• Lowery Sylvest posted an update 1 month, 3 weeks ago

    Natural bioactive compounds have increasingly proved to be promising in evidence- or target-directed treatment or modification of a spectrum of diseases including cerebral ischemic stroke. Hydroxysafflor yellow A (HSYA), a major active component of the safflower plant, has drawn more interests in recent year for its multiple pharmacological actions in the treatment of cerebrovascular and cardiovascular diseases. Although the Janus kinase signaling, such as JAK2/STAT3 pathway, has been implicated in the modulation of the disease, the inhibition or activation of the pathway that contributed to the neuronal prevention from ischemic damages remains controversial. In this study, a series of experiments were performed to examine the dose- and therapeutic time window-related pharmacological efficacies of HSYA with emphasis on the HSYA-modulated interaction of JAK2/STAT3 and SOCS3 signaling in the MCAO rats. We found that HSYA treatment significantly rescued the neurological and functional deficits in a dose-dependent manner in the MCAO rats within 3 h after ischemia. HSYA treatment with a dosage of 8 mg/kg or higher markedly downregulated the expression of the JAK2-mediated signaling that was activated in response to ischemic insult, while it also promoted the expression of SOCS3 coordinately. In the subsequent experiments with the use of the JAK2 inhibitor WP1066, we found that the treatment of WP1066 alone or combination of WP1066/HSYA all exhibited inhibitory effects on JAK2-mediated signaling, while there was no influence on the SOCS3 activity of corresponding efficacious data in the MCAO rats, suggesting that excessive activation of JAK2/STAT3 might be necessary for HSYA to provoke SOCS3-negative feedback signaling. Taking together, our study demonstrates that HSYA might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways that eventually contributed to its therapeutic roles against cerebral ischemic stroke.PURPOSE The objective of this study was to assess the incremental value of myocardial wall motion and thickening compared with perfusion alone obtained from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in diagnosing myocardial viability in patients with ischemic heart failure. METHODS Eighty-three consecutive patients with ischemic heart failure who underwent both 99mTc-MIBI gated SPECT MPI and 18F-FDG positron emission tomography (PET) myocardial metabolic imaging were retrospectively enrolled. SPECT/PET myocardial viability was defined as the reference standard. Segmental myocardial perfusion, wall motion, and thickening were measured by an automated algorithm from gated SPECT MPI. Univariate and stepwise multivariate analysis were conducted to establish an optimal multivariate model for predicting hibernating myocardium and scar. RESULTS Among the 1411 segments evaluated, 774 segments had normal perfusion and 637 segments had decreased perfusion. The latter welity.BACKGROUND To better understand the mechanisms of left ventricular (LV) mechanical dyssynchrony (LVMD), we explored the relative contributions of QRS duration (QRSd), LV ejection fraction (EF), volumes and scar to LVMD measured by gated single-photon emission tomography in a population of consecutive patients with left bundle branch block (LBBB) and right bundle branch block (RBBB) compared to controls. METHODS Myocardial perfusion imaging studies of 275 LBBB and 83 RBBB patients from three centers were analyzed. LVMD was defined as an abnormal phase bandwidth or phase standard deviation. Hospital and gender-specific normal values were obtained from 172 controls. RESULTS The prevalence of LVMD was 85 and 40% in LBBB and RBBB, respectively. Ejection fraction, scar severity, and LBBB morphology independently explained 70% of variance seen in PhaseBW. Ejection fraction had the highest area under the curve (AUC 0.918) in the receiver operating characteristics analysis of LVMD with an optimal cut-off of 47% (sensitivity 73% and specificity 98%). Notably, QRSd was not predictive. CONCLUSION LV mechanical dysfunction plays a greater role than conduction abnormality in the genesis of LVMD, a finding that is intriguing in the context of contemporary literature which suggests that QRSd is the parameter that is most predictive of CRT response.BACKGROUND Metabolic and bariatric surgery (MBS) is currently the only clinically proven method of weight loss that is effective in treating severe obesity and its related comorbidities. However, only about 36% of MBS-eligible patients complete MBS. This qualitative study used the psychosocial framework to identify barriers and facilitators to MBS utilization among patients who had been referred to, or were considering MBS, but had not completed it. METHODS A combination of focus groups and in-depth interviews were utilized (Spring 2019) among ethnically diverse patients (N = 29, 82% female, 62% non-Hispanic Black, 10% Hispanic) who were considering MBS. All data was audio recorded, transcribed, and coded. Interview questions were grouped by the four psychosocial model domains (intrapersonal, interpersonal, organization/clinical interaction, societal/environmental) within the context of why patients would/would not follow through with MBS. The analysis included a combination of deductive and inductive approaches to generate the final codebook. Then, each code was input into Dedoose to identify overarching themes and sub-themes. RESULTS A total of 9 themes and 17 subthemes were found. Two major intrapersonal themes and four subthemes were identified as facilitators to MBS utilization and included a desire for improvement in existing comorbidities, mobility, and anticipated changes in physical appearance. Primary barriers to MBS completion included concerns about potential change in dietary behaviors post-MBS and safety of procedure. GF109203X inhibitor CONCLUSIONS Providing educational materials to address MBS common fears and misconceptions may increase utilization rates. Providing community-based pre- and post-support groups for this patient population may also increase MBS completion rates.