Early outcomes of moderate-to-high-risk pediatric congenital cardiac surgery and predictors of extracorporeal circulatory life support requirement.

Background: Cardiopulmonary failure refractory to medical management after moderate-to-high-risk congenital cardiac surgery may necessitate mechanical support with veno-arterial extracorporeal membrane oxygenation (ECMO). On the extreme, ECMO can also be initiated in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation, ECPR) unresponsive to conventional resuscitative measures. Methods: This was a single-center retrospective cohort study of patients (n = 510) aged <3 years old who underwent cardiac surgery with cardiopulmonary bypass with a RACHS-1 score ≥3 between 2011 and 2014. Perioperative factors were reviewed to identify predictors of ECMO initiation and mortality in the operating room (OR) and the intensive care unit (ICU). Results: A total of 510 patients with a mean surgical age of 10.0 ± 13.4 months were included. Among them, 21 (4%) patients received postoperative ECMO-12 were initiated in the OR and 9 in the ICU. ECMO cannulation was associated with cardiopulmonary bypass duration, aortopulmonary shunt, residual severe mitral regurgitation, vaso-inotropic score, and postprocedural lactate (p < 0.001). Of the 32 (6%) total deaths, 7 (22%) were ECMO patients-4 were elective OR cannulations and 3 were ICU ECPR. Prematurity [hazard ratio (HR): 2.61, p < 0.01), Norwood or Damus-Kaye-Stansel procedure (HR: 4.29, p < 0.001), postoperative left ventricular dysfunction (HR: 5.10, p = 0.01), residual severe tricuspid regurgitation (HR: 6.06, p < 0.001), and postoperative ECMO (ECPR: HR: 15.42, p < 0.001 vs. elective: HR: 5.26, p = 0.01) were associated with mortality. The two patients who were electively cannulated in the ICU survived. Discussion: Although uncommon, postoperative ECMO in children after congenital cardiac surgery is associated with high mortality, especially in cases of ECPR. Patients with long cardiopulmonary bypass time, residual cardiac lesions, or increased vaso-inotropic requirement are at higher risk of receiving ECMO. Pre-emptive or early ECMO initiation before deterioration into cardiac arrest may improve survival.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Interaction of the III-As monolayer with SARS-CoV-2 biomarkers: implications for biosensor development.

The emergence of SARS-CoV-2 in 2019 led to the global COVID-19 pandemic, highlighting the urgency for developing cost-effective and non-invasive methods to detect diseases at an early stage. Human breath, rich in volatile organic compounds (VOCs), is promising for cost-effective and rapid disease detection, with specific VOCs like methanol, ethanal, butanone, acetone, and ethyl butyrate linked to COVID-19. Recent advances in biomarker detection and gas sensing with 2D materials, particularly III-As monolayers like BAs, GaAs, and AlAs, offer high sensitivity at low concentrations, providing a novel avenue for exploring their potential in detecting COVID-19 biomarkers. This article aims to examine the effects of adsorption on different properties of III-Arsenide (BAs, GaAs and AlAs) monolayers, particularly in connection with SARS-CoV-2 biomarkers. In order to examine the interaction between the monolayers and biomarkers, first-principles computations within the framework of density functional theory (DFT) are utilized. The present study involves an investigation of the modifications in the band structure, density of states (DOS), work function, electron density difference, and optical properties (reflectance and absorbance) of III-As monolayers, with the aim of assessing their viability for the detection of SARS-CoV-2 biomarkers along with interfering gases such as CO2 and H2O. It is observed that VOCs induce a notable change in the work function of GaAs which serves as an indicator of the presence of these biomarkers. However, the changes in work function are not as substantial as those for AlAs and BAs. Additionally, the chemiresistive sensitivity, optical sensitivity and recovery time of III-As are investigated. The findings suggest that the pristine GaAs monolayer displays a significant level of sensitivity and selectivity towards the SARS-CoV-2 biomarkers, rendering it a material with potential for utilization in sensing applications. Furthermore, it has been observed that the recovery time of the GaAs monolayer subsequent to its exposure to the VOC biomarkers lies within an acceptable threshold. Upon exposure to UV light, the recovery time is further reduced. The outcomes of our study indicate that GaAs monolayers exhibit considerable potential as chemiresistive, work function-based and optical sensors for the precise and discerning identification of VOCs linked to the SARS-CoV-2 virus compared to the other two III-As monolayers.

Fine root decomposition in forest ecosystems: an ecological perspective.

Fine root decomposition is a physio-biochemical activity that is critical to the global carbon cycle (C) in forest ecosystems. It is crucial to investigate the mechanisms and factors that control fine root decomposition in forest ecosystems to understand their system-level carbon balance. This process can be influenced by several abiotic (e.g., mean annual temperature, mean annual precipitation, site elevation, stand age, salinity, soil pH) and biotic (e.g., microorganism, substrate quality) variables. Comparing decomposition rates within sites reveals positive impacts of nitrogen and phosphorus concentrations and negative effects of lignin concentration. Nevertheless, estimating the actual fine root breakdown is difficult due to inadequate methods, anthropogenic activities, and the impact of climate change. Herein, we propose that how fine root substrate and soil physiochemical characteristics interact with soil microorganisms to influence fine root decomposition. This review summarized the elements that influence this process, as well as the research methods used to investigate it. There is also need to study the influence of annual and seasonal changes affecting fine root decomposition. This cumulative evidence will provide information on temporal and spatial dynamics of forest ecosystems, and will determine how logging and reforestation affect fine root decomposition.

Synergism of vesicle trafficking and cytoskeleton during regulation of plant growth and development: A mechanistic outlook.

The cytoskeleton is a fundamental component found in all eukaryotic organisms, serving as a critical factor in various essential cyto-biological mechanisms, particularly in the locomotion and morphological transformations of plant cells. The cytoskeleton is comprised of three main components: microtubules (MT), microfilaments (MF), and intermediate filaments (IF). The cytoskeleton plays a crucial role in the process of cell wall formation and remodeling throughout the growth and development of cells. It is a highly organized and regulated network composed of filamentous components. In the basic processes of intracellular transport, such as mitosis, cytokinesis, and cell polarity, the plant cytoskeleton plays a crucial role according to recent studies. The major flaws in the organization of the cytoskeletal framework are at the root of the aberrant organogenesis currently observed in plant mutants. The regulation of protein compartmentalization and abundance within cells is predominantly governed by the process of vesicle/membrane transport, which plays a crucial role in several signaling cascades.The regulation of membrane transport in eukaryotic cells is governed by a diverse array of proteins. Recent developments in genomics have provided new tools to study the evolutionary relationships between membrane proteins in different plant species. It is known that members of the GTPases, COP, SNAREs, Rabs, tethering factors, and PIN families play essential roles in vesicle transport between plant, animal, and microbial species. This Review presents the latest research on the plant cytoskeleton, focusing on recent developments related to the cytoskeleton and summarizing the role of various proteins in vesicle transport. In addition, the report predicts future research direction of plant cytoskeleton and vesicle trafficking, potential research priorities, and provides researchers with specific pointers to further investigate the significant link between cytoskeleton and vesicle trafficking.

Targeting caspase pathway by novel N-Me aziridine derivatives for hepatocellular carcinoma drug discovery.

Azaheterocycles are three-membered rings, known as aziridines, that occur naturally and have pharmaceutical applications.These compounds are present as several secondary metabolites produced by plants and microorganisms.Recent studies have demonstrated the effectiveness of aziridine derivatives (N-H/N-Me) as anticancer agents.We synthesized 18 compounds containing an N-Me enone aziridine group, the chemistry of which has been previously published. However, these compounds have drug-likeness properties; therefore, we aimed to demonstrate their drug-like properties using in silico and in vitro investigations.The molecular structures of the compounds were optimized using density functional theory (DFT). The ADMET parameters of the derivatives were calculated using SwissADME and PreADMET. Additionally, these derivatives were evaluated for their ability to bind to caspase-3 and caspase-9 and then subjected to molecular docking. The lead chemical AY128 maintained stable complexes with target proteins during molecular dynamics simulations, as evidenced by the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) parameters. In vitro cytotoxicity and ELISA tests showed that the novel aziridine derivatives, especially AY128, had strong anticancer activity against HepG2 hepatocellular carcinoma cells.Our study suggests that AY128 may be a potential drug candidate for hepatocellular carcinoma through the caspase-3 and caspase-9-dependent apoptotic pathways.Communicated by Ramaswamy H. Sarma.

Automated identification of unstandardized medication data: a scalable and flexible data standardization pipeline using RxNorm on GEMINI multicenter hospital data.

Objective: Patient data repositories often assemble medication data from multiple sources, necessitating standardization prior to analysis. We implemented and evaluated a medication standardization procedure for use with a wide range of pharmacy data inputs across all drug categories, which supports research queries at multiple levels of granularity. Methods: The GEMINI-RxNorm system automates the use of multiple RxNorm tools in tandem with other datasets to identify drug concepts from pharmacy orders. GEMINI-RxNorm was used to process 2 090 155 pharmacy orders from 245 258 hospitalizations between 2010 and 2017 at 7 hospitals in Ontario, Canada. The GEMINI-RxNorm system matches drug-identifying information from pharmacy data (including free-text fields) to RxNorm concept identifiers. A user interface allows researchers to search for drug terms and returns the relevant original pharmacy data through the matched RxNorm concepts. Users can then manually validate the predicted matches and discard false positives. We designed the system to maximize recall (sensitivity) and enable excellent precision (positive predictive value) with efficient manual validation. We compared the performance of this system to manual coding (by a physician and pharmacist) of 13 medication classes. Results: Manual coding was performed for 1 948 817 pharmacy orders and GEMINI-RxNorm successfully returned 1 941 389 (99.6%) orders. Recall was greater than 0.985 in all 13 drug classes, and the F1-score and precision remained above 0.90 in all drug classes, facilitating efficient manual review to achieve 100% precision. GEMINI-RxNorm saved time substantially compared with manual standardization, reducing the time taken to review a pharmacy order row from an estimated 30 to 5 s and reducing the number of rows needed to be reviewed by up to 99.99%. Discussion and Conclusion: GEMINI-RxNorm presents a novel combination of RxNorm tools and other datasets to enable accurate, efficient, flexible, and scalable standardization of pharmacy data. By facilitating efficient manual validation, the GEMINI-RxNorm system can allow researchers to achieve near-perfect accuracy in medication data standardization.

Physician antimicrobial prescribing and patient outcomes on general medical wards: a multicentre retrospective cohort study.

BACKGROUND: Variability in antimicrobial prescribing may indicate an opportunity for improvement in antimicrobial use. We sought to measure physician-level antimicrobial prescribing in adult general medical wards, assess the contribution of patient-level factors to antimicrobial prescribing and evaluate the association between antimicrobial prescribing and clinical outcomes. METHODS: Using the General Medicine Inpatient Initiative (GEMINI) database, we conducted a retrospective cohort study of physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards in 4 academic teaching hospitals in Toronto, Ontario, between April 2010 and December 2019. We stratified physicians into quartiles by hospital site based on volume of antimicrobial prescribing (days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score). The modified spectrum score assigns a value to each antibacterial agent based on the breadth of coverage. We assessed patient-level differences among physician quartiles using age, sex, Laboratory-based Acute Physiology Score, discharge diagnosis and Charlson Comorbidity Index. We evaluated the association of clinical outcomes (in-hospital 30-day mortality, length of stay, intensive care unit [ICU] transfer and hospital readmission) with antimicrobial volume and spectrum using multilevel modelling. RESULTS: The cohort consisted of 124 physicians responsible for 124 158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 (interquartile range 51.7-67.5) days of therapy per 100 patient-days. We did not find any differences in baseline patient characteristics by physician prescribing quartile. The difference in mean prescribing between quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days (95% confidence interval [CI] 9.6-22.0), representing 30% higher antimicrobial prescribing in the fourth quartile than the first quartile. Patient in-hospital deaths, length of stay, ICU transfer and hospital readmission did not differ by physician quartile. In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio 1.13, 95% CI 1.04-1.24). INTERPRETATION: We found that physician-level variability in antimicrobial prescribing was not associated with differences in patient characteristics or outcomes in academic general medicine wards. These findings provide support for considering the lowest quartile of physician antimicrobial prescribing within each hospital as a target for antimicrobial stewardship.

Data-driven approach to identifying potential laboratory overuse in general internal medicine (GIM) inpatients.

BACKGROUND: Reducing laboratory test overuse is important for high quality, patient-centred care. Identifying priorities to reduce low value testing remains a challenge. OBJECTIVE: To develop a simple, data-driven approach to identify potential sources of laboratory overuse by combining the total cost, proportion of abnormal results and physician-level variation in use of laboratory tests. DESIGN, SETTING AND PARTICIPANTS: A multicentre, retrospective study at three academic hospitals in Toronto, Canada. All general internal medicine (GIM) hospitalisations between 1 April 2010 and 31 October 2017. RESULTS: There were 106 813 GIM hospitalisations during the study period, with median hospital length-of-stay of 4.6 days (IQR: 2.33-9.19). There were 21 tests which had a cumulative cost >US$15 400 at all three sites. The costliest test was plasma electrolytes (US$4 907 775), the test with the lowest proportion of abnormal results was red cell folate (0.2%) and the test with the greatest physician-level variation in use was antiphospholipid antibodies (coefficient of variation 3.08). The five tests with the highest cumulative rank based on greatest cost, lowest proportion of abnormal results and highest physician-level variation were: (1) lactate, (2) antiphospholipid antibodies, (3) magnesium, (4) troponin and (5) partial thromboplastin time. In addition, this method identified unique tests that may be a potential source of laboratory overuse at each hospital. CONCLUSIONS: A simple multidimensional, data-driven approach combining cost, proportion of abnormal results and physician-level variation can inform interventions to reduce laboratory test overuse. Reducing low value laboratory testing is important to promote high value, patient-centred care.

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Vinpocetine mitigates DMH-induce pre-neoplastic colon damage in rats through inhibition of pro-inflammatory cytokines.

Colorectal cancer (CRC) is currently recognized as the third most prevalent cancer worldwide. Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine. It has been found effective in ameliorating the growth and progression of cancerous cells. However, its pharmacological effect on colon damage remains elusive. Hence, in this study, we have shown the role of vinpocetine in DMH-induced colon carcinogenesis. At first, male albino Wistar rats were administered with DMH consistently for four weeks to induce pre-neoplastic colon damage. Afterward, animals were treated with vinpocetine (4.2 and 8.4 mg/kg/day p.o.) for 15 days. Serum samples were collected to assess the physiological parameters, including ELISA and NMR metabolomics. Colon from all the groups was collected and processed separately for histopathology and western blot analysis. Vinpocetine attenuated the altered plasma parameters; lipid profile and showed anti-proliferative action as evidenced by suppressed COX-2 stimulation and decreased levels of IL-1ß, IL-2, IL-6, and IL-10. Vinpocetine is significantly effective in preventing CRC which may be associated with its anti-inflammatory and antioxidant potential. Accordingly, vinpocetine could serve as a potential anticancer agent for CRC treatment and thus be considered for future clinical and therapeutic research.

Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines.

BACKGROUND AND AIMS: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. METHODS: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). RESULTS: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. CONCLUSIONS: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. TRIAL REGISTRATION: NCT03186404.

Strong Coupling of Chiral Frenkel Exciton for Intense, Bisignate Circularly Polarized Luminescence.

We show that chiral Frenkel excitons yield intense circularly polarized luminescence with an intrinsic dissymmetry factor in emission glum as high as 0.08. This outstanding value is measured through thin films of cyanine J-aggregates that form twisted bundles. Our measurements, obtained by a Mueller polarization analysis, are artifact-free and reveal a quasi-perfect correlation between the dissymmetry factors in absorption, gabs , and in emission glum . We interpret the bisignate dissymmetry factors as the signature of a strong coupling between chiral Frenkel excitons longitudinally excited along the bundles. We further resolve by polarimetry analysis the split in energy between the excited states with a Davydov splitting as small as 28 meV. We finally show the anti-Kasha nature of the chiral emission bands with opposite optical chirality. These mirror-imaged emissive chiroptical features emerge from the structural rigidity of the bundles that preserves the ground- and excited-state chirality.

Recent developments in the creation of a single molecular sensing tool for ternary iron (III), chromium (III), aluminium (III) ionic species: A review.

Rational design of a molecular sensing tool is an important topic in molecular recognition, signalling, and optoelectronics that has piqued the interest of chemists, biologists, and environmental scientists. Approximately 150 years have passed since the beginning of the fluorescent chemosensor sector. Due to the paramagnetic properties of Cr3+ and Al3+ , it is tough to prepare a photoluminescence plug-in detector. Most dye-based Al3+ sensors must be utilized in organic or mixed solvents for robust hydration of Al3+ in water. The sophisticated molecular design of sensors, conversely, allows for the detection of these metal ions in aqueous medium. The design of chemosensors using various fluorophores and their mechanisms of action have been thoroughly discussed. A literature survey covering the design of chemosensors and their mechanisms of action have been thoroughly discussed covering the period 2010-2022 and that was carried out including innovative and exemplary activities from numerous groups throughout the world that have significantly contributed to this sector. The most important advantages of these probes are their aqueous solubility and quick response with outstanding selectivity and sensitivity for temporal distribution with high fidelity of metals in living cells.

A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy.

PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.

Closure of Left Atrial Appendage Has no Effect on Thromboembolic Rates after Mitral Valve Repair in Patients in Sinus Rhythm.

Closure of the left atrial appendage (LAA) reduces the rates of TIA/stroke in patients in atrial fibrillation (AF) but its role in patients in sinus rhythm who undergo mitral valve repair (MV) for leaflet prolapse remains unknown. This study examined the effects of closing the LAA in TIA/stroke after MV repair. Our database on patients who had MV repair for leaflet prolapse from 2000 through 2019 was reviewed. After excluding patients at higher risk of TIA/stroke, 1050 patients in sinus rhythm were entered into the study: 781 with open LAA and 269 with surgically closed LAA. Using a propensity score analysis to compensate from clinical differences, 267 pairs of patients with open and closed LAA were matched. Follow-up was truncated at 5 years because routine closure of the LAA was performed only during recent years. The cumulative incidence of TIA/stroke at 5 years in the entire cohort was 2.7% [95% CI 1.9, 4.0]; it was 2.9% [95% CI 1.9, 4.4] in patients with open LAA,and 1.8% [95% CI 0.7, 4.9] in patients with closed LAA (P = 0.53). In the matched cohorts, the cumulative incidences of TIA/stroke did not differ significantly (match-adjusted HR [95% CI] = 0.80 [0.21, 2.98], P = 0.74), and multivariable Cox proportional hazard regression analysis also confirmed no difference in the risk of TIA/stroke between the 2 groups (regression-adjusted HR [95% CI] = 0.58 [0.12, 2.9], P = 0.47). This study failed to show a reduction in the risk of TIA/stroke by closing the LAA in patients in sinus rhythm (Figure 6). Closure of the LAA during MV repair warrants a larger and more rigorous study.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.

Visible light-promoted photocatalyst-free activation of persulfates: a promising strategy for C-H functionalization reactions.

The employment of renewable energy resources is highly desirable according to the twelve principles of green chemistry. In this context, visible light promoted organic transformations have gained much attention from synthetic chemists due to the employment of renewable energy. However, the inability of the majority of organic molecules to absorb visible light encouraged the use of photocatalysts in visible light-mediated organic transformations. As a result, different types of photocatalysts like transition-metal containing photoredox catalysts, organophotoredox catalysts, heterogeneous photocatalysts, etc. have emerged over the years. On the other hand, persulphates (K2S2O8, Na2S2O8, and (NH4)2S2O8) have been widely used as oxidants in various oxidative organic transformations under thermal and photochemical conditions. The initial formation of an active persulfate radical anion from a persulfate anion is the crucial step for these oxidative transformations and the conversions under visible light are generally carried out employing different photocatalysts. Although numerous methodologies have been successfully developed employing these photocatalysts, the development of new processes under photocatalyst-free conditions are more preferable from the viewpoint of sustainable development. Persulphates could be very useful for various organic transformations through C-H functionalizations under photocatalyst-free visible light irradiation. In this review, we will exemplify the efficiency of persulphates in various oxidative organic transformations under visible light irradiation without the employment of any photocatalysts. The utilities and mechanistic pathways of the methodologies will also be highlighted.

Diversity among health care leaders in Canada: a cross-sectional study of perceived gender and race.

BACKGROUND: Diverse health care leadership teams may improve health care experiences and outcomes for patients. We sought to explore the race and gender of hospital and health ministry executives in Canada and compare their diversity with that of the populations they serve. METHODS: This cross-sectional study included leaders of Canada's largest hospitals and all provincial and territorial health ministries. We included individuals listed on institutional websites as part of the leadership team if a name and photo were available. Six reviewers coded and analyzed the perceived race and gender of leaders, in duplicate. We compared the proportion of racialized health care leaders with the race demographics of the general population from the 2016 Canadian Census. RESULTS: We included 3056 leaders from 135 institutions, with reviewer concordance on gender for 3022 leaders and on race for 2946 leaders. Reviewers perceived 37 (47.4%) of 78 health ministry leaders as women, and fewer than 5 (< 7%) of 80 as racialized. In Alberta, Saskatchewan, Prince Edward Island and Nova Scotia, provinces with a centralized hospital executive team, reviewers coded 36 (50.0%) of 72 leaders as women and 5 (7.1%) of 70 as racialized. In British Columbia, New Brunswick and Newfoundland and Labrador, provinces with hospital leadership by region, reviewers perceived 120 (56.1%) of 214 leaders as women and 24 (11.5%) of 209 as racialized. In Manitoba, Ontario and Quebec, where leadership teams exist at each hospital, reviewers perceived 1326 (49.9%) of 2658 leaders as women and 243 (9.2%) of 2633 as racialized. We calculated the representation gap between racialized executives and the racialized population as 14.5% for British Columbia, 27.5% for Manitoba, 20.7% for Ontario, 12.4% for Quebec, 7.6% for New Brunswick, 7.3% for Prince Edward Island and 11.6% for Newfoundland and Labrador. INTERPRETATION: In a study of more than 3000 health care leaders in Canada, gender parity was present, but racialized executives were substantially under-represented. This work should prompt health care institutions to increase racial diversity in leadership.