A PROSPECTIVE STUDY ON ANAEMIA AS A MORTALITY RISK FACTOR IN DIABETIC AND NON-DIABETIC PATIENTS FOLLOWING ACUTE MYOCARDIAL INFARCTION.

Introduction: Short-term mortality is related to hyperglycemia, acute myocardial infarction (AMI), and anemia. Diabetes patients are more likely to suffer from anemia. To investigate the impact of diabetes patients also having anemia on myocardial infarction outcomes, we conducted a retrospective study. Methodology: From a registry that is disease-specific and population-based, information about every patient consecutively hospitalized with AMI was gathered. Diabetes and anemia were present in four groups of patients. Results: 32.2% of Group A, 16% of Group B, 21.45% of Group C, and 6.6% of Group D experienced 30-day mortality (all p < 0.001). Groups A, B, C, and D had, in that order, 31 days to 36 months mortality rates of 47.6%, 20.8%, 34.3%, and 10.4% (all p < 0.001). At 36 months, the odds ratios for diabetes and anemia were 1.61 (1.40–1.84, p < 0.001) and 1.58 (1.37–1.86, p < 0.001), respectively, suggesting that both illnesses remained independent risk factors for death. Of the deaths that occurred between 31 days and 36 months, 43.7% in Group A were due to cardiovascular causes, 54.0% in Group B, 47.1% in Group C, and 50.9% in Group D (p < 0.05, A vs. B). Conclusion: When compared to either diabetes or anemia patients alone, patients who have diabetes and anemia both have a greater death rate. In all groups, cardiovascular death continued to be the most common death cause. Recommendation: According to our findings, individuals with anemia who have experienced a myocardial infarction with or without diabetes may safely have prompt primary percutaneous coronary intervention; nevertheless, they should take extra care to maintain hemoglobin levels

A PROSPECTIVE COHORT STUDY OF PROTEINURIA CHANGES AND MYOCARDIAL INFARCTION RISKS IN DIABETIC OR PRE-DIABETIC PATIENTS.

Objective:  This prospective cohort study aimed to investigate the relationship between changes in proteinuria and the risk of myocardial infarction (MI) in individuals with diabetes or pre-diabetes. Methodology: The prospective study was conducted involving 200 participants in India, with data collection occurring during routine medical examinations from 2020 to 2022. The participants were followed up, and data collection concluded in 2023. Results: Among the participants, those with persistent proteinuria exhibited a significantly higher risk of MI, with a 2.5-fold increased hazard compared to those without proteinuria. Furthermore, a reduction in proteinuria over time was associated with a 21% decrease in MI incidence. This relationship was not observed in individuals without proteinuria, highlighting the importance of persistent proteinuria in influencing MI risk.  Conclusion: The findings emphasize the critical role of persistent proteinuria as a predictor of elevated MI risk in individuals with diabetes and pre-diabetes. Monitoring and managing proteinuria could potentially mitigate the risk of future heart attacks in this population. Recommendations: Healthcare professionals should consider routine monitoring of proteinuria levels in outpatient settings for individuals with diabetes and pre-diabetes. Exploring interventions to lower proteinuria levels for heart attack prevention is recommended, including lifestyle modifications, medications, or targeted therapies. Improved comprehension of the mechanisms connecting proteinuria to the risk of MI is essential for the formulation of efficient preventive approaches. This study underscores the significance of early detection and management of proteinuria in diabetic patients and pre-diabetics to reduce the risk of myocardial infarction

Chimeras of Escherichia coli and Mycobacterium tuberculosis Single-Stranded DNA Binding Proteins: Characterization and Function in Escherichia coli

Single stranded DNA binding proteins (SSBs) are vital for the survival of organisms. Studies on SSBs from the prototype, Escherichia coli (EcoSSB) and, an important human pathogen, Mycobacterium tuberculosis (MtuSSB) had shown that despite significant variations in their quaternary structures, the DNA binding and oligomerization properties of the two are similar. Here, we used the X-ray crystal structure data of the two SSBs to design a series of chimeric proteins (mβ1, mβ1′β2, mβ1–β5, mβ1–β6 and mβ4–β5) by transplanting β1, β1′β2, β1–β5, β1–β6 and β4–β5 regions, respectively of the N-terminal (DNA binding) domain of MtuSSB for the corresponding sequences in EcoSSB. In addition, mβ1′β2ESWR SSB was generated by mutating the MtuSSB specific ‘PRIY’ sequence in the β2 strand of mβ1′β2 SSB to EcoSSB specific ‘ESWR’ sequence. Biochemical characterization revealed that except for mβ1 SSB, all chimeras and a control construct lacking the C-terminal domain (ΔC SSB) bound DNA in modes corresponding to limited and unlimited modes of binding. However, the DNA on MtuSSB may follow a different path than the EcoSSB. Structural probing by protease digestion revealed that unlike other SSBs used, mβ1 SSB was also hypersensitive to chymotrypsin treatment. Further, to check for their biological activities, we developed a sensitive assay, and observed that mβ1–β6, MtuSSB, mβ1′β2 and mβ1–β5 SSBs complemented E. coli Δssb in a dose dependent manner. Complementation by the mβ1–β5 SSB was poor. In contrast, mβ1′β2ESWR SSB complemented E. coli as well as EcoSSB. The inefficiently functioning SSBs resulted in an elongated cell/filamentation phenotype of E. coli. Taken together, our observations suggest that specific interactions within the DNA binding domain of the homotetrameric SSBs are crucial for their biological function

Setting the stage for cohesion establishment by the replication fork

Comment on: Rudra S, et al. Cell Cycle 2012; 2114-2

Prevalence of type 1 diabetes mellitus in Karnal district, Haryana state, India

<p>Abstract</p> <p>Background</p> <p>Little work has been done on the prevalence of type 1 diabetes in north India. This paper reports the prevalence of type 1 diabetes in Karnal district of Haryana state, India.</p> <p>Materials and methods</p> <p>Prevalence of type 1 diabetes was assessed by a hospital-based registry and by analysis of data contributed by chemists and other physicians.</p> <p>Results</p> <p>The overall prevalence of type 1 diabetes in Karnal district is 10.20/100,000 population, with a higher prevalence in urban (26.6/100,000) as compared to rural areas (4.27/100,000). Karnal city, with a population of 222017, has a relatively high prevalence of type 1 diabetes (31.9/100,000). The prevalence in men is higher (11.56/100,000) than in women (8.6/100,000).</p> <p>In the 5 to 16 years age group, the prevalence is 22.22/100,000, while in the 0-5 years age group, prevalence is 3.82/100,000.</p> <p>Conclusions</p> <p>This report highlights the urban-rural and male-female gradient in the prevalence of type 1 diabetes in Karnal, north India.</p

Analysis of the impact of a uracil DNA glycosylase attenuated in AP-DNA binding in maintenance of the genomic integrity in Escherichia coli

Uracil DNA glycosylase (Ung) initiates the uracil excision repair pathway. We have earlier characterized the Y66W and Y66H mutants of Ung and shown that they are compromised by ∼7- and ∼170-fold, respectively in their uracil excision activities. In this study, fluorescence anisotropy measurements show that compared with the wild-type, the Y66W protein is moderately compromised and attenuated in binding to AP-DNA. Allelic exchange of ung in Escherichia coli with ung::kan, ungY66H:amp or ungY66W:amp alleles showed ∼5-, ∼3.0- and ∼2.0-fold, respectively increase in mutation frequencies. Analysis of mutations in the rifampicin resistance determining region of rpoB revealed that the Y66W allele resulted in an increase in A to G (or T to C) mutations. However, the increase in A to G mutations was mitigated upon expression of wild-type Ung from a plasmid borne gene. Biochemical and computational analyses showed that the Y66W mutant maintains strict specificity for uracil excision from DNA. Interestingly, a strain deficient in AP-endonucleases also showed an increase in A to G mutations. We discuss these findings in the context of a proposal that the residency of DNA glycosylase(s) onto the AP-sites they generate shields them until recruitment of AP-endonucleases for further repair

Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress

<p>Abstract</p> <p>Background</p> <p>Widespread use of chromium (Cr) contaminated fields due to careless and inappropriate management practices of effluent discharge, mostly from industries related to metallurgy, electroplating, production of paints and pigments, tanning, and wood preservation elevates its concentration in surface soil and eventually into rice plants and grains. In spite of many previous studies having been conducted on the effects of chromium stress, the precise molecular mechanisms related to both the effects of chromium phytotoxicity, the defense reactions of plants against chromium exposure as well as translocation and accumulation in rice remain poorly understood.</p> <p>Results</p> <p>Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. To check whether the Cr-specific motifs were indeed significantly over represented in the promoter regions of Cr-responsive genes, occurrence of these motifs in whole genome sequence was carried out. In the background of whole genome, the lift value for these 14 and 13 motifs was significantly high in the test dataset. Though no functional role has been assigned to any of the motifs, but all of these are present as promoter motifs in the Database of orthologus promoters.</p> <p>Conclusion</p> <p>These findings clearly suggest that a complex network of regulatory pathways modulates Cr-response of rice. The integrated matrix of both transcriptome and metabolome data after suitable normalization and initial calculations provided us a visual picture of the correlations between components. Predominance of different motifs in the subsets of genes suggests the involvement of motif-specific transcription modulating proteins in Cr stress response of rice.</p

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe