De novo and salvage purine synthesis pathways across tissues and tumors.

Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.

Rapid identification of SARS-CoV-2 strains via isothermal enzymatic recombinase amplification and nanopore sequencing.

Surveillance of the SARS-CoV-2 genome has become a crucial technique in the management of COVID-19, aiding the pandemic response and supporting effective public health interventions. Typically, whole-genomic sequencing is used along with PCR-based target enrichment techniques to identify SARS-CoV-2 variants, which is a complicated and time-consuming process that requires central laboratory facilities. Thus, there is an urgent need to develop rapid and cost-effective tools for precise on-site detection and identification of SARS-CoV-2 strains. In this study, we demonstrate the rapid diagnosis of COVID-19 and identification of SARS-CoV-2 variants by amplification and sequencing of the entire SARS-CoV-2 S gene using isothermal enzymatic recombinase amplification combined with the advanced Oxford nanopore sequencing technique. The entire procedure, from sampling to sequencing, takes less than 8 hours and can be performed with limited resources. The newly developed method has noteworthy implications for examining the transmission dynamics of the virus, detecting novel genetic variants, and assessing the effect of mutations on diagnostic approaches, antiviral treatments, and vaccines.

Involvement of the inhibition of mitochondrial apoptotic, p53, NF-κB pathways and the activation of Nrf2/HO-1 pathway in the protective effects of curcumin against copper sulfate-induced nephrotoxicity in mice.

Chronic copper exposure could cause potential nephrotoxicity and effective therapy strategies are limited. This study investigated the protective effects of curcumin on copper sulfate (CuSO4)-induced renal damage in a mouse model and the underlying molecular mechanisms. Mice were administrated orally with CuSO4 (100 mg/kg per day) in combination with or without curcumin (50, 100 or 200 mg/kg per day, orally) for 28 days. Results showed that curcumin supplementation significantly reduce the Cu accumulation in the kidney tissues of mice and improved CuSO4-induced renal dysfunction. Furthermore, curcumin supplantation also significantly ameliorated Cu exposure-induced oxidative stress and tubular necrosis in the kidneys of mice. Moreover, compared to the CuSO4 alone group, curcumin supplementation at 200 mg/kg per day significantly decreased CuSO4-induced the expression of p53, Bax, IL-1ß, IL-6, and TNF-α proteins, levels of NF-κB mRNA, levels of caspases-9 and - 3 activities, and cell apoptosis, and significantly increased the levels of Nrf2 and HO-1 mRNAs in the kidney tissues. In conclusion, for the first time, our results reveal that curcumin could trigger the inhibition of oxidative stress, mitochondrial apoptotic, p53, and NF-κB pathways and the activation of Nrf2/HO-1 pathway to ameliorate Cu overload-induced nephrotoxicity in a mouse model. Our study highlights that curcumin supplementation may be a promising treatment strategy for treating copper overload-caused nephrotoxicity.

Evaluation of the Role of Self-cleaning Capacity on Marine Environmental Carrying Capacity: A Case of Ganh Rai Bay, Vietnam.

Economic activities are constantly increasing in the southern key economic region (SKER), especially in Ho Chi Minh City (HCMC), which leads to the influx of large amounts of wastewater from this region into Ganh Rai Bay (GRB). The problem of assessing the marine environmental carrying capacity (MECC) of coastal areas is urgent, and the role of self-cleaning must be elucidated. Four typical pollution parameters were selected: ammonium (NH4+), biological oxygen demand (BOD), phosphate (PO43-), and coliforms. The study aims to propose a framework to assess the impact of the role of self-cleaning on MECC and to apply the proposed framework to GRB as a case study. A series of models were used to simulate hydrodynamics, and an advection-diffusion model with an ecological parameter set was used for water quality modelling. The land-ocean interactions in the coastal zone model were used to calculate the GRB and East Sea retention time. Finally, a multiple linear regression model was used to clarify the relationship between the MECC and self-cleaning factors. Calculation results show that the self-cleaning factor increased the MECCAmmonium by 60.30% in the dry season and 22.75% in the wet season; similar to MECCBOD, MECCPhosphate increased by 5.26%, 0.21% (dry season), and 11.04%, 0.72% (wet season), respectively. MECCCColiforms in the dry season increased by 14.83%; in the wet season, MECCColiforms doubled. The results provide medium-and long-term solutions to improve the water quality of the GRB, especially the selection of activities that conserve the ecological system and improve the self-cleaning capacity of the bay.

Instrument-free, visual and direct detection of porcine reproductive and respiratory syndrome viruses in resource-limited settings.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is one of the most complicated and dangerous diseases in pigs with high mortality since it modulates the immune system of the lungs and has been closely associated with secondary infection of other lethal bacteria and viruses. The gold standard of molecular diagnosis for PRRSV, reverse transcription (RT)-PCR, is time-consuming, expensive and requires transportation of samples to a specialized laboratory. In this study, a direct colorimetric RT-loop-mediated isothermal amplification (RT-LAMP) method was developed to specifically and rapidly detect PRRSV. The RT-LAMP outcomes can be visualized by the naked eye after 45 min of incubation at 65˚C without any cross-reactivity recorded with the bacteria and other viruses tested. In particular, the mobile, non-instrumented, commercial pocket hand warmers were demonstrated to su-ccessfully provide constant temperature for consistent nucleic acid amplification throughout the RT-LAMP reactions. The limit of detection of the assay was defined as the genomic RNA concentration extracted from a known viral titer of 10-2.5 TCID50/ml. The direct use of clinical serum samples required a simple dilution to maintain the performance of the colorimetric RT-LAMP assay. Therefore, the direct colorimetric RT-LAMP assay developed is well-qualified for producing a ready-to-use kit for PRRSV diagnosis in the field. Keywords: porcine reproductive and respiratory syndrome; rapid testing; RT-LAMP; colorimetric; direct detection; instrument-free.

Cardioinformatics: the nexus of bioinformatics and precision cardiology.

Cardiovascular disease (CVD) is the leading cause of death worldwide, causing over 17 million deaths per year, which outpaces global cancer mortality rates. Despite these sobering statistics, most bioinformatics and computational biology research and funding to date has been concentrated predominantly on cancer research, with a relatively modest footprint in CVD. In this paper, we review the existing literary landscape and critically assess the unmet need to further develop an emerging field at the multidisciplinary interface of bioinformatics and precision cardiovascular medicine, which we refer to as 'cardioinformatics'.

A Systematic Review and Meta-analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers.

BACKGROUND: Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. METHODS: MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12-24 hours, 1-3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. RESULTS: Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12-24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). CONCLUSIONS: Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins.

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and ß-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins.

Spliced X-box Binding Protein 1 Stimulates Adaptive Growth Through Activation of mTOR.

BACKGROUND: The unfolded protein response plays versatile roles in physiology and pathophysiology. Its connection to cell growth, however, remains elusive. Here, we sought to define the role of unfolded protein response in the regulation of cardiomyocyte growth in the heart. METHODS: We used both gain- and loss-of-function approaches to genetically manipulate XBP1s (spliced X-box binding protein 1), the most conserved signaling branch of the unfolded protein response, in the heart. In addition, primary cardiomyocyte culture was used to address the role of XBP1s in cell growth in a cell-autonomous manner. RESULTS: We found that XBP1s expression is reduced in both human and rodent cardiac tissues under heart failure. Furthermore, deficiency of XBP1s leads to decompensation and exacerbation of heart failure progression under pressure overload. On the other hand, cardiac-restricted overexpression of XBP1s prevents the development of cardiac dysfunction. Mechanistically, we found that XBP1s stimulates adaptive cardiac growth through activation of the mechanistic target of rapamycin signaling, which is mediated via FKBP11 (FK506-binding protein 11), a novel transcriptional target of XBP1s. Moreover, silencing of FKBP11 significantly diminishes XBP1s-induced mechanistic target of rapamycin activation and adaptive cell growth. CONCLUSIONS: Our results reveal a critical role of the XBP1s-FKBP11-mechanistic target of rapamycin axis in coupling of the unfolded protein response and cardiac cell growth regulation.

anexVis: visual analytics framework for analysis of RNA expression.

Summary: Although RNA expression data are accumulating at a remarkable speed, gaining insights from them still requires laborious analyses, which hinder many biological and biomedical researchers. This report introduces a visual analytics framework that applies several well-known visualization techniques to leverage understanding of an RNA expression dataset. Our analyses on glycosaminoglycan-related genes have demonstrated the broad application of this tool, anexVis (analysis of RNA expression), to advance the understanding of tissue-specific glycosaminoglycan regulation and functions, and potentially other biological pathways. Availability and implementation: The application is accessible at https://anexvis.chpc.utah.edu/, source codes deposited on GitHub. Supplementary information: Supplementary data are available at Bioinformatics online.

External Validation and Updating of the Cardiac Surgery Score for Prediction of Mortality in a Cardiac Surgery Intensive Care Unit.

OBJECTIVE: To externally validate the predictive performance of the logistic and additive Cardiac Surgery Score (CASUS), a postoperative severity of illness score designed specifically for prediction of mortality in the cardiac surgery intensive care unit. DESIGN: A retrospective analysis of prospectively collected data between July 1, 2012, and September 30, 2015. SETTING: Single university cardiac surgery intensive care unit in Canada. PARTICIPANTS: Consecutive adult patients (n = 4,519) admitted to the intensive care unit after cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The mortality predicted by logistic CASUS was calculated for each patient on admission day 0 and postoperative days 2, 4, 7, and 10 using the original model equation. The mortality predicted by additive CASUS was determined on each day with separate logistic regression models, using the total score as a single variable. The observed mortality was 1.8%. Logistic CASUS overestimated mortality by 78%, 59%, 51%, 52%, and 29% on days 0, 2, 4, 7, and 10, respectively. After model updating with logistic calibration, logistic CASUS consistently provided estimates of death comparable with the observed mortality, as determined with the Hosmer-Lemeshow goodness-of-fit test. The stability of those estimates was confirmed by bootstrapping. Similar calibration results were obtained with additive CASUS. Logistic and additive CASUS had good discrimination with areas under the receiver operating characteristic curve greater than 0.7 on each study day. CONCLUSIONS: Recalibrated logistic CASUS reliably predicts mortality in the intensive care unit after cardiac surgery. Logistic regression models derived from additive CASUS perform as well as logistic CASUS.

Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial.

IMPORTANCE: Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate or fibrinogen concentrate. The 2 products have important differences, but comparative clinical data are lacking. OBJECTIVE: To determine if fibrinogen concentrate is noninferior to cryoprecipitate for treatment of bleeding related to hypofibrinogenemia after cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at 11 Canadian hospitals enrolling adult patients experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery (from February 10, 2017, to November 1, 2018). Final 28-day follow-up visit was completed on November 28, 2018. INTERVENTIONS: Fibrinogen concentrate (4 g; n = 415) or cryoprecipitate (10 units; n = 412) for each ordered dose within 24 hours after cardiopulmonary bypass. MAIN OUTCOMES AND MEASURES: Primary outcome was blood components (red blood cells, platelets, plasma) administered during 24 hours post bypass. A 2-sample, 1-sided test for the ratio of the mean number of units was conducted to evaluate noninferiority (threshold for noninferiority ratio, <1.2). RESULTS: Of 827 randomized patients, 735 (372 fibrinogen concentrate, 363 cryoprecipitate) were treated and included in the primary analysis (median age, 64 [interquartile range, 53-72] years; 30% women; 72% underwent complex operations; 95% moderate to severe bleeding; and pretreatment fibrinogen level, 1.6 [interquartile range, 1.3-1.9] g/L). The trial met the a priori stopping criterion for noninferiority at the interim analysis after 827 of planned 1200 patients were randomized. Mean 24-hour postbypass allogeneic transfusions were 16.3 (95% CI, 14.9 to 17.8) units in the fibrinogen concentrate group and 17.0 (95% CI, 15.6 to 18.6) units in the cryoprecipitate group (ratio, 0.96 [1-sided 97.5% CI, -∞ to 1.09; P < .001 for noninferiority] [2-sided 95% CI, 0.84 to 1.09; P = .50 for superiority]). Thromboembolic events occurred in 26 patients (7.0%) in the fibrinogen concentrate group and 35 patients (9.6%) in the cryoprecipitate group. CONCLUSIONS AND RELEVANCE: In patients undergoing cardiac surgery who develop clinically significant bleeding and hypofibrinogenemia after cardiopulmonary bypass, fibrinogen concentrate is noninferior to cryoprecipitate with regard to number of blood components transfused in a 24-hour period post bypass. Use of fibrinogen concentrate may be considered for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03037424.

High-Throughput Omics and Statistical Learning Integration for the Discovery and Validation of Novel Diagnostic Signatures in Colorectal Cancer.

The advancement of bioinformatics and machine learning has facilitated the discovery and validation of omics-based biomarkers. This study employed a novel approach combining multi-platform transcriptomics and cutting-edge algorithms to introduce novel signatures for accurate diagnosis of colorectal cancer (CRC). Different random forests (RF)-based feature selection methods including the area under the curve (AUC)-RF, Boruta, and Vita were used and the diagnostic performance of the proposed biosignatures was benchmarked using RF, logistic regression, naïve Bayes, and k-nearest neighbors models. All models showed satisfactory performance in which RF appeared to be the best. For instance, regarding the RF model, the following were observed: mean accuracy 0.998 (standard deviation (SD) < 0.003), mean specificity 0.999 (SD < 0.003), and mean sensitivity 0.998 (SD < 0.004). Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Some biomarkers were found to be enriched in epithelial cell signaling in Helicobacter pylori infection and inflammatory processes. The overexpression of TGFBI and S100A2 was associated with poor disease-free survival while the down-regulation of NR5A2, SLC4A4, and CD177 was linked to worse overall survival of the patients. In conclusion, novel transcriptome signatures to improve the diagnostic accuracy in CRC are introduced for further validations in various clinical settings.

Novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.

Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high- and low-metastatic sublines (LM8-H and LM8-L, respectively) from Dunn OS cell line LM8 by using in vivo image-guided screening. Among the genes whose expression was significantly increased in LM8-H compared to LM8-L, the transcription factor lymphoid enhancer-binding factor 1 (LEF1) was identified as a factor that promotes LM8-H cell extravasation into the lungs. To identify downstream effectors of LEF1 that are involved in OS lung metastasis, 13 genes were selected based on LM8 microarray data and genomewide meta-analysis of a public database for OS patients. Among them, the cytoglobin (Cygb) gene was identified as a key effector in promoting OS extravasation into the lungs. CYGB overexpression increased the extravasation ability of LM8-L cells, whereas knocking out the Cygb gene in LM8-H cells reduced this ability. Our results showed a novel LEF1-CYGB axis in OS lung metastasis and may provide a new way of developing therapeutic strategies to prevent OS lung metastasis.

A systematic review on metabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer.

INTRODUCTION: Metabolomics is an emerging approach for early detection of cancer. Along with the development of metabolomics, high-throughput technologies and statistical learning, the integration of multiple biomarkers has significantly improved clinical diagnosis and management for patients. OBJECTIVES: In this study, we conducted a systematic review to examine recent advancements in the oncometabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for relevant studies published before September 2017. We examined the study designs, the metabolomics approaches, and the reporting methodological quality following PRISMA statement. RESULTS AND CONCLUSION: The included 25 studies primarily focused on the identification rather than the validation of predictive capacity of potential biomarkers. The sample size ranged from 10 to 8760. External validation of the biomarker panels was observed in nine studies. The diagnostic area under the curve ranged from 0.68 to 1.00 (sensitivity: 0.43-1.00, specificity: 0.73-1.00). The effects of patients' bio-parameters on metabolome alterations in a context-dependent manner have not been thoroughly elucidated. The most reported candidates were glutamic acid and histidine in seven studies, and glutamine and isoleucine in five studies, leading to the predominant enrichment of amino acid-related pathways. Notably, 46 metabolites were estimated in at least two studies. Specific challenges and potential pitfalls to provide better insights into future research directions were thoroughly discussed. Our investigation suggests that metabolomics is a robust approach that will improve the diagnostic assessment of pancreatic cancer. Further studies are warranted to validate their validity in multi-clinical settings.

Comparison of Two Major Perioperative Bleeding Scores for Cardiac Surgery Trials: Universal Definition of Perioperative Bleeding in Cardiac Surgery and European Coronary Artery Bypass Grafting Bleeding Severity Grade.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Research into major bleeding during cardiac surgery is challenging due to variability in how it is scored. Two consensus-based clinical scores for major bleeding: the Universal definition of perioperative bleeding and the European Coronary Artery Bypass Graft (E-CABG) bleeding severity grade, were compared in this substudy of the Transfusion Avoidance in Cardiac Surgery (TACS) trial. METHODS: As part of TACS, 7,402 patients underwent cardiac surgery at 12 hospitals from 2014 to 2015. We examined content validity by comparing scored items, construct validity by examining associations with redo and complex procedures, and criterion validity by examining 28-day in-hospital mortality risk across bleeding severity categories. Hierarchical logistic regression models were constructed that incorporated important predictors and categories of bleeding. RESULTS: E-CABG and Universal scores were correlated (Spearman ρ = 0.78, P < 0.0001), but E-CABG classified 910 (12.4%) patients as having more severe bleeding, whereas the Universal score classified 1,729 (23.8%) as more severe. Higher E-CABG and Universal scores were observed in redo and complex procedures. Increasing E-CABG and Universal scores were associated with increased mortality in unadjusted and adjusted analyses. Regression model discrimination based on predictors of perioperative mortality increased with additional inclusion of the Universal score (c-statistic increase from 0.83 to 0.91) or E-CABG (c-statistic increase from 0.83 to 0.92). When other major postoperative complications were added to these models, the association between Universal or E-CABG bleeding with mortality remained. CONCLUSIONS: Although each offers different advantages, both the Universal score and E-CABG performed well in the validity assessments, supporting their use as outcome measures in clinical trials.

Prospective External Validation of Three Preoperative Risk Scores for Prediction of New Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and late morbidity and mortality of cardiac surgical patients. Prophylactic treatment of atrial fibrillation (AF) has been recommended to improve outcome in cardiac surgical patients at high risk of developing POAF. Reliable models for prediction of POAF are needed to achieve that goal. This study attempted to externally validate 3 risk models proposed for preoperative prediction of POAF in cardiac surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416 adult patients who underwent nonemergent coronary artery bypass graft and/or valve surgery in a single cardiac surgical center between February 2014 and September 2015. A risk score for each of the 3 prediction models was calculated in each patient. All patients were followed for up to 2 weeks, or until hospital discharge, to observe the primary outcome of new onset AF requiring treatment. Discrimination was assessed using receiver operating characteristic curves. Calibration was assessed using the Pearson χ goodness-of-fit test and calibration plots. Utility of the score to implement AF prophylaxis based on the risk of POAF, in comparison to strategies of treating all patients, or not treating any patients, was assessed via a net benefit analysis. RESULTS: Of the 1416 patients included in this study, 478 had the primary outcome (33.8%). The areas under the receiver operating characteristic curve for prediction of POAF in the population subsets for which the scores were validated were as follows: 0.651 (95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI, 0.557-0.629) for the CHA2DS2-VASc score (P < .001 versus POAF score, P < .222 versus Atrial Fibrillation Risk Index), and 0.563 (95% CI, 0.522-0.604) for the Atrial Fibrillation Risk Index (P < .001 versus POAF score). The calibration analysis showed that the predictive models had a poor fit between the observed and expected rates of POAF. Net benefit analysis showed that AF preventive strategies based on these scores, and targeting patients with moderate or high risk of POAF, improve decision-making in comparison to preventive strategies of treating all patients. CONCLUSIONS: The 3 prediction scores evaluated in this study have limited ability to predict POAF in cardiac surgical patients. Despite this, they may be useful in preventive strategies targeting patients with moderate or high risk of PAOF in comparison with preventive strategies applied to all patients.

Practice meta-environment of the cardiovascular perfusionist.

Though historically the development of cardiovascular perfusion grew out of the need for cardiopulmonary bypass, the application of technologies of extracorporeal support has more recently expanded beyond the traditional domain of the cardiac surgical operative and peri-operative environment. As a result, perfusionists are sometimes required to work in novel clinical settings. As part of our recent national survey to evaluate the effects of changes in entry-to-practice criteria introduced in Canada in 2006, we asked perfusionists if their current position as a perfusionist involves work outside the OR. We found that, in addition to regularly working in the Intensive Care Unit and Cardiac Catheterization Lab, 55.3% of respondents reported working "occasionally" in the Emergency Room and 74.7% reported working "occasionally" or "often" in other clinical areas. However, while 96% of respondents believed their training adequately prepared them for their job as a perfusionist, only 68% felt their training adequately prepared them for their duties outside the operating room. We also noted a trend that admission under experience-based entry-to-practice criteria was associated with a higher likelihood of perceived adequacy of training in preparation for duties outside the OR than education-based admission criteria (72% vs 59.4%, p=0.065). These findings raise important questions pertaining to the sufficiency of perfusion education in Canada and the influence of soft skills in preparing perfusionists for their duties, and indicate that a systematic study of the practice environment of cardiovascular perfusionists is timely.

Effects of a change in entry-to-practice criteria for cardiovascular perfusion in Canada: results of a national survey.

INTRODUCTION: Years of experience and level of education are two important determinants of a clinician's expertise. While entry-to-practice criteria for admission to perfusion training in Canada changed from clinical experience-based criteria to education-based criteria in 2006, the effects of these changes have not been studied. OBJECTIVE: To determine the academic and clinical backgrounds of perfusionists in Canada, ascertain perceptions about the adequacy of training and evaluate the effects of the changes on the composition of the perfusion community of Canada. METHODS: An electronic questionnaire was distributed to all practicing perfusionists in Canada, addressing details regarding clinical experience, academic education and perceptions about the adequacy of training. RESULTS: Two hundred and twenty-eight questionnaires were completed, representing a 72% response rate. Perfusionists admitted under academic-based criteria have significantly higher levels of education (100% degree holders vs 69.1%, p<0.001), but less antecedent clinical training and experience (median, IQR: 0, 0 - 4.5 years vs 2, 2 - 8 years, p<0.0001), are younger (median age range 31-35 years vs 51-55 years, p<0.0001), more likely to be female (58.7% vs 41.3%, p=0.006) and are significantly more likely to enter perfusion because of attraction to the type of work (p=0.045). Many perfusionists (70, 32%) in Canada believe themselves inadequately trained for their clinical assignments outside the OR. In addition, 19% of perfusionists plan to retire over the next 10 years. CONCLUSIONS: The introduction of education-based entry criteria has changed the academic and clinical experience levels of perfusionists in Canada. Strategies designed to better prepare perfusionists for their clinical assignments outside the OR are merited.

Nucling, a novel apoptosis-associated protein, controls mammary gland involution by regulating NF-κB and STAT3.

Postpartum mammary gland involution is the physiological process by which the lactating gland returns to its pre-pregnant state. In rodent models, the microenvironment of mammary gland involution is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Therefore, a deeper understanding of the physiological regulation of involution may provide in-depth information on breast cancer therapy. We herein identified Nucling as an important regulator of involution of the mammary gland. A knock-out mouse model was generated and revealed that postpartum involution were impaired in mice lacking Nucling. Involution is normally associated with an increase in the activation of NF-κB and STAT3, which is required for the organized regulation of involution, and was observed in WT glands, but not in the absence of Nucling. Furthermore, the loss of Nucling led to the suppression of Calpain-1, IL-6, and C/EBPδ factors, which are known to be essential for normal involution. The number of M2 macrophages, which are crucial for epithelial cell death and adipocyte repopulation after weaning, was also reduced in Nucling-KO glands. Taken together, the results of the present study demonstrated that Nucling played an important role in mammary gland involution by regulating NF-κB and STAT3 signaling pathways.