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Background: Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events. Aim: To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI. Methods: Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA. Results: MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples. Conclusions: Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.

Adaptif piyasa hipotezi (APH) güncel finansal literatürde belirgin bir ilgi görmektedir. Bu durum APH’nin yine finansal literatürde sıklıkla araştırma konusu olan etkin piyasa hipotezine bir alternatif olarak ortaya çıkmış olması ile bağlantılıdır. Bu doğrultuda çalışmada, ilk olarak Borsa İstanbul hisse senedi piyasası BIST100 endeksi için APH, getiri öngörülebilirliğinin test edilmesi yoluyla incelenmiştir. Bu bağlamda Ocak 1988 - Aralık 2017 arası günlük kapanış fiyatı verilerine otomatik portmanteau ve genelleştirilmiş spektral (GS) testleri uygulanmıştır. Analizin devamında bu testlerin sonuçları, getiri öngörülebilirliği sağlayan dönemleri incelemek için bir gizli Markov model (GMM) uygulamasında kullanılmıştır. Sonuçlara göre Borsa İstanbul’un APH'ne güçlü bir şekilde uyum sağladığı görülmüştür. Ek olarak, GMM uygulamasının sonuçları, endeksin belirleyicileri ile ilgili olarak da periyodik öngörülebilirliği doğrulamıştır., The adaptive market hypothesis (AMH) has recently attracted significant interest in the financial literature. The AMH has started to be considered an alternative to the efficient market hypothesis. In this respect, this study, first of all, examines the AMH for the BIST100 index of Turkey’s Borsa Istanbul stock exchange market by testing the return predictability. The applications are performed via automatic portmanteau and the generalized spectral (GS) tests using daily closing price data between January 1988 and December 2017. Secondly, the results of these tests are utilized for a hidden Markov model (HMM) application to examine the periods that yield return predictability. According to the results, it is observed that there is strong evidence for the validity of AMH within the scope of Borsa Istanbul’s BIST100. Additionally, the results of the HMM application confirm the periodic predictability regarding the determinants of the index.

Günümüzde her alanda küreselleşen ve değişen dünyaya uyum sağlamak ülkeler için de bir zorunluluk haline gelmiştir. Özellikle gelişmiş ülkeler, değişimin gerekliliğinin farkına varmışlar ve yönetim anlayışlarını performans ölçümü ve kaynakların etkin/verimli kullanımını temel alarak yenilemişlerdir. Dolayısıyla gelişmiş ülkelerin de yaptığı gibi değişime ayak uydurmak isteyen ülkeler çeşitli alanlardaki performanslarını ve dünya üstündeki yerlerini çeşitli göstergeler yardımıyla izlemelidir. Ülkelerin diğer ülkelerle performanslarını karşılaştırmaya ve birçok alanda global olarak zayıf/güçlü yönlerini görmeye yarayan önemli göstergelerden biri küresel endekslerdir. Bu çalışmada CRITIC tabanlı CoCoSo metodu kullanılarak 2015-2019 yılları arasında OECD ülkelerinin performansları sosyo-ekonomik küresel endeksler çerçevesinde karşılaştırılmıştır. Çalışmada öncelikle CRITIC yöntemi kullanılarak söz konusu endekslere ilişkin ağırlıklar elde edilmiştir. CRITIC metodu sonuçlarına göre tüm yıllar için en büyük ağırlığa sahip olan endeksin GINI endeksi olduğu bulunmuştur. Daha sonra, CRITIC metoduyla elde edilen ağırlıklar kullanılarak OECD ülkelerinin ele alınan küresel endeksler çerçevesinde performansları CoCoSo yöntemi ile karşılaştırılmıştır. Yapılan analizler sonucunda 2015-2019 yılları arasında performansı en iyi olan ülkenin Danimarka ve en düşük olan ülkenin ise Meksika olduğu belirlenmiştir., Today, it has become a necessity for countries to adapt to the globalized and changing world in all areas. Developed countries, in particular, have realized the need for change and have updated their management philosophies based on performance measurement and effective/efficient use of resources. Therefore, countries that want to keep up with change, like developed countries, should monitor their performance in various areas and place in the world using various indicators. Global indices are one of the most important indicators that allow countries to compare their performance with other countries and identify their global weaknesses/strengths in many areas. In this study, using the CRITIC-based CoCoSo method, the performances of OECD countries between 2015 and 2019 were compared within the context of socio-economic global indices. First, weights for indices were determined in the study using the CRITIC method. According to the CRITIC method's findings, the GINI index has the most weight for all years. Subsequently, the performances of OECD countries were compared in the context of the global indices with the CoCoSo method using the weights determined according to the CRITIC method. The analysis showed that the best-performing country between 2015 and 2019 was Denmark and the worst-performing country was Mexico.

In today's competitive work environment, it is important for managers to have personnel who can move the company forward and adapt to changes as quickly as possible. Selecting the most suitable personnel has a great influence on the development of the company as well as on the motivation of the personnel. For this reason, the frequently encountered problem of personnel evaluation is a significant one. In this problem, the performance of the personnel is compared and evaluated considering the criteria set. Therefore, the personnel evaluation problem is a multi-criteria, decisionmaking problem. In this study, the personnel performance evaluation problem within Lanse Company was solved using the Analytic Hierarchy Process(AHP), a multi-criteria decision-making method. The criteria that are effective in personnel selection were determined through a literature review and interviews with the owner of the company and the Human Resources Team (HRT). Considering these criteria, a hierarchical model was constructed, and pairwise comparisons were made to obtain judgments. As a result of the pairwise comparisons, the most suitable person for the position of store manager was identified among the six employees working at Lanse. The results were presented to the decision maker in the form of a report. The validity and applicability of the findings were confirmed by the decision maker.

Graphical Abstract

OBJECTIVES Up-regulation of tenascin C (TNC), a matricellular protein, produced mainly by vascular smooth muscle cells (VSMC), is associated with the progression and dilation of abdominal aortic aneurysms (AAA). The aims of this study were (i) to evaluate whether serum levels of TNC in patients with AAA patients correlate with aortic diameter and (ii) to clarify the role of TNC in formation and progression of AAA in a murine model. METHODS In 15 patients with AAA serum levels of TNC were measured and correlated with aortic diameters. Moreover, in a murine calcium chloride AAA model, the impact of TNC deficiency on AAA diameter was evaluated. Finally, human VSMC were incubated with TNC to clarify its regulating potential. RESULTS In the clinical cohort, there was a trend of correlation between serum TNC levels and AAA diameter (P = 0.055). TNC knock out mice with AAA showed significantly lower diameter ratios compared to the wild-type group (WT) 3 weeks (P < 0.05) and 10 weeks (P < 0.05) after AAA induction. Immunohistochemistry revealed increased TNC expression in aortic tissue from WT with AAA as compared sham-operated mice. Furthermore, WT with AAA showed a more disrupted Elastin structure than TNC knock out mice 10 weeks after AAA induction. In human aortic VSMC, TNC incubation induced expression of remodelling associated proteins. CONCLUSIONS TNC might play a causative role in the formation, dilation and progression of AAA. Our results indicate that TNC might be a biomarker as well as a potential therapeutic target in the treatment of AAA.

Introduction: Tenascin-C (TN-C) upregulation is linked to worse clinical outcome in diabetic patients. However, the role of TN-C in the development of diabetic cardiomyopathy is still unknown. Hypothesis: Whether TN-C plays a maladaptive role in diabetic cardiomyopathy. Methods: AJ (n=14) and TNC-KO (n=16) adult male mice were injected with streptozotocin (50mg/kg) to induce diabetes. Cardiac function was measured by echocardiography at 16-18 weeks follow-up. Additionally, cardiomyocyte passive stiffness , vascular endothelial function (aorta), and cardiac fibrosis were assessed. In addition, the hemodynamic effect of human recombinant TN-C (hrTN-C; 80 ng/ml) on the isolated working rat heart (n=3) was evaluated. Isolated primary mouse cardiomyocytes (IPMC) were used to assess TN-C expression. Human ventricular cardiac fibroblasts (HCF) were cultured and treated with 1) TGF-β (20ng/ml); 2) rhTN-C (10μg/ml) and TLR4 inhibitor (TAK-242, 50 mM) in combination with TN-C and mRNA expression of α-SMA, TN-C, Col-1, Col-3 and ACE1 were assessed by RT-qPCR. Finally, HUVEC were treated either with rhTN-C (10μg/ml) or combination with TLR-4 inhibitor and analysed of the expression of NADPH oxidase 1 and 4 (NOX1, NOX4). Results: TN-C deficiency was accompanied by preserved LV ejection fraction and endothelium function in aorta (p Conclusions: TN-C promotes a hostile environment that facilitates fibrosis and oxidative stress leading to cardiomyocyte and endothelial cell dysfunction. Thus, TN-C may play a crucial role in cardiovascular dysfunction in diabetes as well as a potential target for therapy.

Neuregulin-1 (NRG-1) is a stress-mediated transmembrane growth factor. Reduced myocardial damage and higher NRG-1 levels upon treatment with remote ischemic conditioning (RIC) has been described in rats. However, the role of NRG-1 in patients with acute myocardial infarction (MI) is unknown. Thus, we conducted a post hoc analysis of a randomized controlled trial that tested RIC in patients with MI scheduled for primary percutaneous coronary intervention (PCI).Blood was drawn from 30 patients before RIC/PCI, within 1 hour, 4 days and 1 month later. Median left ventricular ejection fraction (LVEF) in the overall study population following MI was 48.5%.NRG-1 plasma levels decreased significantly following PCI/RIC and remained decreased up to 1 month following MI (Thus, we identified NRG-1 may be independently affected by MI. However, further large clinical trials are warranted to clarify this hypothesis.

Tenascin C (TN-C) is considered to play a pathophysiological role in maladaptive left ventricular remodeling. Yet, the mechanism underlying TN-C-dependent cardiac dysfunction remains elusive.The present study was designed to investigate the effect of hypoxia and hypertrophic stimuli on TN-C expression in H9c2 cells and its putative regulation by epigenetic mechanisms, namely DNA promoter methylation and microRNAs. In addition, rats subjected to myocardial infarction (MI) were investigated. H9c2 cells were subjected to oxygen and glucose deprivation; incubated with angiotensin II (Ang II); or human TN-C (hTN-C) purified protein. Hypertrophic and fibrotic markers, TN-C promoter methylation as well as mir-335 expression were assessed by reverse transcription and quantitative polymerase chain reaction while TN-C protein levels were assessed by ELISA.Tn-C mRNA expression was markedly increased by both oxygen and glucose deprivation and Ang II (P 0.01, respectively). In addition, Ang-II-dependent TN-C upregulation was explained by reduced promoter methylation (P 0.05). Cells treated with hTN-C displayed upregulation of Bnp, Mmp2, β-Mhc, integrin α6 and integrin β1. Furthermore, hTN-C treated cells showed a significant reduction in adenosine monophosphate and adenosine triphosphate levels. In vivo, plasma and myocardial TN-C levels were increased 7 days post MI (P 0.05, respectively). This increment in TN-C was accompanied by upregulation of mir-335 (P 0.01). In conclusion, both hypoxic and hypertrophic stimuli lead to epigenetically driven TN-C upregulation and subsequent impairment of cellular energy metabolism in cardiomyoblasts.These findings might enlighten our understanding on maladaptive left ventricular remodeling and direct towards a strong involvement of TN-C.

Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression, however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics.

Ischemic mitral regurgitation (MR) is a frequent complication of myocardial infarction (MI) characterized by adverse remodeling both at the myocardial and valvular levels. Persistent activation of valvular endothelial cells leads to leaflet fibrosis through endothelial-to-mesenchymal transition (EMT). Tenascin C (TNC), an extracellular matrix glycoprotein involved in cardiovascular remodeling and fibrosis, was also identified in inducing epithelial-to-mesenchymal transition. In this study, we hypothesized that TNC also plays a role in the valvular remodeling observed in ischemic MR by contributing to valvular excess EMT. Moderate ischemic MR was induced by creating a posterior papillary muscle infarct (7 pigs and 7 sheep). Additional animals (7 pigs and 4 sheep) served as controls. Pigs and sheep were sacrificed after 6 weeks and 6 months, respectively. TNC expression was upregulated in the pig and sheep experiments at 6 weeks and 6 months, respectively, and correlated well with leaflet thickness (R = 0.68; p R = 0.84; p n = 5). Indeed, TNC was also expressed in the mitral leaflets of these. Furthermore, TNC induced EMT in isolated porcine mitral valve endothelial cells (MVEC). Interestingly, Toll-like receptor 4 (TLR4) inhibition prevented TNC-mediated EMT in MVEC. We identified here for the first time a new contributor to valvular remodeling in ischemic MR, namely TNC, which induced EMT through TLR4. Our findings might set the path for novel therapeutic targets for preventing or limiting ischemic MR.

Introduction The prevalence of chronic renal disease (CKD) is continuously increasing in developed countries. Uremic cardiomyopathy characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) is a common cardiovascular complication of CKD. Cardiac microvascular low-grade inflammation and altered expression of endothelium derived Neuregulin-1 (NRG-1) are contributed to left ventricular DD. Our aim was to charachterize the effects of CKD on the expression of NRG-1 and 2) NRG-1 treatment on myocardial hypertrophy, diastolic dysfunction and renal function in the rat model of CKD. Methods Male Wistar rats were used and randomized into 3 groups: 1) Sham-operated,2) CKD induced by 5/6 nephrectomy (CKD) and 3) NRG-1-treated CKD group (CKD+NRG-1). In this group, 2 weeks after the CKD induction, the rats were treated with recombinant human NRG-1 (rhNRG-1) at the dose of 10 μg/kg/d for consecutive 10 days with tail vein injection of NRG-1. Serum and urea creatinine levels were measured to verify the development of CKD and transthoracic echocardiography was performed to monitor cardiac morphology and function. Furthermore, total RNA was isolated and RT-qPCR was performed to evaluate the expression levels of inflammatory chemokine and cytokines (TNF-α, TGF-β). In addition, NRG-1 protein levels were assessed in both kidney and heart tissue by ELISA. To clarify the underling anti-fibrotic mechanism, human ventricular cardiac fibroblasts (HCF) were cultured and treated with the TGF-β (20 ng/ml), and TGF-β + hrNRG-1 for 24 h, respectively. Confocal microscopy was used to detect α-smooth muscle actin (α-SMA) expression, marker for fibroblast to myofibroblast transtion. Results 10 weeks after the 5/6 nephrectomy, serum carbamide and creatinine levels were significantly increased and creatinine clearence was significantly decreased as compared to sham-operated animals proving the development of chronic kidney disease (CKD). This was accompanied by a significant decrease in NRG-1 protein expression levels in both cardiac and kidney tissue. Of note, NRG-1 treatment markedly reduced these changes, suggesting its renoprotective effects in CKD. In addition, In CKD animals, the significantly increased anterior, posterior and septal wall thicknesses with decreased end-diastolic and end-systolic diameters proved the development of concentric left ventricular hypertrophy. In CKD, the septal e' was significantly decreased and E/e' increased indicating the developemnt of diastolic dysfunction. These parameters were significantly improved by NRG-1 treatment. Mechanistically, NRG-1 treatment reduced the expression of inflammatory cytokines in compared to untreat group. Furthermore, TGF-β induced α-SMA and Col I upregulation was markedly reduced by hrNRG-1 treatment. Conclusions NRG-1 treatment improved both renal and cardiac funtion in CKD, via a mechansim including the anti-inflammatory and anti-fibrotic properties of NRG-1. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Österreichischer Austauschdienst

The service quality presents an important argument in the health-care sector because of its vital importance and serious impacts on human lives. Therefore, in order to provide optimal services, establishments have to consider patients’ perceptions of their service quality. SERVQUAL method has a wide range of applications in the literature. In this study, the quality of services in Yoncalı Physiotherapy and Rehabilitation Hospital in Kütahya, Turkey is evaluated. Because of dependency to linguistic variables when evaluating services, a fuzzy SERVQUAL approach is used. SERVQUAL questionnaires (which include 22 items within 5 dimensions) were applied to 262 patients in order to obtain patients’ perceptions of provided services. In accordance with the hospital administration’s request, all expectation scores were taken at the highest level in order to develop a measurement for an ideal hospital. After collection of the data, the fuzzy perception, expectation and gap scores were calculated. Results indicated negative gap scores for all items, which mean a general dissatisfaction from the provided services. Particularly, the highest gap score was in tangibles dimension and this is followed by responsiveness, reliability, assurance and empathy. A report has been presented to the hospital administration, including results and suggestions in compliance with the findings.

Objective: Vitiligo is a progressive skin pigmentation disorder, which may be acquired or hereditary, frequently seen, and may influence every age group. The melanocortin 1 receptor (MC1R) gene is a major determinant of human pigmentation. In our study, polymorphic differences of the MC1R gene at the DNA level has been investigated in patients with vitiligo. Materials and Methods: In our study, polymorphic differences of the MC1R gene at the DNA level has been investigated in vitiligo 60 patients, whose families had resided in the Thrace region of Turkey for at least three generations. The 60 volunteer healthy individuals have no other systemic and dermatological disease. Results: Totally, five types of Single Nucleotide Polymorphism (SNP) were found in each case and control groups: Val60Leu (G178T), Val92Met (G274A), Arg151Cys (C451T), Arg160Trp (C478T), and Arg163Gln (G488A). Comparing both groups in terms of genotype frequencies, no statistically meaningful difference was detected (p>0.05). However, assessing in terms of allele frequencies, a meaningful difference was found in the Arg163Gln (G488A) allele statistically in favor of the control group (p0.05). Ancak allel sıklıkları yoluyla değerlendirildiğinde kontrol grubunun lehine Arg163Gln (G488A) allelinde istatistiki olarak anlamlı bir fark bulundu(p