Trends in the development and current perspective of thermostable bacterial hemicellulases with their industrial endeavors: A review.

Hemicellulases are enzymes that hydrolyze hemicelluloses, common polysaccharides in nature. Thermophilic hemicellulases, derived from microbial strains, are extensively studied as natural biofuel sources due to the complex structure of hemicelluloses. Recent research aims to elucidate the catalytic principles, mechanisms and specificity of hemicellulases through investigations into their high-temperature stability and structural features, which have applications in biotechnology and industry. This review article targets to serve as a comprehensive resource, highlighting the significant progress in the field and emphasizing the vital role of thermophilic hemicellulases in eco-friendly catalysis. The primary goal is to improve the reliability of hemicellulase enzymes obtained from thermophilic bacterial strains. Additionally, with their ability to break down lignocellulosic materials, hemicellulases hold immense potential for biofuel production. Despite their potential, the commercial viability is hindered by their high enzyme costs, necessitating the development of efficient bioprocesses involving waste pretreatment with microbial consortia to overcome this challenge.

Abridgement of Microbial Esterases and Their Eminent Industrial Endeavors.

Esterases are hydrolases that contribute to the hydrolysis of ester bonds into both water-soluble acyl esters and emulsified glycerol-esters containing short-chain acyl groups. They have garnered significant attention from biotechnologists and organic chemists due to their immense commercial value. Esterases, with their diverse and significant properties, have become highly sought after for various industrial applications. Synthesized ubiquitously by a wide range of living organisms, including animals, plants, and microorganisms, these enzymes have found microbial esterases to be the preferred choice in industrial settings. The cost-effective production of microbial esterases ensures higher yields, unaffected by seasonal variations. Their applications span diverse sectors, such as food manufacturing, leather tanneries, paper and pulp production, textiles, detergents, cosmetics, pharmaceuticals, biodiesel synthesis, bioremediation, and waste treatment. As the global trend shifts toward eco-friendly and sustainable practices, industrial processes are evolving with reduced waste generation, lower energy consumption, and the utilization of biocatalysts derived from renewable and unconventional raw materials. This review explores the background, structural characteristics, thermostability, and multifaceted roles of bacterial esterases in crucial industries, aiming to optimize and analyze their properties for continued successful utilization in diverse industrial processes. Additionally, recent advancements in esterase research are overviewed, showcasing novel techniques, innovations, and promising areas for further exploration.

Improving the genetic potential of okra (Abelmoschus esculentus L.) germplasm to tolerate salinity stress.

Okra (Abelmoschus esculentus L.) is the most consumed vegetable worldwide with the potential for diverse ecological adaptation. However, increasing salinization and changing climatic conditions are posing serious threats to the growth, yield, and quality of okra. Therefore, to mitigate increasing soil salinization and ensure sustainable okra production under rapidly changing climatic conditions, evaluation of new okra germplasm to develop salt tolerant cultivars is direly needed. The present study was designed to evaluate the genetic resources of okra genotypes for salt tolerance at growth and reproductive phases. Based on mophological and physio-biochemical responses of plants under stress condition, genotypes were divided into salt tolerant and succeptible groups. The experiment was comprised of 100 okra genotypes and each genotype was grown under control conditions and 6.5 dS m-1 NaCl concentration in a pot having 10 kg capacity. The experiment was conducted in a completely randomized design and each treatment was replicated three times. The results showed vast genetic variability among the evaluated okra germplasm traits like days to emergence, pod length, pod diameter, plant height, stem girth, and other yield-related parameters. Correlation analysis showed a highly significant positive association among the number of leaves at first flower and plant height at first flower.Likewise, pod weight also revealed a highly significant positive relationship for pod weight plant-1, pod length, and K+: Na+. Principal Component Analysis (PCA) revealed that out of 16 principal components (PCs), five components showed more than one eigenvalue and the first six PCs contributed 67.2% of the variation. Bi-plot analysis illustrated that genotypes 95, 111, 133, 99, and 128, under salt stress conditions, exhibited both high yield per plant and salt-tolerant behavior in other yield-related traits. On the basis of all studied traits, a salt susceptible group and a salt-tolerant group were formed. The salt tolerant group comprised of 97, 68, 95, 114, 64, 99, 111, 133, 128, and 109 genotypes, whereas, the salt susceptible group contained 137, 139, 130, 94, and 125 genotypes. Salt-tolerant okra genotypes were suggested to be used in further breeding programs aimed to develop salt tolerance in okra. These insights will empower precision breeding, underscore the importance of genetic diversity, and bear the potential to address the challenges of salt-affected soils while promoting broader agricultural resilience, economic prosperity, and food security.

Unveiling the Psychedelic Journey: An Appraisal of Psilocybin as a Profound Antidepressant Therapy.

Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope emerges from an unlikely source-Psilocybin, a natural hallucinogen found in certain mushrooms. Recently, this enigmatic compound has garnered attention for its potential therapeutic benefits in addressing various mental health issues, including depression. Psilocybin alters mood, cognition, and perception by acting on a particular subtype of serotonin receptors in the brain. It's feasible that these shifts in consciousness will promote healing development, offering a novel approach to depression management. This comprehensive review explores psilocybin, derived from specific mushrooms, and its implications in the treatment of depression. The study examines new perspectives and therapeutic possibilities surrounding psilocybin, addressing existing gaps in academic literature. It delves into its biosynthesis, unique mechanisms of action, therapeutic applications, and anti-depressive effects. By uncovering the potential of this mind-altering substance, the review aims to advance psychiatric care, offering hope to those globally affected by depression.

Co-production of biohydrogen and biomethane utilizing halophytic biomass Atriplexcrassifolia by two-stage anaerobic fermentation process.

The excessive use of fossil has resulted in the drastic exhaustion of natural energy sources, leading to environmental challenges and energy crises. Owing to rising energy demand there is a dire need to shift towards renewable energies from lignocellulosic biomass. The present study assessed the co-production of biohydrogen (H2) and biomethane (CH4) by utilizing a less explored halophyte Atriplexcrassifolia. Various reaction parameters were evaluated for their effect on biohydrogen and biomethane production in batch experiments. One parameter at a time experimental strategy was chosen for production optimization. Hydrogen and methane yields along with their production rates were assessed at different incubation times, temperatures, pH, substrate concentrations, and inoculum sizes in acidogenesis and methanogenesis stages, respectively. In the first stage, maximum cumulative hydrogen production of 66 ± 0.02 mL, with hydrogen yield of 13.2 ± 0.03 mL/g, and hydrogen production rate (HPR) of 1.37 ± 0.05 mL/h was attained when the reaction mixture (5 g Atriplexcrassifolia and 10 mL pretreated sewage sludge) was processed at 37°C and pH 5.5 after 48 h of incubation. While in the second stage, maximum cumulative methane production, i.e., 343 ± 0.12 mL, methane yield (MY) of 8.5 ± 0.07 mL/mL, and methane production rate (MPR) of 0.8 ± 0.05 mL/h was achieved after 18 days of incubation of reaction mixture (40 mL of hydrogenic slurry with 80 mL inoculum) at 45°C and pH 8. Furthermore, a 51% and 24% rise in biohydrogen and biomethane production respectively were recorded when the gases were produced at these optimized reaction conditions. The results ensure halophyte Atriplexcrassifolia as an imperative renewable energy resource and proposed that effective optimization of the process further increased the coproduction of biohydrogen and biomethane.

Bacterial thermophilic DNA polymerases: A focus on prominent biotechnological applications.

DNA polymerases are the enzymes able to replicate the genetic information in nucleic acid. As a result, they are necessary to copy the complete genome of every living creature before cell division and sustain the integrity of the genetic information throughout the life of each cell. Any organism that uses DNA as its genetic information, whether unicellular or multicellular, requires one or more thermostable DNA polymerases to thrive. Thermostable DNA polymerase is important in modern biotechnology and molecular biology because it results in methods such as DNA cloning, DNA sequencing, whole genome amplification, molecular diagnostics, polymerase chain reaction, synthetic biology, and single nucleotide polymorphism detection. There are at least 14 DNA-dependent DNA polymerases in the human genome, which is remarkable. These include the widely accepted, high-fidelity enzymes responsible for replicating the vast majority of genomic DNA and eight or more specialized DNA polymerases discovered in the last decade. The newly discovered polymerases' functions are still being elucidated. Still, one of its crucial tasks is to permit synthesis to resume despite the DNA damage that stops the progression of replication-fork. One of the primary areas of interest in the research field has been the quest for novel DNA polymerase since the unique features of each thermostable DNA polymerase may lead to the prospective creation of novel reagents. Furthermore, protein engineering strategies for generating mutant or artificial DNA polymerases have successfully generated potent DNA polymerases for various applications. In molecular biology, thermostable DNA polymerases are extremely useful for PCR-related methods. This article examines the role and importance of DNA polymerase in a variety of techniques.

Burgeoning therapeutic strategies to curb the contemporary surging viral infections.

Significant efforts and initiatives were already made in the health care systems, however in the last few years; our world is facing emergences of viral infections which potentially leading to considerable challenges in terms of higher morbidity, mortality, increased and considerable financial loads on the affected populations. Over ten major epidemics or pandemics have been recorded in the twenty-first century, the ongoing coronavirus pandemic being one of them. Viruses being distinct obligate pathogens largely dependent on living beings are considered as one of the prominent causes of death globally. Although effective vaccines and antivirals have led to the eradication of imperative viral pathogens, the emergences of new viral infections as well as novel drug-resistant strains have necessitated the implementation of ingenious and efficient therapeutic approaches to treat viral outbreaks in the future. Nature being a constant source of tremendous therapeutical resources has inspired us to develop multi-target antiviral drugs, overcoming the challenges and limitations faced by pharmaceutical industry. Recent breakthroughs in the understanding of the cellular and molecular mechanisms of viral reproduction have laid the groundwork for potential treatment approaches including antiviral gene therapy relying on the application of precisely engineered nucleic acids for disabling pathogen replication. The development of RNA interference and advancements in genome manipulating tools have proven to be especially significant in this regard. In this review, we discussed mode of actions and pathophysiological events associated with the viral infections; followed by distributions, and advancement made towards the detection strategies for timely diagnosis. In the later section, current approaches to cope up the viral pathogens and their key limitations have also been elaborated. Lastly, we also explored some novel and potential targets to treat such infections, where attentions were made on next generation gene editing technologies.

Effect of pretreatment strategies on halophyte Atriplex crassifolia to improve saccharification using thermostable cellulases.

Bioethanol is believed to be an influential revolutionary gift of biotechnology, owing to its elevating global demand and massive production. Pakistan is home to a rich diversity of halophytic flora, convertible into bounteous volumes of bioethanol. On the other hand, the accessibility to the cellulosic part of biomass is a major bottleneck in the successful application of biorefinery processes. The most common pre-treatment procedures existent include physicochemical and chemical approaches, which are not environmentally benign. To overcome these problems, biological pre-treatment has gained importance but the drawback is the low yield of the extracted monosaccharides. The current research was aimed at exploring the best pre-treatment method for the bioconversion of halophyte Atriplex crassifolia into saccharides using three thermostable cellulases. Atriplex crassifolia was subjected to acid, alkali and microwave pre-treatments, followed by compositional analysis of the pre-treated substrates. Maximum delignification i.e. 56.6% was observed in the substrate pre-treated using 3% HCl. Enzymatic saccharification using thermostable cellulases also validated the results where the highest saccharification yield i.e. 39.5% was observed for the sample pre-treated using same. Maximum enzymatic hydrolysis of 52.7% was obtained for 0.40 g of the pre-treated halophyte Atriplex crassifolia where Endo-1,4- ß -glucanase (300U), Exo-1,4- ß -glucanase (400U) and ß -1,4-glucosidase (1000U) were simultaneously added and incubated for 6 h at 75°C. The reducing sugar slurry obtained after optimization of saccharification was utilized as glucose in submerged fermentation for bioethanol production. The fermentation medium was inoculated with Saccharomyces cerevisiae, incubated at 30°C and 180 rpm for 96 h. Ethanol production was estimated using potassium dichromate method. Maximum production of bioethanol i.e. 16.33% was noted at 72 h. It can be concluded from the study that Atriplex crassifolia owing to its high cellulosic content after pre-treatment using dilute acid method, yields substantial amount of reducing sugars and high saccharification rates when subjected to enzymatic hydrolysis using thermostable cellulases, under optimized reaction conditions. Hence, the halophyte Atriplex crassifolia is a beneficial substrate that can be utilized to extract fermentable saccharides for bioethanol production.

Atrial Appendage Aneurysms: Natural History and Outcomes.

BACKGROUND: Left (LAAA) and right atrial appendage aneurysms (RAAA) are rare entities, and their natural history, management, and long-term outcomes are not well studied. METHODS: This retrospective review includes all patients from 2000 to 2021 with atrial appendage aneurysms at our institution identified using an electronic search tool. LAAA and RAAA were confirmed using multimodality imaging and intraoperative findings. RESULTS: We identified 13 (87%) patients with LAAA and 2 (13%) with RAAA. At diagnosis, 11 (73%) were female, mean age was 51.4 ± 18.8 years, and ejection fraction 56.5 ± 13.1%. Three (20%) patients had congenital heart disease including 2 (13%) with atrioventricular septal defects and 1 (7%) with congenitally corrected transposition. LAAA/RAAA was diagnosed due to new-onset atrial fibrillation (AF) in 6 (40%) patients and embolic stroke in 2 (13%). Ten patients had preexisting AF diagnosed 2.9 ± 1.4 years earlier at a mean age of 50.2 ± 15.5 years. Thrombus within the aneurysm was identified in 2 (15%) LAAA patients. All patients were on anticoagulation and follow-up of the cohort from diagnosis was 7.1 ± 6.2 years. Eleven (73%) patients were surgically managed with 7 (64%) lesions excised, 1 (9%) stapled, and 3 (27%) ligated. Postoperative complications occurred in 2 (18%) patients with 1 (7%) developing tricuspid regurgitation and another with pericardial effusion and tamponade. CONCLUSIONS: Atrial appendage aneurysm is a rare disease and nearly half of patients present with AF. Surgical treatment with concomitant AF ablation is a reasonable and safe management option.

Circular RNAs: Insights into Clinical and Therapeutic Approaches for Various Cancers.

BACKGROUND: With the advent of cancer diagnostics and therapeutics, circular RNAs (circRNAs) are swiftly becoming one of the significant regulators of gene expression and cellular functions. A plethora of multiple molecular mechanisms has been observed to elicit their influence. OBJECTIVE: Circular RNAs (circRNAs) are a distinct category of endogenous noncoding RNAs designed as a result of exon back splicing events in precursor's mRNAs (pre-mRNAs) and are widely distributed in the transcriptome of eukaryotic cells. METHODS: Although the role of circRNAs is still in its infancy, they serve as microRNA sponges, protein scaffolds, and modulators of transcription and splicing and occasionally as templates for the production of peptides. RESULTS: It is well known that abnormal circRNA expression is prevalent in malignancies and has been linked to a number of pathophysiological aspects of cancer. This extensively anomalous expression assists in cellular proliferation and growth, sustaining cellular invasiveness and bypassing cellular senescence and death, thus advocating their promise to serve as both clinical biomarkers and therapeutic targets. CONCLUSION: An overview of the recent status of circRNA will aid in the identification of new biomarkers, therapeutic targets, and their prospect in the diagnosis and therapy of disease. In this review article, we discuss the functional mechanisms of circRNAs, their biomarker potential in disease diagnosis and prognosis, therapeutic approaches, and the associated limitations.

Emergent crisis of antibiotic resistance: A silent pandemic threat to 21st century.

Antibiotic resistance has become an indispensably alarming menace to the global community. The primary factors are overuse and abuse of antibiotics, lack of novel medicines under development, the health care industry's focus on profit, and the absence of diagnostic testing prior to the prescription of antibiotics. Additionally, over the past few decades, the main factors contributing to the global spread of antibiotic resistance have been the overuse of antibiotics in livestock and other animals, drug efficacy, development of fewer new vaccines, environmental toxicity, transmission through travel, and lack of funding for healthcare research and development. These factors have accelerated resistance in microorganisms through structural and functional modifications in bacteria such as reduced drug permeability, increased efflux pumps, enzymatic antibiotic modification, and change in drug target, intracellular infection, and biofilm creation. There has been an increase in resistance during the pandemic and among cancer patients due to improper prescriptions. A number of modern therapeutic alternatives have been developed to curb widespread antibiotic resistance such as nanoparticle, bacteriophage, and antimicrobial biochemical approaches. It is high time to explore new alternatives to curtail enormous increase in resistant pathogens which could be an incurable global confrontation. This review highlights the complete insight on the global drivers of resistance along with the modes of action and impacts, finally discussing the latest therapeutic alternatives.

An Appraisal on Prominent Industrial and Biotechnological Applications of Bacterial Lipases.

Microbial lipases expedite the hydrolysis and synthesis of long-chain acyl esters. They are highly significant commercial biocatalysts to biotechnologists and organic chemists. The market size of lipase is anticipated to reach $590 million by 2023. This is all owing to their versatility in properties, including stability in organic solvents, interfacial activation in micro-aqueous environments, high substrate specificity, and activity in even non-aqueous milieu. Lipases are omnipresent and synthesized by various living organisms, including animals, plants, and microorganisms. Microbial lipases are the preferred choice for industrial applications as they entail low production costs, higher yield independent of seasonal changes, easier purification practices, and are capable of being genetically modified. Microbial lipases are employed in several common industries, namely various food manufactories (dairy, bakery, flavor, and aroma enhancement, etc.), leather tanneries, paper and pulp, textiles, detergents, cosmetics, pharmaceuticals, biodiesel synthesis, bioremediation and waste treatment, and many more. In recent decades, circumspection toward eco-friendly and sustainable energy has led scientists to develop industrial mechanisms with lesser waste/effluent generation, minimal overall energy usage, and biocatalysts that can be synthesized using renewable, low-cost, and unconventional raw materials. However, there are still issues regarding the commercial use of lipases which make industrialists wary and sometimes even switch back to chemical catalysis. Industrially relevant lipase properties must be further optimized, analyzed, and explored to ensure their continuous successful utilization. This review comprehensively describes the general background, structural characteristics, classifications, thermostability, and various roles of bacterial lipases in important industries.

An Insight into Modern Targeted Genome-Editing Technologies with a Special Focus on CRISPR/Cas9 and its Applications.

Genome-editing technology has enabled scientists to make changes in model organisms' DNA at the genomic level to get biotechnologically important products from them. Most commonly employed technologies for this purpose are transcription activator like effector nucleases (TALENs), homing-endonucleases or meganucleases, zinc finger nucleases (ZFNs), and clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9). Among these tools, CRISPR/Cas9 is most preferred because it's easy to use, has a small mutation rate, has great effectiveness, low cost of development, and decreased rate of advancement. CRISPR/Cas9 has a lot of applications in plants, animals, humans, and microbes. It also has applications in many fields such as horticulture, cancer, food biotechnology, and targeted human genome treatments. CRISPR technology has shown great potential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic to provide early and easy detection methods, possible treatment, and vaccine development. In the present review, genome-editing tools with their basic assembly and features have been discussed. Exceptional notice has been paid to CRISPR technology on basis of its structure and significant applications in humans, plants, animals, and microbes such as bacteria, viruses, and fungi. The review has also shed a little light on current CRISPR challenges and future perspectives.

Efficacy of ICD/CRT-D Remote Monitoring in Patients With HFrEF: a Bayesian Meta-analysis of Randomized Controlled Trials.

PURPOSE OF REVIEW: To evaluate remote monitoring using implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) devices as an adjunctive tool to the traditional care of patients with heart failure (HF). RECENT FINDINGS: We included 11 trials encompassing 5965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods. The ARD for mortality was centered at - 0.01 (95% CrI: - 0.03; 0.01, Tau: 0.02), with an 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at - 0.03 (95% CrI: - 0.11; 0.05, Tau: 0.10), with an 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause and cardiovascular mortality compared with standard care alone.

Waste management and green technology: future trends in circular economy leading towards environmental sustainability.

The effective treatment of waste to be used as a resource in future has a major role in achieving environmental sustainability and moving towards circular economy. The current research is aimed to provide in-depth detail regarding prominent trends and research themes, evolution, future research orientation, main characteristics, and mapping of research publications on waste management, technological innovation in circular economy domain from the year 2000 to 2021. Different analyses including text mining and bibliometric and content analyses were applied to answer the research question and provide the details on aforementioned variables. From the bibliometric analyses, a total of 1118 articles were drawn out from the Scopus database to conceptualize the core body of research. As a result, the following themes were identified: electronic waste, circular economy transition, plastic waste, bio-based waste management, lifecycle assessment, and ecological impacts, and construction and demolition waste management. The highlighted features, future research orientation, and prominent research perspective can provide guideline for future research to enrich the literature through conducting studies on provided research directions and help lead waste management and technological innovation policymakers, professionals, and practitioners in moving towards circular transition.

Multifarious revolutionary aspects of microbial keratinases: an efficient green technology for future generation with prospective applications.

Since the dawn of century, tons of keratin bio-waste is generated by the poultry industry annually, and they end up causing environmental havoc. Keratins are highly flexible fibrous proteins which exist in α- and ß- forms and provide mechanical strength and stability to structural appendages. The finding of broad-spectrum protease, keratinase, from thermophilic bacteria and fungi, has provided an eco-friendly solution to hydrolyze the peptide bonds in highly recalcitrant keratinous substances such as nails, feathers, claws, and horns into valuable amino acids. Microorganisms produce these proteolytic enzymes by techniques of solid-state and submerged fermentation. However, solid-state fermentation is considered as a yielding approach for the production of thermostable keratinases. This review prioritized the molecular and biochemical properties of microbial keratinases, and the role of keratinases in bringing prodigious impact for the sustainable progress of the economy. It also emphasizes on the current development in keratinase production with the focus to improve the biochemical properties related to enzyme's catalytic activity and stability, and production of mutant and cloned microbial strains to improve the yield of keratinases. Recently, multitude molecular approaches have been employed to enhance enzyme's productivity, activity, and thermostability which makes them suitable for pharmaceutical industry and for the production of animal feed, organic fertilizers, biogas, clearing of animal hides, and detergent formulation. Hence, it can be surmised that microbial keratinolytic enzymes are the conceivable candidates for numerous commercial and industrial applications.

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, proliferation, metastasis, and drug resistance. CRISPR/Cas9 mediated cancer immunotherapy is a well-known treatment option after surgery, chemotherapy, and radiation therapy. It has marked a turning point in cancer treatment. However, despite its advantages and tremendous potential, there are many challenges such as off-target effects, editing efficiency of CRISPR/Cas9, efficient delivery of CRISPR/Cas9 components into the target cells and tissues, and low efficiency of HDR, which are some of the main issues and need further research and development for completely clinical application of this novel gene editing tool. Here, we present a CRISPR/Cas9 mediated cancer treatment method, its role and applications in various cancer treatments, its challenges, and possible solution to counter these challenges.

Predicting permanent pacemaker implantation following transcatheter aortic valve replacement: A contemporary meta-analysis of 981,168 patients.

Background: Heart block requiring permanent pacemaker (PPM) implantation is a relatively frequent complication of transcatheter aortic valve replacement (TAVR). Objective: The purpose of this study was to perform a contemporary meta-analysis to provide an updated assessment of clinically useful predictors of PPM implantation post-TAVR. Methods: Medline and EMBASE searches were performed to include all studies reporting PPM post-TAVR between 2015 and 2020. Pertinent data were extracted from the studies for further analysis. RevMan was used to create forest plots and calculate risk ratios (RRs). Results: We evaluated 41 variables from 239 studies with a total of 981,168 patients. From this cohort, 17.4% received a PPM following TAVR. Strong predictors for PPM implant were right bundle branch block (RBBB) (RR 3.12; P <.001) and bifascicular block (RR 2.40; P = .002). Intermediate factors were chronic kidney disease (CKD) (RR 1.53; P <.0001) and first-degree atrioventricular block (FDAVB) (RR 1.44; P <.001). Weak factors (RR 1-1.50; P <.05) were male gender, age ≥80 years, body mass index ≥25, diabetes mellitus (DM), atrial fibrillation (AF), and left anterior fascicular block (LAFB). These factors along with increased left ventricular outflow tract (LVOT) area (>435 mm2) and/or aortic annulus diameter (>24.4 mm) were incorporated to propose a new scoring system to stratify patients into high- and low-risk groups. Conclusion: Male gender, age ≥80 years, FDAVB, RBBB, AF, DM, CKD, Medtronic CoreValve, transfemoral TAVR, increased LVOT, and aortic annulus diameter were significant predictors of post-TAVR PPM implantation. Preprocedural assessment should consider these factors to guide clinical decision-making before TAVR. Validation of our scoring system is warranted.

Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model.

Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)-Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)-Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)-Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)-Combination 4; provided ~30% (30 ± 1.1), 70% (12 ± 0.4; P < 0.01), 60% (19 ± 0.2; P < 0.05) and 90% (05 ± 0.1; P < 0.001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0.3) protection (P > 0.05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P < 0.05-0.001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3rd hour of cisplatin administration. In continuation, at the 18th of cisplatin administration reduction in dopamine (P < 0.001) in the AP and 5HT in the brain stem and intestine (P < 0.001) was observed. The said combination did not change the neurotransmitters basal levels and their respective metabolites any significantly. In conclusion, all the tested combinations offered protection against cisplatin induced vomiting to variable degrees, where combination 4 provided enhanced attenuation by antiserotonergic mechanism at the 3rd hour while a blended antidopaminergic and antiserotonergic mechanism at the 18th hour after cisplatin administration.