Indian Journal of Medical Research最新文献

Background & objectives Sickle cell disease (SCD) is a common, life-limiting genetic disorder in India. It is best managed when diagnosed early through newborn screening, which requires a reliable, rapid and an affordable point-of-care test for diagnosis. The study aimed to evaluate the diagnostic accuracy of HemoTypeSC as point-of care for detecting SCD in newborn screening. Additionally, the study assessed the feasibility of implementing HemoTypeSC in poor resource settings. Methods We conducted a prospective multicentre diagnostic accuracy study using an investigational assay HemoTypeSC, and compared it with the reference ('Gold-standard') High performance liquid chromatography (HPLC) during the year 2019-20. Six different study centers were selected to evaluate the performance of the test across different climatic and geographical locations. Results A total of 1725 newborn babies were screened from six participating centers. The samples were analyzed by both HemoTypeSC and HPLC. HemoTypeSC correctly identified the 14/15 SCD cases [sensitivity 93.3% (95% confidence interval (CI): 68-99.8%) and specificity 100% (95% CI: 99.7-100%)] and 192/200 sickle cell trait cases [sensitivity 96% (92.2-98.2%, CI 95%) and specificity 99.8% (95% CI: 99.5-99.9%)]. The accuracy of HemoTypeSC to detect SCD and sickle cell trait was found to be 99.9 per cent (95% CI: 99.6-100%) and 99.5 per cent (95% CI: 99-99.7%), respectively. Interpretation & conclusions HemoTypeSC can be a viable alternative to HPLC in resource-limited regions with a high prevalence of SCD to provide timely diagnosis and support newborn screening programmes.

Background & objectives Non-alcoholic fatty liver disease (NAFLD) is considered as the most prevalent chronic metabolic disease, characterised by steatosis, inflammation, and metabolic dysfunctions with impaired functions of liver enzymes. The fat mass and obesity-associated gene (FTO) plays an important role in fat accumulation in hepatocytes. We investigated how FTO regulated the expression of its target genes via m6A modification leading to the pathophysiology of NAFLD. Methods A NAFLD mouse model was developed by feeding C57Bl/6 male mice on high-fat, high-carbohydrate (HFHC) diet supplemented with fructose and sucrose up to 24 wk. Changes in the liver histology were examined in serial sections by microscopy and immunohistochemistry, the serum parameters were monitored by bioanalyser and ELISA. Expression of hepatic murine FTO (mFTO) and metabolic gene transcripts were quantified by qPCR and mRNA sequencing. mFTO protein expression was analysed by immunohistochemistry and western blotting. Results The NAFLD mouse model developed steatosis, inflammation, and fibrosis at 19-24 wk, along with elevated liver enzyme levels, altered lipid profiles, and increased mFTO expression. Transcriptomic analysis identified differentially expressed genes and pathways associated with NAFLD progression. Pharmacological inhibition of mFTO by entacapone restored m6A marks on gene transcripts and reversed the NAFLD phenotype. Interpretation & conclusions Gene expression profiling identified key metabolic pathways and molecular targets associated with NAFLD progression. It underscored the role of mFTO in altering the m6A methylation landscape essential for establishing NAFLD and highlighted its therapeutic potential for NAFLD-associated morbidities.

Background & objectives This study was carried out to identify association of chronic pesticide exposure with cognitive impairment, depression, and movement disorder by utilising a comprehensive paradigm of symptom-based validated screening; and estimation of RBC acetylcholinesterase (AChE), plasma butyrylcholinesterase (BChE) and paraoxonase 1 (PON1) levels among high risk rural population, particularly agricultural workers in West Bengal, India. Methods Galsi II block, Purba Bardhaman district, West Bengal was selected as the study site. Samples were drawn among residents aged 50 yr and above of either sex, continuously living in the area for at least last five years. Primary screening was applied to enquire about target neuropsychiatric disorders. On getting an affirmative reply to any of the questions, participants were further screened for cognitive impairment and depression. Any participant screening 'positive' for either of the three conditions fulfilled criteria for recruitment as a 'case'. Blood samples were collected from participants for estimation of AChE, BChE and PON1. Results Of 808 participants, 180 (22.3%) were screened as 'Cases'. Pesticide exposure was a significant risk for detection as a 'Case' [Odds ratio (OR)=2.9], which supports premise of this study. Additionally, male gender (OR=1.98), more years of pesticide exposure (>30 yr) (OR=1.8) and more frequent use of pesticides (1/week) (OR=2.5) were significant risks of screening as a 'Case'. Agricultural workers, who were exclusively engaged with agriculture as occupation, had the lowest cognition score (77.5±19.6) (P<0.001), highest impairment in daily living (2.1±1.7) (P=0.01) and highest BDI (Beck Depression Inventory) score (15±7) (P=0.003), i.e., a higher risk of depression. Paraoxonase 1 (PON1) expression was significantly increased among workers engaged in agricultural activity for more than 8 h in a day (82.3±42) (P=0.03) and who applied pesticides at least once a week (80.3±40) (P=0.02). Interpretation & conclusions This population-based study among rural agricultural population in West Bengal has identified a prevalence of 18.9 per cent of cognitive impairment with or without depression; 8.3 per cent depression with or without cognitive impairment and 1.5 per cent possible movement disorder. We also identified that pesticide exposure is a risk for development of these neuropsychiatric disorders of neuroinflammatory origin. Among biomarkers, PON1 was identified to be significantly higher among participants who spent more hours in agricultural work and applied pesticides more frequently.

Background & objectives Adrenoleukodystrophy (ALD), caused by a mutation in the ABCD1 gene has a heterogenous clinical spectrum. Very long chain fatty acid (VLCFA) levels, neuroimaging findings and genetic analysis play a role in the final diagnosis. This paper presents a single centre experience on clinical, biochemical and molecular characteristics of ALD. Methods In this cross-sectional study, 35 individuals with ALD were included. Apart from their clinical characterisation, evaluation of their VLCFA levels was done. VLCFA levels and their ratios were also analysed in 383 healthy controls, and ROC curves were prepared to identify suitable cut-offs for the Indian population. Molecular characterisation by ABCD1 gene sequencing was also done. Molecular modelling techniques were used to ascertain the structural effect of mutations in those carrying novel variants in the ABCD1 gene. Results Adolescent ALD (13/35, 37.1%) was the most common subtype identified in our study, and muscle weakness (19/29, 65.5%) was the most common clinical feature. At cut-offs of 0.907 and 0.604 (µmol/3.2mm punch), C24:0 and C26:0 LPCs, respectively, were found to have a sensitivity and specificity of 100 per cent each for the identification of ALD. Sequencing of ABCD1 gene revealed that the mutations were most commonly seen in exon 1. Out of the four novel variations in ABCD1 gene identified in our study, a three-dimensional visualisation of the ABCD-1 gene revealed that three of them resulted in significant alterations in the protein structure, while no changes at the protein level was reported for the g.11476 [G>A] mutation. Interpretation & conclusions This study highlights the importance of considering the ratios of VLCFAs, along with the individual values, for establishing ALD diagnosis. We also identified a mutational hotspot in exon 1 of the ABCD1 gene, which may also help strategize the preliminary screening of the ABCD1 gene.

Background & objectives Road traffic accidents (RTAs) are increasing globally and its relationship with climatic factors are less studied. This study aimed to determine the trends and patterns of RTAs and its relationship with climate factors in Urban Ernakulam district, Kerala. Methods This retrospective analysis used 47,582 RTA records from the Crime Records Bureau, Ernakulam City Police, Kerala, India and daily meteorological data of 2,149 days (2018-2023) from the department of Atmospheric Science, Cochin University for Science and Technology, Kerala. The combined dataset was analysed using Python, with descriptive statistics, time series analysis, autocorrelation function (ACF) analysis, and the seasonal autoregressive integrated moving average (SARIMA) model conducted. Results Of the total RTAs, one-fifth (n=9817, 20.6%) occurred in 2023. Two wheelers (motorcycles) were the most common (n=27515, 57.8%) vehicle type, minor roads were the most frequent sites (n=29801, 62.6%), and over-speeding contributed to over one third (n=17489, 36%) of the RTAs. RTAs were most common (n=15829, 33.3%) in the afternoon 12.00-18.00 PM and the majority (n=33799 ,71%) of RTA victims suffered grievous injuries. Minimum temperature (<21.71°C) and rainfall (<2.15 mm) were significantly associated with RTAs. Lower minimum temperatures had a negative correlation with RTAs during winter (-0.21 to -0.28) in 2022-23, and the monsoon season (-0.20 to -0.26) in 2020-21. Higher rainfall was negatively correlated (-0.2 to - 0.22) with RTAs during the monsoon in 2018-19. Grievous injury patterns were influenced by past three-month trends and recurring cycles every three yr, reflecting a mix of short-term seasonal, medium-term biennial, and long-term triennial factors. Interpretation & conclusions Adverse weather conditions such as lower temperatures and less rainfall increased the risk of RTAs. Long term studies, free from external interruptions, are needed to get deeper insights into these relations. Targeted interventions and advisories to reduce RTAs, especially before monsoon season are essential.

Background & objectives Lactate can be estimated by point-of-care testing (POCT) devices such as blood gas analysers (BGA) as well as central lab autoanalysers (AA); both have their advantages. Studies have compared lactate and electrolyte values on arterial blood; none used venous samples which are preferred in children. We planned to compare venous lactate by BGA and AA in children admitted to Paediatric Intensive Care Unit (PICU). Methods Fifty children aged one month to 18 yr admitted in PICU were included in the study after parental consent. Paired venous samples were collected in heparinised syringes for BGA, in fluoride containing vacutainers for AA and were analysed immediately. Results Lactate levels were assessed in 29 male and 21 female children [Median age: 4 yr interquartile range (IQR)=1-10)]. AA reported higher lactate levels but mean difference between two methods (0.34±1.56 mmol/L) was not statistically significant (P= 0.062). The methods showed statistically significant correlation [95% confidence interval (CI), Spearman correlation coefficient (rs)=0.816, P=<0.001]. Bland Altman plot showed 95 per cent of paired values had differences which was within limits of agreement (-2.71, +3.39); differences were more variable above 2 mmol/L. Both devices classified multiple samples into different clinically significant ranges. Interpretation & conclusion Venous lactate by BGA and AA was found comparable, but critical values requiring clinical intervention were not reported similarly by both analysers. Variability between them was higher at higher venous lactate levels (>2 mmol/L) which represent critically ill children. Use of the same analyser, either BGA or AA, is therefore recommended for monitoring.

Background & objectives Limited data exist on the effects of metformin on asthma outcomes in patients having type 2 diabetes (T2D) along with asthma. This meta-analysis seeks to determine whether metformin influences asthma outcomes in these patients. Methods Studies involving adults with T2D and asthma, using metformin in the intervention group and other glucose-lowering drugs in the control group, were systematically searched through databases. The primary outcome was the adjusted risk of asthma exacerbations in metformin users (MU) vs. non-metformin users (non-MU). Other outcomes included asthma-related emergency room visits, hospitalisations, and the need for rescue steroids. Meta-analysis was conducted using RevMan with random-effects models. Outcomes were reported as hazard ratios (HRs) with 95 per cent confidence intervals (95% CI). Results Six retrospective cohort studies with moderate overall risk of bias, involving 317,905 patients, were included. The risk of asthma exacerbation was comparable in MU and non-MU (HR 0.95, 95% CI: 0.86, 1.04, P=0.27). The risk of asthma-related emergency room visits appeared lower in MU than in non-MU, though the difference did not gain statistical significance (HR 0.63, 95% CI: 0.39, 1.01, P=0.06). The two groups also had statistically identical risks of asthma-related hospitalisations (HR 0.76, 95% CI: 0.54, 1.07, P=0.12) and use of rescue steroids (HR 0.95, 95% CI: 0.87, 1.03, P=0.24). However, after excluding a study from Taiwan (n=115486), a significantly lower risk of asthma exacerbation (HR 0.89, 95% CI: 0.83-0.97, P=0.005) and asthma-related hospitalisations (HR 0.68, 95% CI: 0.49-0.93, P=0.02) was observed in MU. Interpretation & conclusions Metformin therapy for T2D does not influence asthma outcomes; however, certain outcomes appear to improve when a Taiwanese study is excluded. Such results must be considered cautiously, as the included studies are observational and have a moderate risk of bias. Randomised controlled trials with diverse global representation are essential for clarifying the relationship between metformin use and asthma outcomes.