Balkan Medical Journal is an institutional initiative designed to disseminate scientific knowledge produced by long-established human communities residing in the Balkan Peninsula. In this editorial, we aimed to analyze the relationship of Balkan Medical Journal with its scientific partners from the Balkans. A 5.5-fold increase in the number of articles submitted from the Balkans is a favorable indication for the future. Notably, the acceptance rate of articles from the Balkans has now reached 10.68%, however the citation rate of these articles highlights the importance of increasing the quality of research. Overall, our findings indicate the need to gain broader recognition especially in the Balkans and also other countries.

Recently, the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand, and the osteoprotegerin system has been recognized as more important in the pathogenesis of cardiovascular disease. No consensus is yet available on the function of osteoprotegerin, but all these studies have concluded that osteoprotegerin is a promising biomarker for coronary artery disease, regardless of whether it plays a protective role against atherosclerosis or causes atherosclerosis with its proatherogenic features. Cardiovascular disease is one of the most frequent causes of mortality and morbidity worldwide. Several variables have been identified as risk factors for cardiovascular disease. Recently, the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand, and the osteoprotegerin system has been recognized as more important in the pathogenesis of cardiovascular disease. Besides their roles in the regulation of bone resorption, these molecules have been reported to be associated with the pathophysiology of cardiovascular disease. There are conflicting data regarding the impact of osteoprotegerin, a glycoprotein with a regulatory role in the cardiovascular system. The aim of this review is to discuss the current knowledge and the role of osteoprotegerin in cardiovascular disease.

Staple line leak is one of the most frequent and serious complications of laparoscopic sleeve gastrectomy. This study aims to evaluate the effects of different bougie diameters on tissue oxygen partial pressure (PtO2) at the esophagogastric junction after sleeve gastrectomy. The use of narrower bougie along with fibrin sealant has not had a negative effect on tissue perfusion and wound healing. Background: Staple-line leak is the most frightening complication of laparoscopic sleeve gastrectomy and several predisposing factors such as using improper staple sizes regardless of gastric wall thickness, narrower bougie diameter and ischemia of the staple line are asserted. Aims: To evaluate the effects of different bougie diameters on tissue oxygen partial pressure at the esophagogastric junction after sleeve gastrectomy. Study Design: A randomized and controlled animal experiment with 1:1:1:1 allocation ratio. Methods: Thirty-two male Wistar Albino rats were randomly divided into 4 groups of 8 each. While 12-Fr bougies were used in groups 1 and 3, 8-Fr bougies were used in groups 2 and 4. Fibrin sealant application was also carried out around the gastrectomy line after sleeve gastrectomy in groups 3 and 4. Burst pressure of gastrectomy line, tissue oxygen partial pressure and hydroxyproline levels at the esophagogastric junction were measured and compared among groups. Results: Mortality was detected in 2 out of 32 rats (6.25%) and one of them was in group 2 and the cause of this mortality was gastric leak. Gastric leak was detected in 2 out of 32 rats (6.25%). There was no significant difference in terms of burst pressures, tissue oxygen partial pressure and tissue hydroxyproline levels among the 4 groups. Conclusion: The use of narrower bougie along with fibrin sealant has not had a negative effect on tissue perfusion and wound healing.

Ovotesticular disorder is an extremely rare cause of disorder of sexual development, once known as true hermaphroditism. Herein, we report a 3-month-old phenotypically female baby in whom differentiated tissues of both Müllerian and Wolffian ducts were detected on pathological analysis of laparoscopic biopsy material. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic hybridisation. Background: Ovotesticular disorder is characterized by the presence of testicular and ovarian tissues in the same individual. Single gene mutations in SRY, SOX9, DMRT1 and DAX1 can lead to ovotesticular disorder of sexual development.Case Report: Herein, we report a 3-month-old phenotypically female baby in whom differentiated tissues of both Müllerian and Wolffian ducts were detected on pathological analysis of laparoscopic biopsy material. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic hybridisation.Conclusion: In support of previous literature, we found that haploinsufficiency of the DMRT gene cluster leads to ovotesticular disorder of sexual development. In addition, we emphasize that array comparative genomic hybridisation is an important technique in the molecular diagnosis of ovotesticular disorder of sexual.

This article is intended to bring about a change in the way of thinking about the molecular nature of functional magnetic resonance imaging (fMRI). The underlying assumption in our hypothesis is that fMRI may report mitochondrial activity in the synaptic area of the activated neuron, as well as an increased nitric oxide synthase activity at the same locus. The hypothesis is based on the uniqueness of the structure and functioning of the activated synapse and the major biochemical consequences of this structural–functional phenomenon. To the Editor, This article is intended to bring about a change in the way of thinking about the molecular nature of functional magnetic resonance imaging (fMRI) (1). The underlying assumption in our hypothesis is that fMRI may report mitochondrial activity in the synaptic area of the activated neuron, as well as an increased nitric oxide synthase activity at the same locus. The hypothesis is based on the uniqueness of the structure and functioning of the activated synapse and the major biochemical consequences of this structural–functional phenomenon. The synapse is the primary energy source in the neuron, and the secret of fMRI might be hidden in the processes occurring in this locus. What is unique in the synapse? It contains a large amount of neurotransmitter vesicles, as well as a large amount of mitochondria due to the huge energy demand in this part of the neuron. In the synaptic mitochondria, 34-38 molecules of adenosine triphosphate (ATP) per molecule of glucose are synthesized based on glucose metabolism in the tricarboxylic acid (TCA) cycle (Figure 1) (2,3). It must be emphasized that “activity-driven ATP synthesis” in the synapse occurs for a short time in a very limited space – only in the area of the activated neuron. What are the consequences of the “activity-driven ATP synthesis” in the synaptic mitochondria? Electrons are derived through the mitochondrial electron transport chain (ETC), and a proton gradient is established across the inner mitochondrial membrane as an energy source for ATP synthesis. The most important biochemical event, associated with this process, is the production of a large amount of superoxide in the activated synapse for a very short time, due to the large amount of metabolically active mitochondria in this locus (Figure 2a). It must be clarified that this is not a permanent hyperproduction of superoxide, which can cause oxidative stress in the neuron. This is just a momentary event, which is precisely controlled by various factors (ETC complexes, antioxidant enzymes, uncoupling proteins, etc.) (3,4). Superoxide radicals are paramagnetic species that are detectable directly by imaging techniques such as MRI (5). Moreover, hyperproduction of superoxide in metabolically active synaptic mitochondria may affect either T1 and/or T2 relaxation times of the surrounding protons. This will change the 1H MRI contrast in the activated synapse for a very short time – a well-known principle of enhancement of MRI contrast by other radicals (e.g., nitroxides) (6). Тo clarify the role of superoxide in the relaxivity of water molecules, we performed a very simple MRI experiment in a pure chemical system, deionized water (DIW) plus potassium superoxide. Potassium superoxide rapidly decomposes into superoxide radicals in water, which is accompanied by enhancement of T1 and T2 MRI contrast (Figure 2b). Superoxide is also an intermediate involved in the paramagnetic or diamagnetic transformations of hemoglobin during the transport of oxygen in the activated neuron (7). The hemoglobin transformations are considered as the primary factors for BOLD signals in fMRI measurements. It is interesting to note that nitric oxide (NO), derived from NO adducts (as nitroglycerine or NOC9) in DIW, also increased T1 and T2 MRI contrast. However, the enhancement disappeared very rapidly, and it was difficult to obtain reproducible data due to the time required for MRI setting (data are not shown). NO is one of the major mediators of neurovascular coupling, and its local concentration in the activated synaptic area must also be high (8). The hyperproduction of NO and superoxide is spatially separated – production of superoxide occurs in the synaptic mitochondria, whereas that of NO occurs in the vascular endothelium. This eliminates the possibility of interaction between NO and superoxide with the formation of toxic peroxynitrite. The described data suggest that local and relatively long-lasting hyperproduction of superoxide by “activity-driven mitochondria” and NO in the synaptic area may be a major factor, changing proton relaxivity, and a root cause of the fMRI signals. Therefore, fMRI can be used not only as a tool for detecting neural activity but also for detecting other metabolically active cells and tissues (e.g., cancer). We believe that the hypothesis could be proved theoretically and experimentally using Overhauser-enhanced MRI (OMRI) based on proton–electron cross-relaxation phenomenon (9). However, the OMRI hybrid instruments are still “home-made,” expensive, and not available on the market. In addition, the experimental verification of the hypothesis requires a unique team of specialists – neurophysiologists, biochemists, biophysicists, specialists in molecular imaging, and mathematicians. This article aims to provoke the creation of such teams and to set their efforts in a direction that can open new trends in the concept of “functional imaging.” The described hypothesis could have a significant impact in all areas of molecular and functional imaging using MRI, positron emission tomography, optical, etc. Acknowledgements: We would like to thank Mr. Yoshikazu Ozawa from the National Institute for Radiological Sciences, QST/NIRS, Chiba, Japan, for his assistance during MRI experiment. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: No financial disclosure was declared by the authors.