Regional consequences of the economic and social transformation: Case study Slovakia

Regional situation in time of changes, just before the beginning of the transformation process: * regional monostructure and " district industrialisation", flagships and big enterprises, * full regional employment , but rather low competitiveness, * structural problems (the structure of sectors, low share of the service activities, huge concentration of arm industry in the selected regions etc.), * regional consequences of the eastern trade orientation. The process of global economic and regional transformation: * the radical economic reform, the regional differentiation process of the production's declining and unemployment, * the disintegration of large enterprises , a new western trade reorientation, * the investment's declining But in the same time the beginning of positive trends: the massive development of the private sector, explosion of SME * a steady growing share of service activities connected with foreign direct investments (banks, financial institutions, hotel chains, consulting, audit and marketing agencies etc. ) Generally: a very different reaction of the regions on this development and the adaptability on the transformation process. An active regional policy at the beginning: * the regional development programs * the new regional institutions * the governmental support for the depressed regions * EU support ( cross-border co-operation, the regional development agency and investment fund) The core region of the capital Bratislava and Slovak periphery. Challenges and risks of Bratislava-Vienna region. Spatial consequences on the location of economic activities.

Regional consequences of the economic and social transformation: Case study Slovakia

Regional situation in time of changes, just before the beginning of the transformation process: * regional monostructure and " district industrialisation", flagships and big enterprises, * full regional employment , but rather low competitiveness, * structural problems (the structure of sectors, low share of the service activities, huge concentration of arm industry in the selected regions etc.), * regional consequences of the eastern trade orientation. The process of global economic and regional transformation: * the radical economic reform, the regional differentiation process of the production's declining and unemployment, * the disintegration of large enterprises , a new western trade reorientation, * the investment's declining But in the same time the beginning of positive trends: the massive development of the private sector, explosion of SME * a steady growing share of service activities connected with foreign direct investments (banks, financial institutions, hotel chains, consulting, audit and marketing agencies etc. ) Generally: a very different reaction of the regions on this development and the adaptability on the transformation process. An active regional policy at the beginning: * the regional development programs * the new regional institutions * the governmental support for the depressed regions * EU support ( cross-border co-operation, the regional development agency and investment fund) The core region of the capital Bratislava and Slovak periphery. Challenges and risks of Bratislava-Vienna region. Spatial consequences on the location of economic activities

Ataxia Telangiectasia Mutated Dysregulation Results in Diabetic Retinopathy

Ataxia telangiectasia mutated (ATM) acts as a defense against a variety of bone marrow (BM) stressors. We hypothesized that ATM loss in BM-hematopoietic stem cells (HSCs) would be detrimental to both HSC function and microvascular repair while sustained ATM would be beneficial in disease models of diabetes. Chronic diabetes represents a condition associated with HSC depletion and inadequate vascular repair. Gender mismatched chimeras of ATM(-/-) on wild type background were generated and a cohort were made diabetic using streptozotocin (STZ). HSCs from the STZ-ATM(-/-) chimeras showed (a) reduced self-renewal; (b) decreased long-term repopulation; (c) depletion from the primitive endosteal niche; (d) myeloid bias; and (e) accelerated diabetic retinopathy (DR). To further test the significance of ATM in hematopoiesis and diabetes, we performed microarrays on circulating angiogenic cells, CD34(+) cells, obtained from a unique cohort of human subjects with long-standing (>40 years duration) poorly controlled diabetes that were free of DR. Pathway analysis of microarrays in these individuals revealed DNA repair and cell-cycle regulation as the top networks with marked upregulation of ATM mRNA compared with CD34(+) cells from diabetics with DR. In conclusion, our study highlights using rodent models and human subjects, the critical role of ATM in microvascular repair in DR

Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy

Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy

The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor

Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR

Finding the Why

My sculptural practice focuses on the aesthetic appropriation of industrial materials, consumer goods, and organic detritus. Having been diagnosed with OCD and anxiety in my twenties, I find myself being attracted to excessive amounts of found objects which inform much of my work. I habitually collect spent and discarded objects and let them suggest unexpected spatial or utilitarian relationships, often through accumulation and mass. This process intuitively acknowledges a compulsive drive to confront elements that society has rejected and transform their abject status through absurd or playful juxtapositions and the application of lighthearted color palettes. The physicality of rendering unwieldy elements in balance is therapeutic, soothing my anxiety while fostering mental space to develop ideas. Aspects of scale and precarity encourage an investigation of the whole, both in the sum of its parts and as a cooperative endeavor of disparate elements. Sculpture is interactive in terms of the physicality of occupied space, and I approach my work with an awareness that it will be completed by the viewers' physical and emotional encounters in communion with the object

Endothelial progenitor cells in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DMO, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests the number and function of EPCs is altered in patients with varying degrees of diabetes duration, metabolic control and in the presence of absence of DR. While there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DMO and PDR in the context of cell therapy. This review presents basic clinical concepts of DR and combines this with a general insight on EPCs and how they relate to future directions in understanding and treating this important diabetic complication

Increase in acid sphingomyelinase level in human retinal endothelial cells and CD34+ circulating angiogenic cells isolated from diabetic individuals is associated with dysfunctional retinal vasculature and vascular repair process in diabetes

BACKGROUND: Diabetic retinopathy is a microvascular disease that results from retinal vascular degeneration and defective repair due to diabetes-induced endothelial progenitor dysfunction. OBJECTIVE: Understanding key molecular factors involved in vascular degeneration and repair is paramount for developing effective diabetic retinopathy treatment strategies. We propose that diabetes-induced activation of acid sphingomyelinase (ASM) plays essential role in retinal endothelial and CD34+ circulating angiogenic cell (CAC) dysfunction in diabetes. METHODS: Human retinal endothelial cells (HRECs) isolated from control and diabetic donor tissue and human CD34+ CACs from control and diabetic patients were used in this study. ASM messenger RNA and protein expression were assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To evaluate the effect of diabetes-induced ASM on HRECs and CD34+ CACs function, tube formation, CAC incorporation into endothelial tubes, and diurnal release of CD34+ CACs in diabetic individuals were determined. RESULTS: ASM expression level was significantly increased in HRECs isolated from diabetic compared with control donor tissue, as well as CD34+ CACs and plasma of diabetic patients. A significant decrease in tube area was observed in HRECs from diabetic donors compared with control HRECs. The tube formation deficiency was associated with increased expression of ASM in diabetic HRECs. Moreover, diabetic CD34+ CACs with high ASM showed defective incorporation into endothelial tubes. Diurnal release of CD34+ CACs was disrupted with the rhythmicity lost in diabetic patients. CONCLUSION: Collectively, these findings support that diabetes-induced ASM upregulation has a marked detrimental effect on both retinal endothelial cells and CACs

Carbon Monoxide and Nitric Oxide Mediate Cytoskeletal Reorganization in Microvascular Cells via Vasodilator-Stimulated Phosphoprotein Phosphorylation: Evidence for Blunted Responsiveness in Diabetes

OBJECTIVE— We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) on the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation