Cu-catalyzed click reaction in synthesis of eugenol derivatives as potent antimalarial agents.

Eugenol(1), a terpenoid found in Ocimum, has various biological activities. The present study aims at extraction, isolation of the plant secondary metabolite eugenol (1), it's derivatisation and structure identification as bioactive molecules. Synthesis and antiplasmodial activity (in-vitro and in-vivo), of a series of fourteen novel eugenol-based 1,2,3-triazole derivatives was done in the present study. Derivatives 5a-5n showed good antimalarial activity against the strain Plasmodium falciparum NF54. Derivative 5 m, IC50 at 2.85 µM was found to be several times better than its precursor 1 (106.82 µM) whereas the derivative 5n showed three fold better activity than compound 1, in vitro. The structure-activity relationship of the synthesised compounds indicated that the presence of triazole ring in eugenol analogues is responsible for their good activity. Compound 5m, was further evaluated for in-vivo antimalarial activity which showed about 79% parasitemia suppression. It is the first report on antimalarial activity of triazole eugenol derivatives.

Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

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.

HIV1-Nef perturbs the integrity of blood testis barrier in rat model.

The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

Established a rodent model to study the integrity of the blood testis barrier (BTB).Recombinant Nef (rNef) of HIV1 can breach the toughest physiological barrier of BTB.Integrity of BTB gets interrupted by rNef through the 'disengagement' and 'engagement' mechanisms of BTB dynamics.Major constituent proteins of BTB, including Occludin and ZO-1 were found to be highly disrupted by rNef; and seem to be the key aberrant for the compromised BTB.rNef also dislocated the localization of N & E cadherins in the rat testes; which would have affected the cadherin-based epithelial adhesion system of BTB and finally caused the breach.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

Bystander cardiopulmonary resuscitation differences by sex - The role of arrest recognition.

PURPOSE: To assess whether bystander cardiopulmonary resuscitation (CPR) differed by patient sex among bystander-witnessed out-of-hospital cardiac arrests (OHCA). METHODS: This study is a retrospective analysis of paramedic-attended OHCA in New South Wales (NSW) between January 2017 to December 2019 (restricted to bystander-witnessed cases). Exclusions included OHCA in aged care, medical facilities, with advance care directives, from non-medical causes. Multivariate logistic regression examined the association of patient sex with bystander CPR. Secondary outcomes were OHCA recognition, bystander AED application, initial shockable rhythm, and survival outcomes. RESULTS: Of 4,491cases, females were less likely to receive bystander CPR in private residential (Adjusted Odds ratio [AOR]: 0.82, 95%CI: 0.70-0.95) and public locations (AOR: 0.58, 95%CI:0.39-0.88). OHCA recognition during the emergency call was lower for females arresting in public locations (84.6% vs 91.6%, p = 0.002) and this partially explained the association of sex with bystander CPR (∼44%). This difference in recognition was not observed in private residential locations (p = 0.2). Bystander AED use was lower for females (4.8% vs 9.6%, p < 0.001); however, after adjustment for location and other covariates, this relationship was no longer significant (AOR: 0.83, 95%CI: 0.60-1.12). Females were less likely to be in an initial shockable rhythm (AOR: 0.52, 95%CI: 0.44-0.61), but more likely to survive the event (AOR: 1.34, 95%CI: 1.15-1.56). There was no sex difference in survival to hospital discharge (AOR: 0.96, 95%CI: 0.77-1.19). CONCLUSION: OHCA recognition and bystander CPR differ by patient sex in NSW. Research is needed to understand why this difference occurs and to raise public awareness of this issue.

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.

Fabrication of Novel 3-D Nanocomposites of HAp-TiC-h-BN-ZrO2: Enhanced Mechanical Performances and In Vivo Toxicity Study for Biomedical Applications.

Due to excellent biocompatibility, bioactivities, and osteoconductivity, hydroxyapatite (HAp) is considered as one of the most suitable biomaterials for numerous biomedical applications. Herein, HAp was fabricated using a bottom-up approach, i.e., a wet chemical method, and its composites with TiC, h-BN, and ZrO2 were fabricated by a solid-state reaction method with enhanced mechanical and biological performances. Structural, surface morphology, and mechanical behavior of the fabricated composites were characterized using various characterization techniques. Furthermore, transmission electron microscopy study revealed a randomly oriented rod-like morphology, with the length and width of these nanorods ranging from 78 to 122 and from 9 to 13 nm. Moreover, the mechanical characterizations of the composite HZBT4 (80HAp-10TiC-5h-BN-5ZrO2) reveal a very high compressive strength (246 MPa), which is comparable to that of the steel (250 MPa), fracture toughness (14.78 MPa m1/2), and Young's modulus (1.02 GPa). In order to check the biocompatibility of the composites, numerous biological tests were also performed on different body organs of healthy adult Sprague-Dawley rats. This study suggests that the composite HZBT4 could not reveal any significant influence on the hematological, serum biochemical, and histopathological parameters. Hence, the fabricated composite can be used for several biological applications, such as bone implants, bone grafting, and bone regeneration.

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.

Air-Abrasion in Dentistry: A Short Review of the Materials and Performance Parameters.

The selection of abrasive material and parameters of the Air-Abrasion device for a particular application is a crucial detail. However, there are no standard recommendations or manuals for choosing these details; the operator must depend on his experience and knowledge of the procedure to select the best possible material and set of parameters. This short review attempts to identify some of the effects that the selection of material and parameters could have on the performance of the Air-Abrasion procedure for a particular application. The material and parameter data are collected from various studies and categorized according to the most popular materials in use right now. These studies are then analyzed to arrive at some inferences on the performance of Air-Abrasion materials and parameters. This review arrives at a few conclusions on the effectiveness of a material and parameter set, and that there is potential for developments in the area of standardizing parameter selection; also, there is scope for further studies on Bio-Active Glass as an alternative to the materials currently used in Air-Abrasion.

Adeno-associated virus-mediated gene therapy for cardiac tachyarrhythmia: A systematic review and meta-analysis.

Cardiac tachyarrhythmia presents a significant health care challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential risks, resulting in an elevated disease burden. Adeno-associated virus (AAV)-mediated gene therapy holds promise as a potential future treatment option. Therefore, we aimed to provide a measured overview of the latest developments in this rapidly growing field. PubMed and Embase databases were searched up to January 2024. Studies that employed AAV as a vector for delivery of therapeutic agents to treat cardiac tachyarrhythmia were included. Of the 26 studies included, 20 published in the last 5 years. There were 22 novel molecular targets identified. More than 80% of the included studies employed small-animal models or used AAV9. In atrial fibrillation preclinical studies, AAV-mediated gene therapy reduced atrial fibrillation inducibility by 81% (odds ratio, 0.19 [0.08-0.45]; P < .01). Similarly, for acquired and inherited ventricular arrhythmia, animal models receiving gene therapy had less inducible ventricular arrhythmia (odds ratio, 0.06 [0.03-0.11]; P < .01). This review highlights the rapid progress of AAV-mediated gene therapy for cardiac tachyarrhythmia. Although these investigations are currently in the early stages of clinical application, they present promising prospects for gene therapy. (PROSPERO registry: CRD42023479448).

The Role of Platelet Parameters in Predicting the Disease Severity of COVID-19 Patients: A Hospital-Based Study.

Background and objective Globally, a large number of people have been impacted by the extremely contagious coronavirus disease 2019 (COVID-19) infection, and several pieces of literature were published on hematological parameter changes in this infection, particularly focusing on leucocytes. In this study, we have analyzed the platelet parameters and platelet-leucocyte ratios in COVID-19 patients and correlated them with the disease severity. Methods The COVID-19 patients who were hospitalized during the second peak of the pandemic were assessed. The platelet count and indices, platelet to lymphocyte ratio (PLR), neutrophil to platelet ratio (NPR), and clinical severity of each patient were analyzed. The significance of parameters and clinical severity was evaluated using analysis of variance (ANOVA) and the Kruskal Wallis test. A bivariate analysis was performed to assess the strength of the association. Receiver operating characteristic (ROC) curves were plotted to detect the predictive value of parameters for disease severity. Results The data of 132 COVID-19 patients has been evaluated. The average mean age was 45.60 ± 15.76 years with slight female predominance. Thrombocytopenia was found in 33% of cases with the majority of them being mild. Age, platelet distribution width (PDW), and PLR and NPR parameters were significantly (p-value <0.05) associated with disease severity. ROC curves showed age, PDW, PLR, NPR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) had significant prediction values for clinical severity. Conclusions Platelet parameters may not accurately reflect the severity of the disease, but when combined with leucocyte parameters and their ratios (PLR and NPR), they offer important information about disease severity.

UltraSOUND-based characterization of ventricular tachycardia SCAR and arrhythmogenic substrate: The SOUNDSCAR study.

BACKGROUND: Intracardiac echocardiography (ICE) represents a valuable image integration technique, with the unique advantage of dynamic real-time scar characterization. OBJECTIVES: The goals of this study were to assess the correlation between ICE-defined and electroanatomic mapping (EAM)-defined scar in patients with ischemic cardiomyopathy and to define the outcomes of ICE-guided ventricular tachycardia (VT) ablation. METHODS: Thirty-eight patients with ischemic cardiomyopathy (SOUNDSCAR cohort) underwent full left ventricular (LV) ICE imaging and EAM. ICE-defined scar parameters (end-diastolic and end-systolic wall diameter [EDWD and ESWD], end-systolic wall thickening [percentage difference between EDWD and ESWD with respect to EDWD], slope [end-diastole to end-systole wall thickening], and American Heart Association wall motion scoring) were correlated with EAM-defined scar (voltage <1.5 mV). In a separate cohort (n = 21), outcomes of an ICE-guided VT ablation approach (EAM focused to ICE-defined scar regions) were compared with those of conventional ablation (full left ventricular mapping with EAM only; n = 21). RESULTS: In the 38 SOUNDSCAR patients (mean age 67 ± 11 years; 35 male [92%]; left ventricular ejection fraction 31% ± 10%; 2474 ICE segments; 524 ICE sectors), all ICE-defined parameters strongly predicted EAM-defined scar (area under the curve: American Heart Association score 0.873; ESWD 0.880; EDWD 0.827; slope 0.855; percentage difference between EDWD and ESWD with respect to EDWD, 0.851). All ICE-defined parameters had large effect sizes for predicting EAM-defined scar (logistic regression, P < .001). A detailed topographical comparison of ICE-defined (slope) and EAM-defined scar was possible in 25 patients and demonstrated 88% ± 10% overlap. Compared with conventional VT ablation, ICE-guided ablation was associated with shorter procedure times and comparable VT-free survival (ICE-guided vs conventional: procedure time 240 ± 20 minutes vs 298 ± 39 minutes; P < .001; VT recurrence 3 [14%] vs 7 [31%]; P = .19). CONCLUSION: ICE-defined scar demonstrates a strong correlation with EAM-defined scar. ICE-guided VT ablation is associated with enhanced procedural efficiency.

Structure based docking and biological evaluation towards exploring potential anti-cancerous and apoptotic activity of 6-Gingerol against human prostate carcinoma cells.

BACKGROUND: 6-Gingerol (6-G) is the primary active phytocomponent of ginger and has been shown to regulate multiple targets against cancer and its treatment. Androgen receptors (ARs) remain critical in the progression of prostate cancer (PCa). This study focuses on investigating 6-G as a promising anti-cancerous agent that inhibits AR activity significantly. METHODS: In this study, molecular docking simulation was done to investigate the binding affinity of 6-G and control drug Bicalutamide (BT) against oncogenic AR and tumor suppressor estrogen receptor ß (ERß). The crystal structure of AR and ERß was retrieved from Protein Data Bank (PDB) and docked with 3D Pubchem structures of 6-G using iGEMDOCK and AutoDock. Further in vitro study was done to evaluate the antioxidant, anti-cancerous, apoptotic, and wound healing potential of 6-G. RESULTS: The result displays that 6-G shows good binding affinity with AR and ERß. Condensation of the nucleus, change in mitochondrial membrane potential (MMP) and the ability to induce reactive oxygen species (ROS) were done in human PCa PC-3 cells. Results from the MTT assay demonstrated that 6-G and control drug BT showed significant (p < 0.01) dose and time dependent inhibition of human PCa PC-3 cells. 6-G increased the ROS generation intracellularly and decreased the MMP, and cell migration in treated PCa PC-3 cells. 6-G treated cells showed fragmented, condensed chromatin and nuclear apoptotic bodies. CONCLUSIONS: Thus, this study validates 6-G as a potential drug candidate against human PCa. However, further study of the anticancer potency of 6-G has to be done before its use for PCa treatment.

Fabrication, structural, and enhanced mechanical behavior of MgO substituted PMMA composites for dental applications.

The most common denture material used for dentistry is poly-methyl-methacrylate (PMMA). Usually, the polymeric PMMA material has numerous biological, mechanical and cost-effective shortcomings. Hence, to resolve such types of drawbacks, attempts have been made to investigate fillers of the PMMA like alumina (Al2O3), silica (SiO2), zirconia (ZrO2) etc. For the enhancement of the PMMA properties a suitable additive is required for its orthopedic applications. Herein, the main motive of this study was to synthesize a magnesium oxide (MgO) reinforced polymer-based hybrid nano-composites by using heat cure method with superior optical, biological and mechanical characteristics. For the structural and vibrational studies of the composites, XRD and FT-IR were carried out. Herein, the percentage of crystallinity for all the fabricated composites were also calculated and found to be 14.79-30.31. Various physical and optical parameters such as density, band gap, Urbach energy, cutoff energy, cutoff wavelength, steepness parameter, electron-phonon interaction, refractive index, and optical dielectric constant were also studied and their values are found to be in the range of 1.21-1.394 g/cm3, 5.44-5.48 eV, 0.167-0.027 eV, 5.68 eV, 218 nm, 0.156-0.962, 4.273-0.693, 1.937-1.932, and 3.752-3.731 respectively. To evaluate the mechanical properties like compressive strength, flexural strength, and fracture toughness of the composites a Universal Testing Machine (UTM) was used and their values were 60.3 and 101 MPa, 78 and 40.3 MPa, 5.85 and 9.8 MPa-m1/2 respectively. Tribological tests of the composites were also carried out. In order to check the toxicity, MTT assay was also carried out for the PM0 and PM15 [(x)MgO + (100 - x) (C5O2H8)n] (x = 0 and 15) composites. This study provides a comprehensive insight into the structural, physical, optical, and biological features of the fabricated PMMA-MgO composites, highlighting the potential of the PM15 composite with its enhanced density, mechanical strength, and excellent biocompatibility for denture applications.

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.