Glaucoma-associated long-term mortality in a rural cohort from India: the Andhra Pradesh Eye Disease Study.

AIM: To evaluate glaucoma-associated mortality in a rural cohort in India. METHODS: The study cohort comprised individuals aged 40 years and above who took part in the Andhra Pradesh Eye Disease Study (APEDS1) during 1996-2000. All participants underwent detailed comprehensive eye examination. Glaucoma was defined using International Society of Geographic and Epidemiologic Ophthalmology criteria. This cohort was followed up after a decade (June 2009 to January 2010; APEDS2). Mortality HR analysis for ocular risk factors was performed using Cox proportional hazards regression after adjusting for sociodemographic, lifestyle and clinical variables. RESULTS: In APEDS1, 2790 individuals aged more than or equal to 40 years were examined. 47.4% were male. Forty-five participants had primary open angle glaucoma (POAG) and 66 had primary angle closure disease (PACD). Ten years later, 1879 (67.3%) were available, 739 (26.5%) had died and 172 (6.2%) had migrated; whereas 22 of the 45 (48.8%) with POAG and 22 of the 66 (33.3%) with PACD had died. In univariate analysis, a higher mortality was associated with POAG (HR 1.9; 95% CI 1.23 to 2.94), pseudoexfoliation (HR 2.79; 95% CI 2.0 to 3.89), myopia (HR 1.78; 95% CI 1.54 to 2.06) and unit increase in cup:disc ratio (HR 4.49; 95% CI 2.64 to 7.64). In multivariable analysis, only cup:disc ratio remained independently associated with mortality (HR 2.5; 95% CI 1.3 to 5.1). The association remained significant when other ocular parameters were included in the model (HR 2.1; 95% CI 1.03 to 4.2). CONCLUSIONS: This is the first longitudinal study to assess the association of glaucoma and mortality in a rural longitudinal cohort in India. Increased cup:disc ratio could be a potential marker for ageing and would need further validation

Fifteen-year incidence rate and risk factors of pterygium in the Southern Indian state of Andhra Pradesh.

PURPOSE: To report 15-year incidence rate and associated risk factors of pterygium among people aged 30 years and above at baseline in the rural clusters of longitudinal Andhra Pradesh Eye Disease Study (APEDS III). METHODS: The baseline APEDS I included 7771 participants of which 6447 (83%) were traced and 5395 (83.7%) were re-examined in APEDS III. To estimate the incidence of pterygium, we selected participants who were 30 years and above at baseline (4188), of which 2976 were traced and 2627 (88.3%) were examined, and based on inclusion criteria, 2290 participants were included in the study. The incidence rate of pterygium was defined as the proportion of people free of pterygium at baseline who had developed the condition at 15-year follow-up (range 13-17 years). Univariate and multivariable analyses for risk factors were undertaken. RESULTS: The sex-adjusted incidence rate of pterygium was 25.2 per 100 person-years (95% CI 24.8 to 25.7) which was significantly higher for men than women (26.3 per 100 person-years (95% CI 25.6 to 27.0) and 24.7 (95% CI 24.1 to 25.3) respectively). At the multivariable analysis, male gender (RR: 1.35, 95% CI 1.0 to 1.83), no formal education (RR: 2.46, 95% CI 1.22 to 4.93), outdoor occupation (RR: 1.47, 95% CI 1.14 to 1.9) and lower body mass index (BMI) (<18.5) (RR: 1.25, 95% CI 1.02 to 1.55) were associated with increased risk of pterygium. CONCLUSIONS: The overall incidence rate of pterygium was high in this rural population, especially in men and those engaged in outdoor activities, lack of formal education and with lower BMI. It is likely that greater exposure to ultraviolet light is a major contributing factor, thus warranting preventive strategies

Cataract, visual impairment and long-term mortality in a rural cohort in India: the Andhra Pradesh Eye Disease Study.

BACKGROUND: A large-scale prevalence survey of blindness and visual impairment (The Andhra Pradesh Eye Diseases Study [APEDS1]) was conducted between 1996-2000 on 10,293 individuals of all ages in three rural and one urban clusters in Andhra Pradesh, Southern India. More than a decade later (June 2009-March 2010), APEDS1 participants in rural clusters were traced (termed APEDS2) to determine ocular risk factors for mortality in this longitudinal cohort. METHODS AND FINDINGS: Mortality hazard ratio (HR) analysis was performed for those aged >30 years at APEDS1, using Cox proportional hazard regression models to identify associations between ocular exposures and risk of mortality. Blindness and visual impairment (VI) were defined using Indian definitions. 799/4,188 (19.1%) participants had died and 308 (7.3%) had migrated. Mortality was higher in males than females (p<0.001). In multivariable analysis, after adjusting for age, gender, diabetes, hypertension, body mass index, smoking and education status the mortality HR was 1.9 (95% CI: 1.5-2.5) for blindness; 1.4 (95% CI: 1.2-1.7) for VI; 1.8 (95% CI: 1.4-2.3) for pure nuclear cataract, 1.5 (95% CI: 1.1-2.1) for pure cortical cataract; 1.96 (95% CI: 1.6-2.4) for mixed cataract, 2.0 (95% CI: 1.4-2.9) for history of cataract surgery, and 1.58 (95% CI: 1.3-1.9) for any cataract. When all these factors were included in the model, the HRs were attenuated, being 1.5 (95% CI: 1.1-2.0) for blindness and 1.2 (95% CI: 0.9-1.5) for VI. For lens type, the HRs were as follows: pure nuclear cataract, 1.6 (95% CI: 1.3-2.1); pure cortical cataract, 1.5 (95% CI: 1.1-2.1); mixed cataract, 1.8 (95% CI: 1.4-2.2), and history of previous cataract surgery, 1.8 (95% CI: 1.3-2.6). CONCLUSIONS: All types of cataract, history of cataract surgery and VI had an increased risk of mortality that further suggests that these could be potential markers of ageing

Impact of age-related macular degeneration on diabetic retinopathy: An electronic health record based big data analysis from a tertiary eye centre in South India.

PURPOSE: To determine whether the presence of age-related macular degeneration (AMD) decreases the risk of diabetic retinopathy. METHODS: This was a retrospective, case-cohort study performed in patients with a systemic diagnosis of diabetes at a tertiary health care center from May 2011 to April 2020. A total of 43,153 patients (1,024 AMD patients and 42,129 non-AMD patients) were included in the analysis. A total of 1,024 age and diabetes mellitus (DM) duration-matched controls were chosen from the non-AMD group for risk factor analysis. The severity of diabetic retinopathy was compared between the patients with AMD and the patients without AMD. RESULTS: Out of the enrolled 43,153 diabetic patients, 26,906 were males and 16,247 were females. A total of 1,024 patients had AMD and 42,129 had no AMD. The mean age of the cohort was 58.60 ± 0.09 years. The overall prevalence of DR was noted to be 22.8% (9,825 out of 43,153 eyes). A significantly lower prevalence of diabetic retinopathy (DR) (23% in non-AMD, 11.4% in AMD, OR = -0.43, P < 0.001), non-proliferative diabetic retinopathy (NPDR) (12% in non-AMD, 8.2% in AMD, OR = -0.66, P < 0.001), and proliferative diabetic retinopathy (PDR) (11% in non-AMD, 3.2% in AMD, OR = -0.27, P < 0.001) was seen in the AMD patients. No significant difference was seen between the dry and wet AMD. On multivariate logistic regression analysis, the lower age, absence of AMD, and male gender were associated with a higher risk of PDR. CONCLUSION: The presence of AMD was noted to statistically reduce the risk of DR. Our results may be useful in the field of resource allocation and awareness of DR

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence

Ultrasonic intensification as a tool for enhanced microbial biofuel yields

peer-reviewedUltrasonication has recently received attention as a novel bioprocessing tool for process intensification in many areas of downstream processing. Ultrasonic intensification (periodic ultrasonic treatment during the fermentation process) can result in a more effective homogenization of biomass and faster energy and mass transfer to biomass over short time periods which can result in enhanced microbial growth. Ultrasonic intensification can allow the rapid selective extraction of specific biomass components and can enhance product yields which can be of economic benefit. This review focuses on the role of ultrasonication in the extraction and yield enhancement of compounds from various microbial sources, specifically algal and cyanobacterial biomass with a focus on the production of biofuels. The operating principles associated with the process of ultrasonication and the influence of various operating conditions including ultrasonic frequency, power intensity, ultrasonic duration, reactor designs and kinetics applied for ultrasonic intensification are also described

Strong Association of 677 C>T Substitution in the MTHFR Gene with Male Infertility - A Study on an Indian Population and a Meta-Analysis

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies.We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility.677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor

Incidence, Incident Causes, and Risk Factors of Visual Impairment and Blindness in a Rural Population in India: 15-Year Follow-up of the Andhra Pradesh Eye Disease Study.

PURPOSE: To report 15-year incidence rate of visual loss (blindness and visual impairment [VI]), causes, and risk factors for participants in Andhra Pradesh Eye Disease Study III (APEDS III). DESIGN: Population-based cohort study. METHODS: From 2012 to 2016, all rural participants were interviewed and underwent a comprehensive eye examination, including dilated fundus examination and imaging. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using a standard logarithm of Minimum Angle of Resolution chart at 3 meters. World Health Organization (WHO) and United States of America (USA) categories of VI and blindness were used. Incident visual loss was defined as the development of or worsening of visual loss of one or more categories. RESULTS: In APEDS I, 7,771 rural participants were examined using stratified, random-cluster systematic sampling; in APEDS III, 5,395 participants (69.4% of rural or 52.4% of total participants) were re-examined. Using WHO categories, the crude incidence rate of any visual loss based on PVA and BCVA were 14.6 (95% confidence interval [CI]:13.6-15.7) and 6.3 (95% CI: 6.1-6.4) per 100 person-years, respectively. Using USA criteria, the values were 22.6 (95% CI: 22.3-23.0) and 10.6 (95% CI: 10.3-10.8) per 100 person-years, respectively. More than 90% of visual loss was attributable to cataract and uncorrected refractive error. Using WHO categories, significant independent risk factors for the incident visual loss were increasing age, female gender, illiteracy, past or current smoker, and current use of alcohol. Using the USA definition, an additional risk factor was lower level of education. CONCLUSIONS: The high incidence likely reflects poor access to eye care in this population, which needs to be taken into account when planning eye care programs

Fifteen-Year Incidence Rate of Primary Angle Closure Disease in the Andhra Pradesh Eye Disease Study.

PURPOSE: To report on the 15-year incidence of primary angle closure disease (PACD) among participants aged ≥40 years in rural southern India DESIGN: Population-based longitudinal incidence rate study METHODS: Setting: 3 rural study centres. STUDY POPULATION: Phakic participants aged ≥40 years who participated in both examination time points. OBSERVATION PROCEDURES: All participants at the baseline and at the mean 15-year follow-up visit underwent a detailed interview, anthropometry, blood pressure measurement, and comprehensive eye examination. Automated perimetry was attempted based on predefined criteria. Main outcome measures included development of any form of PACD, as defined by the International Society for Geographical and Epidemiological Ophthalmology (ISGEO), during the follow-up period in phakic participants, who did not have the disease at baseline. RESULTS: We analyzed data obtained from 1,197 (81.4% out of available 1,470) participants to calculate the incidence of the disease. The mean age (standard deviation) of the study participants at the baseline was 50.2 (8.1) years, with 670 male (45.5%) and 800 female (54.4%) participants. The incidence rate per 100 person-years (95% confidence interval) for primary angle closure suspect, primary angle closure, and primary angle closure glaucoma was 8.8 (8.4, 9.2), 6.2 (5.9, 6.6), and 1.6 (1.4, 1.8), respectively. Thus, the incidence of all forms of PACD was 16.4 (15.9, 17) per 100 person-years. On logistic regression analysis, female gender was a significant risk factor whereas presence of myopia was protective. CONCLUSIONS: This study reports long-term incidence of PACD from rural India. It has implications for eye health care policies, strategies, and planning

An investigation into aripiprazole's partial D(2) agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. Objectives: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole’s prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole’s unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. Method: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. Results: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d’) and speeded reaction times. In contrast to aripiprazole’s neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d’ and additionally had reduced errors of commission compared with placebo. Conclusion: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone’s serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade