A prediction model for new-onset atrial fibrillation following coronary artery bypass graft surgery: A multicenter retrospective study.

Objective: Developing and assessing a risk prediction model of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG), and aims to provide a reference for the prediction and prevention. Design: A retrospective case-control study. Setting: Three major urban teaching and university hospitals and tertiary referral centers. Participants: consecutive patients undergoing CABG. Interventions: The study was retrospective and no interventions were administered to patients. Measurements and main results: In the study, the overall new-onset POAF prevalence was approximately 28%. A prediction model for POAF with nine significant indicators was developed, and identified new predictors of POAF: left ventricular end diastolic diameter (LVEDD), intraoperative defibrillation, and intraoperative temporary pacing lead implantation. The model had good discrimination in both the derivation and validation cohorts, with the area under the receiver operating characteristic curves (AUCs) of 0.621 (95% CI = 0.602-0.640) and 0.616 (95% CI = 0.579-0.651), respectively, and showed good calibration. Compared with CHA2DS2-VASc, HATCH score, and the prediction model of POAF after CABG developed based on a small sample of clinical data from a single center in China, the model in this study had better discrimination. Conclusion: We have developed and validated a new prediction model of POAF after CABG using multicenter data that can be used in the clinic for early identification of high-risk patients of POAF, and to help effectively prevent POAF in postoperative patients.

Cannabinoid Receptor Agonist WIN55, 212-2 Attenuates Injury in the Hippocampus of Rats after Deep Hypothermic Circulatory Arrest.

OBJECTIVES: Postoperative neurological deficits remain a challenge in cardiac surgery employing deep hypothermic circulatory arrest (DHCA). This study aimed to investigate the effect of WIN55, 212-2, a cannabinoid agonist, on brain injury in a rat model of DHCA. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into three groups: a control group (which underwent cardiopulmonary bypass (CPB) only), a DHCA group (CPB with DHCA), and a WIN group (WIN55, 212-2 pretreatment before CPB with DHCA). Histopathological changes in the brain were evaluated by hematoxylin-eosin staining. Plasma levels of superoxide dismutase (SOD) and proinflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-a) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression of SOD in the hippocampus was detected by Western blot and immunofluorescence staining. Levels of apoptotic-related protein caspase-3 and type 1 cannabinoid receptor (CB1R) in the hippocampus were evaluated by Western blot. RESULTS: WIN55, 212-2 administration attenuated histopathological injury of the hippocampus in rats undergoing DHCA, associated with lowered levels of IL-1ß, IL-6, and TNF-α (p < 0.05, p < 0.001, and p < 0.01, vs. DHCA, respectively) and an increased level of SOD (p < 0.05 vs. DHCA). WIN55, 212-2 treatment also increased the content of SOD in the hippocampus. The protein expression of caspase-3 was downregulated and the expression of CB1R was upregulated in the hippocampus by WIN55, 212-2. CONCLUSIONS: the administration of WIN55, 212-2 alleviates hippocampal injury induced by DHCA in rats by regulating intrinsic inflammatory and oxidative stress responses through a CB1R-dependent mechanism.

Inhibition of the Activating Transcription Factor 6 Branch of Endoplasmic Reticulum Stress Ameliorates Brain Injury after Deep Hypothermic Circulatory Arrest.

Neurological dysfunction is a common complication of deep hypothermic circulatory arrest (DHCA). Endoplasmic reticulum (ER) stress plays a role in neuronal ischemia-reperfusion injury; however, it is unknown whether it contributes to DHCA-induced brain injury. Here, we aimed to investigate the role of ER stress in a rat DHCA model and cell hypothermic oxygen-glucose deprivation reoxygenation (OGD/R) model. ER stress and apoptosis-related protein expression were identified using Western blot analysis. Cell counting assay-8 and flow cytometry were used to determine cell viability and apoptosis, respectively. Brain injury was evaluated using modified neurological severity scores, whereas brain injury markers were detected through histological examinations and immunoassays. We observed significant ER stress molecule upregulation in the DHCA rat hippocampus and in hypothermic OGD/R PC-12 cells. In vivo and in vitro experiments showed that ER stress or activating transcription factor 6 (ATF6) inhibition alleviated rat DHCA-induced brain injury, increased cell viability, and decreased apoptosis accompanied by C/EBP homologous protein (CHOP). ER stress is involved in DHCA-induced brain injury, and the inhibition of the ATF6 branch of ER stress may ameliorate this injury by inhibiting CHOP-mediated apoptosis. This study establishes a scientific foundation for identifying new therapeutic targets for perioperative brain protection in clinical DHCA.

Comparison of in-hospital outcomes after coronary artery bypass graft surgery in elders and younger patients: a multicenter retrospective study.

OBJECTIVES: We aimed to identify in-hospital outcomes in young (≤ 65 years) and old (> 65 years) patients after coronary artery bypass grafting (CABG) by analyzing the effect of age on adverse events after on-pump or off-pump CABG. METHODS: Patients older than 65 years were defined as older patients and others were defined as younger patients. The qualitative data were compared by chi-square or Fisher's exact tests. The quantitative data were compared by the two-sample independent t-test or Mann-Whitney U test. Multifactor binary logistic regression was used to control for confounders and to investigate the effect of age on dichotomous outcome variables such as death. RESULTS: In the on-pump CABG population, the postoperative in-hospital mortality, the incidence of postoperative symptomatic cerebral infarction (POSCI) and postoperative atrial fibrillation (POAF) was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with postoperative in-hospital mortality (OR = 2.370, P value = 0.031), POSCI (OR = 5.033, P value = 0.013), and POAF (OR = 1.499, P value < 0.001). In the off-pump CABG population, the incidence of POAF was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with POAF (OR = 1.392, P value = 0.011). CONCLUSION: In-hospital outcomes after CABG are strongly influenced by age. In on-pump CABG, the risk of postoperative death, POSCI, and POAF was higher in older patients, and in off-pump CABG, the risk of POAF was higher in older patients.

Association of LDL to HDL ratio with new-onset atrial fibrillation after on-pump coronary artery bypass graft surgery.

OBJECTIVE: This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. METHODS: A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. RESULTS: In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529-0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775-0.886) and a specificity of 30.02% (95% CI = 0.257-0.346). CONCLUSION: Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.

CXCL7-Mediated Stimulation of Lymphangiogenic Factors VEGF-C, VEGF-D in Human Breast Cancer Cells.

Increased expression of lymphangiogenesis factors VEGF-C/D and heparanase has been correlated with the invasion of cancer. Furthermore, chemokines may modify matrix to facilitate metastasis, and they are associated with VEGF-C and heparanase. The chemokine CXCL7 binds heparin and the G-protein-linked receptor CXCR2. We investigated the effect of CXCR2 blockade on the expression of VEGF-C/D, heparanase, and on invasion. CXCL7 siRNA and a specific antagonist of CXCR2 (SB225002) were used to treat CXCL7 stably transfected MCF10AT cells. Matrigel invasion assays were performed. VEGF-C/D expression and secretion were determined by real-time PCR and ELISA assay, and heparanase activity was quantified by ELISA. SB225002 blocked VEGF-C/D expression and secretion (P < .01). CXCL7 siRNA knockdown decreased heparanase (P < .01). Both SB225002 and CXCL7 siRNA reduced the Matrigel invasion (P < .01). The MAP kinase signaling pathway was not involved. The CXCL7/CXCR2 axis is important for cell invasion and the expression of VEGF-C/D and heparanase, all linked to invasion.

Immunohistochemical analysis of ocular platelet basic protein expression during infection with Pseudomonas aeruginosa.

Platelet basic protein (PBP) and several of its derivatives are known to express a wide range of biological characteristics. It is the precursor of connective tissue activating peptide (CTAP-III), beta thromboglobulin (beta-TG) and neutrophil activating peptide (NAP-2), which is the proteolytic derived end product. The temporal ocular expression of the chemokine PBP before and during corneal infection over several days by Pseudomonas aeruginosa was examined by immunohistochemistry. Prior to corneal infection, immunohistochemical staining demonstrated the constitutive expression of PBP in the cornea, lens and retina. PBP expression was present in the corneal epithelium, stromal fibroblasts and endothelium. There was a temporal increase in PBP expression in the cornea after infection. The entire cornea exhibited extensive cellular infiltration by positive PBP staining infiltrating cells within 6 days post-infection. The cornea, lens and retina underwent extensive degradation within 5-6 days post-infection with some apparent selective increase in PBP staining in the lens and retina.

Increased invasion through basement membrane by CXCL7-transfected breast cells.

BACKGROUND: CXC chemokines may modify breast cancer cells and surrounding extracellular matrix to facilitate metastasis. CXCL7 is heparin binding, has heparanase activity, and is a ligand to CXCR2, a G-protein-linked receptor. METHODS: Isogenic cell lines, malignant MCF10CA1a.cl1 cells, and premalignant MCF10AT cells were used. CXCR2 and CXCL7 expression levels were quantified by reverse transcriptionase-polymerase chain reaction and Western blot. MCF10AT cells were stably transfected with CXCL7, and matrigel invasion assays were performed. Antibody to CXCL7 was used to inhibit invasion. CXCL7 secretion by transfectants and heparanase activity were quantified by enzyme-linked immunosorbent assay. RESULTS: CXCL7 and CXCR2 expression were significantly higher in malignant MCF10CA1a.cl1 cells than in premalignant MCF10AT cells. Secreted CXCL7, secreted heparanase activity, and invasiveness were all increased in CXCL7-transfected MCF10AT cells. CXCL7 antibody inhibited invasion of CXCL7-transfected MCF10AT cells. CONCLUSIONS: Malignant MCF10CA1a.cl1 cells express more CXCL7 and CXCR2 than premalignant MCF10AT cells. CXCL7-transfected MCF10AT cells are as invasive as malignant breast cancer cells.

The Kolb learning cycle in American Board of Surgery In-Training Exam remediation: the Accelerated Clinical Education in Surgery course.

BACKGROUND: Surgical training integrates the 4 steps of the Kolb learning cycle. Residents who scored at 30th percentile or less on the American Board of Surgery In-Training Exam (ABSITE) were enrolled in the Accelerated Clinical Education in Surgery (ACES) course that incorporated the Kolb cycle. METHODS: For concrete experience, Surgical Education and Self-Assessment Program (SESAP-13) was completed according to the syllabus. For reflective consideration, further reading was done on SESAP 13 topics and corresponding ABSITE Keywords. For the abstract hypotheses step; these keywords and topics were reviewed with the mentor. Active testing involved a required weekly on-line quiz based on the syllabus. RESULTS: Correct scores on the ABSITE increased for 78.6% of residents in the ACES course, with 28.6% scoring 30th percentile or greater. Senior percent correct scores increased by 7.3% and junior percentile scores by 12.5%. CONCLUSIONS: Remediation using the Kolb cycle improved ABSITE performance for a majority of participants.

Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells.

Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade-CCAAT/Enhancer binding protein-beta, peroxisome proliferator-activated receptor-gamma, and fatty acid-binding protein-and consequentially increased lipid accumulation in a time- and viral dose-dependent manner. Induction of hASC to the adipocyte state by Ad-36 was further supported by increased expression of lipoprotein lipase and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce adipogenesis in hASC, which may contribute to adiposity induced by the virus.

Expression patterns of lymphangiogenic and angiogenic factors in a model of breast ductal carcinoma in situ.

BACKGROUND: Foci of invasion are found in greater than 20% of excised specimens of breast ductal carcinoma in situ (DCIS). Since lymphangiogenesis markers are associated with the potential for increased lymph node metastasis, the purpose of the current study was to determine expression of lymphangiogenesis molecular markers in a model of aggressive DCIS. METHODS: From the MCF10A xenograft model, comedo type MCF10DCIS.com cells, premalignant MCF10AT, and invasive MCF10CA1a.cl1 cells were tested. Invasion was tested by Matrigel invasion assays (Becton-Dickinson, Bedford, MA). Gene expression was determined by reverse transcriptase-polymerase chain reaction and protein expression by immunoblot, normalized to beta-actin. RESULTS: MCF10DCIS.com cells were 4-fold more invasive than MCF10AT cells (P < .01), and expressed several-fold more mRNA and protein than MCF10AT and MCF10CA1a.cl1 cells for vascular endothelial growth factor C, vascular endothelial growth factor D, and lymphatic vessel endothelial hyaluronan receptor 1 (P < .01). CONCLUSIONS: A subset of comedo-type DCIS cells are invasive, and expression of lymphangiogenesis markers is greater at the mRNA and protein levels than by invasive cancer cells (P < .01). These additional molecular markers may characterize aggressive DCIS more precisely.

Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats.

OBJECTIVE: Human adenovirus 36 (Ad-36) increases adiposity and reduces serum lipids in chicken, mouse, and non-human primate models, and it is linked to obesity in sero-epidemiological studies in humans. Involvement of the central nervous system (CNS) or adipose tissue in the mechanism of Ad-36-induced adiposity is unknown. The effects of Ad-36 on adiposity and on the neuroendocrine system were investigated in a rat model. RESEARCH METHODS AND PROCEDURES: Five-week-old male Wistar rats were inoculated intraperitoneally with Ad-36 or medium. RESULTS: Despite similar food intakes, infected rats attained significantly greater body weight and fat pad weight by 30 weeks post-inoculation. Epididymal-inguinal, retroperitoneal, and visceral fat pad weights of the infected group were greater by 60%, 46%, and 86%, respectively (p < 0.00001). The fasting serum insulin level and homeostasis model assessment index indicated greater insulin sensitivity in the infected group. Visceral adipose tissue expression of glycerol 3-phosphate dehydrogenase, peroxisome proliferator-activated receptor gamma, and CCAAT/enhancer-binding protein alpha and beta was markedly increased in the infected animals compared with controls. Ad-36 decreased norepinephrine levels significantly in the paraventricular nucleus in infected vs. control rats (mean +/- standard error, 8.9 +/- 1.1 vs. 12.8 +/- 1.2 pg/microg protein; p < 0.05). Ad-36 markedly decreased serum corticosterone in infected vs. control rats (mean +/- standard error, 97 +/- 41.0 vs. 221 +/- 111 ng/mL; p < 0.005). DISCUSSION: The results suggest that the pro-adipogenic effect of Ad-36 may involve peripheral as well as central effects. The male Wistar rat is a good model for the elucidation of metabolic and molecular mechanisms of Ad-36-induced adiposity.

Genomic organization and promoter regulation of human cytochrome c oxidase subunit VII heart/muscle isoform (COX7AH).

We have isolated and characterized the human gene (COX7AH) for the contractile muscle isoform of cytochrome c oxidase (COX) subunit VIIa. This subunit is one of the 10 nuclear encoded subunits of the 13-subunit holoenzyme that carries out the terminal step in the electron transport chain. Using transient transfection assays, we have located a 5'-flanking region sufficient to direct high level, skeletal myotube-specific reporter gene expression. This 792 bp basal promoter, which contains the single transcription start but no canonical TATA or CCAAT boxes, contains one MEF2 site, three E boxes, and an Sp1 site that show binding to their cognate factors, and are all required for full expression. Mutation and transactivation analysis suggest that there is functional interaction between these binding sites.