Genetic diversity, spatial connectivity, and population structure of Asian silurid catfish Wallago attu (Bloch and Schneider, 1801) in the Ganga River System: insights from mitochondrial DNA analysis.

BACKGROUND: The Ganga River System (GRS) is a biodiversity hotspot, its ecological richness is shaped by a complex geological history. In this study, we examined the genetic diversity, spatial connectivity, and population structure of the Asian Silurid catfish, Wallago attu, across seven tributaries of the GRS. METHODS AND RESULTS: We employed three mitochondrial DNA (mtDNA) regions: cytochrome c oxidase subunit I (COXI), cytochrome b (Cyt b), and control region (CR). Our comprehensive dataset encompassed 2420 bp of mtDNA, derived from 176 W. attu individuals across 19 sampling sites within the seven rivers of GRS. Our findings revealed high gene diversity (Hd:0.99) within W. attu populations. Analysis of Molecular Variance (AMOVA) highlighted that maximum genetic variations were attributed within the populations, and the observed genetic differentiation among the seven populations of W. attu ranged from low to moderate. Network analysis uncovered the presence of three distinct genetic clades, showing no specific association with seven studied rivers. Bayesian skyline plots provided insights into the demographic history of W. attu, suggesting a recent population expansion estimated to have occurred approximately 0.04 million years ago (mya) during the Pleistocene epoch. CONCLUSIONS: These results significantly enhance our understanding of the genetic diversity and spatial connectivity of W. attu, serving as a vital foundation for developing informed conservation strategies and the sustainable management of this economically valuable resource within the Ganga River System.

Comparison of intravascular ultrasound, optical coherence tomography, and conventional angiography-guided percutaneous coronary interventions: A systematic review, network meta-analysis, and meta-regression.

BACKGROUND: Intracoronary imaging modalities, including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), provide valuable supplemental data unavailable on coronary angiography (CA) and have shown to improve clinical outcomes. We sought to compare the clinical efficacy of IVUS, OCT, and conventional CA-guided percutaneous coronary interventions (PCI). METHODS: Frequentist and Bayesian network meta-analyses of randomized clinical trials were performed to compare clinical outcomes of PCI performed with IVUS, OCT, or CA alone. RESULTS: A total of 28 trials comprising 12,895 patients were included. IVUS when compared with CA alone was associated with a significantly reduced risk of major adverse cardiovascular events (MACE) (risk ratio: [RR] 0.74, 95% confidence interval: [CI] 0.63-0.88), cardiac death (RR: 0.64, 95% CI: 0.43-0.94), target lesion revascularization (RR: 0.68, 95% CI: 0.57-0.80), and target vessel revascularization (RR: 0.64, 95% CI: 0.50-0.81). No differences in comparative clinical efficacy were found between IVUS and OCT. Rank probability analysis bestowed the highest probability to IVUS in ranking as the best imaging modality for all studied outcomes except for all-cause mortality. CONCLUSION: Compared with CA, the use of IVUS in PCI guidance provides significant benefit in reducing MACE, cardiac death, and revascularization. OCT had similar outcomes to IVUS, but more dedicated studies are needed to confirm the superiority of OCT over CA.

Busulfan and cyclophosphamide-based conditioning regimen still holds the promise of being a safe and efficacious regimen for allogeneic transplantation in patients with transfusion-dependent thalassemia, even in high risk.

Busulfan and cyclophosphamide (BuCy)-based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan-based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion-dependent thalassemia (TDT) conducted at our institute (2013-2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1-12) and 9 (1-15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2-9.1) versus 5 (1.65-8.01) 106 /kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14-21) and 16 (9-47) days in Flu/Bu/Cy/ATG and 15 (10-20) and 13 (9-41) days in Treo/Thio/Flu group. Median duration of follow-up was 28 (23-32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients (p = .047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival (p = .038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival (p = .031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five-year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% (p = .251), 97 + 3% versus 80.7 + 6% (p = .041) and 100% versus 90.4 + 5% (p = .067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high-risk TDT. However, one needs to be vigilant for mixed chimerism.

The analgesic efficacy of intravenous dexamethasone for post-caesarean pain: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Analgesic efficacy of intravenous dexamethasone has not been well defined after caesarean delivery. We performed a systematic review and meta-analysis to evaluate the impact of peri-operative dexamethasone administration on postoperative pain after caesarean delivery. OBJECTIVES: We investigated the impact of perioperative intravenous dexamethasone on postoperative pain after caesarean delivery. The two primary outcomes of interest were early (4 to 6 h) resting pain scores and time to first rescue analgesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, EMBASE, Scopus and the Cochrane central registers of controlled trials were searched to identify RCTs from inception to April 2021. ELIGIBILITY CRITERIA: Prospective RCTs comparing the role of intravenous dexamethasone with non-active control were eligible for inclusion. Exclusion criteria included trials comparing various doses of dexamethasone without any control treatment arm, dexamethasone with other active drugs and trials comparing different routes of dexamethasone, for example, wound infiltration. RESULTS: Thirteen RCTs constituting of 988 parturients undergoing caesarean delivery were included. Patients receiving dexamethasone had lower pain scores at rest at 4 to 6 h after surgery, mean difference -1.29 [95% confidence interval (CI), -1.85 to -0.73], P < 0.0001, with low quality of evidence (I2 = 94%). Moderate quality of evidence (I2 = 17%) suggested that the time to first rescue analgesia in the dexamethasone group was significantly longer, mean difference 2.64 h (95% CI, 1.85 to 3.42), P  < 0.0001. Trial sequential analysis for pain scores suggested the benefit of dexamethasone; however, the requisite information size (RIS) could not be reached, whereas RIS was adequate for time to rescue analgesia. Significant reduction in pain scores at all times and opioid consumption at 24 h with dexamethasone were observed with sparse reporting on adverse effects. CONCLUSION: Peri-operative intravenous dexamethasone was associated with a significant decrease in postoperative pain scores at rest and a longer time to first rescue analgesia, along with a small but statistically significantly reduced opioid consumption after caesarean delivery compared with nonactive control.

Experience with combination of hydroxyurea and low-dose thalidomide in transfusion-dependent beta thalassemia patients.

Hydroxyurea (HU) and thalidomide have been reported to improve clinical and hematological parameters in transfusion-dependent beta thalassemia (TDT). Therefore, we retrospectively analyzed the combination of HU and thalidomide in 140 transplant ineligible TDT, ≥ 10 years old, visiting our thalassemia clinic between October 2014 and November 2019. Responses were defined as maintenance of hemoglobin ≥9gm/dl without transfusion as complete response (CR) and with at least 50% reduction in transfusion burden as partial response (PR). Patients with less than 50% transfusion burden reduction for consecutive 6 months of therapy were defined as non-responders (NR), and treatment was discontinued thereafter. Primary end point was overall response rate (ORR) at last follow-up. At median follow-up of 22.6 (95% CI 16.4-28.7) months, 76 (57.2%) patients achieved CR and 19 (14.3%) achieved PR, accounting to an ORR of 71.5%. Among responders at last follow-up, a significant increase in the post-treatment hemoglobin (0.88±0.37gm/dl, p<0.0001) and drop in serum ferritin (-1490.5ng/ml, p<0.0001) were observed. Median time to CR was 124 (95% CI 75.3-172.6) days. Median longest continuous CR was 791 (95% CI 662.2-919.7) days. Common toxicities observed were sedation (25%), hyperbilirubinemia {(23.57%, grade 3/4 =17 (12.14%)}, and constipation (22.8%). Nearly three-fourth of the patients has responded with majority having CR. Adverse events are a concern; hence, regular close monitoring is a prerequisite.

Follow-up colonoscopy after an abnormal stool-based colorectal cancer screening result: analysis of steps in the colonoscopy completion process.

BACKGROUND: Delays in receiving follow-up colonoscopy after an abnormal fecal immunochemical test (FIT) result are associated with increased colorectal cancer incidence and mortality. Little is known about patterns of follow-up colonoscopy completion in federally qualified health centers. METHODS: We abstracted the medical records of health center patients, aged 50-75 years, who had an abnormal FIT result between August 5, 2017 and August 4, 2018 (N = 711). We assessed one-year rates of colonoscopy referral, pre-procedure visit completion, colonoscopy completion, and time to colonoscopy; associations between these outcomes and patient characteristics; and reasons for non-completion found in the medical record. RESULTS: Of the 711 patients with an abnormal FIT result, 90% were referred to colonoscopy, but only 52% completed a pre-procedure visit, and 43% completed a colonoscopy within 1 year. Median time to colonoscopy was 83 days (interquartile range: 52-131 days). Pre-procedure visit and colonoscopy completion rates were relatively low in patients aged 65-75 (vs. 50-64), who were uninsured (vs. insured) or had no clinic visit in the prior year (vs. ≥ 1 clinic visit). Common reasons listed for non-completion were that the patient declined, or the provider could not reach the patient. DISCUSSION: Efforts to improve follow-up colonoscopy rates in health centers might focus on supporting the care transition from primary to specialty gastroenterology care and emphasize care for older uninsured patients and those having no recent clinic visits. Our findings can inform efforts to improve follow-up colonoscopy uptake, reduce time to colonoscopy receipt, and save lives from colorectal cancer. TRIAL REGISTRATION: National Clinical Trial (NCT) Identifier: NCT03925883.

First-principles study of a 2-dimensional C-silicyne monolayer as a promising anode in Na/K ion secondary batteries.

With the depleting resources of energy and increasing demand, the need for sustainable and renewable energy resources has become the need of the hour. The low storage capacity of current materials for Na/K ion batteries has led to the quest to identify suitable materials for an electrode with excellent electrochemical properties. In the present work, a systematic theoretical investigation of C-silicyne, a planar 2-dimensional hexagonal lattice, is performed to establish the geometric and thermal properties and stability. The electronic properties illustrate the metallic nature of C-silicyne, which is conserved even after the effective adsorption of Na/K ions on the surface of the monolayer. For the practical functionality, the storage capacity of C-silicyne is evaluated as 591 mA h g-1 for Na ions and 443 mA h g-1 for K ions. Moreover, the low diffusion barriers for the Na (0.57 eV) and K (0.34 eV) ions display their feasible movement across the monolayer as the electrochemical cycle progresses. The average working voltage is found to lie in the range of 0.1-1 V, which is required for the effective functioning of the anode in a Na/K ion battery. These results demonstrate the potential of C-silicyne as a material for the anode in Na/K ion batteries.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

Impact of COVID-19 on life expectancy at birth in India: a decomposition analysis.

BACKGROUND: Quantifying excess deaths and their impact on life expectancy at birth (e0) provide a more comprehensive understanding of the burden of coronavirus disease of 2019 (COVID-19) on mortality. The study aims to comprehend the repercussions of the burden of COVID-19 disease on the life expectancy at birth and inequality in age at death in India. METHODS: The mortality schedule of COVID-19 disease in the pandemic year 2020 was considered one of the causes of death in the category of other infectious diseases in addition to other 21 causes of death in the non-pandemic year 2019 in the Global Burden of Disease (GBD) data. The measures e0 and Gini coefficient at age zero (G0) and then sex differences in e0 and G0 over time were analysed by assessing the age-specific contributions based on the application of decomposition analyses in the entire period of 2010-2020. RESULTS: The e0 for men and women decline from 69.5 and 72.0 years in 2019 to 67.5 and 69.8 years, respectively, in 2020. The e0 shows a drop of approximately 2.0 years in 2020 when compared to 2019. The sex differences in e0 and G0 are negatively skewed towards men. The trends in e0 and G0 value reveal that its value in 2020 is comparable to that in the early 2010s. The age group of 35-79 years showed a remarkable negative contribution to Δe0 and ΔG0. By causes of death, the COVID-19 disease has contributed - 1.5 and - 9.5%, respectively, whereas cardiovascular diseases contributed the largest value of was 44.6 and 45.9%, respectively, to sex differences in e0 and G0 in 2020. The outcomes reveal a significant impact of excess deaths caused by the COVID-19 disease on mortality patterns. CONCLUSIONS: The COVID-19 pandemic has negative repercussions on e0 and G0 in the pandemic year 2020. It has severely affected the distribution of age at death in India, resulting in widening the sex differences in e0 and G0. The COVID-19 disease demonstrates its potential to cancel the gains of six to eight years in e0 and five years in G0 and has slowed the mortality transition in India.

A Meta-analysis and Systematic Review of Valvular Heart Disease in Systemic Lupus Erythematosus and Its Association With Antiphospholipid Antibodies.

BACKGROUND: Valvular heart disease (VHD) is a known cardiac manifestation of systematic lupus erythematosus (SLE). This systematic review aims to pool data from studies to estimate the frequency of valvular lesions in SLE patients. It also aims to demonstrate the association between VHD in SLE and antiphospholipid antibodies positivity. METHODS: We included 27 studies after identifying relevant abstracts from PubMed, Scopus, and Google Scholar from the time of inception of database to 2019. Inclusion criteria consisted of English-language case-control and cohort studies. Three reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale for assessing risk for bias. RESULTS: For VHD in SLE patients, the most commonly involved valve was the mitral valve, with 19.7% lesions being mitral regurgitation. In terms of morphological lesions, valve thickening (11.06%) and vegetations (11.76%) were among the most prevalent. Other commonly encountered lesions were mitral valve prolapse and tricuspid regurgitation in 9.25% and 10.86% of patients, respectively. A meta-analysis of 21 studies with 2163 SLE patients, of which 23.3% had valvular lesions, showed a significant association of anticardiolipin antibodies positivity with VHD (relative risk, 1.55; confidence interval, 1.10-2.18). CONCLUSIONS: Systemic lupus erythematosus is associated with VHD, and it should be considered a clinical manifestation of SLE in the absence of other valvular pathologies. There is a clear association between VHD in SLE and immunoglobulin G anticardiolipin antibodies positivity. This association suggests that this subgroup of SLE patients might benefit from a screening echocardiogram.

Advances in the Pharmacogenomics of Antiplatelet Therapy.

BACKGROUND: Acute coronary syndrome (ACS) is a highly thrombotic state, and a sustained antiplatelet effect is vital to the prevention of thrombotic complications. Clopidogrel, the most widely used oral P2Y12 receptor antagonist in ACS, has attracted considerable attention because of significant variability in antiplatelet effect depending on the presence of CYP2C19 allele. Other P2Y12 receptor antagonists offer sustained and more predictable antiplatelet effects than clopidogrel albeit at an increased cost. Several studies have demonstrated the promising application of pharmacogenetics in choosing personalized antiplatelet therapy using the point-of-care genotype assays. AREAS OF UNCERTAINTY: Guidelines regarding the genotype-guided approach to the selection of antiplatelet therapy have been conflicting, and studies evaluating the effect of pharmacogenetic-guided selection of antiplatelet therapy on the outcomes have demonstrated mixed results. DATA SOURCES: A literature search was conducted using MEDLINE and EMBASE for studies reporting the association of pharmacogenetic-guided selection of antiplatelet therapy and the outcomes in patients with ACS until December 2018. RESULTS: Presence of specific CYP2C19 allele significantly influences clopidogrel metabolism and associated outcomes in patients with ACS. Thrombotic and bleeding complications are more common in patients with loss-of-function (LOF) and gain-of-function (GOF) alleles, respectively. Although the pharmacogenetic-guided approach to the selection of antiplatelet therapy appears promising in ACS, studies have shown conflicting results, and direct randomized evidence linking this approach with the better outcomes is lacking. CONCLUSIONS: Genotype-guided selection of antiplatelet therapy is expected to be useful in patients undergoing percutaneous coronary intervention (PCI) with a high risk of adverse outcomes. The patient-physician discussion should be an essential part of this decision-making process. Large-scale multicenter randomized controlled trials using the point-of-care genotype assay are needed to investigate this approach further before its use can be recommended in all comers.

Rate and impact of venous thromboembolism in patients with ST-segment elevation myocardial infarction: Analysis of the Nationwide Inpatient Sample database 2003-2013.

Venous thromboembolism (VTE) and coronary artery disease are major health issues that cause substantial morbidity and mortality. New data have emerged suggesting that these two conditions could have a close relationship. Thus, we sought to determine the trends in annual rate of VTE occurrence in patients with ST-segment elevation myocardial infarction (STEMI) and measure its impact on in-hospital mortality, bleeding complications, and cost and length of hospitalization. We queried the 2003-2013 Nationwide Inpatient Sample databases to identify adults with primary diagnosis of STEMI. VTE events were then allocated. Inpatient outcomes of patients with VTE were compared to those without VTE. Out of 2,495,757 hospitalizations for STEMI, VTE was diagnosed in 25,149 (1%) hospitalizations. Patients who experienced VTE were older (mean age: 67.5 vs 64.8, p < 0.01) and had a higher proportion of black patients (10.1% vs 7.7%, p < 0.001) and females (40.1% vs 35%, p < 0.001) compared to patients without VTE. There was an increasing trend in the rate of VTE during the study period (2003: 0.8% vs 2013: 1.0%, p < 0.001). Patients with VTE had a prolonged hospitalization (median: 9 vs 3 days, p < 0.001), increased cost, higher risk of gastrointestinal bleeding (OR: 2.13, p < 0.001), intracranial hemorrhage (OR: 2.14, p < 0.001), blood transfusions (OR: 1.94, p < 0.001), and mortality (OR: 1.39, p < 0.001). The rate of VTE occurrence in patients with STEMI in our study was 10 per 1000 admissions. VTE was associated with more bleeding complications, longer hospital stays, higher costs, and mortality. These findings suggest that a more aggressive approach for VTE prophylaxis may be warranted in this population.

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma.

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23-68 years). Median time from diagnosis to transplant was 7 months (3-79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9-144.7 months) and 73.8 months (95% C.I. 57.7-89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p = 0.024), while OS was better with CR/VGPR post-ASCT (p < 0.001) and lenalidomide maintenance therapy (p = 0.009). PFS was affected by CR/VGPR pre-ASCT (p = 0.021), CR/VGPR post-ASCT (p < 0.001), and transplant in first remission (p = 0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p = 0.007) and CR/VGPR response post-ASCT (p = 0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p = 0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p = 0.073). CONCLUSION: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.

Synthesis, pharmacological evaluation and molecular docking of pyranopyrazole-linked 1,4-dihydropyridines as potent positive inotropes.

1,4-Dihydropyridines are well-known calcium channel blockers, but variations in the substituents attached to the ring have resulted in their role reversal making them calcium channel activators in some cases. We describe the microwave-assisted eco-friendly approach for the synthesis of pyranopyrazole-1,4-dihydropyridines, a new class of 1,4-DHPs, under solvent-free conditions in good yield, and screen them for various in silico, in vitro and in vivo activities. The in vivo experimentation results show that the compounds possess positive inotropic effect, and the docking results validate their good binding with calcium channels. Compounds 7c, 7g and 7i appear to be the most effective positive inotropes, even at low doses, and bind with the calcium channels even more strongly than Bay K 8644, a well-known calcium channel activator. The chronotropic effect for the new compounds was also studied. The target and off-target affinity profiling supported the in vivo results and revealed that the hybridized pyranopyrazole dihydropyridine scaffold has delivered new moderate hits, to be optimized, for the cytochrome P450 3A4 enzymes, opening avenues for combined pharmacological activity through standard structural modification.

Effect of GA3 and calcium on growth, biochemical, and fatty acid composition of linseed under chloride-dominated salinity.

The accumulation of salts in soil is an environmental threat affecting plant growth and crop yield. Linseed or flax is an ancient crop that has multifarious utilities in terms of industrial oil, textile fiber, and products. Salt susceptibility adversely affects linseed production, particularly to meet the growing demand for nutritional and nutraceutical products. In the present study, the ameliorative potential of gibberellic acid (GA3) and calcium (Ca2+) in mitigating the adverse effects of chloride-dominated salinity stress on the growth and physiological and biochemical processes in linseed was determined. Severe salinity treatment (10 dSm-1) resulted in stunted growth of tested linseed genotypes causing a significant reduction in biomass while proline content, phenol, H2O2, lipid peroxidation, and DPPH activity were increased in comparison to control. The exogenous application of 10-6 M GA3 and/or 10 mg CaCl2 kg-1 was found to mitigate the adverse effects of salinity stress. The mitigation was accomplished through the improvement of growth indicators, increased osmoprotectants such as proline and phenol content, stimulating DPPH activity, and reduction of H2O2 content and lipid peroxidation. The comparative evaluation of different saline treatments imposed individually and in combination with GA3 and Ca2+ revealed that combined GA3 and Ca2+ application exhibited synergistic effects and was most effective in mitigating the negative impacts of salt stress. The present study unravels the ameliorative role of GA3 and Ca2+ (individual or combined) in the physiologic-biochemical adaptive response of linseed plants grown under chloride-dominated salinity and thus aids in a better understanding of the underlying tolerance mechanisms of plants to withstand stress in saline environments.

Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.

Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa. In the year 1966, the Noble prize was awarded to Huggins and Hodge for their groundbreaking discovery of AR. As it is a pioneer transcription factor, it belongs to the steroid hormone receptor family and consists of domains, including DNA binding domain (DBD), hormone response elements (HRE), C-terminal ligand binding domain (LBD), and N-terminal regulatory domains. Structural variations in AR, such as AR gene amplification, LBD mutations, alternative splicing of exons, hypermethylation of AR, and co- regulators, are major contributors to PCa. It's signaling is crucial for the development and functioning of the prostate gland, with the AR being the key player. The specificity of AR for testosterone and dihydrotestosterone is important in prostate physiology. However, when it is dysregulated, AR contributes significantly to PCa. However, the structural variations in AR, such as gene amplification, mutations, alternative splicing, and epigenetic modifications, drive the PCa progression. Therefore, understanding AR function and dysregulation is essential for developing effective therapeutic strategies. Thus, the aim of this review was to examine how AR was initially pivotal for prostate development and how it turned out to show both positive and detrimental implications for the prostate.

Assessing 30-day readmissions and outcomes in acute heart failure patients with concurrent COVID-19: A nationwide study during the 2020 pandemic.

BACKGROUND: Acute heart failure (HF) is a significant cause of readmission and mortality, particularly within 30 days post-discharge. The interplay between COVID-19 and HF is still being studied. METHODS: This retrospective study utilized The National Readmission Database to examine outcomes and predictors among patients with COVID-19 and concomitant acute HF between January 1, 2020, and November 31, 2020. 53,336 index hospitalizations and 8,158 readmissions were included. The primary outcome was the 30-day all-cause readmission rate. Predictor variables included patient demographics, medical comorbidities and discharge disposition. RESULTS: The primary outcome was 21.2 %. COVID-19 infection was the most predominant all-cause reason for acute HF readmission (24.7 %). Hypertensive heart disease with chronic kidney disease was the most prevalent cardiac cause (7.7 %). Mortality rate during index hospitalization was significantly higher compared to readmission. CONCLUSIONS: The highlighted prevalent complications, comorbidities, and demographics driving readmissions offer valuable insights to improve outcomes in this population.

Comparative Outcomes of Peritoneal and Hemodialysis in ESRD Patients with STEMI: A National Inpatient Sample Analysis (2016-2020).

End-stage renal disease (ESRD) patients are at increased risk of mortality, particularly due to cardiovascular events such as acute myocardial infarction. Hemodialysis and peritoneal dialysis are the two main treatment modalities for ESRD patients. Using data from the National Inpatient Sample (NIS) database, we conducted a retrospective study involving 25,435 ESRD patients diagnosed with ST-elevation myocardial infarction (STEMI) between 2016 and 2020, categorized by their dialysis regimen. Our analysis revealed comparable mortality rates between peritoneal dialysis (PD) and hemodialysis (HD) patients, but lower hospitalization costs and fewer complications among PD recipients. Over five years, we observed a notable decrease in STEMI mortality despite increased STEMI cases among HD patients. Conversely, HD patients experienced increased hospital stays and associated costs over the study period than PD patients, who demonstrated stable trends. This study highlights the implications of dialysis modality selection in managing costs and reducing morbidity among STEMI patients with ESRD.

Interference of hemoglobin variants in HbA1c quantification.

Fasting blood glucose and glycated hemoglobin (HbA1c) are routine biomarkers to screen and monitor diabetes mellitus. HbA1c results from glycation at the N-terminus of the ß globin chain of tetrameric human hemoglobin. Fasting blood glucose level varies with the nature and amount of food intake, physical exercise, etc., and, accordingly, is a short-term measure of glucose control. In contrast, HbA1c provides an average measure of glucose control for the long-term (8-12 weeks). Unfortunately, genetic variants of hemoglobin may interfere with HbA1c quantification using ion exchange chromatography, capillary electrophoresis, immunoassay and boronate affinity chromatography. Mass spectrometry, however, measures total glycation of hemoglobin across both α and ß globin chains and correlates well with the ion exchange based method. Additionally, mass spectrometry based quantification is not impacted by the presence of genetic variants of hemoglobin and thus might be a better analytical choice for diabetes mellitus.