts to develop an analytical structural model to study the contextual relationship among the identified CSFs and determine the most influential CSFs with the aid of fuzzy Interpretive Structural Modeling (ISM). The results obtained from fuzzy-ISM are further used as an input to fuzzy Matrix Impact of Cross-Multiplication Applied to Classification (MICMAC) analysis to classify the listed factors into four groups on the basis of their driving and dependence power. The uncertainty in the decision making environment is handled effectively using fuzzy set theory. The analytical model developed in the study yields a practical tool for the supply chain managers to centre focus primarily on the CSFs which exert the maximum dominance, to ensure effective implementation of RL under sustainable collaboration.

Growing environmental issues, social concerns, enforced regulations and intense competition have motivated electronic companies to inculcate Reverse Logistics (RL) practices in action for sustainable Reverse Supply Chain (RSC). Due to lack of expertise and the heavy costs associated with the setting up of reverse logistics system, RL practices are widely embraced by most companies through Third Party Reverse Logistics Providers (3PRLPs). Due to the dependency of companies on 3PRLPs, the evaluation and selection of 3PRLP is a matter of strategic concern and requires critical decision-making. The main challenge in this regard that the companies face is to identify the appropriate criteria for assessing the performance of 3PRLP under a sustainable environment. In this sense, the main intent of the current study is to provide a systematic framework for an electronics company to (i) identify the most relevant 3PRLP performance evaluation criteria under three sustainability dimensions namely, economic, environmental and social, (ii) extract the most influential list of sustainable criteria and (iii) determine the weights of importance of the influential criteria. In order to attain this objective, a decision-making model is proposed in which firstly, the economic, environmental and social criteria are derived from an extensive literature survey. Secondly, Delphi technique is used to shortlist the most influential criteria. Thirdly, the Best Worst Method (BWM) is used to determine the importance of the shortlisted criteria. The result analysis shows that environmental sustainability is the primary focus of the companies for the implementation of RL, contrary to the assumption that economic performance is always the major motivation. ‘Quality’, ‘RL Practices’ and ‘Health and Safety’ are accorded the highest ranking under economic, environmental and social dimensions, respectively. The proposed model can assist electronic companies in determining the most important criteria for sustainable 3PRLP selection for outsourcing RL activities.

Fuchs' endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet's membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet's membrane (CE-DM) specimens using the Illumina HumanHT-12 v4.0 expression array. RNA from pools of FECD-affected (n = 3 per pool) and individual unaffected (n = 3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤ 0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD.

Purpose Ultraviolet radiation from sunlight contributes to age-related cataract and skin cancer. The EPHA2 gene is implicated in both these diseases. The purpose of this study was to determine whether age-related cataract and skin cancer are associated in a cohort of older Australians. Methods A cross-sectional study was performed using the Historical Cohort of the Registry of Senior Australians. Individuals aged ≥65 years or aged ≥50 years and of Aboriginal or Torres Strait Islander descent, who had an aged care eligibility assessment between July 2005 and June 2015, and had a history of cataract surgery and/or skin cancer according to the Australian Government Medicare Benefits Schedule dataset, during the 3-year period prior, were evaluated (N = 599,316). A multivariable logistic regression model was used to determine association and multiple hypothesis correction was employed. Results Of the evaluated individuals, 87,097 (14.5%) had a history of cataract and 170,251 (28.4%) a history of skin cancer. Among those with a history of cataract, 20,497 (23.5%), 1127 (1.3%), and 14,730 (16.9%) individuals had a concurrent history of keratinocyte, melanoma, and premalignant/solar keratosis, respectively. Those with a history of cataract were 19% more likely to have a history of skin cancer (odds ratio [OR], 1.19; 95% confidence interval [CI], (1.17-1.21). Co-occurrence of keratinocyte skin cancer was 16% (OR, 1.16; 95% CI, 1.14-1.18), melanoma 21% (OR, 1.21; 95% CI, 1.13-1.29), and premalignant/solar keratosis 19% (OR, 1.19; 95% CI, 1.17-1.22) more in the presence than absence of history of cataract. Conclusions Age-related cataract is positively associated with skin cancer and its subtypes, including premalignant lesions in an older Australian population.

Increasing global demands for food have necessitated a comprehensive and informed approach to meet food and nutritional security. Agricultural policies framed a few decades back were aimed at the production and availability of surplus staple food crops. Green Revolution, as an outcome of the successful implementation of science, technology, strategy, and distribution, helped the world to feed the people. The rising monotony in agricultural staple food crops leads us to the trap of malnourishment and hidden pangs of hunger. Agricultural challenges and mitigation strategies need to be reframed for integrated and planned efforts spanning the complete agricultural cycle ranging from production to the distribution of agricultural products without neglecting effective waste management. Current scenario of increasing global populations, dwindling resources, and scarce reuse/recycle practices highlights the need to employ such frugal steps actively throughout the world. In addition to critical innovations in scientific methods and techniques, effective management of infrastructure, distribution of farm products, waste treatment, skill development of the workforce, and engaging collaborations between public and private sectors would help equip farmers and producers to meet the increasing food security challenges. Moreover, effective and dynamic policies need to be tailored and implemented, which would cater to a wide array of economic, geographical, and resource availability for different regions of the world. This chapter briefly explains the building blocks of agriculture and efficient integration among them in terms of global food and nutritional security.

A case of suspicious anterior chest wall mass due to Salmonella enterica serotype Typhi in a middle aged, non- diabetic male is being described. The infection was successfully treated with timely institution of antibiotic treatment. This case highlights the fact that a focal Salmonella infection involving the anterior chest wall should be considered as a differential diagnosis and not treated as tuberculosis empirically. Submission of specimens for microbiological analysis should be performed for an accurate diagnosis and management.

Purpose Age-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice. Methods Cataract development was monitored in Epha2+/+, Epha2+/-, and Epha2-/- mice (Epha2Gt(KST085)Byg) on C57BL/6J and FVB:C57BL/6J (50:50) backgrounds. Cellular architecture of lenses, endoplasmic reticulum (ER) stress, and redox state were determined using histological, molecular, and analytical techniques. Results Epha2-/- and Epha2+/- mice on C57BL/6J background developed severe cortical cataracts by 18 and 38 weeks of age, respectively, compared to development of similar cataract significantly later in Epha2-/- mice and no cataract in Epha2+/- mice in this strain on FVB background, which was previously reported. On FVB:C57BL/6J background, Epha2-/- mice developed severe cortical cataract by 38 weeks and Epha2+/- mice exhibited mild cortical cataract up to 64 weeks of age. Progression of cataract in Epha2-/- and Epha2+/- female mice on C57BL/6J and mixed background, respectively, was slower than in matched male mice. N-cadherin and β-catenin immunolabeling showed disorganized lens fiber cells and disruption of lens architecture in Epha2-/- and Epha2+/- lenses, coinciding with development of severe cataracts. EPHA2 immunolabeling showed intracellular accumulation of the mutant EPHA2-β-galactosidase fusion protein that induced a cytoprotective ER stress response and in Epha2+/- lenses was also accompanied by glutathione redox imbalance. Conclusions Both, Epha2-/- and Epha2+/- mice develop age-related cortical cataract; age as a function of Epha2 genotype, sex, and genetic background influence Epha2-related cataractogenesis in mice.

Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency 60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P, Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.

The members of the tribe Proteeae, Morganella and Providencia are being increasingly recognized as important pathogens. The spectrum of disease caused by them is wide and in reported cases, the mortality is high. Previously both of these pathogens were considered to be rare pathogens as the potential to cause nosocomial transmission and infection was not much studied. But their phenomenal evolution and increase in multidrug-resistance (MDR) strains of these pathogens are posing a major threat toward public health throughout the world.This present study was carried out from July 2018 to December 2018 on all the pus and body fluid samples that were received in the Department of Microbiology. Samples were processed as per the standard Microbiological guidelines and also were analyzed for their antimicrobial susceptibility profile as per Clinical Laboratory Standards Institute.Out of 8425 samples received, 2140 were culture positive, amongst which 19 samples (0.89%) were positive for Providencia species (9) and Morganella morganii(10). The male : female ratio of these 19 patients was 2.8 : 1 and maximum patients (13) belonged to 20-60 years. As far as risk factors are concerned, maximum patients were diabetics (7) followed by abnormal liver function tests (6), concomitant UTI (6), history of invasive procedure (5), prior exposure to antibiotics (5) and urinary catheterization (4). About 6 were polymicrobial infections. Antibiotic susceptibility patterns revealed that Providencia strains were sensitive to ampicillin- sulbactum (77.7%) and amikacin (77.7%), while all Morganella strains were 100% sensitive to tobramycin and piperacillintazobactam.This study heralds in need for more research in this area as infections caused by these two pathogens are on the rise. Moreover, resistance to antimicrobials is also an increasingly common problem thus delaying the treatment and prognosis of the disease.

Background: Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane. Methods: Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MSE ) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemical techniques. Results: Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis. Conclusions: This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.

Multiferroic BiFeO3 was synthesized by means of high-energy ball milling (HEBM) followed by thermal annealing at various temperatures and the effect of Gd3+ substitution (x=0.0–0.20) at Bi3+ site was investigated in this study. It is found that the Gd-substitution tends to decrease the impurity phases and the crystallization of single phase BiFeO3 is observed at x=0.1. Scanning electron micrograph of Bi1−xGdxFeO3 sintered sample indicated a decrease in particle size and change in shape with increasing x. For all the studied samples, the measured dielectric constant values tend to increase from 110 (x=0.0) to 250 (x=0.10). The dielectric loss is found to be more for the pure BiFeO3 as compared to the Bi1−xGdxFeO3. Ferroelectric loops show a maximum polarization of 1.63 μC/cm2 for the Bi0.9Gd0.1FeO3. Magnetization (M) versus magnetic field (H) hysteresis loops at 300 K BiFeO3 and Bi0.9Gd0.1FeO3 demonstrated non-saturated loops, suggesting the antiferromagnetic nature of the samples. The M–H behavior of the Bi1−xGdxFeO3 at 300 K shows the antiferromagnetic nature of the samples. The estimated magnetization value at 10 kOe for the Bi0.9Gd0.1FeO3 sample (0.23 emu/g) is found to be higher than that of the pure BiFeO3 (0.037 emu/g).

Background Genome-wide association studies (GWAS) have identified association of common alleles with primary open-angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease-associated genes contribute to POAG. Methods Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103 local screened nonglaucoma controls then joint-called with exomes of 993 previously sequenced Australian controls. GWAS-associated genes were assessed for enrichment of rare predicted pathogenic variants in POAG. Significantly enriched genes were compared against Exome Aggregation Consortium (ExAC) public control. Results Eighty-six GWAS disease or trait-associated glaucoma genes were captured and sequenced. CARD10 showed enrichment after Bonferroni correction for rare variants in glaucoma cases (OR = 13.2, P = 6.94 9 10�5) with mutations identified in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was significantly associated with optic disc parameters in previous GWAS. The whole GWAS gene set showed no enrichment in POAG overall (OR = 1.12,P = 0.51). Conclusion We report here an enrichment of rare predicted pathogenic coding variants within a GWAS-associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis.

Pseudoexfoliation (PEX) syndrome is a systemic disease involving the extracellular matrix. It increases the risk of glaucoma, an irreversible cause of blindness, and susceptibility to heart disease, stroke and hearing loss. Single nucleotide polymorphisms (SNPs) in the LOXL1 (Lysyl oxidase-like 1) gene are the major known genetic risk factor for PEX syndrome. Two coding SNPs, rs1048861 (G > T; Arg141Leu) and rs3825942 (G > A; Gly153Asp), in the LOXL1 gene are strongly associated with the disease risk in multiple populations worldwide. In the present study, we investigated functional effects of these SNPs on the LOXL1 protein. We show through molecular modelling that positions 141 and 153 are likely surface residues and hence possible recognition sites for protein-protein interactions; the Arg141Leu and Gly153Asp substitutions cause charge changes that would lead to local differences in protein electrostatic potential and in turn the potential to modify protein-protein interactions. In RFL-6 rat fetal lung fibroblast cells ectopically expressing the LOXL1 protein variants related to PEX (Arg141_Gly153, Arg141_Asp153 or Leu141_Gly153), immunoprecipitation of the secreted variants showed differences in their processing by endogenous proteins, possibly Bone morphogenetic protein-1 (BMP-1) that cleaves and leads to enzymatic activation of LOXL1. Immunofluorescence labelling of the ectopically expressed protein variants in RFL-6 cells showed no significant difference in their extracellular accumulation tendency. In conclusion, this is the first report of a biological effect of the coding SNPs in the LOXL1 gene associated with PEX syndrome, on the LOXL1 protein. The findings indicate that the disease associated coding variants themselves may be involved in the manifestation of PEX syndrome. Refereed/Peer-reviewed

BiFeO3 (BFO) thin films with uniform thickness of ~200 nm were prepared by the sol–gel assisted spin coating method. Different grain size distributions in the as-grown BFO films were then induced by varying the annealing temperature between 525 and 600 °C. It is found that the grain size distribution become wider as the annealing temperature increases. All the films showed a well-saturated magnetization (M) versus magnetic field (H) hysteresis loops at 300 K. A strong dependence of M on the grain size distribution is observed. An optimal grain size distribution with average grain size ~90 nm is responsible for high M in the BFO films. The non-saturated M–H loops obtained at 10 K suggest the spin glass behaviour of BFO films. The zero field cooled (ZFC) and field cooled (FC) magnetization curves shows split at 300 K and a cusp at ~50 K in the ZFC curve, which further confirms the spin glass state of polycrystalline BFO thin films.

The effect of thickness induced grain size distribution on the magnetic and ferroelectric behaviour of sol–gel driven BiFeO3 (BFO) thin films was investigated in this study. FESEM micrographs showed well-crystallized equiaxed grains with minimal porosity. The magnetization (M) versus magnetic field (H) indicated the well saturated hysteresis loops at 300 K. The saturation magnetization (M s) is found to decrease from 18.9 to 0.93 emu/cm3 on increasing the film thickness from 156 to 388 nm. The high M s value obtained in the BFO films due to the uncompensated spins originated at grain boundary tends to decrease with the film thickness. At low temperature (10 K), non-saturated M–H loops are observed due to spin freezing effect. The dielectric and ferroelectric properties improve with better growth and densification of grains in the BFO thin films with increasing thickness.

The nucleolus has emerged as a key regulator of cellular growth and the response to stress, in addition to its traditionally understood function in ribosome biogenesis. The association between nucleolar function and neurodegenerative disease is increasingly being explored. There is also recent evidence indicating that the nucleolus may well be crucial in the development of the eye. In this present review, the role of the nucleolus in retinal development as well as in neurodegeneration with an emphasis on the retina is discussed.

Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease. Epha2 knockout and UV-B radiation independently lead to cataract in mice, and UV-B radiation reportedly alters EPHA2 expression in cultured cells. We hypothesised that an interaction between UV-B radiation exposure and Epha2 signalling may influence cataract development. To test this hypothesis, 5-week-old Epha2+/+ and Epha2+/- mice (n = 8 per group) were exposed to repeated below-threshold doses of UV-B radiation (0.0125-0.05 J/cm2), before development of Epha2-mediated cataract. Cataract development was monitored after termination of exposure and at least one month later. Histological analysis of exposed and unexposed lenses was performed to assess pathological changes, and gene expression analysis to investigate the mechanism underlying cataract. Both Epha2+/+ and Epha2+/- mice developed UV-B dose-dependent anterior polar cataract; cataract severity in both genotypes of mice exposed to either 0.025 or 0.05 J/cm2 UV-B was significantly higher than that in matched unexposed mice (p

Pseudomonas monteilii (P. monteilii) is a gram negative, rod shaped, nonsporing, motile, non-fermenting bacterium belonging to family Pseudomonadaceae. It is a known environmental contaminant, has been seen as an emerging opportunistic pathogen and is closely related to Pseudomonas putida. We isolated this organism from a young immunocompetent patient with meningoencephalitis, who despite of treatment had a fatal outcome.

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - “response to fluid shear stress” and “abnormal retina morphology” - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

Recent genome-wide association studies reported strong association of genetic variation at the CDKN2B/CDKN2B-AS1 locus on 9p21 with normal-tension glaucoma (NTG) in multiple populations. The mechanism by which this locus causes disease remains to be elucidated. We investigated the association of DNA methylation of CpG islands at this locus with NTG.We conducted a retrospective case-control study of 178 NTG cases and 202 unaffected controls from Australia. CDKN2B and CDKN2B-AS1 promoter methylation was measured quantitatively using the MassCleave assay, and assessed for association with the disease, and the genotype of the associated risk variants using IBM SPSS statistics 22.0 CpG sites at which methylation status was associated with NTG were validated using pyrosequencing.We identified one CpG site (F1:13-14) in the CDKN2B promoter which showed significant association with NTG (p = 0.001). The association was highly significant in female cases (p = 0.006) but not in male cases (p = 0.054). The association was validated using an independent method confirming the likely association of DNA methylation with NTG in females (p = 0.015), but not in males (p = 0.497). In addition, methylation at CpG sites in CDKN2B was also associated with genotype at rs1063192, which is known to confer risk for NTG.This study reveals an association of methylation status in the CDKN2B promoter with NTG, particularly in females. This suggests that the observed genetic association with the disease at this locus could be in part due to epigenetic mechanisms, and is likely to be independent of the association of nonsynonymous coding variation within the gene.

Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

[Purpose] This study aimed to determine the effects of task-oriented training on upper extremity function and performance of daily activities in chronic stroke patients with impaired cognition. [Subjects and Methods] In this study, 2 chronic hemiplegic stroke patients underwent task-oriented training. The training was conducted once a day for 30 minutes, 5 times/week, for 2 weeks. The patients were evaluated 3 times before and after the task-oriented training. Changes in upper extremity function were assessed using the manual function test, and changes in the ability to carry out daily activities were assessed using the functional independence measure. [Results] The patients showed improvement in both the upper extremity function and ability to perform daily activities after task-oriented training. [Conclusion] Task-oriented training was proven effective in improving upper extremity function and ability to perform daily activities in chronic hemiplegic stroke patients with impaired cognition.

Background Cataract is a major cause of severe visual impairment in childhood. The purpose of this study was to determine the genetic cause of syndromic congenital cataract in an Australian mother and son. Method Fifty-one genes associated with congenital cataract were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal Genome Machine (PGM). Reads were aligned against the human genome (hg19) and variants were annotated. Variants were prioritised for validation by Sanger sequencing if they were novel, rare or previously reported to be associated with paediatric cataract and were predicted to be protein changing. Variants were assessed for segregation with the phenotype in the affected mother. Result A novel likely pathogenic variant was identified in the transactivation domain of the MAF gene (c.176C > G, p.(Pro59Arg)) in the proband and his affected mother., but was absent in 326 unrelated controls and absent from public variant databases. Conclusion The MAF variant is the likely cause of the congenital cataract, Asperger syndrome, seizures, hearing loss and facial characteristics in the proband, providinga diagnosis of Aymé-Gripp syndrome for the family. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0414-7) contains supplementary material, which is available to authorized users.

PURPOSE. Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) with Mendelian inheritance are caused by mutations in at least nine genes. Utilizing whole-exome sequencing, we examined the disease burden accounted for by these known Mendelian glaucoma genes in a cohort of individuals with advanced early-onset POAG. METHODS. The cases exhibited advanced POAG with young age of diagnosis. Cases and examined local controls were subjected to whole-exome sequencing. Nine hundred ninetythree previously sequenced exomes of Australian controls were called jointly with our dataset. Qualifying variants were selected based on predicted pathogenicity and rarity in public domain gene variant databases. Case-control mutational burdens were calculated for glaucoma-linked genes. RESULTS. Two hundred eighteen unrelated POAG participants and 103 nonglaucomatous controls were included in addition to 993 unexamined controls. Fifty-eight participants (26.6%) harbored rare potentially pathogenic variants in known glaucoma genes. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. After multiple testing correction, only MYOC showed statistically significant enrichment of qualifying variants (odds ratio [OR] = 16.62, P = 6.31310-16). CONCLUSIONS. Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases. MYOC variants represented the largest monogenic cause in POAG. The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes. © 2017 The Authors.

Congenital cataract is a rare but severe paediatric visual impediment, often caused by variants in one of several crystallin genes that produce the bulk of structural proteins in lens. Here we describe a pedigree with autosomal dominant isolated congenital cataract and linkage to the crystallin gene cluster on chromosome 22. No rare single nucleotide variants or short indels were identified by whole-exome sequencing, yet copy number variant analysis revealed a duplication spanning both CRYBB1 and CRYBA4. While the CRYBA4 duplication was complete, the CRYBB1 duplication was not, with the duplicated CRYBB1 product predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract.Grant informationSupported by the National Health and Medical Research CouncilConflict of interestthe authors declare no conflict of interest.

Purpose: Recent genome-wide association studies reported strong association of genetic variation at the CDKN2B/CDKN2B-AS1 locus on 9p21 with normal-tension glaucoma (NTG) in multiple populations. The mechanism by which this locus causes disease remains to be elucidated. We investigated the association of DNA methylation of CpG islands at this locus with NTG. Methods: We conducted a retrospective case–control study of 178 NTG cases and 202 unaffected controls from Australia. CDKN2B and CDKN2B-AS1 promoter methylation was measured quantitatively using the MassCleave assay, and assessed for association with the disease, and the genotype of the associated risk variants using IBM SPSS statistics 22.0 CpG sites at which methylation status was associated with NTG were validated using pyrosequencing. Results: We identified one CpG site (F1:13–14) in the CDKN2B promoter which showed significant association with NTG (p = 0.001). The association was highly significant in female cases (p = 0.006) but not in male cases (p = 0.054). The association was validated using an independent method confirming the likely association of DNA methylation with NTG in females (p = 0.015), but not in males (p = 0.497). In addition, methylation at CpG sites in CDKN2B was also associated with genotype at rs1063192, which is known to confer risk for NTG. Conclusion: This study reveals an association of methylation status in the CDKN2B promoter with NTG, particularly in females. This suggests that the observed genetic association with the disease at this locus could be in part due to epigenetic mechanisms, and is likely to be independent of the association of nonsynonymous coding variation within the gene.

List of reported paediatric cataract genes selected for sequencing in this study. (DOCX 39Â kb)

Fuchs' endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10-22; OR = 15.66 (95% CI: 7.79-31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

Purpose: Cataract is the major cause of vision-related disability worldwide. Mutations in the crystallin genes are the most common known cause of inherited congenital cataract. Mutations in the genes associated with intercellular contacts, such as Nance-Horan Syndrome (NHS) and Ephrin type A receptor-2 (EPHA2), are other recognized causes of congenital cataract. The EPHA2 gene has been also associated with age-related cataract, suggesting that intercellular junctions are important in not only lens development, but also in maintaining lens transparency. The purpose of this study was to analyze the expression and localization of the key cell junction and cytoskeletal proteins, and of NHS and EPHA2, in established lens epithelial cell lines to determine their suitability as model epithelial systems for the functional investigation of genes involved in intercellular contacts and implicated in cataract. Methods: The expression and subcellular localization of occludin and zona occludens protein-1 (ZO-1), which are associated with tight junctions; E-cadherin, which is associated with adherence junctions; and the cytoskeletal actin were analyzed in monolayers of a human lens epithelial cell line (SRA 01/04) and a mouse lens epithelial cell line (αTN4). In addition, the expression and subcellular localization of the NHS and EPHA2 proteins were analyzed in these cell lines. Protein or mRNA expression was respectively determined by western blotting or reverse transcription-polymerase chain reaction (RT–PCR), and localization was determined by immunofluorescence labeling. Results: Human SRA 01/04 and mouse αTN4 lens epithelial cells expressed either the proteins of interest or their encoding mRNA. Occludin, ZO-1, and NHS proteins localized to the cellular periphery, whereas E-cadherin, actin, and EPHA2 localized in the cytoplasm in these cell lines. Conclusions: The human SRA 01/04 and mouse αTN4 lens epithelial cells express the key junctional proteins. The localization patterns of these proteins suggest that these cell lines form tight junctions but do not form E-cadherin-based adherence junctions. These data further indicate that the regulatory role of NHS in actin remodeling, suggested in another study, is cell type dependent. In conclusion, the SRA 01/04 and αTN4 lens epithelial cell lines model some characteristics of an epithelium., This work was funded by the National Health and Medical Research Council (NHMRC) of Australia project grant GNT1009955, and Channel 7 Children’s Research Foundation, South Australia. JEC is a recipient of an Australian NHMRC Practitioner Fellowship.

Introduction: Helicobacter pylori (H.pylori) infection is very common worldwide. A reliable diagnosis is crucial for better treatment of the patients. However, there is no single diagnostic method that can meet the criteria in identification of H.pylori. Aim: To detect H.pylori from endoscopic biopsies in dyspeptic patients and to compare the sensitivity and specificity of different diagnostic methods for H. pylori infection. Materials and Methods: This observational and crosssectional study was conducted in the Department of Microbiology and Medicine, Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, over a period of 12 months. Biopsies of gastric antrum from 100 patients with dyspepsia were studied for the detection of H.pylori by various methods like bacterial culture, Rapid Urease Test (RUT) and Christensen‘s Tube Urease (CTU) test. Stool samples from all the patients were also screened for H.pylori stool antigen (HpSA) test. Bacterial culture was considered as gold standard in this study and other diagnostic tests were compared with the gold standard. Results: Out of 100 patients H.pylori was detected by bacterial culture, RUT, CTU and HpSA in 34%, 61%, 53% and 28% cases respectively. Sensitivity of RUT, CTU and HpSA were 100%, 91% and 73.5% respectively and specificity of RUT, CTU and HpSA were 59%, 66.7% and 95.3% respectively. Thus, RUT was the most sensitive (100%) and HpSA (95.3%) was the most specific test, when culture was being considered as gold standard. Conclusion: RUT is best considered as a screening test and not as the gold standard for H. pylori. The HpSA test is also rapid, simple and non-invasive test with acceptable results that can be used for monitoring.

Significance of education in the development process has been well recognized by the educational planners, economists and development planners the world over. Based on empirical evidences of connection between education and socio-economic development, this paper posits that education is instrumental in the socio-economic development. Specifically, this paper examines the impact of educational progress on fertility rate, population growth rate, child/infant mortality rate, life expectancy, gender disparity, poverty of the state. The analysis is based on information of the entire state on various variables such as literacy rate, enrolment, per capita income, fertility rate, population growth rate, incidence of poverty, etc. gathered from the secondary sources from 1966 onward. To sort out the strength and direction of relationships between education and various components of social developments, data have been analyzed by employing simple regression models. The findings show that female education at all levels has been found to be highly significant in lowering infant mortality. Male and female life expectancy at birth and at specific ages have been found to be positively related with enrolment at different educational levels.In line with the research conducted in different parts of the world, this study also confirms that increased female education at all the stages (i.e. primary, elementary, secondary and for all education levels put together) consistently lowers fertility rates. Our regression results show positive relationship between the progress of education at different stages and the gender disparity in infant mortality. Further, The poverty reduction effect of education has been confirmed from the inverse relationship of the educational progress at different stages of schooling with the incidence of deprivation (poverty).

Background Genome‐wide association studies (GWAS) have identified association of common alleles with primary open‐angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease‐associated genes contribute to POAG. Methods Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103 local screened nonglaucoma controls then joint‐called with exomes of 993 previously sequenced Australian controls. GWAS‐associated genes were assessed for enrichment of rare predicted pathogenic variants in POAG. Significantly enriched genes were compared against Exome Aggregation Consortium (ExAC) public control. Results Eighty‐six GWAS disease or trait‐associated glaucoma genes were captured and sequenced. CARD10 showed enrichment after Bonferroni correction for rare variants in glaucoma cases (OR = 13.2, P = 6.94 × 10−5) with mutations identified in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was significantly associated with optic disc parameters in previous GWAS. The whole GWAS gene set showed no enrichment in POAG overall (OR = 1.12, P = 0.51). Conclusion We report here an enrichment of rare predicted pathogenic coding variants within a GWAS‐associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis.

Background Cataract is a major cause of childhood blindness worldwide. The purpose of this study was to determine the genetic cause of paediatric cataract in a South Australian family with a bilateral lamellar paediatric cataract displaying variable phenotypes. Case presentation Fifty-one genes implicated in congenital cataract in human or mouse were sequenced in an affected individual from an Australian (Caucasian) family using a custom Ampliseq library on the Ion Torrent Personal Genome Machine. Reads were mapped against the human genome (hg19) and variants called with the Torrent Suite software. Variants were annotated to dbSNP 137 using Ion Reporter (IR 1.6.2) and were prioritised for validation if they were novel or rare and were predicted to be protein changing. We identified a previously reported oligomerization disrupting mutation, c.62G > A (p.R21Q), in the Crystallin alpha A (CRYAA) gene segregating in this three generation family. No other novel or rare coding mutations were detected in the known cataract genes sequenced. Microsatellite markers were used to compare the haplotypes between the family reported here and a previously published family with the same segregating mutation. Haplotype analysis indicated a potential common ancestry between the two South Australian families with this mutation. The work strengthens the genotype-phenotype correlations between this functional mutation in the crystallin alpha A (CRYAA) gene and paediatric cataract. Conclusion The p.R21Q mutation is the most likely cause of paediatric cataract in this family. The recurrence of this mutation in paediatric cataract families is likely due to a familial relationship. Electronic supplementary material The online version of this article (doi:10.1186/s13104-016-1890-0) contains supplementary material, which is available to authorized users.

Additional file 1: A table that lists reported pediatric cataract genes selected for sequencing in this study.

Introduction: Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. Aim: To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. Materials and Methods: A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. Results: A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. Conclusion: A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty.

Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large data sets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls, respectively, is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time. This method has profound implications for translation of modern genetic approaches to a multitude of diseases and traits yet to be analyzed by GWAS, and will enable developing nations to participate in GWAS.

Pseudoexfoliation (PEX) syndrome is the commonest cause of secondary glaucoma. Many extracellular matrix proteins and elastic fibre structure components are present in the pathological PEX deposits in the anterior segment of the eye including the anterior lens capsule. Common coding variants in the lysyl oxidase-like 1 (LOXL1) gene, involved in cross-linking elastin, have been reported to be strongly associated with PEX syndrome in various human populations. The mechanism by which the LOXL1 protein contributes to the formation of PEX material is unknown. A comprehensive map of the component proteins of PEX deposits can aid the understanding of disease pathogenesis. The purpose of this study was to identify additional protein constituents of pathological PEX deposits. We employed a novel proteomics approach by performing mass spectrometry on "isolated" PEX material surgically removed from the anterior lens capsule of affected eyes. This approach led to the identification of LOXL1 protein and Apolipoprotein E (ApoE) in PEX material. Previously identified protein constituents, latent-transforming growth factor beta-binding protein-2, complement 3 and clusterin were also detected. Immunohistochemical analysis of lens capsules from affected eyes confirmed the presence of both LOXL1 and ApoE in pathological PEX deposits. ApoE is a novel component of these deposits. This is the first report where a direct analytical approach has led to the identification of LOXL1 in PEX deposits and is consistent with its detection in these deposits by immunolabelling in another recent report. LOXL1 is both genetically associated with PEX syndrome and present in pathological PEX deposits. Hence it clearly has an important and direct role in pathophysiology of the disease. In conclusion, additional as yet unknown components are present in pathological PEX deposits and mass spectrometry of "isolated" PEX material is an effective strategy for their identification.