Door-to-balloon Time for ST-elevation MI in the Coronavirus Disease 2019 Era

In patients presenting with ST-elevation MI, prompt primary coronary intervention is the preferred treatment modality. Several studies have described improved outcomes in patients with door-to-balloon (D2B) and symptom onset-to-balloon (OTB) times of less than 2 hours, but the specific implications of the coronavirus disease 2019 (COVID-19) pandemic on D2B and OTB times are not well-known. This review aims to evaluate the impact of COVID-19 on D2B time and elucidate both the factors that delay D2B time and strategies to improve D2B time in the contemporary era. The search was directed to identify articles discussing the significance of D2B times before and during COVID-19, from the initialization of the database to December 1, 2020. The majority of studies found that onset-of-symptom to hospital arrival time increased in the COVID-19 era, whereas D2B time and mortality were unchanged in some studies and increased in others

Development and application of non-rejectable skin substitute to improve wound healing

Skin substitutes consist of dermal and epidermal components are very beneficial to improve the current strategies of wound healing. However, these substitutes are not yet a routine treatment for burns or non-healing wounds mainly due to the difficulty of timely obtaining autologous skin cells. The aim of this study is to investigate the immunoprotective role of IDO in bilayer skin substitutes made out of non-autologous cells. To address this aim, first we asked the question of whether tryptophan deficient environment caused by IDO expression is safe for the survival of nonimmune cells, mainly primary skin cells. The results of our study showed a significant activation of apoptotic pathway as well as GCN2 kinase pathway in T cells, but not in skin cells, in response to the tryptophan deficient environment mediated by IDO expression. We then studied whether there is any differences between the main T cell populations in response to IDO mediated low tryptophan environment. Our results showed a marked immunosuppressive effect of IDO expression on human T cells with more suppressive effect on proliferation of CD8⁺ compared to that of CD4⁺ T cells which is, at least in part, due to differences in the level of GCN2 kinase pathway activation between these two sets of immune cells. Thereafter, we developed a bilayer skin substitute equipped with IDO expression ability. We found that IDO expressed by treated fibroblasts of this skin substitute suppress the proliferation of bystander lymphocytes in vitro considerably. Further, in our in vivo experiments, we found that the expression of IDO by cells of skin substitute significantly improved the wound healing rate, reduce the number of infiltrating T cells, and induced more revascularization in the wounds received IDO expressing skin substitutes compared to the non-IDO expressing ones. In conclusion, the results of this thesis research revealed that IDO expression can improve the efficacy of non-autologous bilayer skin substitutes to be used not oniy as a wound coverage, but also as a source of wound healing process improvement. A better revascularization seen in IDO grafted skin substitute further improved the graft take and survival.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat

Role of Mechanical Circulatory Support in Acute MI Management

Cardiogenic shock complicating acute MI carries high mortality and morbidity in many cases. Mechanical circulatory support devices are often used in these cases, aimed at improving patient-centered outcomes, although there is a lack of large randomized clinical trial-based evidence for many of such devices. Various circulatory support devices are available with their associated risks and benefits. Ideal circulatory support device intends to unload the myocardium, halt the spiral of ischemia, provide support for revascularization, and/or allow time for myocardial recovery. In this review paper, the commonly used mechanical circulatory support devices available for use in acute myocardial infarction settings are discussed, and the pros and cons of these devices are examined, considering the contemporary data for each. While this is an evolving field, the authors believe this paper can be helpful to review the current status of the use of mechanical support devices in the setting of acute MI and highlight some of the unmet needs in this field

PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases

Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT) and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA), a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE) signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity