Urokinase plasminogen activator (uPA) is required for both endogenous and vascular endothelial growth factor (VEGF)-augmented angiogenesis in normal tissues, leading us to hypothesize that uPA augmentation by gene transfer might promote angiogenesis in ischemic tissues. Overexpression of uPA was studied in rat myocardial infarction (MI) and mouse hind limb ischemia models and compared with VEGF overexpression effects. Animals were divided into control and three experimental groups (n = 6), receiving intramuscular injections of plasmids as follows: (i) control (empty vector or expressing beta-galactosidase); (ii) uPA; (iii) VEGF(165); (iv) a 1:1 mixture of uPA and VEGF(165). The capillary densities in both ischemic models were greater (P < 0.05) in tissues treated with uPA, VEGF, or a combination of both than in controls. Infarct size was reduced in hearts from uPA and VEGF experimental groups compared with controls (P < 0.05). Local overexpression of uPA induced a marked increase in the number of macrophages and myofibroblasts present within infarcts. Hind limb blood flow was greater in all experimental groups by day 10 (P < 0.05). Overall, the effects of uPA and VEGF were uniformly comparable. Additional analysis revealed association of local edema with VEGF but not with uPA treatment. This study established that uPA gene therapy effectively induces functionally significant angiogenesis in models of acute MI and hind limb ischemia.

The provision of quality health care is of utmost importance for a physician. Over the years, there has been much debate regarding work-life imbalance and physician burnout, which may, in turn, have adverse effects on the quality of care. Medical school students, residents, interview candidates for residency, and internal medicine faculty are all under a varying degree of stress, which may impact their personal and professional lives. We distributed questionnaires to investigate our hypothesis: Progression in training years leads to a decline in well-being. The main objective of our assessment was to help devise interventions to improve the quality of training and the productivity of internal medicine physicians. Understanding the emotional functioning of physicians will help us improve the learning environment and, in turn, have a positive impact in the future for medical professionals. Medical students are burdened with excessive loans for undergraduate and graduate studies, which contributes to higher rates of burnout, depression, and suicide among medical professionals, which can lead to a direct and negative impact on quality of care. Our study showed that well-being scores declined with increasing financial stress; they were also affected by the visa status and training background of our subjects as medical students.

Although collateral circulation is the essential means of perfusion for ischemized myocardium, its efficiency varies substantially within and between the species. There is both experimental and clinical evidence for association of glycemic disorders with inadequate col- lateral circulation. Current article reviews general mechanisms of collateral circulation failure due to such metabolic disturbances with regard for stages of arteriogenesis. We also highlight horizons of further studies in this field.

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