Antiarrhythmic drug therapy and catheter ablation in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF. METHODS: We searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software. RESULTS: Twelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups. CONCLUSIONS: For symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.

Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Biogenic engineered zinc oxide nanoparticle for sulfur black dye removal from contaminated wastewater: comparative optimization, simulation modeling, and isotherms.

This research work aimed to isolate and culture the bacterium Bacillus paramycoides for biogenic fabrication of zinc oxide nanoparticles, specifically ZnO and ZnO-ME nanoparticles (nanoparticles fabricated from bacterial extracts only - ZnO, and from bacterial cell mass including extract - ZnO-ME). SEM investigation revealed the spherical-shaped NPs with 22.33 and 39 nm in size for ZnO and ZnO-ME, respectively. The Brunauer, Emmett, and Teller (BET) studies revealed mesoporous structure with pore diameters of 13.839 and 13.88 nm and surface area of 7.617 and 33.635 m2/gm for ZnO and ZnO-ME, respectively. Various parameters for the adsorption of sulfur black dye onto both ZnO and ZnO-ME were screened and optimized using Plackett-Burman Design (PBD), Full Factorial Design (FFD) and Central Composite Design (CCD). The results of the optimization modeling study revealed that FFD yielded the most predictable and best-fitting results among all the models studied, with R2 values of 0.998 for ZnO and 0.993 for ZnO-ME. Notably, ZnO-ME exhibited a greater dye removal efficiency 80% than ZnO i.e., 71%, it may be due to the presence of amorphous carbon on the surface of ZnO-ME. Among the various isothermal models, the Freundlich model displayed the strongest correlation with the dye removal data, confirming the multilayer adsorption of dye on both nanoparticles and supporting physisorption. Therefore, ZnO and ZnO-ME nanoparticles have been proven as potential tools for mitigating environmental impacts associated with dye-containing wastewater.

Improving healthcare quality by unifying the American electronic medical report system: time for change.

BACKGROUND: In recent years, innovation in healthcare technology has significantly improved the efficiency of the healthcare system. Advancements have led to better patient care and more cost-effective services. The electronic medical record (EMR) system, in particular, has enhanced interoperability and collaboration across healthcare departments by facilitating the exchange and utilization of patient data. The COVID-19 pandemic further accelerated this trend, leading to a surge in telemedicine services, which rely on electronic communication to deliver healthcare remotely. MAIN BODY: Integrating artificial intelligence (AI) and machine learning (ML) in healthcare have been instrumental in analyzing vast data sets, allowing for identifying patterns and trends that can improve care delivery and pinpoint potential issues. The proposal of a unified EMR system in the USA aims to capitalize on these technological advancements. Such a system would streamline the sharing of patient information among healthcare providers, improve the quality and efficiency of care, and minimize the likelihood of errors in patient treatment. CONCLUSION: A unified electronic medical record system represents a promising avenue for enhancing interoperability within the US healthcare sector. By creating a more connected and accessible network of patient information, it sets the stage for a transformation in healthcare delivery. This change is imperative for maintaining the momentum of progress in healthcare technology and realizing the full potential of recent advancements in patient care and system efficiency.

Evaluating the efficacy of different volume resuscitation strategies in acute pancreatitis patients: a systematic review and meta-analysis.

INTRODUCTION: Acute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive. METHODS: A comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to < 20 ml/kg/h), and low (5 to < 10 ml/kg/h) fluid therapy in acute pancreatitis were considered. RESULTS: Twelve studies met our inclusion criteria. Results indicated improved clinical outcomes with low versus moderate fluid therapy (OR = 0.73; 95% CI [0.13, 4.03]; p = 0.71) but higher mortality rates with low compared to moderate (OR = 0.80; 95% CI [0.37, 1.70]; p = 0.55), moderate compared to high (OR = 0.58; 95% CI [0.41, 0.81], p = 0.001), and low compared to high fluids (OR = 0.42; 95% CI [0.16, 1.10]; P = 0.08). Systematic complications improved with moderate versus low fluid therapy (OR = 1.22; 95% CI [0.84, 1.78]; p = 0.29), but no difference was found between moderate and high fluid therapy (OR = 0.59; 95% CI [0.41, 0.86]; p = 0.006). DISCUSSION: This meta-analysis revealed differences in the clinical outcomes of patients with AP receiving low, moderate, and high fluid resuscitation. Low fluid infusion demonstrated better clinical outcomes but higher mortality, systemic complications, and SIRS persistence than moderate or high fluid therapy. Early fluid administration yielded better results than rapid fluid resuscitation.

Mortality and mode of dialysis: meta-analysis and systematic review.

BACKGROUND: The global use of kidney replacement therapy (KRT) has increased, mirroring the incidence of acute kidney injury and chronic kidney disease. Despite its growing clinical usage, patient outcomes with KRT modalities remain controversial. In this meta-analysis, we sought to compare the mortality outcomes of patients with any kidney disease requiring peritoneal dialysis (PD), hemodialysis (HD), or continuous renal replacement therapy (CRRT). METHODS: The investigation was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Cochrane Library, and Embase databases were screened for randomized trials and observational studies comparing mortality rates with different KRT modalities in patients with acute or chronic kidney failure. A random-effects model was applied to compute the risk ratio (RR) and 95% confidence intervals (95%CI) with CRRT vs. HD, CRRT vs. PD, and HD vs. PD. Heterogeneity was assessed using I2 statistics, and sensitivity using leave-one-out analysis. RESULTS: Fifteen eligible studies were identified, allowing comparisons of mortality risk with different dialytic modalities. The relative risk was non-significant in CRRT vs. PD [RR = 0.95, (95%CI 0.53, 1.73), p = 0.92 from 4 studies] and HD vs. CRRT [RR = 1.10, (95%CI 0.95, 1.27), p = 0.21 from five studies] comparisons. The findings remained unchanged in the leave-one-out sensitivity analysis. Although PD was associated with lower mortality risk than HD [RR = 0.78, (95%CI 0.62, 0.97), p = 0.03], the significance was lost with the exclusion of 4 out of 5 included studies. CONCLUSION: The current evidence indicates that while patients receiving CRRT may have similar mortality risks compared to those receiving HD or PD, PD may be associated with lower mortality risk compared to HD. However, high heterogeneity among the included studies limits the generalizability of our findings. High-quality studies comparing mortality outcomes with different dialytic modalities in CKD are necessary for a more robust safety and efficacy evaluation.

Simple cryopreservation protocol for Luffa pollen: enhancing breeding efficiency.

This study aimed to develop a long-term pollen storage protocol for Luffa species (L. acutangula, L. cylindrica, L. echinata, and L. graveolens) and assess its potential for crop improvement. The optimal medium for in vitro pollen germination varied by species, with Brewbaker and Kwack (BK) medium with 10% sucrose suitable for L. acutangula, L. cylindrica, and L. echinata, and BK medium with 3% sucrose ideal for L. graveolens. Overestimation in staining tests compared to in vitro pollen germination was observed. The best results for cryopreservation were achieved with desiccation periods of 20, 30, and 40 min, maintaining moisture content between 14.04% and 18.55%. Pollen viability was negatively correlated with storage temperature (25, 4, and -20°C) and duration. Cryopreserved pollen at -196°C exhibited the highest viability over a prolonged period (2 months) and was comparable to fresh pollen in terms of germination, ovule fertilization, and fruit and seed set. This study presents a simple and reproducible pollen cryopreservation protocol applicable across Luffa species, facilitating long-term storage and its use in crop improvement efforts.

Recent Progress in Synthesis, POM Analyses and SAR of Coumarin-Hybrids as Potential Anti-HIV Agents-A Mini Review.

The human immunodeficiency virus (HIV) is the primary cause of acquired immune deficiency syndrome (AIDS), one of the deadliest pandemic diseases. Various mechanisms and procedures have been pursued to synthesise several anti-HIV agents, but due to the severe side effects and multidrug resistance spawning from the treatment of HIV/AIDS using highly active retroviral therapy (HAART), it has become imperative to design and synthesise novel anti-HIV agents. Literature has shown that natural sources, particularly the plant kingdom, can release important metabolites that have several biological, mechanistic and structural representations similar to chemically synthesised compounds. Certainly, compounds from natural and ethnomedicinal sources have proven to be effective in the management of HIV/AIDS with low toxicity, fewer side effects and affordability. From plants, fungi and bacteria, coumarin can be obtained, which is a secondary metabolite and is well known for its actions in different stages of the HIV replication cycle: protease, integrase and reverse transcriptase (RT) inhibition, cell membrane fusion and viral host attachment. These, among other reasons, are why coumarin moieties will be the basis of a good building block for the development of potent anti-HIV agents. This review aims to outline the synthetic pathways, structure-activity relationship (SAR) and POM analyses of coumarin hybrids with anti-HIV activity, detailing articles published between 2000 and 2023.

Ecological engineering in low land rice for brown plant hopper, Nilaparvata lugens (Stål) management.

Rice field bunds and edges can act as near crop habitats, available for planting flowering plants to attract and conserve the natural enemies. We evaluated the effect of ecological engineering on the incidence of Brown Planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera; Delphacidae) and the abundance of its predators in the rice variety Pusa Basmati-1121. Plots included the oilseed crops viz. sesamum, sunflower and soybean, with plantings of flowering crops marigold, balsam and gaillardia as bund flora around the edges of rice plots. Ecologically engineered plots contained both crops+flowers and resulted in a significantly reduced BPH population per hill in rice plots for 2019 (6.3) and 2020 (9.4) compared to the control plots (9.8 and 14.4). Ecologically engineered plots also witnessed the delayed appearance of BPH during each growing season. Peak BPH populations are lower in the ecologically engineered plots than in the control grounds. Furthermore, the activity of natural enemies, viz., spiders, mirid bugs and rove beetles was the highest in rice fields planted with oilseed crops like sesamum, sunflower and soybean. Olfactory response studies showed that the attraction response of spiders toward sesamum and balsam leaves was more significant than in other crop plants. Rice yield was enhanced in plots planted with crops+flowers during both seasons compared to control plots. Planting of oilseed crops plants such as sesamum, sunflower and soybean with flowering crops such as marigold, balsam and gaillardia as bund flora on the bunds around the main rice field enhanced the natural enemy activity, suppressed the planthopper population, and increased yields. Based on the results, we recommend including ecological engineering techniques as one of the management components in the Integrated Pest Management programme for rice crops.

Sequestration of Ni (II), Pb (II), and Zn (II) utilizing biogenic synthesized Fe3O4/CLPC NCs and modified Fe3O4/CLPC@CS NCs: Process optimization, simulation modeling, and feasibility study.

The present study reports low-cost novel biogenic magnetite Citrus limetta peels carbon (Fe3O4/CLPC) nanocomposites and modified Fe3O4/CLPC@CS nanocomposites cross-linked with glutaraldehyde and subsequently employed in batch mode sequestration of heavy metals ions. Diverse techniques fully characterized them, and the influence of operating variables on adsorption reactions from aqueous solutions was investigated. The Brunauer, Emmett, and Teller (BET) surface areas of synthesized Fe3O4/CLPC and Fe3O4/CLPC@CS NCs were 53.91 and 32.16 m2/g, while the mesoporous diameters were 7.69 and 7.57 nm, respectively. The Langmuir isotherm and Pseudo second order kinetic were well-fitting and capable of explaining the adsorption reaction. The Langmuir-based monolayer adsorption (qmax) for Fe3O4/CLPC@CS NCs was 82.65, 95.24, and 64.10 mg/g, higher than Fe3O4/CLPC NCs, which were 70.92, 84.75, and 59.17 mg/g for Ni (II), Pb (II), and Zn (II), respectively. Each metal's pseudo second order correlation coefficient (R2 ≥ 0.99) reveals that nanocomposites surface binding functional groups controlled the adsorption rate via chemisorption. Further, thermodynamic results confirm that each studied metal ions' adsorption was spontaneous, endothermic, and characterized by an increase in randomness. In addition to magnetic separability, three ad-desorption cycles yielded exceptional adsorption efficacy and > 93% regenerability. The present study also reveals the effective utilization of Fe3O4/CLPC and Fe3O4/CLPC@CS NCs as cost-effective magnetic separable green adsorbents for heavy metals sequestration from electroplating wastewater.

Gender and racial differences in first and senior authorship of high-impact critical care randomized controlled trial studies from 2000 to 2022.

BACKGROUND: Females and ethnic minorities are underrepresented in the first and senior authorships positions of academic publications. This stems from various structural and systemic inequalities and discrimination in the journal peer-review process, as well as educational, institutional, and organizational cultures. METHODS: A retrospective bibliometric study design was used to investigate the representation of gender and racial/ethnic groups in the authorship of critical care randomized controlled trials in 12 high-impact journals from 2000 to 2022. RESULTS: In the 1398 randomized controlled trials included in this study, only 24.61% of the first authors and 16.6% of the senior authors were female. Although female authorship increased during the study period, authorship was significantly higher for males throughout (Chi-square for trend, p < 0.0001). The educational attainment [χ2(4) = 99.2, p < 0.0001] and the country of the author's affiliated institution [χ2(42) = 70.3, p = 0.0029] were significantly associated with gender. Male authorship was significantly more prevalent in 10 out of 12 journals analyzed in this study [χ2(11) = 110.1, p < 0.0001]. The most common race/ethnic group in our study population was White (85.1% women, 85.4% males), followed by Asians (14.3% females, 14.3% males). Although there was a significant increase in the number of non-White authors between 2000 and 2022 [χ2(22) = 77.3, p < 0.0001], the trend was driven by an increase in non-White male and not non-White female authors. Race/ethnicity was significantly associated with the country of the author's affiliated institution [χ2(41) = 1107, p < 0.0001] but not with gender or educational attainment. CONCLUSIONS: Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.

Clinical Profile and Outcome of Snake Bite Patients from Tertiary Healthcare Center: In Sub-Himalayan Region: A Medical College-based Study.

OBJECTIVE: Snake bite is an emergency in tropical and subtropical countries. It is a neglected disease and is most commonly seen in rural setups, where people are ignorant about the venomous snake bites. It results in increased mortality and morbidity because precious time is wasted, either in consulting traditional healers or waiting for the development of signs and symptoms of envenomation. Then only the patient is shifted to a health center. Here we studied the clinical profile, management, and outcome of snake bite patients. MATERIALS AND METHODS: This study was done by retrieving the records of patients with snake bites admitted to the Department of Medicine, Indira Gandhi Medical College & Hospital, Shimla, from 1st January 2017 through December 2019. The recorded data was entered in a precoded performa, and analysis was done with respect to various variables. RESULT: We evaluated the records of 190 patients. The incidence of the bite was higher among females, 62.1% (n = 118). The commonest age group involved was 21-50 years, 70.1% (n = 34). In 55.8% (n = 106), the site of the bite was the upper limb. The daytime bite was present in 54.7% (n = 106). The maximum incidence of snake bites was found during the rainy season, 81.5% (n = 155). 28.4% (n = 54) of patients presented within 6 hours of the bite. Coagulopathy [whole blood clotting test (WBCT) of >20 minutes] and neurotoxicity were seen in 77.9 and 7.9% of patients, respectively. Anti-snake venom (ASV) was given to 87.8% (n = 167) of patients. In 80% (n = 152) of the cases, hospital stay was up to 3 days. Mortality was seen in only two (1.05%) cases. CONCLUSION: There is a need to create awareness among the community, particularly in rural areas, about snake bite envenomation and early transportation of victims to the nearest health center. Training of health professionals is also needed to manage cases of snake bites efficiently and judiciously, thereby reducing morbidity and morbidity.

Wheat as a new host for potato aphid Macrosiphum euphorbiae Thomas (Hemiptera: Aphididae) and construction of its age-stage two-sex life tables.

Wheat (Triticum aestivum L.) is the major global staple food crop that meets the food security demands of various nations across the continents. The recent reduction in wheat production is attributed to several biotic and abiotic factors especially, temperature and rainfall patterns, and pest occurrence. Among insect pests, aphid species are emerging as new pests of economic importance in India and elsewhere. The present investigation identified a new association of Macrosiphum euphorbiae Thomas with the wheat crop. Life table parameters were studied for M. euphorbiae and Rhopalosiphum padi fed on wheat foliage. The total nymphal duration and life cycle duration, respectively, of R. padi (4.76 ± 0.54 and 9.71 ± 1.38 days) and M. euphorbiae (5.84 ± 0.69 and 9.96 ± 1.31 days) were significantly different for these species. The fecundity of the two aphid species was 23.95 ± 8.67 and 11.6 ± 4.10 progeny/female, respectively. Age-specific survival rate (lx), age-specific fecundity (fx), and population age-specific fecundity (mx) were higher in R. Padi compared to M. euphorbiae. Reproductive value (Vxj) was high in R. padi and the duration of reproduction was less, while these parameters showed an opposite trend in M. euphorbiae. The gross reproduction rate (GRR) was found higher in R. Padi (29.17 offspring/adult lifetime) compared to M. euphorbiae (19.58 offspring/adult lifetime). The M. euphorbiae being a pest of solanaceous crops seems to have shifted to a new host, i.e., wheat. This new adaptation strategy to survive for long periods on a wheat crop might pose a serious threat to wheat crop cultivation in near future.

The Evolution and Future of Intensive Care Management in the Era of Telecritical Care and Artificial Intelligence.

Critical care practice has been embodied in the healthcare system since the institutionalization of intensive care units (ICUs) in the late '50s. Over time, this sector has experienced many changes and improvements in providing immediate and dedicated healthcare as patients requiring intensive care are often frail and critically ill with high mortality and morbidity rates. These changes were aided by innovations in diagnostic, therapeutic, and monitoring technologies, as well as the implementation of evidence-based guidelines and organizational structures within the ICU. In this review, we examine these changes in intensive care management over the past 40 years and their impact on the quality of care available to patients. Moreover, the current state of intensive care management is characterized by a multidisciplinary approach and the use of innovative technologies and research databases. Advancements such as telecritical care and artificial intelligence are being increasingly explored, especially since the COVID-19 pandemic, to reduce the length of hospitalization and ICU mortality. With these advancements in intensive care and ever-changing patient needs, critical care experts, hospital managers, and policymakers must also explore appropriate organizational structures and future enhancements within the ICU.

Glycemic Control in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis.

Background: Given the mortality risk in COVID-19 patients, it is necessary to estimate the impact of glycemic control on mortality rates among inpatients by designing and implementing evidence-based blood glucose (BG) control methods. There is evidence to suggest that COVID-19 patients with hyperglycemia are at risk of mortality, and glycemic control may improve outcomes. However, the optimal target range of blood glucose levels in critically ill COVID-19 patients remains unclear, and further research is needed to establish the most effective glycemic control strategies in this population. Methods: The investigation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources were drawn from Google Scholar, ResearchGate, PubMed (MEDLINE), Cochrane Library, and Embase databases. Randomized controlled trials, non-randomized controlled trials, retrospective cohort studies, and observational studies with comparison groups specific to tight glycemic control in COVID-19 patients with and without diabetes. Results: Eleven observational studies (26,953 patients hospitalized for COVID-19) were included. The incidence of death was significantly higher among COVID-19 patients diagnosed with diabetes than those without diabetes (OR = 2.70 [2.11, 3.45] at a 95% confidence interval). Incidences of death (OR of 3.76 (3.00, 4.72) at a 95% confidence interval) and complications (OR of 0.88 [0.76, 1.02] at a 95% confidence interval) were also significantly higher for COVID-19 patients with poor glycemic control. Conclusion: These findings suggest that poor glycemic control in critically ill patients leads to an increased mortality rate, infection rate, mechanical ventilation, and prolonged hospitalization.

Design, synthesis, anti-acetylcholinesterase evaluation and molecular modelling studies of novel coumarin-chalcone hybrids.

The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 µM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 µM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 µM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.Communicated by Ramaswamy H. Sarma.

Spotlight on 4-substituted quinolines as potential anti-infective agents: Journey beyond chloroquine.

Continued emerging resistance of pathogens against the clinically approved candidates and their associated limitations continuously demand newer agents having better potency with a more suited safety profile. Quinoline nuclei containing scaffolds of natural and synthetic origin have been documented for diverse types of pharmacological activities, and a number of drugs are clinically approved. In the present review, we unprecedentedly covered the biological potential of 4-substituted quinoline and elaborated a rationale for its special privilege to afford the significant number of approved clinical drugs, particularly against infectious pathogens. Compounds with 4-substituted quinoline are well documented for antimalarial activity, but in the last two decades, they have been extensively explored for activity against cancer, tuberculosis, and several other pathogens including viruses, bacteria, fungi, and other infectious pathogens. In the present study, the anti-infective spectrum of this scaffold is discussed against viruses, mycobacteria, malarial parasites, and fungal and bacterial strains, along with recent updates in this area, with special emphasis on the structure-activity relationship.

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies.

Mucormycosis or "black fungus" has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions.