Genome-wide methylation landscape during somatic embryogenesis in Medicago truncatula reveals correlation between Tnt1 retrotransposition and hyperactive methylation regions.

Medicago truncatula is a model legume for fundamental research on legume biology and symbiotic nitrogen fixation. Tnt1, a retrotransposon from tobacco, was used to generate insertion mutants in M. truncatula R108. Approximately 21 000 insertion lines have been generated and publicly available. Tnt1 retro-transposition event occurs during somatic embryogenesis (SE), a pivotal process that triggers massive methylation changes. We studied the SE of M. truncatula R108 using leaf explants and explored the dynamic shifts in the methylation landscape from leaf explants to callus formation and finally embryogenesis. Higher cytosine methylation in all three contexts of CG, CHG, and CHH patterns was observed during SE compared to the controls. Higher methylation patterns were observed in assumed promoter regions (~2-kb upstream regions of transcription start site) of the genes, while lowest was recorded in the untranslated regions. Differentially methylated promoter region analysis showed a higher CHH methylation in embryogenesis tissue samples when compared to CG and CHG methylation. Strong correlation (89.71%) was identified between the differentially methylated regions (DMRs) and the site of Tnt1 insertions in M. truncatula R108 and stronger hypermethylation of genes correlated with higher number of Tnt1 insertions in all contexts of CG, CHG, and CHH methylation. Gene ontology enrichment and KEGG pathway enrichment analysis identified genes and pathways enriched in the signal peptide processing, ATP hydrolysis, RNA polymerase activity, transport, secondary metabolites, and nitrogen metabolism pathways. Combined gene expression analysis and methylation profiling showed an inverse relationship between methylation in the DMRs (regions spanning genes) and the expression of genes. Our results show that a dynamic shift in methylation happens during the SE process in the context of CG, CHH and CHG methylation, and the Tnt1 retrotransposition correlates with the hyperactive methylation regions.

Activity limitations, use of assistive devices, and mortality and clinical events in 25 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: The focus of most epidemiological studies has been mortality or clinical events, with less information on activity limitations related to basic daily functions and their consequences. Standardised data from multiple countries at different economic levels in different regions of the world on activity limitations and their associations with clinical outcomes are sparse. We aimed to quantify the prevalence of activity limitations and use of assistive devices and the association of limitations with adverse outcomes in 25 countries grouped by different economic levels. METHODS: In this analysis, we obtained data from individuals in 25 high-income, middle-income, and low-income countries from the Prospective Urban Rural Epidemiological (PURE) study (175 660 participants). In the PURE study, individuals aged 35-70 years who intended to continue living in their current home for a further 4 years were invited to complete a questionnaire on activity limitations. Participant follow-up was planned once every 3 years either by telephone or in person. The activity limitation screen consisted of questions on self-reported difficulty with walking, grasping, bending, seeing close, seeing far, speaking, hearing, and use of assistive devices (gait, vision, and hearing aids). We estimated crude prevalence of self-reported activity limitations and use of assistive devices, and prevalence standardised by age and sex. We used logistic regression to additionally adjust prevalence for education and socioeconomic factors and to estimate the probability of activity limitations and assistive devices by age, sex, and country income. We used Cox frailty models to evaluate the association between each activity limitation with mortality and clinical events (cardiovascular disease, heart failure, pneumonia, falls, and cancer). The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: Between Jan 12, 2001, and May 6, 2019, 175 584 individuals completed at least one question on the activity limitation questionnaire (mean age 50·6 years [SD 9·8]; 103 625 [59%] women). Of the individuals who completed all questions, mean follow-up was 10·7 years (SD 4·4). The most common self-reported activity limitations were difficulty with bending (23 921 [13·6%] of 175 515 participants), seeing close (22 532 [13·4%] of 167 801 participants), and walking (22 805 [13·0%] of 175 554 participants); prevalence of limitations was higher with older age and among women. The prevalence of all limitations standardised by age and sex, with the exception of hearing, was highest in low-income countries and middle-income countries, and this remained consistent after adjustment for socioeconomic factors. The use of gait, visual, and hearing aids was lowest in low-income countries and middle-income countries, particularly among women. The prevalence of seeing close limitation was four times higher (6257 [16·5%] of 37 926 participants vs 717 [4·0%] of 18 039 participants) and the prevalence of seeing far limitation was five times higher (4003 [10·6%] of 37 923 participants vs 391 [2·2%] of 18 038 participants) in low-income countries than in high-income countries, but the prevalence of glasses use in low-income countries was half that in high-income countries. Walking limitation was most strongly associated with mortality (adjusted hazard ratio 1·32 [95% CI 1·25-1·39]) and most consistently associated with other clinical events, with other notable associations observed between seeing far limitation and mortality, grasping limitation and cardiovascular disease, bending limitation and falls, and between speaking limitation and stroke. INTERPRETATION: The global prevalence of activity limitations is substantially higher in women than men and in low-income countries and middle-income countries compared with high-income countries, coupled with a much lower use of gait, visual, and hearing aids. Strategies are needed to prevent and mitigate activity limitations globally, with particular emphasis on low-income countries and women. FUNDING: Funding sources are listed at the end of the Article.

Clinical and clonal characteristics of monoclonal immunoglobulin M-associated type I cryoglobulinaemia.

Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.

Genomes of Aegilops umbellulata provide new insights into unique structural variations and genetic diversity in the U-genome for wheat improvement.

Aegilops umbellulata serve as an important reservoir for novel biotic and abiotic stress tolerance for wheat improvement. However, chromosomal rearrangements and evolutionary trajectory of this species remain to be elucidated. Here, we present a comprehensive investigation into Ae. umbellulata genome by generating a high-quality near telomere-to-telomere genome assembly of PI 554389 and resequencing 20 additional Ae. umbellulata genomes representing diverse geographical and phenotypic variations. Our analysis unveils complex chromosomal rearrangements, most prominently in 4U and 6U chromosomes, delineating a distinct evolutionary trajectory of Ae. umbellulata from wheat and its relatives. Furthermore, our data rectified the erroneous naming of chromosomes 4U and 6U in the past and highlighted multiple major evolutionary events that led to the present-day U-genome. Resequencing of diverse Ae. umbellulata accessions revealed high genetic diversity within the species, partitioning into three distinct evolutionary sub-populations and supported by extensive phenotypic variability in resistance against several races/pathotypes of five major wheat diseases. Disease evaluations indicated the presence of several novel resistance genes in the resequenced lines for future studies. Resequencing also resulted in the identification of six new haplotypes for Lr9, the first resistance gene cloned from Ae. umbellulata. The extensive genomic and phenotypic resources presented in this study will expedite the future genetic exploration of Ae. umbellulata, facilitating efforts aimed at enhancing resiliency and productivity in wheat.

Bioinspired Diiron Complex with Proton Shuttling and Redox-Active Ligand for Electrocatalytic Hydrogen Evolution.

A µ-oxo diiron complex, featuring the pyridine-2,6-dicarboxamide-based thiazoline-derived redox-active ligand, H2L (H2L = N2,N6-bis(4,5-dihydrothiazol-2-yl)pyridine-2,6-dicarboxamide), was synthesized and thoroughly characterized. [FeIII-(µ-O)-FeIII] showed electrocatalytic hydrogen evolution reaction activity in the presence of different organic acids of varying pKa values in dimethylformamide. Through electrochemical analysis, we found that [FeIII-(µ-O)-FeIII] is a precatalyst that undergoes concerted two-electron reduction to generate an active catalyst. Fourier transform infrared spectrum of reduced species and density functional theory (DFT) investigation indicate that the active catalyst contains a bridged hydroxo unit which serves as a local proton source for the Fe(III) hydride intermediate to release H2. We propose that in this active catalyst, the thiazolinium moiety acts as a proton-transferring group. Additionally, under sufficiently strong acidic conditions, bridged oxygen gets protonated before two-electron reduction. In the presence of exogenous acids of varying strengths, it displays electro-assisted catalytic response at a distinct applied potential. Stepwise electron-transfer and protonation reactions on the metal center and the ligand were studied through DFT to understand the thermodynamically favorable pathways. An ECEC or EECC mechanism is proposed depending on the acid strength and applied potential.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

A Novel Method for Prediction of Raised Intracranial Pressure Through Automated ONSD and ETD Ratio Measurement From Ocular Ultrasound.

The paper presents a novel framework for the prediction of the raised Intracranial Pressure (ICP) from ocular ultrasound images of traumatic patients through automated measurement of Optic Nerve Sheath Diameter (ONSD) and Eyeball Transverse Diameter (ETD). The measurement of ONSD using an ocular ultrasound scan is non-invasive and correlates with the raised ICP. However, the existing studies suggested that the ONSD value alone is insufficient to indicate the ICP condition. Since the ONSD and ETD values may vary among patients belonging to different ethnicity/origins, there is a need for developing an independent global biomarker for predicting raised ICP condition. The proposed work develops an automated framework for the prediction of raised ICP by developing algorithms for the automated measurement of ONSD and ETD values. It is established that the ONSD and ETD ratio (OER) is a potential biomarker for ICP prediction independent of ethnicity and origin. The OER threshold value is determined by performing statistical analysis on the data of 57 trauma patients obtained from the AIIMS, New Delhi. The automated OER is computed and compared with the conventionally measured ICP by determining suitable correlation coefficients. It is found that there is a significant correlation of OER with ICP (r = .81, p ≤ .01), whereas the correlation of ONSD alone with ICP is relatively less (r = .69, p = .004). These correlation values indicate that OER is a better parameter for the prediction of ICP. Further, the threshold value of OER is found to be 0.21 for predicting raised ICP conditions in this study. Scatter plot and Heat map analysis of OER and corresponding ICP reveal that patients with OER ≥ 0.21, have ICP in the range of 17 to 35 mm Hg. In the data available for this research work, OER ranges from 0.17 to 0.35.

Importance of Dyslipidemias in Very Premature Coronary Artery Disease in India: A Registry-based Study.

BACKGROUND AND OBJECTIVE: Premature coronary artery disease (CAD) is an important cause of death in India. To identify risk factors in patients with premature CAD, we performed a registry-based study. METHODS: Consecutive patients admitted for percutaneous coronary intervention (PCI) from October 2020 to June 2021 were recruited. The patients were classified into three groups-group I (very premature CAD < 40 years), group II (premature CAD 40-59 years), and group III (nonpremature CAD > 60 years). Major risk factors were determined, and intergroup comparison was performed. RESULTS: A total of 627 patients were enrolled (men 541, women 86). Group I had 79 (12.4%), group II had 420 (66.9%), and group III had 128 (20.4%) patients. The prevalence of risk factors in groups I, II, and III, respectively, were-CAD family history in 45.1, 41.1, and 26.6% (p = 0.005), current smoking/tobacco use in 29.1, 21.0, and 10.2% (p = 0.002), hypertension in 31.6, 43.6, and 59.4% (p < 0.001), and diabetes in 22.8, 34.3, and 46.1% (p < 0.001). High total cholesterol (>170 mg/dL) was present in 50.0, 38.0, and 29.9% (p = 0.005), nonhigh-density lipoprotein (HDL) cholesterol (>100 mg/dL) in 76.9, 64.4, and 54.5% (p = 0.001), low-density lipoprotein (LDL) cholesterol (>70 mg/dL) in 85.9, 76.8, and 76.4% (p = 0.167), triglycerides (>150 mg/dL) in 56.4, 45.3, and 33.1% (p = 0.001), and very low density lipoprotein (VLDL) cholesterol (>30 mg/dL) in 24.4, 10.4, and 9.4% (p = 0.005). Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) for smoking/tobacco use in groups I and II compared to group III, respectively, were 3.17 (1.60-6.27) and 2.59 (1.51-4.46); high total cholesterol 2.39 (1.29-4.13) and 1.42 (0.92-2.17); high non-HDL cholesterol 2.70 (1.45-5.03) and 1.48 (0.99-2.20); and high triglycerides 2.57 (1.44-4.58) and 1.64 (1.08-2.49). CONCLUSION: Important coronary risk factors in very premature and premature CAD in India are a family history of CAD, any tobacco use, and dyslipidemias (raised total, LDL, non-HDL, and VLDL cholesterol and triglycerides).

Declining Trend in Antimicrobial Sensitivity in Respiratory Tract Bacterial Pathogens against Commonly Used Drugs at a Tertiary Care Hospital.

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target.

Recent studies have implicated mitochondrial dysfunction as a trigger of inflammatory bowel diseases, including Crohn's disease (CD) and ulcerative colitis (UC). We have investigated the role of the mitochondria gate-keeper protein, the voltage-dependent-anion channel 1 (VDAC1), in gastrointestinal inflammation and tested the effects of the newly developed VDAC1-interacting molecules, VBIT-4 and VBIT-12, on UC induced by dextran sulfate sodium (DSS) or trinitrobenzene sulphonic acid (TNBS) in mice. VDAC1, which controls metabolism, lipids transport, apoptosis, and inflammasome activation, is overexpressed in the colon of CD and UC patients and DSS-treated mice. VBIT-12 treatment of cultured colon cells inhibited the DSS-induced VDAC1 overexpression, oligomerization, and apoptosis. In the DSS-treated mice, VBIT-12 suppressed weight loss, diarrhea, rectal bleeding, pro-inflammatory cytokine production, crypt and epithelial cell damage, and focal inflammation. VBIT-12 also inhibited the infiltration of inflammatory cells, apoptosis, mtDNA release, and activation of caspase-1 and NRLP3 inflammasome to reduce the inflammatory response. The levels of the ATP-gated P2X7-Ca2+/K+ channel and ER-IP3R-Ca2+ channel, and of the mitochondrial anti-viral protein (MAVS), mediating NLRP3 inflammasome assembly and activation, were highly increased in DSS-treated mice, but not when VBIT-12 treated. We conclude that UC may be promoted by VDAC1-overexpression and may therefore be amenable to treatment with novel VDAC1-interacting molecules. This VDAC1-based strategy exploits a completely new target for UC treatment and opens a new avenue for treating other inflammatory/autoimmune diseases.

High-Resolution Melting-Based Marker Development for Wheat Leaf Rust Resistance Gene Lr34.

Deploying adult plant resistance (APR) against rust diseases is an important breeding objective of most wheat-breeding programs. The gene Lr34 is an effective and widely deployed broad-spectrum APR gene in wheat against leaf rust fungus Puccinia triticina. Various molecular markers have been developed for Lr34, but they either require post-PCR handling processes or are not economical. Herein, we developed a high-resolution melting (HRM)-based diagnostic assay for Lr34 based on a 3-bp 'TTC' deletion in exon 11 of the resistant allele. The susceptible cultivar Thatcher (Tc) and the near-isogenic Thatcher line (RL6058) with Lr34 yielded distinct melting profiles and were differentiated with high reproducibility. For further validation, all three copies of Lr34 were cloned in plasmid vectors, and HRM analysis using individual and combination (equimolar mixture of three copies) homoeologs yielded distinct melting profiles. An additional layer of genotyping was provided by a LunaProbe assay. The allele-specific probes successfully distinguished the homoeologs but not Tc and RL6058. Furthermore, the practical deployment of the HRM assay was tested by running the marker on a set of breeding lines. When compared with a kompetitive allele-specific PCR (KASP) Lr34 assay, the HRM assay had similar genotyping results and was able to accurately differentiate the resistant and susceptible breeding lines. However, our HRM assay was unable to detect the heterozygote. To our knowledge, this is the first report of an HRM assay for genotyping a wheat rust resistance gene.

Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy.

AIM: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia. METHODS AND RESULTS: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%). CONCLUSION: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.

Discriminative 'Turn-on' Detection of Al3+ and Ga3+ Ions as Well as Aspartic Acid by Two Fluorescent Chemosensors.

In this work, two Schiff-base-based chemosensors L1 and L2 containing electron-rich quinoline and anthracene rings were designed. L1 is AIEE active in a MeOH-H2O solvent system while formed aggregates as confirmed by the DLS measurements and fluorescence lifetime studies. The chemosensor L1 was used for the sensitive, selective, and reversible 'turn-on' detection of Al3+ and Ga3+ ions as well as Aspartic Acid (Asp). Chemosensor L2, an isomer of L1, was able to selectively detect Ga3+ ion even in the presence of Al3+ ions and thus was able to discriminate between the two ions. The binding mode of chemosensors with analytes was substantiated through a combination of 1H NMR spectra, mass spectra, and DFT studies. The 'turn-on' nature of fluorescence sensing by the two chemosensors enabled the development of colorimetric detection, filter-paper-based test strips, and polystyrene film-based detection techniques.

Greater COVID-19 Severity and Mortality in Hospitalized Patients in the Delta-phase Compared to the Others: A Single Center Prospective Registry.

BACKGROUND AND OBJECTIVE: To compare clinical and laboratory features, and outcomes in the second COVID-19 phase (delta variant) with the first and third phases in India we performed a registry-based study. METHODS: Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were recruited over the study period from March 2020 to July 2022. In the first phase (wild type, March-December 2020) of the 7,476 suspected, 1,395 (18.7%) were positive and 863 (61.8%) were hospitalized, in the second phase (delta, January-July 2021) out of 8,680 suspected, 1,641 (19.4%) tested positive and 388 (23.6%) were hospitalized, and in the third phase (omicron, January-July 2022) out of 5,188 suspected patients, 886 (17.1%) tested positive and 94 (10.6%) were hospitalized. We compared details of admission clinical and laboratory features and in-hospital management and outcomes in the three phases. RESULTS: A total of 2,352 patients were recruited. The majority of the patients were men, aged <45 years were 20% and about 20% of patients had hypertension, diabetes, and cardiovascular diseases. Patients in the second phase had significantly more cough, fever, shortness of breath, and lower oxygen saturation (SpO2) at admission and also had more lymphopenia, C-reactive proteins (CRPs), interleukin-6, ferritin, lactic dehydrogenase, and transaminases than patients in the other two phases. In the second vs the first and third phases, the requirement of supplementary oxygen (47.9 vs 33.1 and 23.4%), proning (89.2 vs 37.1 and 5.3%), high flow nasal oxygen (15.7 vs 8.71 and 5.3%), noninvasive ventilation (14.4 vs 9.1 and 11.7%), invasive ventilation (16.2 vs 9.1 and 9.6%), steroids (94.1 vs 83.4 and 37.2%), remdesivir (91.2 vs 73.8 and 39.4%), and anticoagulants (94.3 vs 83.0 and 61.7%) was significantly more (p < 0.001). The median length of stay in days [interquartile range (IQR)] was longer in the second phase [8 (6-10)] vs the first [7 (5-10)] and the third phase [4 (3-6) days]. The intensive care unit (ICU) stay in the second phase [9 (5-13) days] was also significantly more than the first [6 (2-10)] and third [0 (0-3)] phases (p <0.001). Overall, in-hospital deaths occurred in 176 patients (12.8%). Deaths were significantly higher in the second phase (19.3%), compared to the first (11.0%) and the third (3.3%) phases (p <0.01). We also observed that greater disease severity at presentation was associated with higher mortality in all the phases. CONCLUSION: This study shows that COVID-19 patients that were hospitalized in the second (delta) phase of the epidemic had more severe disease compared to the first and third phases. In the second phase of patients, there was a significantly higher duration of hospitalization, ICU hospitalization, greater oxygen requirement, noninvasive and invasive ventilatory support, and more deaths.

Tyrosine kinase inhibitors induced thyroid dysfunction: myth or reality?

Background: Chronic myelogenous leukemia (CML) is a hematopoietic stem cell disorder. It is associated with acquired genetic changes in the hematopoietic stem cells in the form of BCR-ABL fusion gene also known as Philadelphia chromosome. Materials and methods: We prospectively studied thyroid function at baseline and at 6 months of imatinib treatment in 26 newly diagnosed BCR-ABL positive CML patients. Result: The thyroid-stimulating hormone (TSH) levels increased significantly from baseline (3.20 ± 0.978 mIU/L vs. 3.724 ± 1.726 mIU/L, p < 0.05) after 6 months of treatment, 88.4% of the patients remained euthyroid. Only 2 patients had subclinical hypothyroidism, 1 had hypothyroidism after 6 months of tyrosine kinase inhibitors (TKI) therapy. Conclusion: Imatinib did not have any significant effect on thyroid function in CML patients in this study.

A vegetative storage protein improves drought tolerance in maize.

Vegetative storage proteins (VSPs) are known to serve as nitrogen reserves in many dicot plants but remain undiscovered in grasses, most widely grown group of crops globally. We identified and characterized a VSP in maize and demonstrated that its overexpression improved drought tolerance. Nitrogen supplementation selectively induced a mesophyll lipoxygenase (ZmLOX6), which was targeted to chloroplasts by a novel N-terminal transit peptide of 62 amino acids. When ectopically expressed under the control of various tissue-specific promoters, it accumulated to a fivefold higher level upon expression in the mesophyll cells than the wild-type plants. Constitutive expression or targeted expression specifically to the bundle sheath cells increased its accumulation by less than twofold. The overexpressed ZmLOX6 was remobilized from the leaves like other major proteins during grain development. Evaluated in the field over locations and years, transgenic hybrids overexpressing ZmLOX6 in the mesophyll cells significantly outyielded nontransgenic sibs under managed drought stress imposed at flowering. Additional storage of nitrogen as a VSP in maize leaves ameliorated the effect of drought on grain yield.

Tailored Inorganic-Organic Architectures via Metalloligands.

This article discusses the design principles and strategies and the structural outcome of various supramolecular architectures constructed by utilizing well-defined coordination complexes as the metalloligands. We have included selected examples of metalloligands, offering either pyridyl or arylcarboxylic acid groups as the appended functional groups, for illustrating the construction of their supramolecular architectures. Both geometrical position and the number of the appended functional groups emerging from a metalloligand were found to critically regulate the structural aspects and dimensionality of the resultant material. The article concludes by delineating the structure-directing lessions as well as the potential applications of the metalloligand-based supramolecular architectures for the generation of next-level materials.

Hydration of Nitriles Catalyzed by Ruthenium Complexes: Role of Dihydrogen Bonding Interactions in Promoting Base-Free Catalysis.

Ru(II) complexes of amide-phosphine-based tridentate ligands additionally containing pyridine, isoquinoline, and quinoline rings have been synthesized, and their catalytic utility for the selective hydration of nitriles to amides is explored under the base-containing as well as base-free conditions. The chloride-ligated complexes 1-3 exhibited significant catalytic activity in the presence of a base, whereas hydride-ligated complexes 4-6 carried out the hydration of nitrile without the requirement of any base. The mechanistic studies revealed the involvement of [Ru-H] species as the active catalyst in the catalytic cycle. The [Ru-H] species assisted in the polarization of an incoming water molecule through [Ru-H···H-OH] dihydrogen bonding interaction and consequently aided in the attack of a positioned water molecule to a nitrile coordinated to a ruthenium center. Substrate binding studies and kinetic experiments further supported the mechanism. A wide variety of aromatic nitriles containing both electron-withdrawing and electron-releasing groups as well as other substrates including aliphatic nitriles, base-sensitive nitriles, and a few biologically relevant nitriles were employed for the selective hydration.

Encapsulation-Led Adsorption of Neutral Dyes and Complete Photodegradation of Cationic Dyes and Antipsychotic Drugs by Lanthanide-Based Macrocycles.

Molecular architectures offering large cavities can accommodate guest molecules, while their compositional engineering allows tunability of the band gap to support photocatalysis using visible light. In this work, two lanthanide (Ln)-based macrocycles, synthesized using a cobalt-based metalloligand and offering large rectangular cavities, exhibited selective adsorption of neutral dyes over both anionic and cationic dyes. Both Ln macrocycles illustrated complete photodegradation of cationic dyes using visible light without the use of any oxidant. Both Ln macrocycles exhibited complete photodegradation of not only cationic dyes but also a few phenothiazine-based antipsychotic drugs. Photocatalysis involved the generation of reactive oxygen species (ROS), which was corroborated with the band gap of two Ln macrocycles. These results were supported by radical scavenger studies and the quantitative estimation of superoxide and hydroxyl radicals. Complete photodegradation of both dyes and drugs was confirmed by spectral studies, while the generation of CO2 and N2 gases was established by gas chromatography. Importantly, Ln macrocycles were able to distinguish between the neutral dyes that were quantitatively adsorbed and the cationic dyes/drugs that were completely photodegraded.