A novel interplay between PRC2 and miR-3189 regulates epithelial-mesenchymal transition (EMT) via modulating COL6A2 in glioblastoma.

Recent studies have shed light on disrupted collagen signaling in Gliomas, yet the regulatory landscape remains largely unexplored. This study enquired into the role of polycomb repressive complex-2 (PRC2)-mediated H3K27me3 modification, a key epigenetic factor in glioma. Using in-house data, we identified miRNAs downregulated in glioblastoma (GBM) with the potential to regulate Collagen VI family genes. Notably, miR-3189 emerged as a prime PRC2 target. Its expression was significantly downregulated in Indian GBM patients as well as other glioma cohorts. Mechanistic insights, involving Luciferase assays, mutagenesis, and Western blot analysis, confirmed direct targeting of Collagen VI member COL6A2 by miR-3189-3p. Functional assays demonstrated that miR-3189-3p restrained GBM malignancy by inhibiting proliferation, migration, and epithelial-mesenchymal transition (EMT). Conversely, COL6A2 overexpressed in GBM patients, countered miR-3189, and promoted the malignant phenotype. Gene set enrichment analysis highlighted EMT enrichment in GBM patients with elevated COL6A2 expression, carrying prognostic implications. This study uncovers intricate interactions between two epigenetic regulators-H3K27me3 and miR-3189-working synergistically to modulate Collagen VI gene; thus, influencing the malignancy of GBM. Targeting this H3K27me3|miR-3189-3p|COL6A2 axis presents a potential therapeutic avenue against GBM.

Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database.

BACKGROUND: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. METHODS: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. RESULTS: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls. CONCLUSIONS: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

Peri-Alkylated Terrylenes and Ternaphthalenes Building-Blocks Towards Multi-Edge Nanographenes.

Since its first synthesis by Clar in 1948, terrylene - a fully connected ternaphthalene oligomer via naphthalene's peri-positions - has gained special focus within the rylene family, drawing interest for its unique chemical, structural, optoelectronic and single photon emission properties. In this study, we introduce a novel synthetic pathway that enhances the solubility of terrylene derivatives through complete peri-alkylation, while also facilitating extensions at the bay-positions. This approach not only broadens the scope of terrylene's chemical versatility but also opens new avenues for developing solution processable novel multi-edge nanographenes and tailoring electronic energy levels through topological edge structures. Our findings include a comprehensive structural and spectroscopic characterization along with transient absorption spectroscopy and photophysics of both the synthesized peri-alkylated terrylene and its phenylene-fused derivative.

In-vitro and in-silico investigations of SLC-0111 hydrazinyl analogs as human carbonic anhydrase I, II, IX, and XII inhibitors.

Two novel series of hydrazinyl-based benzenesulfonamides 9a-j and 10a-j were designed and synthesized using SLC-0111 as the lead molecule. The newly synthesized compounds were evaluated for their inhibitory activity against four different human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Both the series reported here were practically inactive against the off-target isozyme hCA I. Notably, derivative 10a exhibited superior potency (Ki of 10.2 nM) than acetazolamide (AAZ) against the cytosolic isoform hCA II. The hCA IX and XII isoforms implicated in tumor progression were effectively inhibited with Kis in the low nanomolar range of 20.5-176.6 nM and 6.0-127.5 nM, respectively. Compound 9g emerged as the most potent and selective hCA IX and XII inhibitor with Ki of 20.5 nM and SI of 200.1, and Ki of 6.0 nM and SI of 683.7, respectively, over hCA I. Furthermore, six compounds (9a, 9h, 10a, 10g, 10i, and 10j) exhibited significant inhibition toward hCA IX (Kis = 27.0, 41.1, 27.4, 25.9, 40.7, and 30.8 nM) relative to AAZ and SLC-0111 (Kis = 25.0 and 45.0 nM, respectively). These findings underscore the potential of these derivatives as potent and selective inhibitors of hCA IX and XII over the off-target hCA I and II.

Benzenesulfonamides functionalized with triazolyl-linked pyrazoles possess dual cathepsin B and carbonic anhydrase inhibitory action.

The design and synthesis of a library of 21 novel benzenesulfonamide-bearing 3-functionalized pyrazole-linked 1,2,3-triazole derivatives as dual inhibitors of cathepsin B and carbonic anhydrase enzymes are reported. The target 1,2,3-triazole-linked pyrazolic esters (16) were synthesized by the condensation of 1,2,3-triazolic diketo esters with 4-hydrazinobenzenesulfonamide hydrochloride, and these were further converted into the corresponding carboxylic acid (17) and carboxamide (18) analogs. The synthesized compounds were assayed in vitro for their inhibition potential against human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. They were found to be potent inhibitors at the low nanomolar level against the cancer-related hCA IX and XII and to be selective towards the cytosolic isoform hCA I. The physiologically important isoform hCA II was potently inhibited by all the newly synthesized compounds showing KI values ranging between 0.8 and 561.5 nM. The ester derivative 16c having 4-fluorophenyl (KI = 5.2 nM) was the most potent inhibitor of hCA IX, and carboxamide derivative 18b (KI = 2.2 nM) having 4-methyl substituted phenyl was the most potent inhibitor of hCA XII. The newly synthesized compounds exhibited potent cathepsin B inhibition at 10-7 M concentration. In general, the carboxamide derivatives (18) showed higher % inhibition as compared with the corresponding ester derivatives (16) and carboxylic acid derivatives (17) for cathepsin B. The interactions of the target compounds with the active sites of cathepsin B and CA were studied through molecular docking studies. Further, the in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of the target compounds were also studied.

Modulation of gut-microbiota through probiotics and dietary interventions to improve host health.

Dietary patterns play an important role in regards to the modulation and control of the gut microbiome composition and function. The interaction between diet and microbiota plays an important role in order to maintain intestinal homeostasis, which ultimately affect the host's health. Diet directly impacts the microbes that inhabit the gastrointestinal tract (GIT), which then contributes to the production of secondary metabolites, such as short-chain fatty acids, neurotransmitters, and antimicrobial peptides. Dietary consumption with genetically modified probiotics can be the best vaccine delivery vector and protect cells from various illnesses. A holistic approach to disease prevention, treatment, and management takes these intrinsically linked diet-microbes, microbe-microbe interactions, and microbe-host interactions into account. Dietary components, such as fiber can modulate beneficial gut microbiota, and they have resulting ameliorative effects against metabolic disorders. Medical interventions, such as antibiotic drugs can conversely have detrimental effects on gut microbiota by disputing the balance between Bacteroides and firmicute, which contribute to continuing disease states. We summarize the known effects of various dietary components, such as fibers, carbohydrates, fatty acids, vitamins, minerals, proteins, phenolic acids, and antibiotics on the composition of the gut microbiota in this article in addition to the beneficial effect of genetically modified probiotics and consequentially their role in regards to shaping human health. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

MED12 is overexpressed in glioblastoma patients and serves as an oncogene by targeting the VDR/BCL6/p53 axis.

Glioblastoma is the most life-threatening tumor of the central nervous system. Despite recent therapeutic advancements, maximum survival of glioblastoma patients remains dismal. The mediator complex is a set of proteins, essential for eukaryotic gene expression. Abnormal expression/mutations of specific mediator genes have been associated with progression of various cancers, however, its role and status in glioblastoma remains largely unknown. Our work shows overexpression of a subunit of kinase assembly of mediator complex, MED12, in various glioblastoma patient cohorts including Indian glioblastoma patients and cell lines. Functional characterization of MED12 using both overexpression and knockdown approach revealed that it promotes glioblastoma cell proliferation, migration and inhibits apoptosis. Transcriptome analysis post MED12 knockdown revealed Vitamin D receptor (VDR) pathway to be one of the key pathways affected by MED12 in glioblastoma. We studied direct interaction of MED12 with VDR protein using docking studies and co-immunoprecipitation assay. We identify BCL6, a secondary regulator of VDR signaling, to be directly regulated by MED12 through a combination of chromatin immunoprecipitation, qRT-PCR and western analyses. We further show that MED12 brings about the inhibition of p53 levels and apoptosis partly through induction of BCL6 in glioblastoma. Overall, this stands as the first report of MED12 over-expression and involvement in glioblastoma pathogenesis and identifies MED12 as an important mediator of VDR signaling and an attractive molecule for development of new therapeutic interventions.

Serum PTH at 4 h after total thyroidectomy as a predictor of hypocalcemia: a prospective time frame analysis in search of evidence.

INTRODUCTION: There has not been a universal agreement about the timings and the threshold level of PTH that can accurately predict the risk of hypocalcemia. Our study aimed to investigate the changes in the serum PTH levels at various time intervals and correlate it with the development of subsequent hypocalcemia. MATERIALS AND METHODS: All patients had a pre-operative serum PTH done and were again assessed intra-operatively, at 4 h, 24 h, 72 h, and 1 month after the thyroid surgery. Absolute serum PTH value at various time points, absolute change in serum PTH values compared to pre-operative level, and relative change (percentage change) in serum PTH values compared with pre-operative levels were used to predict post-operative Hypocalcemia. RESULTS: 49 patients were included in the study. The sensitivity and negative predictive value was 100% for serum PTH at 4 h. There was a statistically significant difference between the groups that required calcium supplementation versus the group that did not require it. The maximum relative reduction in serum PTH value with respect to the pre-operative level occurred at 4 h in the calcium supplement required group which was 82.5%. Use of combination of 4 h serum PTH and relative change at 4 h yielded the best results. CONCLUSION: A combination of absolute serum PTH level at 4 h and the relative decline in serum PTH at 4 h has the highest diagnostic accuracy. The use of this combined parameter helps to reliably predict patients who would require supplementation.

Benzenesulfonamides with trisubstituted triazole motif as selective carbonic anhydrase I, II, IV, and IX inhibitors.

Twenty novel 1,2,3-triazole benzenesulfonamides featuring nitrile 8a-g, carbothioamide 9a-f, and N'-hydroxycarboximidamide 10a-g functionalities were designed and synthesized to improve potency and selectivity as carbonic anhydrase inhibitors (CAIs). The synthesized 1,2,3-triazole compounds were tested in vitro as CAIs against four physiologically and pharmacologically relevant isoforms of human carbonic anhydrase (hCA I, II, IV, and IX). Compounds 8a-g, 9a-f, and 10a-g displayed variable inhibition constants ranging from 8.1 nM to 3.22 µM for hCA I, 4.7 nM to 0.50 µM for hCA II, 15.0 nM to 3.7 µM for hCA IV, and 29.6 nM to 0.27 µM for hCA IX. As per the inhibition data profile, compounds 9a-e exhibited strong efficacy for hCA IV, whereas the inhibition was found to be somewhat diminished in the case of hCA IX by nearly all the compounds. A computational protocol based on docking and MM-GBSA was conducted to reveal the plausible interactions of the targeted sulfonamides within the hCA II and IX binding sites. The outcomes of appending various functionalities at the C-4 position of the 1,2,3-triazole motif over the inhibition potential and selectivity of the designed sulfonamides were examined with a potential for the discovery of new isoform selective CAIs. The CAI and SAR data established the significance of the synthesized 1,2,3-triazoles as building blocks for developing CAI drugs.

Potent inhibitors of tumor associated carbonic anhydrases endowed with cathepsin B inhibition.

Twenty-one novel extended analogs of acetazolamide were synthesized and screened in vitro for their inhibition efficacy against human carbonic anhydrase (hCA) isoforms I, II, IX, XII, and cathepsin B. The majority of the compounds were found to be effective inhibitors of tumor-associated hCA IX and XII, and poor inhibitors of cytosolic hCA I. Despite the strong to moderate inhibition potential possessed by these compounds toward another cytosolic isoform hCA II, some of them demonstrated better potency against hCA IX and/or XII isoforms as compared to hCA II. Four compounds (11f, 11g, 12c, and 12g) effectively inhibited hCA IX and/or XII isoforms with considerable selectivity over the off-targets hCA I and II. Interestingly, five compounds, including 11f, 11g, 12c, 12d, and 12g, inhibited hCA IX even better than the clinically used acetazolamide. Some of the novel synthesized compounds exhibited higher anti-cathepsin B potential than acetazolamide, with % inhibition of around 50%, at a concentration of 10-7 M. Further, two compounds (12g and 12c) that showed effective and selective inhibition activity profiles against hCA IX and XII were additionally found to be effective inhibitors of cathepsin B.

Climate plays a dominant role over land management in governing soil carbon dynamics in North Western Himalayas.

The soil carbon (C) dynamics is strongly influenced by climate and land-use patterns in the Himalayas. Therefore, soils under five prominent land use [e.g., maize (Zea mays), horticulture, natural forest, grassland, and wasteland] were sampled down up to 30 cm depth under two climatic conditions viz., temperate and subtropical to assess the impacts of climate and landuse on soil C dynamics. Results demonstrated that irrespective of land use, temperate soil contains 30.66% higher C than subtropical soils. Temperate soils under natural forests had the higher total organic carbon (TOC, 21.90 g kg-1), Walkley-Black carbon (WBC, 16.42 g kg-1), contents, and stocks (TOC, 66.92 Mg ha-1 and WBC, 50.24 Mg ha-1), and total soil organic matter (TSOM, 3.78%) concentration as compared to other land uses like maize, horticulture, grassland, and wasteland. Under both climatic conditions, maize land use had the lowest TOC 9.63, 6.55 g kg-1 and WBC 7.22, 4.91 g kg-1 at 0-15 and 15-30 cm soil depth, respectively. Horticulture land use had 62.58 and 62.61% higher TOC and WBC over maize-based land use under subtropical and temperate climatic conditions at 0-30 cm soil depth, respectively. However, soils of maize land use under temperate conditions had ∼2 times more TOC than in subtropical conditions. The study inferred that the C-losses is more in the subtropical soil than in temperate soils. Hence, the subtropical region needs more rigorous adoption of C conservation farming practices than the temperate climatic setting. Although, the adoption of C storing and conserving practices is crucial under both climatic settings to arrest land degradation. Horticultural land uses along with conservation effective soil management practices may be encouraged to restore more soil C and to improve the livelihood security of the hill populace in the North Western Himalayas.

Indigenous Practices of Soil and Water Conservation for Sustainable Hill Agriculture and Improving Livelihood Security.

In the foothills of the North-West Himalayan region of India, agriculture is the main occupation of the residents. The soil and water resources are becoming the major constraints in agricultural production in the erosion-prone fragile ecosystem of the region. However, due to intensive rains and sloping lands of the region, erosion of the topsoil becoming the major problem for practicing sustainable agriculture in the region, which further dissects the lands, reduces the fertility potentials and land productivities of the region. The root cause of this huge erosion in the region is the intensive rains within a short interval of time on the bare sloping hillsides and handling this problem in both ways could reduce their erosion damage. Socio-economically the farmers are illiterate, poor, and hesitate to adopt innovative techniques of both land and water conservation. All this makes the challenge of reducing erosion losses quite difficult. Farmers in the region do have the skills to manage the problem of soil erosion which they learned from their forefathers and have faith in them. These technologies put together are termed as "Indigenous Technical Knowledge" (ITKs) and these ITKs have helped them a lot for sustainable agriculture in the region. Among different ITKs bunding of field, plowing before monsoon, filter strips, earthing-up in maize, mulching, compression of soil in sugarcane are the important ones for restoring the fertility of soils, reducing erosion losses, improving land productivity, and ultimately livelihoods in the region.

Drought and global hunger: biotechnological interventions in sustainability and management.

MAIN CONCLUSION: Drought may be efficiently managed using the following strategies: prevention, mitigation, readiness, recovery, and transformation. Biotechnological interventions may become highly important in reducing plants' drought stress in order to address key plant challenges such as population growth and climate change. Drought is a multidimensional construct with several triggering mechanisms or contributing factors working at various spatiotemporal scales, making it one of the known natural catastrophes. Drought is among the causes of hunger and malnutrition, decreasing agricultural output, and poor nutrition. Many deaths caused in children are due to hunger situations, and one in four children face stunted growth. All this hunger and malnutrition may be responsible for the reduction in agricultural productivity caused due to the drought situations affecting food security. Global Hunger Index has been accelerating due to under-nutrition and under-5 deaths. Drought has been covering more than 20% of the world's agricultural areas, leading to significantly less food production than what is required for consumption. Drought reduces soil fertility and adversely affects soil biological activity reducing the inherent capacity of the soil to support vegetation. Recent droughts have had a much greater effect on people's lives, even beyond causing poverty and hunger. Drought may have substantial financial consequences across the globe it may cause a severe impact on the world economy. It is a natural feature of the environment that will appear and disappear as it has in history. Due to increasing temperatures and growing vulnerabilities, it will undoubtedly occur more often and seriously in the coming years. To ensure sustainable socio-economic and social development, it is critical to reducing the effects of potential droughts worldwide using different biotechnological interventions. It's part of a long-term growth plan, and forecasting is essential for early warnings and global hunger management.

Comparative genomics reveals the evolution of antimicrobial resistance in Bacteroides nordii.

Bacteroides nordii, is an understudied member of the pathogenic B. fragilis group which comprises several multidrug-resistant (MDR) strains. Thus, it is of great interest to study the genome biology of Bacteroides nordii. However, no detailed study is available that characterized B. nordii at the genetic level and explored its role as a potential pathogen. We isolated an MDR strain viz., B. nordii PGMM4098 from the pus sample and subjected it to whole genome sequencing using Illumina technology. The draft genome was de-novo assembled and annotated, followed by comprehensive comparative genomics analyses using the publicly available genome dataset of B. nordii. The pan-genome analysis revealed the open nature of B. nordii, indicating the continuous accumulation of novel genes in non-core components leading to the emergence of new strains of this species. The thirteen antimicrobial resistance (AMR) genes identified in the genomes of all B. nordii strains were part of the non-core component of the pan-genome. Of these, four AMR genes, nimE, aadS, mef(En2), and ermB/F/G were found to be acquired via the process of horizontal gene transfer (HGT) from anaerobic Bacteroidetes. Importantly, the nimE gene conferring metronidazole resistance was found to be present only in B. nordii PGMM4098, which harbors five other AMR genes encoded in its genome. Of these, nimE (metronidazole resistance), ermB/F/G (macrolide-lincosamide-streptogramin B resistance), and cfxA2/A3 (class A ß-lactam resistance) genes were further validated using targeted polymerase chain reaction assay. Notably, these three genes were also found to be under the operation of positive selective pressure suggesting the diversification of these genes, which might lead to the emergence of new MDR strains of B. nordii in the near future. Our study reported and characterized the genome of the first MDR strain of B. nordii and revealed the AMR evolution in this species using a comprehensive comparative genomics approach.

Anticancer Activity of Cordia dichotoma against a Panel of Human Cancer Cell Lines and Their Phytochemical Profiling via HPLC and GCMS.

The current study was conducted to examine the in vitro anticancer potential of Cordia dichotoma (bark, leaves, pulp and seed). The plant material was collected from UT of J&K and methodical bioassays were carried out on ten human cancer cell lines (Michigan Cancer Foundation-7 (MCF-7), M.D. Anderson-Metastatic Breast (MDA-MB-231), Neuroblastoma-2a (N2A), SH-SY5Y, U-251, HCT-116, SW-620, A-549, MIA PaCa-2, Panc-1) from five different origins (breast, CNS, colon, lung, pancreas) respectively. Methanolic extracts were produced and fractions were then obtained from the extracts and evaluated for cytotoxicity. Mechanistic assays, HPLC, and GCMS profiling were performed on the highest active fraction. The Sulforhodamine B (SRB) assay determined the in vitro cytotoxicity. The findings revealed that the bark portion had in vitro cytotoxicity against the A-549 human lung cancer cell line. To our knowledge, this is the first study to show that the plant's bark has anticancer properties and induced chromatin condensation, confirmed cell death via ROS generation, and significantly decreased colony formation in A-549 cell line from lung origin in a dose-dependent manner. Furthermore, HPLC and GCMS investigations indicated the presence of a number of bioactive molecules such as gallic acid (144,969.86) uV*sec, caffeic acid (104.26) uV*sec, ferulic acid (472.87) uV*sec, vanillic acid (13,775.39) uV*sec, palmitic acid (18.34%), cis vaccenic acid (28.81%), etc. and one of the compounds was reported for the first time from the bark. As a result of its promising efficacy, it may become an essential cancer chemopreventive or chemotherapeutic medication for patients with lung carcinoma.

Single-Atom Catalysts: A Sustainable Pathway for the Advanced Catalytic Applications.

A heterogeneous catalyst is a backbone of modern sustainable green industries; and understanding the relationship between its structure and properties is the key for its advancement. Recently, many upscaling synthesis strategies for the development of a variety of respectable control atomically precise heterogeneous catalysts are reported and explored for various important applications in catalysis for energy and environmental remediation. Precise atomic-scale control of catalysts has allowed to significantly increase activity, selectivity, and in some cases stability. This approach has proved to be relevant in various energy and environmental related technologies such as fuel cell, chemical reactors for organic synthesis, and environmental remediation. Therefore, this review aims to critically analyze the recent progress on single-atom catalysts (SACs) application in oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, and chemical and/or electrochemical organic transformations. Finally, opportunities that may open up in the future are summarized, along with suggesting new applications for possible exploitation of SACs.

Cyanobacterial inoculation as resource conserving options for improving the soil nutrient availability and growth of maize genotypes.

Harnessing the benefits of plant-microbe interactions towards better nutrient mobilization and plant growth is an important challenge for agriculturists globally. In our investigation, the focus was towards analyzing the soil-plant-environment interactions of cyanobacteria-based formulations (Anabaena-Nostoc consortium, BF1-4 and Anabaena-Trichoderma biofilm, An-Tr) as inoculants for ten maize genotypes (V1-V10). Field experimentation using seeds treated with the formulations illustrated a significant increase of 1.3- to 3.8-fold in C-N mobilizing enzyme activities in plants, along with more than five- to six-fold higher values of nitrogen fixation in rhizosphere soil samples. An increase of 22-30% in soil available nitrogen was also observed at flag leaf stage, and 13-16% higher values were also recorded in terms of cob yield of V6 with An-Tr biofilm inoculation. Savings of 30 kg N ha-1 season-1 was indicative of the reduced environmental pollution, due to the use of microbial options. The use of cyanobacterial formulations also enhanced the economic, environmental and energy use efficiency. This was reflected as 37-41% reduced costs lowered GHG emission by 58-68 CO2 equivalents and input energy requirement by 3651-4296 MJ, over the uninoculated control, on hectare basis. This investigation highlights the superior performance of these formulations, not only in terms of efficient C-N mobilization in maize, but also making maize cultivation a more profitable enterprise. Such interactions can be explored as resource-conserving options, for future evaluation across ecologies and locations, particularly in the global climate change scenario.

Validation of the provisional seven-item criteria for the diagnosis of polyarteritis nodosa.

The 1990 American College of Rheumatology (ACR) criteria for the classification of polyarteritis nodosa (PAN) have many pitfalls and performed poorly when used for diagnostic purposes. Recently, a provisional seven-item diagnostic criteria for PAN was proposed. To validate the provisional seven-item diagnostic criteria for PAN in a cohort of PAN patients from a tertiary care centre in India. Clinical details of patients diagnosed as PAN as per the European Medicines Agency algorithm between 2005 and 2020 were collected retrospectively. Age and sex-matched anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients were included in the non-PAN group. Patients with a deficiency of adenosine deaminase 2 (DADA2) were included as a separate group. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for ACR criteria, the Ministry of Health, Labour and Welfare (MHLW) in Japan diagnostic criteria and the seven-item diagnostic criteria were calculated. Thirty-seven PAN, 14 DADA2 and 37 AAV patients were included in the analysis. The sensitivity, specificity, PPV and NPV of the seven-item criteria were 83.7%, 96.8%, 97.3% and 81.1% respectively. For the ACR criteria, sensitivity was 82.9% and specificity was 79.5%. The sensitivity, specificity for MHLW criteria were 77.3% and 90% respectively. The sensitivity and specificity of seven-item criteria for DADA2 patients were 58.8% and 88.2% respectively. There was very poor agreement between the ACR criteria and the seven-item and MHLW criteria and fair agreement between seven-item and MHLW criteria (κ = 0.279). The provisional seven-item criteria for PAN performed well with high specificity and PPV.

Transient recovery of epicardial and torso ST-segment ischemic signals during cardiac stress tests: A possible physiological mechanism.

BACKGROUND: Acute myocardial ischemia has several characteristic ECG findings, including clinically detectable ST-segment deviations. However, the sensitivity and specificity of diagnosis based on ST-segment changes are low. Furthermore, ST-segment deviations have been shown to be transient and spontaneously recover without any indication the ischemic event has subsided. OBJECTIVE: Assess the transient recovery of ST-segment deviations on remote recording electrodes during a partial occlusion cardiac stress test and compare them to intramyocardial ST-segment deviations. METHODS: We used a previously validated porcine experimental model of acute myocardial ischemia with controllable ischemic load and simultaneous electrical measurements within the heart wall, on the epicardial surface, and on the torso surface. Simulated cardiac stress tests were induced by occluding a coronary artery while simultaneously pacing rapidly or infusing dobutamine to stimulate cardiac function. Postexperimental imaging created anatomical models for data visualization and quantification. Markers of ischemia were identified as deviations in the potentials measured at 40% of the ST-segment. Intramural cardiac conduction speed was also determined using the inverse gradient method. We assessed changes in intramyocardial ischemic volume proportion, conduction speed, clinical presence of ischemia on remote recording arrays, and regional changes to intramyocardial ischemia. We defined the peak deviation response time as the time interval after onset of ischemia at which maximum ST-segment deviation was achieved, and ST-recovery time was the interval when ST deviation returned to below thresholded of ST elevation. RESULTS: In both epicardial and torso recordings, the peak ST-segment deviation response time was 4.9±1.1 min and the ST-recovery time was approximately 7.9±2.5 min, both well before the termination of the ischemic stress. At peak response time, conduction speed was reduced by 50% and returned to near baseline at ST-recovery. The overall ischemic volume proportion initially increased, on average, to 37% at peak response time; however, it recovered to only 30% at the ST-recovery time. By contrast, the subepicardial region of the myocardial wall showed 40% ischemic volume at peak response time and recovered much more strongly to 25% as epicardial ST-segment deviations returned to baseline. CONCLUSION: Our data show that remote ischemic signal recovery correlates with a recovery of the subepicardial myocardium, whereas subendocardial ischemic development persists.

Premature atrial stimulation accentuates conduction abnormalities in cardiac surgery patients that develop postoperative atrial fibrillation.

BACKGROUND: postoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF. METHODS: High-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity < 0.1, 0.1 ≤ x < 0.2 and < 0.2 m/s, respectively were quantified. RESULTS: For a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19 ± 6.59 versus 6.06 ± 4.22 mm2, p = 0.028) and CDCB (17.36 ± 8.75 versus 7.41 ± 6.39 mm2, p = 0.034), and a trend toward a larger area for CB (4.17 ± 3.66 versus 1.34 ± 2.86 mm2, p = 0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF. CONCLUSION: In comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in the posterior left atrial wall of cardiac surgery patients that developed POAF.