Modified Glucose-Insulin-Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery

Background Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin-glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double-blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in-hospital major adverse cardiac events including all-cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate-1 and protein kinase B in the hearts of GIK-treated patients. Systemic blood lactate was also reduced in GIK-treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in-hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis.

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9-CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9\u27s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis

Large-scale Huygens metasurfaces for holographic 3D near-eye displays

Novel display technologies aim at providing the users with increasingly immersive experiences. In this regard, it is a long-sought dream to generate three-dimensional (3D) scenes with high resolution and continuous depth, which can be overlaid with the real world. Current attempts to do so, however, fail in providing either truly 3D information, or a large viewing area and angle, strongly limiting the user immersion. Here, we report a proof-of-concept solution for this problem, and realize a compact holographic 3D near-eye display with a large exit pupil of 10mm x 8.66mm. The 3D image is generated from a highly transparent Huygens metasurface hologram with large (>10^8) pixel count and subwavelength pixels, fabricated via deep-ultraviolet immersion photolithography on 300 mm glass wafers. We experimentally demonstrate high quality virtual 3D scenes with ~50k active data points and continuous depth ranging from 0.5m to 2m, overlaid with the real world and easily viewed by naked eye. To do so, we introduce a new design method for holographic near-eye displays that, inherently, is able to provide both parallax and accommodation cues, fundamentally solving the vergence-accommodation conflict that exists in current commercial 3D displays.Comment: 21 pages, 9 figure

Molla's music

Magister Artium - MAMolla's Music is a novella about Maureen (Molla), a white Afrikaans woman born in 1935 in Cape Town, who faced poverty and abandonment before apartheid and who, during apartheid, faced the choice between an unwanted pregnancy with a married man, and a carreer in music funded by the father who had betrayed her. Maureen is introduced in three sections with very different voices in each. In the first section she is depicted in the context of being cared for by a single mother with severe post natal depression. The short chapters and long sentences reflect the naïvity of the subject, whose unfiltered observations allow the reader to bear witness to the traumas that dictate her character later in life. She was so ashamed of her poverty, her father's abandonment, and her pregnancy, that she hid all memories of her past from her children and grandchildren and almost managed to die with all her secrets in tact. The second section becomes more sophisticated with longer chapters. The reader is guided through the fifties by a young adult whose adolescent memories inform the events that unfold over a mere two days. Finally, the last section consists of only one chapter, but it reviews an entire life. It is written in the first person, revealing the identity of the narrator. Maureen taught herself piano before school. Her father played the violin and her dedication to music seems to be a mechanism for connecting to him and what his absence from her life represents. It is an absense that eludes consolidation until her death. Molla proved to be such a gifted child that she skipped two years of school and took on music as an extra subject until matric, but financial strain and the shackles of patriarchy limited her options and only after years of working, does she apply to the UCT college of music. She inherits a piano from her landlords, who are evicted during the implementation of the Group Areas Act of 1957. In the years after that, playing piano becomes her private liberation practised in plain sight, on the only heirloom that persists from her past. When she dies, her granddaughter has a heritage that beckons to be resolved and remembered. She does not play the piano she inherited from her grandmother, but starts to investigate its past. In the course of Molla's Music, I explore themes of Afrikaner identity, and question modes of being for white Afrikaans women in South Africa today. By offering an intimate depiction of an individual's search for meaning, while negotiating the forces of Apartheid and patriarchy, especially as a confluence of forces, I hope to gain clarity with regard to my own questions about identity