20 research outputs found

    The Creation, Importance and Economic Benefits of Industrial Clusters for Serbian Companies

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    This is the first study of industrial clusters in Serbia ever. The aim of this study is to gather information regarding companies, clusters and process of cluster development in Serbia. Having in mind cultural and historical context of the business environment within clusters are working, it was interesting examining what kind of attitude Serbian companies have towards competition, development and important business topics. The main goals of this research is to examine and explore are: 1.) How do clusters form in Serbian economy; 2.) What motivates clustering in Serbia; 3.) What is Serbian Government's approach to clusters; 4.) How does clustering influence local economy, suppliers and buyers; 5.) How is it helping in developing and branding a region; and 6.) What are the implications of clustering on Serbian small and medium enterprises and Serbian market. In order to create comprehensive study, both quantitative and qualitative research methods have been implemented. Therefore, the quantitative research consists out of questioner divided into 18 questions. In total 33 companies have been surveyed in 5 Serbian clusters gaining for the first time valuable answers regarding companies who joined clusters and the expectations and aspirations of cooperation within cluster. Qualitative research has been conducted through 7 in-depth interviews with relevant cluster members and supporting organization members, who's answers will be utilized in order to gain a full picture of the companies, clusters and processes of clustering in Serbia. The study came across interesting conclusions, initially Serbian companies did not start cooperating because they were all aware of the benefits clusters are offering, but they grouped out of need to overcome some of the common legal and business problems. Majority of the companies within clusters are micro and small companies, without research and development. This study showed that even clusters in Serbia do not have R&D division, leading us to the conclusion that companies need to improve knowledge management in the companies, to support innovations and invest in new material and products development. Serbian clusters could play a key role in national economy revitalization, if government recognised entrepreneurship and small and medium companies as a driving force of economy

    Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls

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    This is the published version.We previously showed that increases in mean arterial pressure (MAP) following administration of midodrine hydrochloride (MH) and nitro-L-arginine methyl ester (L-NAME) resulted in increased mean cerebral blood flow velocity (MFV) during head-up tilt in hypotensive individuals with spinal cord injury (SCI) and question if this same association was evident during cognitive activation. Herein, we report MAP and MFV during two serial subtraction tasks (SSt) given before (predrug) and after (postdrug) administration of MH; (10 mg), L-NAME (1 mg/kg) or no drug (ND) in 15 subjects with SCI compared to nine able-bodied (AB) controls. Three-way factorial analysis of variance (ANOVA) models were used to determine significant main and interaction effects for group (SCI, AB), visit (MH, L-NAME, ND), and time (predrug, postdrug) for MAP and MFV during the two SSt. The three-way interaction was significant for MAP (F = 4.262; P = 0.020); both MH (30 ± 26 mmHg; P < 0.05) and L-NAME (27 ± 22 mmHg; P < 0.01) significantly increased MAP in the SCI group, but not in the AB group. There was a significant visit by time interaction for MFV suggesting an increase from predrug to postdrug following L-NAME (6 ± 8 cm/sec; P < 0.05) and MH (4 ± 7 cm/sec; P < 0.05), regardless of study group, with little change following ND (3 ± 3 cm/sec). The relationship between change in MAP and MFV was significant in the SCI group following administration of MH (r2 = 0.38; P < 0.05) and L-NAME (r2 = 0.32; P < 0.05). These antihypotensive agents, at the doses tested, raised MAP, which was associated with an increase MFV during cognitive activation in hypotensive subjects with SCI

    The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer’s Disease and Spinal Cord Injury

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    The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in eukaryotes. Herein, we will review advances in the understanding of the role of several proteins of the UPS in Alzheimer’s disease (AD) and functional recovery after spinal cord injury (SCI). The UPS consists of many factors that include E3 ubiquitin ligases, ubiquitin hydrolases, ubiquitin and ubiquitin-like molecules, and the proteasome itself. An extensive body of work links UPS dysfunction with AD pathogenesis and progression. More recently, the UPS has been shown to have vital roles in recovery of function after SCI. The ubiquitin hydrolase (Uch-L1) has been proposed to increase cellular levels of mono-ubiquitin and hence to increase rates of protein turnover by the UPS. A low Uch-L1 level has been linked with Ab accumulation in AD and reduced neuroregeneration after SCI. One likely mechanism for these beneficial effects of Uch-L1 is reduced turnover of the PKA regulatory subunit and consequently, reduced signaling via CREB. The neuron-specific F-box protein Fbx2 ubiquitinates b-secretase thus targeting it for proteasomal degradation and reducing generation of Ab. Both Uch-L1 and Fbx2 improve synaptic plasticity and cognitive function in mouse AD models. The role of Fbx2 after SCI has not been examined, but abolishing ß-secretase reduces neuronal recovery after SCI, associated with reduced myelination. UBB+1, which arises through a frame-shift mutation in the ubiquitin gene that adds 19 amino acids to the C-terminus of ubiquitin, inhibits proteasomal function and is associated with increased neurofibrillary tangles in patients with AD, Pick’s disease and Down’s syndrome. These advances in understanding of the roles of the UPS in AD and SCI raise new questions but, also, identify attractive and exciting targets for potential, future therapeutic interventions

    Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients

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    We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients

    Cancer-Induced Resting Sinus Tachycardia: An Overlooked Clinical Diagnosis

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    Elevated resting heart rate is frequently observed in cancer patients, and is associated with increased mortality. Although specific chemotherapeutic agents can induce cardiotoxicity, the presence of sinus tachycardia in chemotherapy-naive patients suggests other factors likely contribute to this clinical presentation. Despite its prevalence, cancer-associated resting sinus tachycardia has not been fully recognized and comprehensively described as a separate clinical entity. Secondary effects of cancer, especially structural cardiac changes, secretory factors (inflammatory cytokines), and thromboembolic disease can cause resting tachycardia. Alternatively, rapid heart rate may reflect compensatory mechanisms responding to increased metabolic demands, raised cardiac output states, and even pain. Hence, cancer-associated tachycardia presents a clinical dilemma; acute life-threatening conditions (such as sepsis, pulmonary embolism, etc.) must be ruled out, but cancer itself can explain resting sinus tachycardia and more conservative management can avoid unnecessary testing, cost and patient stress. Furthermore, identification and management of cardiac conditions associated with cancer may improve survival and the quality of life of cancer patients

    The Creation, Importance and Economic Benefits of Industrial Clusters for Serbian Companies

    No full text
    This is the first study of industrial clusters in Serbia ever. The aim of this study is to gather information regarding companies, clusters and process of cluster development in Serbia. Having in mind cultural and historical context of the business environment within clusters are working, it was interesting examining what kind of attitude Serbian companies have towards competition, development and important business topics. The main goals of this research is to examine and explore are: 1.) How do clusters form in Serbian economy; 2.) What motivates clustering in Serbia; 3.) What is Serbian Government's approach to clusters; 4.) How does clustering influence local economy, suppliers and buyers; 5.) How is it helping in developing and branding a region; and 6.) What are the implications of clustering on Serbian small and medium enterprises and Serbian market. In order to create comprehensive study, both quantitative and qualitative research methods have been implemented. Therefore, the quantitative research consists out of questioner divided into 18 questions. In total 33 companies have been surveyed in 5 Serbian clusters gaining for the first time valuable answers regarding companies who joined clusters and the expectations and aspirations of cooperation within cluster. Qualitative research has been conducted through 7 in-depth interviews with relevant cluster members and supporting organization members, who's answers will be utilized in order to gain a full picture of the companies, clusters and processes of clustering in Serbia. The study came across interesting conclusions, initially Serbian companies did not start cooperating because they were all aware of the benefits clusters are offering, but they grouped out of need to overcome some of the common legal and business problems. Majority of the companies within clusters are micro and small companies, without research and development. This study showed that even clusters in Serbia do not have R&D division, leading us to the conclusion that companies need to improve knowledge management in the companies, to support innovations and invest in new material and products development. Serbian clusters could play a key role in national economy revitalization, if government recognised entrepreneurship and small and medium companies as a driving force of economy

    Therapeutic Strategies for Treatment of Inflammation-related Depression

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    Background: Mounting evidence demonstrates enhanced systemic levels of inflammatory mediators in depression, indicating that inflammation may play a role in the etiology and course of mood disorders. Indeed, proinflammatory cytokines induce a behavioral state of conservation- withdrawal resembling human depression, characterized by negative mood, fatigue, anhedonia, psychomotor retardation, loss of appetite, and cognitive deficits. Neuroinflammation also contributes to non-responsiveness to current antidepressant (AD) therapies. Namely, response to conventional AD medications is associated with a decrease in inflammatory biomarkers, whereas resistance to treatment is accompanied by increased inflammation. Methods: In this review, we will discuss the utility and shortcomings of pharmacologic AD treatment strategies focused on inflammatory pathways, applied alone or as an adjuvant component to current AD therapies. Results: Mechanisms of cytokine actions on behavior involve activation of inflammatory pathways in the brain, resulting in changes of neurotransmitter metabolism, neuroendocrine function, and neuronal plasticity. Selective serotonin reuptake inhibitors exhibit the most beneficial effects in restraining the inflammation markers in depression. Different anti-inflammatory agents exhibit AD effects via modulating neurotransmitter systems, neuroplasticity markers and glucocorticoid receptor signaling. Anti-inflammatory add-on therapy in depression highlights such treatment as a candidate for enhancement strategy in patients with moderate-to-severe depression. Conclusion: The interactions between the immune system and CNS are not only involved in shaping behavior, but also in responding to therapeutics. Even though, substantial evidence from animal and human research support a beneficial effect of anti-inflammatory add-on therapy in depression, further research with special attention on safety, particularly during prolonged periods of antiinflammatory co-treatments, is required
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