Well-Defined Mn(II)-complex Catalyzed Switchable De(hydrogenative) Csp3 -H Functionalization of Methyl Heteroarenes: A Sustainable Approach for Diversification of Heterocyclic Motifs.

Catalytic activities of Mn(I) complexes derived from expensive MnBr(CO)5 salt have been explored in various dehydrogenative transformations. However, the reactivity and selectivity of inexpensive high spin Mn(II) complexes are uncommon. Herein, we have synthesized four new Mn(II) complexes and explored switchable alkenylation and alkylation of methyl heteroarenes employing a single Mn(II)catalyst. The developed protocol selectively furnishes a series of functionalized E-heteroarenes and C-alkylated heteroarenes with good to excellent yields. Various medicinally and synthetically useful compounds are successfully synthesized using our developed protocol. Various controls and kinetics experiments were executed to shed light on the mechaism,which reveals that α-C-H bond breaking of alcohol is the slowest step.

Mind over Microbes: Investigating the Interplay between Lifestyle Factors, Gut Microbiota, and Brain Health.

BACKGROUND: The gut microbiota (GM) of the human body comprises several species of microorganisms. This microorganism plays a significant role in the physiological and pathophysiological processes of various human diseases. METHODS: The literature review includes studies that describe causative factors that influence GM. The GM is sensitive to various factors like circadian rhythms, environmental agents, physical activity, nutrition, and hygiene that together impact the functioning and composition of the gut microbiome. This affects the health of the host, including the psycho-neural aspects, due to the interconnectivity between the brain and the gut. Hence, this paper examines the relationship of GM with neurodegenerative disorders in the context of these aforesaid factors. CONCLUSION: Future studies that identify the regulatory pathways associated with gut microbes can provide a causal link between brain degeneration and the gut at a molecular level. Together, this review could be helpful in designing preventive and treatment strategies aimed at GM, so that neurodegenerative diseases can be treated.

Biodiesel-Derived Waste Glycerol as a Green Template for Creating Mesopores in the ZSM-5 Catalyst for Aromatics Production Applications.

The present study provides a novel sustainable approach for the synthesis of the ZSM-5 catalyst using biodiesel-derived waste glycerol as a green template as well as a mesopore creator, which is here reported for the first time, to the best of our knowledge. The use of bioglycerol in the preparation of ZSM-5 (Zn-Z-G and Zn-Z-T) materials exhibited a typical MFI zeolite structure, indicating glycerol played a similar role to that of a typical (TPA+) template in the formation of the ZSM-5 zeolite structure. The Zn-Z-G material also exhibited a large mesopore in the ZSM-5 pore structure, suggesting that glycerol played both template and mesopore creator roles. Interestingly, Zn-Z-GT prepared by the dual-template route using bioglycerol along with typical TPA+ showed a MFI zeolite structure with special catalytic features such as hierarchical micromesopores and well-balanced acid sites. These results reveal that the use of bioglycerol along with a typical TPA+ template had a promotional effect on creating such special properties in the Zn-Z-GT material. The Zn-Z-GT catalyst exhibited excellent catalytic performance in the naphtha aromatization reaction, resulting in achieving ∼58 wt % of the aromatic product and useful gas byproduct (14 wt %) with a minimum coke content (∼4 wt %) in a 12 h reaction period ascribed to its combined effect of hierarchical micromesopores and well-balanced acidity with optimum Lewis acid sites. The liquid product possessing high alkyl-aromatics with a high octane value (RON ∼ 109) produced in the present study can be used as an octane booster for liquid gasoline. The high alkyl-aromatics (>50 wt %) content of the liquid product also attracts various petrochemical applications. The effective utilization of waste bioglycerol as a green template and mesopore creator for the preparation of Zn-Z-GT can exhibit sustainability in the resultant material.

Electro-oxidative coupling of Bunte salts with aryldiazonium tetrafluoroborates: a benign access to unsymmetrical sulfoxides.

An electrochemical strategy for the synthesis of unsymmetrical sulfoxides has been explored using Bunte salts and aryldiazonium tetrafluoroborates under constant current electrolysis at room temperature. In addition to being eco-safe and using mild conditions, the present protocol is free from the use of metal/oxidant, and is endowed with a broad substrate scope and good functional group tolerance.

Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society.

Electrical storm (ES) is a state of electrical instability, manifesting as recurrent ventricular arrhythmias (VAs) over a short period of time (three or more episodes of sustained VA within 24 h, separated by at least 5 min, requiring termination by an intervention). The clinical presentation can vary, but ES is usually a cardiac emergency. Electrical storm mainly affects patients with structural or primary electrical heart disease, often with an implantable cardioverter-defibrillator (ICD). Management of ES requires a multi-faceted approach and the involvement of multi-disciplinary teams, but despite advanced treatment and often invasive procedures, it is associated with high morbidity and mortality. With an ageing population, longer survival of heart failure patients, and an increasing number of patients with ICD, the incidence of ES is expected to increase. This European Heart Rhythm Association clinical consensus statement focuses on pathophysiology, clinical presentation, diagnostic evaluation, and acute and long-term management of patients presenting with ES or clustered VA.

The Current Landscape of Ventricular Tachycardia Trials: A Systematic Review of Registered Studies.

BACKGROUND: Although there are evolving techniques and technologies for treating ventricular tachycardia (VT), the current landscape of clinical trials for managing VT remains understudied. OBJECTIVE: The objective of this study was to provide a systematic characterisation of the interventional management of VT through an analysis of the ClinicalTrials.gov, clinicaltrialsregister.eu, anzctr.org.au and chictr.org.cn databases. METHODS: We queried all phase II to IV interventional trials registered up to November 2023 that enrolled patients with VT. Published, completed but unpublished, terminated, or ongoing trials were included for final analysis. RESULTS: Of the 698 registered studies, 135 were related to VT, with 123 trials included in the final analysis. Among these trials, 25 (20%) have been published, enrolling a median of 35 patients (interquartile range [IQR] 20-132) over a median of 43 months (IQR 19-62). Out of the published trials, 14 (56%) were randomised, and 12 (48%) focused on catheter ablation. Twenty-two (18%) have been completed but remain unpublished, even after a median of 36 months (IQR 15-60). Furthermore, 27 (22%) trials were terminated or withdrawn, with the most common cause being poor enrolment. Currently, 49 (40%) trials are ongoing and novel non-ablative technologies, such as radioablation and autonomic modulation, account for 35% and 8% of ongoing trials, respectively. CONCLUSIONS: Our analysis revealed that many registered trials remain unpublished or incomplete, and randomised controlled trial evidence is limited to only a few studies. Furthermore, many ongoing trials are focused on non-catheter ablation-based strategies. Therefore, larger pragmatic trials are needed to create stronger evidence in the future.

Altitudinal and aspect-driven variations in soil carbon storage potential in sub-tropical Himalayan forest ecosystem: assisting nature to combat climate change.

Forest soils serve as the greatest sink of terrestrial carbon (C) and have a significant impact on worldwide or regional C cycling. By reducing emissions and enhancing the C storage in forests, the environmental monitoring function of a forest ecosystem may be ensured. The study focused on measuring the densities of major nutrients in soil to gain insight into the C and nitrogen dynamics of the Himalayan sub-tropical forest ecosystem of India besides supplementing the information about the C storage potential of these forest soils. The study examined the physico-chemical properties and nutrient densities across three altitudinal ranges viz., 600-800 m (A1), 800-1000 m (A2) and 1000-1200 m (A3) and two aspects, i.e. Northern (N) and Southern (S) in a randomized complete block design and data collection was done from 24 main sample plots (3 altitudinal ranges × 2 aspects × 4 replications). The soil pH, electrical conductivity, and bulk density observed a decreasing pattern with an increase in altitude, whereas a reverse trend was observed in soil organic C (SOC), total nitrogen and available phosphorus. The SOC and total nitrogen densities ranged from 20.08 to 48.35 Mg ha-1 and 2.56 to 4.01 Mg ha-1, respectively in an increasing trend from A1 to A3. The northern aspect exhibited significantly higher SOC and nitrogen densities than the southern aspects. The C storage potential of forest soils followed the order A1 < A2 < A3 with significantly higher potential (nearly 1.5 times) compared to those on the southern aspect. There was a consistently significant increase in the C:N ratio (CNR) with a maximum value (10.51) at A3 and minimum value (8.37) at A1, however the effect of aspect remained insignificant. This research underscores the importance of considering altitude and aspect when planning forest restoration efforts, as these factors have a substantial influence on soil properties, C storage potential and CNR. Understanding the significance of CNR is critical, as it serves as a key indicator of greenhouse gas (GHG) emissions from forest soils. Ultimately, these findings empower policymakers and conservationists to make informed decisions that can contribute to the sustainable management of Himalayan forests and the global fight against climate change.

Correlation of spatial patterns of endocardial pace mapping to underlying scar topography in patients with scar-related ventricular tachycardia.

INTRODUCTION: Endocardial pace mapping (PM) can identify conducting channels for ventricular tachycardia (VT) circuits in patients with structural heart disease (SHD). Recent findings show the temporal and spatial pattern of PM may aid identification of the surface harboring VT isthmii. The specific correlation of PM patterns to scar topography has not been examined. OBJECTIVE: To correlate the pattern of endocardial PMs to underlying scar topography in SHD patients with VT. METHODS: Data from patients undergoing VT ablation from August 2018 to February 2022 were reviewed. RESULTS: Sixty-three patients with SHD-related VT (mean age 65 ± 14 years) with 83 endocardial PM correlation maps were analysed. Two main correlation patterns were identified, an "abrupt-change correlation pattern (AC-pattern)" and "centrifugal-attenuation correlation pattern (CA-pattern)." AC-pattern had lower scar ratio (unipolar/bipolar % scar area; 1.1 vs. 1.5, p < .001), had longer maximal stimulus-QRS intervals (97.5 vs. 68 ms, p = .002), and higher likelihood of endocardial dominant scar (11/21 [52%] vs. 3/38 [8%], p < .001) than CA-pattern seen on intracardiac echocardiography (ICE). In contrast, CA-pattern was more likely to have epicardial dominant scar or mid-intramural scar on ICE (epicardial dominant scar; CA-pattern: 12/38 [32%] vs. AC-pattern: 1/21 [5%], p = .02, mid-intramural scar; CA-pattern: 15/38 [39%] vs. AC-pattern: 1/21 [5%], p = .005). CONCLUSIONS: The spatial pattern of endocardial PM in SHD-related VT directly correlates with scar topography. AC-pattern is associated with endocardial dominant scar on ICE with lower scar ratio and longer stimulus-QRS intervals, whereas CA-pattern is strongly associated with epicardial dominant or mid-intramural scar with higher scar ratio and shorter stimulus-QRS intervals.

Whole-chromosome hitchhiking driven by a male-killing endosymbiont.

Neo-sex chromosomes are found in many taxa, but the forces driving their emergence and spread are poorly understood. The female-specific neo-W chromosome of the African monarch (or queen) butterfly Danaus chrysippus presents an intriguing case study because it is restricted to a single 'contact zone' population, involves a putative colour patterning supergene, and co-occurs with infection by the male-killing endosymbiont Spiroplasma. We investigated the origin and evolution of this system using whole genome sequencing. We first identify the 'BC supergene', a broad region of suppressed recombination across nearly half a chromosome, which links two colour patterning loci. Association analysis suggests that the genes yellow and arrow in this region control the forewing colour pattern differences between D. chrysippus subspecies. We then show that the same chromosome has recently formed a neo-W that has spread through the contact zone within approximately 2,200 years. We also assembled the genome of the male-killing Spiroplasma, and find that it shows perfect genealogical congruence with the neo-W, suggesting that the neo-W has hitchhiked to high frequency as the male-killer has spread through the population. The complete absence of female crossing-over in the Lepidoptera causes whole-chromosome hitchhiking of a single neo-W haplotype, carrying a single allele of the BC supergene and dragging multiple non-synonymous mutations to high frequency. This has created a population of infected females that all carry the same recessive colour patterning allele, making the phenotypes of each successive generation highly dependent on uninfected male immigrants. Our findings show how hitchhiking can occur between the physically unlinked genomes of host and endosymbiont, with dramatic consequences.

Production of polyhydroxyalkanoates from renewable resources: a review on prospects, challenges and applications.

Bioplastics replace synthetic plastics of petrochemical origin, which contributes challenge to both polymer quality and economics. Novel polyhydroxyalkanoates (PHA)-composite materials, with desirable product quality, could be developed, thus targeting the global plastics market, in the coming years. It is possible that PHA can be a greener substitute for their petroleum-based competitors since they are simply decomposed, which may lessen the pressure on municipal and industrial waste management systems. PHA production has proven to be the bottleneck in industrial application and commercialization because of the high price of carbon substrates and downstream processes required to achieve reliability. Bacterial PHA production by these municipal and industrial wastes, which act as a cheap, renewable carbon substrate, eliminates waste management hassles and acts as an efficient substitute for synthetic plastics. In the present review, challenges and opportunities related to the commercialization of polyhydroxyalkanoates are discussed and presented. Moreover, it discusses critical steps of their production process, feedstock evaluation, optimization strategies, and downstream processes. This information may provide us the complete utilization of bacterial PHA during possible applications in packaging, nutrition, medicine, and pharmaceuticals.

Emergency out-of-hours catheter ablation for ventricular arrhythmia storm: a UK and Australian experience.

AIMS: There are limited data on emergency catheter ablation (CA) for ventricular arrhythmia (VA) storm. We describe the feasibility and safety of performing emergency CA in an out-of-hours setting for VA storm refractory to medical therapy at 2 tertiary hospitals. METHODS AND RESULTS: Twenty-five consecutive patients underwent out-of-hours (5pm-8am [weekday] or Friday 5pm-Monday 8am [weekend]) CA for VA storm refractory to anti-arrhythmic drugs and sedation. Baseline and procedural characteristics along with outcomes were compared to 91 consecutive patients undergoing weekday daytime-hours (8am-5pm) CA for VA storm. More patients undergoing out-of-hours CA had a left ventricular ejection fraction ≤35% (68% vs. 42%, P = 0.022), chronic kidney disease (60% vs. 20%, P < 0.001), and presented following a resuscitated out-of-hospital cardiac arrest (56% vs. 5%, P < 0.001), compared to the daytime-hours group. During median follow-up (377 [interquartile range 138-826] days), both groups experienced similar survival free from recurrent VA and VA storm. Survival free from cardiac transplant and/or mortality was lower in the out-of-hours group (44% vs. 81%, P = 0.007), but out-of-hours CA was not independently associated with increased cardiac transplant and/or mortality (hazard ratio 1.34, 95% confidence interval 0.61-2.96, P = 0.47). Of the 11 patients in the out-of-hours group who survived follow-up, VA-free survival was 91% and VA storm-free survival was 100% at 1-year after CA. CONCLUSION: Out-of-hours CA may occasionally be required to control VA storm and can be safe and efficacious in this scenario. During follow-up, cardiac transplant and/or mortality is common but undergoing out-of-hours CA was not predictive of this composite endpoint.

Contemporary updates on ventricular arrhythmias: from mechanisms to management.

Ventricular arrhythmias (VAs) are a group of heart rhythm disorders that can be life-threatening and cause significant morbidity. VA in the presence of structural heart disease (SHD) has distinct prognostic implications and requires a comprehensive and multifaceted approach for investigation and management. Early specialist referral should be considered for all patients with VA. Particular urgency is recommended in patients with syncope, nonsustained/sustained VA on Holter monitor and SHD on cardiac imaging because of the heightened risk of sudden cardiac death. Comprehensive phenotyping is recommended for most patients with VA, encompassing noninvasive cardiac functional testing, multimodality imaging and genetic testing in select circumstances. Management of idiopathic VA is guided heavily by symptom burden and the presence of ventricular systolic impairment. In SHD, guideline-directed heart failure therapy and device implantation are critical considerations. Whilst commonly used and well-established, antiarrhythmic drugs can be hampered by toxicity and failure of adequate arrhythmia control. Catheter ablation is increasingly being considered a feasible first-line alternative to medical therapy, where outcomes are influenced by disease aetiology and scar burden in SHD. Catheter ablation is associated with reduced arrhythmia recurrence and burden and improved quality of life at follow-up.

Correlation of exit sites of inducible ventricular tachycardia post-ST elevation myocardial infarction on electrophysiology study, with region of infarct.

BACKGROUND: Ventricular arrhythmia (VA) is the most common cause of sudden cardiac death post-ST elevation myocardial infarction (STEMI). Ventricular tachycardia (VT) may be inducible in electrophysiology studies (EPS) early (<40 days) post-STEMI. Whether it originates from the infarct site remains unknown. We examined the correlation between inducible VT and infarct location post-STEMI. AIMS: To investigate the correlation between inducible VT and infarct location post-STEMI. METHODS: We retrospectively analysed 46 patients from 2005 to 2017 with STEMI who underwent early programmed ventricular stimulation through EPS (>48 h post-STEMI and <40 days from admission). Gated heart pool scans were used to visualise infarct scar regions, and VT exit sites were derived from induction 12-lead electrocardiography. Patients were followed up for primary outcomes of recurrent VA and all-cause mortality. RESULTS: Forty-six patients were included for analysis, with 50 uniquely induced VT exit sites. Mean left ventricular ejection fraction was 30 ± 8.7% and 22% had impaired right ventricular ejection fraction. Mean time from presentation to EPS was 16 ± 31.3 days. Of the induced VT, 44 (88%) were from within scar and scar-border regions, whereas 6 (12%) of the induced VT were found to be remote to imaging-derived scar. Over a median follow-up period of 75 months, 6 (13%) patients died, and 7 (15%) patients had recurrent VA. No deaths occurred in patients with remote VT. CONCLUSION: The majority of early inducible post-infarct VT arises from acute myocardial scar; however, a small portion arises from sites remote from scars with a possible focal aetiology.

Comparative genomics reveals the diversity of CRISPR-Cas locus in Azotobacter organisms.

Clustered regularly interspaced short palindromic repeats (CRISPRs) are known to provide adaptive immunity to bacteria against invading bacteriophages. In recent years, CRISPR-based technologies have been used for creating improved plant varieties; however, the indigenous CRISPR-Cas elements of plant growth-promoting bacteria are usually neglected. These indigenous genetic cassettes have evolved over millions of years and have shaped the bacterial genome. Therefore, these genetic loci can be used to study the adaptive capability of the bacteria in the environment. This study aims to bioinformatically analyze the genomes of a common free-living nitrogen-fixing Azotobacter spp. to assess their CRISPR-Cas diversity. Strains of Azotobacter vinelandii and Azotobacter chroococcum were found to harbor a large number of spacers. The phylogeny of different Cas and Cse1 proteins revealed a close evolutionary relationship among A. chroococcum B3, A. chroococcum NCIMB 8003 locus II, and A. vinelandii DJ locus I. The secondary structure of the hairpin loop of the repeat was also analyzed, and a correlation was derived between the structural stability of the hairpin loop and the number of spacers acquired by the CRISPR loci. These findings revealed the diversity and evolution of the CRISPR sequences and Cas proteins in Azotobacter species. Although the adaptive immune system of bacteria against bacteriophage, CRISPR-Cas, has been identified in many bacteria, studies of plant growth-promoting bacteria have been neglected. These indigenous CRISPRs have shaped the genome over millions of years and their study can lead to the understanding of the genome composition of these organisms. Our results strengthen the idea of using A. chroococcum and A. vinelandii as biofertilizer strains as they possess more spacers with highly stable repeat sequences, thereby imparting them higher chance of survival against mobile genetic elements like phages and plasmids.

Algorithmic Approach to Virtual Machine Migration in Cloud Computing with Updated SESA Algorithm.

Cloud computing plays an important role in every IT sector. Many tech giants such as Google, Microsoft, and Facebook as deploying their data centres around the world to provide computation and storage services. The customers either submit their job directly or they take the help of the brokers for the submission of the jobs to the cloud centres. The preliminary aim is to reduce the overall power consumption which was ignored in the early days of cloud development. This was due to the performance expectations from cloud servers as they were supposed to provide all the services through their services layers IaaS, PaaS, and SaaS. As time passed and researchers came up with new terminologies and algorithmic architecture for the reduction of power consumption and sustainability, other algorithmic anarchies were also introduced, such as statistical oriented learning and bioinspired algorithms. In this paper, an indepth focus has been done on multiple approaches for migration among virtual machines and find out various issues among existing approaches. The proposed work utilizes elastic scheduling inspired by the smart elastic scheduling algorithm (SESA) to develop a more energy-efficient VM allocation and migration algorithm. The proposed work uses cosine similarity and bandwidth utilization as additional utilities to improve the current performance in terms of QoS. The proposed work is evaluated for overall power consumption and service level agreement violation (SLA-V) and is compared with related state of art techniques. A proposed algorithm is also presented in order to solve problems found during the survey.

Prevalence and Prognostic Implication of Atrial Fibrillation in Heart Failure Subtypes: Systematic Review and Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) portends a poor outcome. The HF universal definition has incorporated Heart Failure with mildly reduced Ejection Fraction (HFmrEF). We sought to evaluate the relationship between AF and different HF subtypes, with emphasis on HFmrEF. METHODS: PubMed and Embase databases were searched up to July 2022. Studies that classified HF with EF≥50% as Heart Failure with Preserved Ejection Fraction (HFpEF); EF 40%-49% as HFmrEF; and EF <40% as Heart Failure with Reduced Ejection Fraction (HFrEF) were included. RESULTS: Fifty (50) eligible studies, with 126,720 acute HF and 109,683 chronic HF patients, were included. Ten percent (10%) and 12% of patients constituted HFmrEF subtype in patients with acute and chronic HF, respectively. The AF prevalence was 38% (95%CI [33, 44], I2=96.9%) in HFmrEF, as compared to 43% (95%CI [39, 47], I2=97.9%) in HFpEF, and 32% (95%CI [29, 35], I2=98.6%) in HFrEF in acute HF patients. Meta-regression showed HFmrEF shared age as a determinant for AF prevalence with HFrEF and HFpEF. Similar AF prevalence also was observed in chronic HF. Compared to sinus rhythm, AF was associated with an increased risk of all-cause mortality in all HF subtypes: HFmrEF (n=6; HR 1.28, 95%CI [1.08, 1.51], I2=71%), HFpEF (n=10; HR 1.14, 95%CI [1.06, 1.23], I2=55%) and HFrEF (n=9; HR 1.11, 95%CI [1.02, 1.21], I2=78%). CONCLUSION: The prevalence of AF was intermediate for HFmrEF in between HFpEF and HFrEF, with determinants shared with either HF subtype. The co-existence of AF and HF predicts an increased all-cause mortality across all categories of HF. (PROSPERO registry: CRD42021189411).

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

Utility of cardiac imaging in patients with ventricular tachycardia.

Ventricular tachycardia (VT) is a life-threatening arrhythmia that may be idiopathic or result from structural heart disease. Cardiac imaging is critical in the diagnostic workup and risk stratification of patients with VT. Data gained from cardiac imaging provides information on likely mechanisms and sites of origin, as well as risk of intervention. Pre-procedural imaging can be used to plan access route(s) and identify patients where post-procedural intensive care may be required. Integration of cardiac imaging into electroanatomical mapping systems during catheter ablation procedures can facilitate the optimal approach, reduce radiation dose, and may improve clinical outcomes. Intraprocedural imaging helps guide catheter position, target substrate, and identify complications early. This review summarises the contemporary imaging modalities used in patients with VT, and their uses both pre-procedurally and intra-procedurally.

SARS-CoV-2 infection of human-induced pluripotent stem cells-derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS-CoV-2 readily infected and replicated in human-induced pluripotent stem cell-derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell-specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant-induced lung injury. Cytokines, such as TNF-α, INF-γ, IL-6, and IL-13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS-CoV-2 infection similar to that seen in COVID-19 patients. Some of our key findings were validated using COVID-19-affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS-CoV-2 infection and to discover and test therapeutic drugs against COVID-19 or its consequences.

Integrative omics approaches for biosynthetic pathway discovery in plants.

Covering: up to 2022With the emergence of large amounts of omics data, computational approaches for the identification of plant natural product biosynthetic pathways and their genetic regulation have become increasingly important. While genomes provide clues regarding functional associations between genes based on gene clustering, metabolome mining provides a foundational technology to chart natural product structural diversity in plants, and transcriptomics has been successfully used to identify new members of their biosynthetic pathways based on coexpression. Thus far, most approaches utilizing transcriptomics and metabolomics have been targeted towards specific pathways and use one type of omics data at a time. Recent technological advances now provide new opportunities for integration of multiple omics types and untargeted pathway discovery. Here, we review advances in plant biosynthetic pathway discovery using genomics, transcriptomics, and metabolomics, as well as recent efforts towards omics integration. We highlight how transcriptomics and metabolomics provide complementary information to link genes to metabolites, by associating temporal and spatial gene expression levels with metabolite abundance levels across samples, and by matching mass-spectral features to enzyme families. Furthermore, we suggest that elucidation of gene regulatory networks using time-series data may prove useful for efforts to unwire the complexities of biosynthetic pathway components based on regulatory interactions and events.