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Background: Vitamin B12 deficiency is widely prevalent in all age groups which is of major concern. However, there is no valid Food Frequency Questionnaire (FFQ) for dietary vitamin B12 estimation. Hence, we aimed to develop and validate an FFQ for the estimation of dietary intake of Vitamin B12. Materials and Methods: Commonly consumed B12-rich food items were selected from literature and filtered using a market survey. For concordant and discriminant validation, B12 and homocysteine levels were estimated. To establish convergent validity, the Cobalamin Intake in North Indians by Food Frequency Questionnaire (COIN-FFQ) and 72-hour dietary recall (72HrDR) were both administered to the same subjects. The COIN-FFQ was readministered after initial administration for test–retest reliability. Internal consistency of the FFQ was then tested using Cronbach’s alpha. Results: We enrolled 115 adults with a mean age and weight of 31.9 ± 8.7 years and 66.0 ± 11.8 kg, respectively. In total, 19.1% were vegetarian. The dietary B12 using COIN-FFQ (n = 60; mean = 4.3 ± 1.8 µg/d) was significantly correlated (r = 0.255; P = 0.049) with serum levels (mean = 120.1 ± 62.6 pmol/L) establishing concordant validity. A significant difference was noted between the dietary, serum B12, and homocysteine levels of vegetarians versus nonvegetarians establishing discriminant validity (mean diff 1.4 (0.5–2.4), P = 0.004; Z-statistic −2.182, P value 0.029, and Z-statistic −2.438; P value 0.015), respectively. FFQ was strongly correlated with 72HrDR and test–retest FFQ (n = 27; r = 0.814, P < 0.001 and r = 0.869, P < 0.001, respectively) establishing convergent validity and test–retest reliability. The internal consistency with Cronbach’s alpha was in the acceptable range, 0.631 (n = 115). Conclusion: The newly developed COIN-FFQ is valid and reliable in estimating dietary B12 intake.

Background Research has shown that cultural activities may bring about improved health. However, large-scale quantitative analyses on cultural engagement and biomarkers are lacking to date. As a result, the mechanisms through which cultural activities may be associated with health are unclear.Aim Test quantitative associations between cultural engagement pattern (including active and passive engagement in arts, sports, and heritage activities) and indicators of biological dysregulation in a large dataset.Subjects and methods Understanding Society data were used to conduct cross-sectional linear regression analyses between a data-driven latent class model of cultural engagement and indicators of anthropometric, cardiovascular, metabolic, immune, and neuroendocrine function. Analyses were adjusted for age, gender, ethnicity, childcare responsibility, urbanicity, leisure time satisfaction, capacity-related factors, socioeconomic position, social and economic capital indicators, physical activity, and medication use.Results More culturally participants had better indicators of biological health, such as lower waist circumference and fibrinogen blood concentration. Specific associations between cultural engagement pattern and the different biological outcomes were also observed. The associations were explained in part by correlated factors (accounting for around half of the association).Conclusions Cultural engagement is cross-sectionally associated with biomarkers, although the characteristics of people who engage with culture are an important consideration when interpreting these findings.

Abstract The present research aims to predict effluent soluble chemical oxygen demand (SCOD) in anaerobic digestion (AD) process using machine-learning based approach. Anaerobic digestion is a highly sensitive process and depends upon several environmental and operational factors, such as temperature, flow, and load. Therefore, predicting output characteristics using modeling is important not only for process monitoring and control, but also to reduce the operating cost of the treatment plant. It is difficult to predict COD in a real time mode, so it is better to use Complex Mathematical Modeling (CMM) for simulating AD process and forecasting output parameters. Therefore, different Machine Learning algorithms, such as Linear Regression, Decision Tree, Random Forest and Artificial Neural Networks, have been used for predicting effluent SCOD using data acquired from in situ anaerobic wastewater treatment system. The result of the predicted data using different algorithms were compared with experimental data of anaerobic system. It was observed that the Artificial Neural Networks is the most effective simulation technique that correlated with the experimental data with the mean absolute percentage error of 10.63 and R2 score of 0.96. This research proposes an efficient and reliable integrated modeling method for early prediction of the water quality in wastewater treatment.

The present investigation was carried out in Himachal Pradesh, India. Nine different species of ladybird beetles were found feeding on the green apple aphid Aphis pomi De Geer in an apple orchard and apple nursery plants in Himachal Pradesh. These species belong to the order Coleoptera and family Coccinellidae. Coelophora saucia (Mulsant) is a formidable predator of Aphis pomi De Geer in Himachal Pradesh, India. This study investigated the life cycle of Coelophora saucia (a mussel). Both the larval and adult stages of this predator vigorously consumed green apple aphids. Therefore, studying the biology and feeding capacity of Coelophora saucia (a mussel) on green apple aphids from the perspective of biological control in apple-growing regions of Himachal Pradesh is useful.

The foetal vasculature gives nourishment to the developing lens and retina during embryonic development and then regresses after the formation of the retinal vessels. The failure of the foetal ocular vasculature to go through the usually planned involution results in persistent foetal vasculature (PFV), which causes blindness or severe vision loss. In this case, we are reporting a 6-week-old baby with unilateral PFV, which was not evident on ultrasound and was diagnosed incidentally during surgery. The dense, vascularized membrane typically seen behind the lens in these patients may seriously compromise cataract surgery, causing intraoperative bleeding that is sometimes severe enough to force the surgeon to abandon the surgery. The creation of new treatment approaches has been made possible by the recent improvements in micro-invasive surgical methods, which made the early treatment of PFV safer and more successful.

Abstract Background Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-β-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. Methods In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer’s disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer’s Project (N = 54,162), respectively. Both strong (P

Abstract Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card (‘nurse collection’) or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card (‘self-collection’). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk.

Abstract Background While medical studies generally provide health feedback to participants, in observational studies this is not always the case due to logistical and financial difficulties, or concerns about changing observed behaviours. However, evidence suggests that lack of feedback may deter participants from providing biological samples. This paper investigates the effect of offering feedback of blood results on participation in biomeasure sample collection. Methods Participants aged 16 and over from a longitudinal study – the Understanding Society Innovation Panel—were randomised to three arms – nurse interviewer, interviewer, web survey – and invited to participate in biomeasures data collection. Within each arm they were randomised to receive feedback of their blood results or not. For those interviewed by a nurse both venous and dried blood samples (DBS) were taken in the interview. For the other two arms, they were asked if they would be willing to take a sample, and if they agreed a DBS kit was left or sent to them so the participant could take their own sample and return it. Blood samples were analysed and, if in the feedback arms, participants were sent their total cholesterol and HbA1c results. Response rates for feedback and non-feedback groups were compared: overall; in each arm of the study; by socio-demographic and health characteristics; and by previous study participation. Logistic regression models of providing a blood sample by feedback group and data collection approach controlling for confounders were calculated. Results Overall 2162 (80.3% of individuals in responding households) took part in the survey; of those 1053 (48.7%) consented to provide a blood sample. Being offered feedback had little effect on overall participation but did increase consent to provide a blood sample (unadjusted OR 1.38; CI: 1.16–1.64). Controlling for participant characteristics, the effect of feedback was highest among web participants (1.55; 1.11–2.17), followed by interview participants (1.35; 0.99 –1.84) and then nurse interview participants (1.30; 0.89–1.92). Conclusions Offering feedback of blood results increased willingness to give samples, especially for those taking part in a web survey.

Although a significant body of research has shown that married people are healthier and live longer, empirical research on sex differences in the link between marital status and health suggests results are mixed. Moreover, the sex disparities in marital status and health relationships vary across adulthood. The literature on partnership status and measures of ageing is largely focused on older age groups and is limited in its view of early adulthood. Data from waves 2 and 3 (2010–2012) of Understanding Society: UKHLS were used to examine the association of current partnership status with epigenetic age acceleration (AA) assessed with DNA methylation (DNAm) algorithms 'Phenoage' and ' DunedinPACE ' in 3492 participants (aged 16–97). Regression models were estimated separately for men and women, and further stratified by age groups.Divorced/separated and widowed people showed positive age acceleration compared to the married/cohabiting people (reference group). Some sex differences were apparent, especially, among the single and divorced/separated groups. Age differences were also apparent, for example in men, being single was negatively associated with DNAmAA in the youngest group, but positively in the oldest group compared to partnered counterparts.These findings illustrate the importance of partnerships on the ageing process, in particular marital change through divorce and widowhood for positive age acceleration in adults. For single groups, observations were heterogenous by age and sex.

Background: Classically subclavian vein catheterization is done in neutral arm position; recently, it has been done in different arm positions to compare success rate and catheter misplacement. There is a paucity of literature for comparing abducted and neutral arm position for right infraclavicular subclavian vein cannulation. Aim: Comparison of success rate of abducted and neutral arm position for right infraclavicular subclavian vein cannulation under real-time ultrasound guidance in patients undergoing elective neurosurgery under general anesthesia. Design: Randomized comparative study. Materials and Methods: After approval from Institutional Review Board and Ethical Committee, 100 patients of 18–70 years of age, of either sex, posted for elective neurosurgery under general anesthesia, requiring right subclavian vein cannulation were included in our study. They were randomly divided into two groups: abducted arm position (group 1-AG) and neutral arm position (group 2-NG) using sealed envelope technique. Results: First attempt success rate was higher in AG group compared to NG group (P value- 0.741). Times taken (seconds) for cannulation in NG and AG group, catheter misplacement and hematoma (P value- 0.37, P value- 0.37, P value- 1, respectively) were lesser in AG Group. Conclusion: For USG-guided infraclavicular subclavian vein cannulation, abducted arm position, and neutral arm position in terms of first attempt success rate, number of attempts and associated complications has comparable results; however, further studies with larger group of patients are required to assess the overall advantage of abducted arm position over neutral arm position.

An uncommon ophthalmic emergency condition, bilateral acute angle-closure glaucoma (AACG), is a potentially sight-threatening adverse effect of several local and systemic drugs in high-risk individuals. The majority of cases with drug-induced pupillary block closed-angle glaucoma are preventable, if high-risk patients are recognized and treated prophylactically. We report one such case that highlights the risk factors and rare pathophysiological mechanism of developing bilateral AACG attack after consumption of an antitussive drug orally.

Purpose: Our study was designed to determine ophthalmologists' dexterity in performing standard ophthalmic procedures at various levels of expertise via a structured questionnaire. Methods: A structured questionnaire was administered via the Google platform from August 20 to September 19, 2022, to assess the perspectives and preferences of ophthalmologists concerning their proficiency in using their right hand, left hand, or both hands to perform routine tasks required in the practice of ophthalmic medicine and surgery. Results: Two hundred and three participants took part in the survey. A majority (n = 162, 79.8%) of the clinicians considered themselves right-handed, nine (4.4%) considered themselves left-handed, and 32 (15.7%) considered themselves ambidextrous. Also, 86% (n = 174) of the participants considered ambidexterity an essential trait in the practice of ophthalmic medicine and surgery. The number of cataract surgeries performed had an impact on the comfort of using both hands for performing anterior vitrectomy (P < 0.001), injection of viscoelastic (P < 0.001), and toric marking (P < 0.05), but not on the performance of capsulorhexis and switching of foot pedals. The number of procedures carried out had an impact on the comfort of using both hands in gonioscopy (P < 0.001), 90 D evaluation (P < 0.001), and 20 D evaluation (P < 0.05). More years of experience had an impact on skills involving the use of both hands for slit lamp joystick usage (P < 0.05) and laser procedures (P < 0.001). Conclusion: Irrespective of a person's handedness, trained ambidexterity in the required fields is achievable and has a significant impact on one's ability to perform the required skill optimally and appropriately.

Vascular brain damage can manifest as various ophthalmic pathologies. It is important to understand cerebral circulation to understand the aetiopathogenesis of the disease. It can manifest as various ocular pathologies with visual field defects, cranial nerve palsies, orbital diseases, etc. In this review, with the help of three-dimensional (3D) images, various ophthalmology-related cerebrovascular diseases, their diagnostic methods and their treatment modalities are explained in detail for neophytes.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract Disadvantaged socio-economic position (SEP) is associated with greater biological age, relative to chronological age, measured by DNA methylation (positive ‘age acceleration’, AA). Social mobility has been proposed to ameliorate health inequalities. This study aimed to understand the association of social mobility with positive AA. Diagonal reference modelling and ordinary least square regression techniques were applied to explore social mobility and four measures of age acceleration (first-generation: ‘Horvath’, ‘Hannum’ and second-generation: ‘Phenoage’, DunedinPoAm) in n = 3140 participants of the UK Household Longitudinal Study. Disadvantaged SEP in early life is associated with positive AA for three (Hannum, Phenoage and DunedinPoAm) of the four measures examined while the second generation biomarkers are associated with SEP in adulthood (p

WOFOST and InfoCrop crop growth simulation models were used to assess the impact of climate change on potato cultivars and to develop adaptation strategies for future climatic scenarios (2030, 2050 and 2080) under representative concentration pathways (RCP’s) 4.5 and 6.0 in Bihar. Potato cultivars belonging to late (Kufri Badshah), medium (Kufri Jyoti) and early (Kufri Pukhraj) maturity groups were selected. The simulated results revealed variations in potential productivity of potato under both RCP’s (4.5 & 6.0) with baseline yields of 43.80 t ha-1 for Kufri Badshah, 41.5 t ha-1 for Kufri Jyoti and 43.6 t ha-1 for Kufri Pukhraj. Under RCP 4.5, elevated concentration of CO2 projected to increase the productivity of Kufri Badshah, Kufri Jyoti, and Kufri Pukhraj. However, a decline in yield is expected when individual effect of temperature is considered for future climatic scenarios (2030, 2050 & 2080). However, these yield loss is negated when combined effect of CO2 and temperature is considered by 1.3, 0.7 and 0.3 % in 2030, by -0.4, -1.1 and -2.2 % in 2050 and by 3.5, 4.4 and 5.9 % in 2080, respectively. Likewise, for RCP 6.0, combined effect of CO2 and temperature offset the yield losses by 2.6, 2.4 and 2.3% in 2030, 2.1, 1.7 and 1.1 in 2050 and 1.1, -0.1 and -1.8 in 2080. In addition, selection of suitable cultivars, shifting the date of planting and proper irrigation and nitrogen management practices can counterbalance the yield losses.

A 25-year-old male presented with recurrent swelling in the left upper eyelid despite multiple surgeries in the past 6 years. He was initially misdiagnosed as capillary hemangioma elsewhere, for which multiple surgical excision procedures were done. In 2020, he presented to us for a second opinion regarding the same painless swelling which recurred at the same site. Clinical examination and Doppler ultrasound shifted the diagnosis in favor of arteriovenous malformation (AVM). Computed tomography of the brain and cerebral angiogram (three-dimensional reconstructed) images confirmed the AVM in the left upper eyelid with an arterial feeder from the left ophthalmic artery branch. The patient had multiple recurrences due to the inadvertent misdiagnosis and missed management of the feeder vessel from the ophthalmic artery. We highlight this case, to bring to light the deceptive diagnosis and management of recurrent and refractory AVM due to a feeder vessel from the ophthalmic artery.

Abstract Evidence suggests that there are social inequalities in multimorbidity, with a recent review indicating that area levels of deprivation are consistently associated with greater levels of multimorbidity. Definitions of multimorbidity, the most common of which is the co-occurrence of more than one long term condition, can include long term physical conditions, mental health conditions or both. The most commonly used measure of deprivation in England and Wales is the Index of Multiple Deprivation (IMD), an index of seven different deprivation domains. It is unclear which features of IMD may be mediating associations with multimorbidity. Thus, there may be associations because of the individual characteristics of those living in deprived areas, characteristics of the areas themselves or overlap in definitions. Data from over 25,000 participants (aged 16+) of Understanding Society (Wave 10, 1/2018–3/2020) were used to understand the most salient features of multimorbidity associated with IMD and whether physical or mental conditions are differentially associated with the seven domains of IMD. 24% of participants report multimorbidity. There is an increased prevalence of multimorbidity composed of only long-term physical conditions in the most deprived decile of deprivation (22%, 95% CI[19,25]) compared to the least deprived decile (16%, 95% CI[14,18]). Mental health symptoms but not reporting of conditions vary by decile of IMD. Associations with multimorbidity are limited to the health, income, education and employment domains of IMD. We conclude that multimorbidity represents a substantial population burden, particularly in the most deprived areas in England and Wales.

Aims: This study aims to evaluate the non-mydriatic fundus image quality obtained with a confocal fundus device. Also, to evaluate the influence of non-mydriatic pupil size on image quality. Settings and Design: A cross-sectional study was conducted in the outpatient department of a high-volume tertiary eye care centre in South India during the third phase of the COVID-19 lockdown. Subjects and Methods: 831 consenting, consecutive patients (1539 eyes) were photographed from May 5 to May 17, 2020, and were graded excellent, fair, adequate, or inadequate; based on white noise, black noise, and image acquisition signals. Pupil diameters were obtained with light-emitting diode flash technology. Statistical Analysis: The collected data were analyzed using SPSS software. Descriptive statistics in the form of frequencies and percentages were calculated. Simple (univariate) linear regression analysis and adjusted regression analysis were used to establish the relationship between pupil size and fundus photo quality. Results: The quality of the fundus photo was excellent in 70.12% (n = 1079), fair in 15.72% (n = 242), adequate in 5.78% (n = 89), and inadequate in 8.38% (n = 129). Of the 1410 obtained images (subtracting the inadequate quality images), 87.66% (n = 1236) were normal and 12.34% (n = 174) were pathological. There was a positive linear relationship between pupil size and quality of retinal photograph; OS (R2 = 0.935) had a slightly better association than OD (R2 = 0.901). Conclusions: The majority of the confocal images were excellent in quality. Our four-point grading system serves as a reliable measure of non-mydriatic photograph quality. Pupil size is a significant predictor of image quality for non-mydriatic photographs in surveillance programs.

The coronicle (corona + cubicle) provides state-of-the-art features required for comprehensive ocular evaluation. Assembling this cubicle requires acrylic sheets, aluminum beading, fevicol, araldite paste, and a jigsaw cutting blade, which can be done in a do-it-yourself template. Dimensions of the cubicle are 16 × 16 × 8 feet with only a total area of 256 square feet; thus, restricting patient movement inside hospital premises. Social distancing norms with three feet distance between the machines were incorporated while installing the ophthalmic gadgets within the cubicle. The cubicle encompasses slit-lamps, auto refractometer, lensometer, fundus capture device, optical coherence tomography, optical biometry, manual keratometry, corneal topography, and noncontact tonometer. Customized openings in the cubicle were made in front of each device, for the patient's head and chin rest positioning during the examination, and can be closed with sliding doors during times of disuse. An acrylic groove was provided to accommodate the patient's feet. Coronicle has helped instil, both patient and medical personal safety during COVID-19 and has withstood the test of time since its inception in May 2020. In this manuscript, we have discussed the economics and validated the utility of the cubicle, in terms of the quantitative usage of ophthalmic gadgets present inside the cubicle versus outside the cubicle for the past 19 months, since the installation of the cubicle; along with the cubicle's additive highlights and its role after the pandemic is over.

Purpose: For diagnosing glaucomatous damage, we have employed a novel convolutional neural network (CNN) from TrueColor confocal fundus images to conquer the black box dilemma in artificial intelligence (AI). This neural network with CNN architecture with human-in-the-loop (HITL) data annotation helps not only in diagnosing glaucoma but also in predicting and locating detailed signs in the glaucomatous fundus, such as splinter hemorrhages, glaucomatous optic atrophy, vertical glaucomatous cupping, peripapillary atrophy, and retinal nerve fiber layer (RNFL) defect. Methods: The training was done on a well-curated private dataset of 1,400 high-resolution confocal fundus images, out of which 1,120 images (80%) were used exclusively for training and 280 images (20%) were used exclusively for testing. A custom trained You Only Look Once version 5 (YOLOv5)-based object detection methodology was used to identify the underlying conditions precisely. Twenty-six predefined medical conditions were annotated by a team of humans (comprising two glaucoma specialists and two optometrists) by using the Microsoft Visual Object Tagging Tool (VoTT) tool. The 280 testing images were split into three groups (90,100, and 90 images) for three test runs done once every 15 days. Results: Test results showed consistent increments in the accuracy, from 94.44% to 98.89%, in predicting the glaucoma diagnosis along with the detailed signs of the glaucomatous fundus. Conclusion: Utilizing human intelligence in AI for detecting glaucomatous fundus images by using HITL machine learning has never been reported in the literature before. This AI model not only has good sensitivity and specificity in accurate glaucoma predictions but is also an explainable AI, thus overcoming the black box dilemma.

Abstract Context Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. Objectives and methods To evaluate the causal role of reduced blood 25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration. Results Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would significantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 × 10–32; Z score 11.86, which, however, had no significant association with 25(OH)D status (Beta -0.02nmol/L ± SE 0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles significantly decreased 25(OH)D concentrations (-2.1nmol/L ± SE 0.1nmol/L, p = 7.92 × 10–78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p = 0.12; Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L ± SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p = 0.004; Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC rs2282679, CYP2R1 rs12794714) when used as an individual instrument. Conclusion Our new data on this bidirectional Mendelian randomization study suggests that genetically instrumented T2D risk does not cause changes in 25(OH)D levels. However, genetically regulated 25(OH)D deficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of T2D.

Abstract Background Sex is an important covariate of epigenome-wide association studies due to its strong influence on DNA methylation patterns across numerous genomic positions. Nevertheless, many samples on the Gene Expression Omnibus (GEO) frequently lack a sex annotation or are incorrectly labelled. Considering the influence that sex imposes on DNA methylation patterns, it is necessary to ensure that methods for filtering poor samples and checking of sex assignment are accurate and widely applicable. Results Here we presented a novel method to predict sex using only DNA methylation beta values, which can be readily applied to almost all DNA methylation datasets of different formats (raw IDATs or text files with only signal intensities) uploaded to GEO. We identified 4345 significantly (p

The development of a lens in intrauterine life reacts to any insults by losing its clarity and developing opacity, which manifests as congenital or developmental cataract. Developmental mixed morphology cataracts are seen when there is occurrence of multiple forms of cataracts in a single crystalline lens. Although the prevalence of mixed morphology cataract is 23%, this combination of blue dot cataract with lamellar cataract has never been reported in the literature before, as per our knowledge. The blue dot and lamellar cataracts develop in childhood and progress throughout life. Cataract extraction is rarely necessary before adulthood and is mainly managed with periodic cataract progression assessment. In this manuscript, we have studied the morphology of this mixed morphology cataract with anterior segment imaging tools to throw more light on their optical properties and densitometry.

Big data has been a game changer of machine learning. But, big data is a form of centralized version of data only available and accessible to the technology giants. A way to decentralize this data and make machine learning accessible to the smaller organizations is via the blockchain technology. This peer-to-peer network creates a common database accessible to those in the network. Furthermore, blockchain helps in securing the digital data and prevents data tampering due to human interactions. This technology keeps a constant track of the document in terms of creation, editing, etc., and makes this information accessible to all. It is a chain of data being distributed across many computers, with a database containing details about each transaction. This record helps in data security and prevents data modification. This technology also helps create big data from multiple sources of small data paving way for creating a well serving artificial intelligence model. Here in this manuscript, we discuss about the usage of blockchain, its current role in machine learning and challenges faced by it.

A 10-year-old male child presented with blunt force injury to his right eye (OD), with best-corrected visual acuity of 20/200. Posterior segment evaluation showed vitreous hemorrhage, Berlin's edema, and choroidal rupture anterior to the equator, parallel to the ora serrata, associated with subretinal hemorrhages. In this manuscript, we have reported a rare traumatic manifestation of multiple direct choroidal ruptures in a child. According to our knowledge, this has never been reported in the literature before. This manuscript also highlights the importance of vigilant optical coherence tomography (macula) follow-up in such scenarios, despite the choroidal rupture not involving the macular region.

A day-old male neonate presented with white forelock on his forehead. On evaluation, the neonate had telecanthus, broad nasal bridge, and surprisingly homochromic but hypochromic irides bilaterally. The W-index was 2.38 which was an indication of Type 1 Waardenburg syndrome (WS) with dilated fundus evaluation revealing pigmentary deficit in the retina depicting a orangish hue. The corneal diameter was 9 mm in both eyes. Both the external auditory meatus and external ears appeared normal. The parents who had a history of second-degree consanguineous marriage had visual acuity of 20/20 with normal dark brown irides and normal fundi. Genetic counseling, visual rehabilitation, and auditory evaluation to rule out sensory neural hearing loss were stressed upon for good quality of life, which is mandatory among neonates diagnosed with van der Hoeve-Halbertsma-Waardenburg syndrome.

In the present study, we have designed a series of novel 1,2,3-triazole-aurone hybrids, which were synthesized by a one-pot click reaction between a terminal alkyne and an in-situ generated azide, and evaluated as potential cathepsin B inhibitors. The structures of the synthesized compounds were confirmed by various spectroscopic techniques (1H & 13C NMR and HRMS data). The in-vitro cathepsin B inhibitory study of the synthesized compounds showed that the hybrids named 3o, 3p, and 3r are the excellent inhibitors with percentage inhibition of 83.05–87.16% at the concentration of 10−5 ​M, in comparison to standards, Aspirin (48.21% at 10−7 ​M), and Curcumin (52.27% at 10−7 ​M). The docking study was also in support of the in-vitro assay. Furthermore, the anti-proliferative impact of these synthesized compounds was also evaluated against the gastric adenocarcinoma cell line (AGS cell line). The in-vitro MTT assay suggested that out of all the synthesized hybrids, compounds 3a with an IC50 value of 16 ​μM and 3b with an IC50 value of 11 ​μM possessed maximum cytotoxic activity against the AGS cell line in comparison to the reference, Oxaliplatin (IC50 ​= ​29 ​μM).

Aim: The aim of this study was to evaluate the efficacy of various routinely used analgesics in the management of pulpal pain preoperatively. Materials and Methods: A total of 150 patients were randomly selected and divided into five groups each. At initial visit, a self-administered questionnaire was given, and patients were asked to mark on the Visual Analog Scale (VAS) indicating severity of pain at that moment which is taken as a pretreatment VAS score. Group I patients received aceclofenac + paracetamol, Group II: ketorolac tromethamine, Group III: lornoxicam + paracetamol, Group IV: tramadol + paracetamol, and Group V: paracetamol. All the patients are requested to record their pain levels at 4 h, 6 h, 8 h, 24 h, and 48 h by means of VAS scores before and after treatment. Results: There was no significant decrease in frequency of pain when compared in the first three groups, whereas in Group III and Group IV, the patients experienced an effective reduction in pain because of sustained releasing ability of these drugs. Overall, there was no statistically significant differences among all the groups. Conclusion: This study suggests that there was no significant difference in reduction of pain preoperatively. However, lornoxicam + paracetamol and tramadol + paracetamol were effective because of their sustained releasing ability. Ketorolac was effective to reduce the pain for shorter duration. Paracetamol can be advised in compromised patients where safety is concerned.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

A 35-year-old female presented with severe headache and left-sided hemifacial spasm to the ophthalmic outpatient department. Ocular examination revealed normal visual acuity and color vision, with a presumably normal posterior pole in OU, except for parafoveal central serous chorioretinopathy (CSCR) in OD. Infrared imaging of both fundi revealed generalized retinal pigment epithelial (RPE) mottling, despite the color fundus appearing apparently normal in OU. Complete history taking, systemic workup, and hematological workup was performed and was normal, except for severe Vitamin B12 deficiency. Visual evoked potential was performed and showed delayed latency in OU, diagnosing subclinical demyelinating optic neuropathy. The patient was then started on methylcobalamin 1500 mcg and was reviewed. Signs resolved completely at 1 month follow-up. RPE disturbance (due to severe Vitamin B12 deficiency) may be a possible indirect contributor for CSCR. Hence, Vitamin B12 deficiency manifesting as bilateral optic neuropathy with extensive RPE mottling should be closely monitored for the evolution of CSCR.

Cathepsin B represents a group of lysosomal-encapsulated cellular cysteine proteases, whose upregulation is the critical risk factor for cancer progression and in the regulation of degenerative processes like apoptosis. Therefore, cysteine cathepsins are used as effective biomarkers for cancers and other neurodegenerative disorders and have become specific targets in drug designing. To diversify the pharmacological potential of aurones, a total of eighteen novel 1,2,3-triazole decorated aurone hybrids were synthesized in very good yields, utilizing click chemistry and an ultrasound-assisted one-pot, multicomponent and greener protocol, straight from hydroxy-substituted aurones. These hybrids have been evaluated as useful cathepsin B inhibitors and further explored their in-vitro study over AGS cell line using MTT assay. The in-vitro cathepsin B inhibitory potential of the synthesized hybrids revealed that the hybrid 3p possesses a very significant inhibition (% inhibition ​= ​85.02) at the concentration of 10−6 M compared to the standard aspirin (% inhibition ​= ​48.21 ​at 10−7 M) and curcumin (% inhibition ​= ​57.72 ​at 10−7 M), which further supported by the in-silico studies. In addition to this, the cytotoxic assay of the hybrids showed that the hybrids 3d (IC50 ​= ​24 ​μM), 3i (IC50 ≈ 24 ​μM), and 3m (IC50 ​= ​26 ​μM) exhibit comparable anti-tumor activity against AGS cell line than the standard, oxaliplatin (IC50 ​= ​29 ​μM). The results suggested that the reported novel aurone-1,2,3-triazole hybrids are a promising candidate for the development of new cathepsin B inhibitors as well as anti-cancer leads.

The present study investigates the applicability of sequential anaerobic aerobic integrated settler-based biofilm reactor (SAABR) for the onsite treatment of domestic wastewater. The main aim of the study is to overcome the inherent flaws in an anaerobic system as well as enhancing the effluent quality by means of aerobic post-treatment. The sequential system consisted of an anaerobic settler is followed by two biofilters, anaerobic as well aerobic in series. The first biofilter is anaerobic and the second one is aerobic. The system was run on two hydraulic loading conditions (steady and non-steady flow) with a 24-hour hydraulic retention time (HRT) for the anaerobic system and a 2-hour HRT of aerobic filters. It was found that the performance of the system at steady flow stood at 93.9 ± 2.6, 93.3 ± 1.8, 91.2 ± 4.2, 75.8 ± 3.8 and 98.7 ± 1.1% in terms of total suspended solids (TSS), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total nitrogen (TN) and faecal coliform (FC), respectively while at non-steady flow, it decreased slightly. The Field Emission Scanning Electron Microscope (FESEM) showed the presence of anaerobic bacteria in the system. The system is able to overcome the major flaws of the anaerobic systems and able to deliver high effluent quality. The study demonstrated that the sequential system can be a sustainable alternative for the onsite treatment of domestic wastewater, particularly in rural areas of the developing countries like India.

Abstract Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.

World glaucoma week is celebrated annually in the 2nd week of March, to raise awareness on glaucoma. In the light of the existing manpower and resource constraints, we propose this novel concept of glaucoma awareness, through the green glaucoma cricket championship. The overarching goal of this cricket championship was to screen the general public attending the event with noncontact tonometry, confocal fundus scanner and portable virtual reality perimetry; and refer suspicious patients to the base hospital. Every single protocol of this cricket match was specifically designed with a glaucomatous nomenclature, so that the public gathering, can be educated with those terminologies at various phases of the match. Two hundred and twenty people visited during the 3 h awareness cricket match. A total of 154 people above the age of 40 years were screened for glaucoma, of which 15 (9.7%) were found to be glaucoma suspects, and were referred to the base hospital. Ten out of 15 (66.6%) glaucoma suspects presented to the hospital during the glaucoma awareness week 2020, of which 4 (40%) were confirmed to have glaucoma. This manuscript highlights the promotion of awareness and knowledge toward glaucoma, to the general public through cricket, because in India cricket is like religion and Indian's love for the sport is unparalleled.

Accommodative spasm (AS) is a rare involuntary asthenopic condition occurring in children, adolescents and young adults who engage more in near work. It presents as a repetitive condition of accommodation, which shows a tendency to maintain accommodation in the absence of a stimulus. Here, we discuss in brief about AS with reference to a patient who reported to us with such a condition.

Traumatic retinopathy may occur secondary to direct or indirect trauma to the globe. Presentation of retinopathy may either be a coup (direct site of injury) and or contre-coup (distant sites including the macula). Commotio retinae in the posterior pole is referred to as Berlin's edema. The fovea is extremely thin, and blunt trauma may cause a full-thickness macular hole by either one or a combination of mechanisms, including contusion necrosis and vitreous traction. Holes may be noted immediately or soon after blunt trauma due to severe Berlin's edema, or after a subretinal hemorrhage caused by a choroidal rupture, or following severe cystoid macular edema, or after a whiplash separation of the vitreous from the retina. Post-traumatic macular holes (TMHs) may be successfully closed with vitrectomy and gas injection. We report a case of blunt trauma leading to Berlin's edema and TMH.

The number of critically-ill coronavirus disease 2019 (Covid-19) patients requiring mechanical ventilation is on the rise. Most guidelines suggest keeping the patient intubated and delay elective tracheostomy. Although the current literature does not support early tracheostomy, the number of patients undergoing it is increasing. During the pandemic, it is important that surgeons and anesthesiologists know the different aspects of tracheostomy in terms of indication, procedure, tube care and complications. A literature search was performed to identify different guidelines and available evidence on tracheostomy in Covid-19 patients. The purpose of the present article is to generate an essential scientific evidence for life-saving tracheostomy procedures.

The experiment was conducted at experimental farm situated at 30◦5’N latitude and about 77◦11’E longitudes, an elevation of 1260 m above mean sea level of Department of Environmental Science, Dr YS Parmar University of Horticulture and Forestry Nauni, Solan, Himachal Pradesh during 2014 and 2015, to study the effect of elevated CO2 (eCO2) and elevated temperature (eT) on growth, development and nutritional indices of Spodopteralitura on bell pepper plant. Feeding trials with foliage feeding insect S. litura was conducted using foliage of bell pepper plants grown under four concentrations of CO2 and temperature, viz. three Open Top Chambers, (T1: OTC eCO2 550±10 ppm; T2: OTC with elevated temperature 1°C higher and eCO2 550±10 ppm; T3: OTC with ambient temperature and CO2 and T4: natural ambient air and temperature in open. Biochemical analysis of foliage revealed that plants grown under elevated CO2 had lower nitrogen. The larvae fed on eCO2 as well as eCO2 and temperature foliage exhibited greater consumption compared to the larvae fed on foliage under ambient CO2. Larval duration also increased by two days. The eCO2 and eCO2 and temperature foliage was more digestible with higher values of approximate digestibility. The relative consumption rate increased whereas the efficiency parameters, viz. efficiency of conversion of ingested food (ECI), efficiency of conversion of digested food (ECD), and relative growth rate (RGR) decreased in eCO2 and eCO2 and temperature. The consumption and weight gain of the larvae were negatively and significantly influenced by leaf nitrogen.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Abstract Background We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.