Bosnian Journal of Basic Medical Sciences <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> en-US (Faruk Skenderi) (Armin Sehovic) Mon, 02 Nov 2020 00:00:00 +0100 OJS 60 Immunohistochemical study of dental pulp cells with 3D collagen type I gel in demineralized dentin tubules in vivo <p>Dental pulp cells (DPCs) represent good candidates for the regeneration of dental tissue. This study aimed to evaluate the growth and differentiation potential of DPCs cultured inside demineralized dentin tubules <em>in vivo</em>. Six green fluorescent protein-transgenic rats (body weight 100 g each) and thirty-two Sprague-Dawley (SD) male rats (body weight 250 g each) were used for DPC collection and dentin tubules preparation and transplantation, respectively. Third-passage DPCs with or without collagen gels were loaded into demineralized dentin tubules. Both types of grafts were transplanted into the rectus abdominis muscles of SD rats and were harvested after 21 days. The expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteopontin (OPN), nestin, and dentin sialoprotein (DSP) was analyzed by immunohistochemistry. Histological analysis showed that DPCs in the collagen gel formed an osteodentin-like hard tissue matrix after 21 days. Increased positive immunoreactivity for ALP, BSP, OPN, nestin, and DSP was observed in experimental groups compared with control. Our results demonstrate that DPCs in collagen gel inside demineralized dentin tubules show increased growth and differentiation.</p> Sultan Zeb Khan, Sana Mirza, Samina Karim, Takashi Inoue, Mohammed S. Bin-Shuwaish, Laila Al Deeb, Khold Al Ahdal, Rana S. Al-Hamdan, Ahmed M. Maawadh, Fahim Vohra, Tariq Abduljabbar Copyright (c) 2020 Sultan Zeb Khan, Sana Mirza, Samina Karim, Takashi Inoue, Mohammed S. Bin-Shuwaish, Laila Al Deeb, Khold Al Ahdal, Rana S. Al-Hamdan, Ahmed M. Maawadh, Fahim Vohra, Tariq Abduljabbar Mon, 02 Nov 2020 00:00:00 +0100 Inflammation-related cytokines and their roles in gastroenteropancreatic neuroendocrine neoplasms <p>Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we explored the immunohistochemical expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-2, and IL-6 in tissues from 43 GEP-NEN patients with tumors of gastric, duodenal, ileal, appendiceal, and colonic origin. The immunohistochemical expression of TNF-α was increased in tumor groups with high proliferation rates (Ki-67; <em>p</em> = 0.034), as well as in those with higher tumor grades (<em>p</em> = 0.05). Moreover, the immunohistochemical expression of TNF-α positively correlated with death outcomes (<em>p</em> = 0.016). Expression of IL-6, IL-1β, and IL-2 displayed similar immunohistochemical expression patterns regardless of Ki-67, although the expression between the ILs differed. Most GEP-NENs had high levels of IL-6 and lower levels of IL-1β and IL-2. Although further comprehensive studies are required for a complete understanding of activated mechanisms in proinflammatory protumoral microenvironment of GEP-NENs, TNF-α is a potential marker in the prognosis of those tumors.</p> Davorka Herman Mahečić, Maja Cigrovski Berković, Vanja Zjačić-Rotkvić, Tamara Čačev, Sanja Kapitanović, Monika Ulamec Copyright (c) 2020 Davorka Herman Mahečić, Maja Cigrovski Berković, Vanja Zjačić-Rotkvić, Tamara Čačev, Sanja Kapitanović, Monika Ulamec Mon, 02 Nov 2020 00:00:00 +0100 Endothelial loss during the surgical procedure in saphenous veins harvested by open and endoscopic techniques in coronary artery bypass surgery <p>The patency of the vein graft in coronary artery bypass grafting could be dependent on the conventional open (vsO) or endoscopic (vsE) harvesting and on the hypoxic damage of endothelial cells. We aimed to evaluate both surgical techniques according to endothelial loss that occurs in the time between harvesting and implantation. Twenty-six saphenous veins were divided into vsO (n = 16) and vsE (n = 10) group. Three samples were taken from each vein. The first sample was taken after removal, the second before implantation of the distal part, and the third before the implantation of the proximal part, and they were stained with HE, Movat, and immunohistochemically with CD31. A significant loss of endothelial cells within both groups was found at the time of implantation of the distal and the proximal part of the vein graft compared to the endothelial cells at the time of harvesting. There were no significant differences in the endothelial loss between vsE and vsO groups at the time of harvesting and at the time before the implantation of the distal part. A higher number of endothelial cells was found in vsE group compared to vsO group at the time just before the implantation of the proximal part. The comparison of the implanted portions of vsE and vsO grafts to mammary arteries revealed a significant loss of endothelial cells only in vsO graft. We conclude that, at the time of implantation, the endothelial layer of the vein graft harvested endoscopically is more preserved than of the vein graft harvested openly.</p> Aleksandra Milutinović, Ruda Zorc-Pleskovič Copyright (c) 2020 Aleksandra Milutinović, Ruda Zorc-Pleskovič Mon, 02 Nov 2020 00:00:00 +0100 Percutaneous coronary intervention assisted by invasive mechanical ventilation and intra-aortic balloon pump for acute myocardial infarction with cardiogenic shock: Retrospective cohort study and meta-analyses <p>There is little evidence to recommend the optimal invasive mechanical ventilation (IMV) modes and ideal positive end-expiratory pressure stress levels for acute myocardial infarction-cardiogenic shock (AMI-CS) patients. The aim of this study was to compare the mortality outcome in patients with AMI-CS who were treated with percutaneous coronary intervention (PCI) assisted by intra-aortic balloon pump (IABP) + IMV with historical controls. From January 1, 2016 to June 1, 2017, 60 patients were retrospectively enrolled at Tianjin Chest Hospital. Out of these, 88.3% of patients achieved thrombolysis in myocardial infarction (TIMI) flow 3 after PCI. The all-cause mortality rate in-hospital and at 1 year was 25% (95% CI: 0.14–0.36) and 33.9% (0.22–0.46), respectively. A systematic review followed by meta-analysis was performed with four historical studies of patients treated by PCI + IMV with partial IABP, which found an in-hospital mortality rate of 66.0% (95% CI: 0.62–0.71). Recently, a meta-analysis of patients receiving PCI + IABP with partial IMV showed that the 1 year mortality rate was 52.2% (95% CI: 0.47–0.58). In Cox regression analysis of patient data from the current study, lactic acid level ≥4.5 mmol/L, hyperuricemia, and TIMI flow &lt;3 were independent predictors of death at 1 year. All-cause mortality, in-hospital and at 1 year, in patients with AMI-CS treated with PCI + IABP and IMV was lower than in those treated with PCI + partial IABP or IMV. Larger, longer-term direct comparisons are warranted.</p> Yin Liu, Chang-Ping Li, Peng-Ju Lu, Xu-Ying Wang, Jian-Yong Xiao, Ming-Dong Gao, Ji-Xiang Wang, Xiao-Wei Li, Nan Zhang, Chun-Jie Li, Jun Ma, Jing Gao Copyright (c) 2019 The author(s) Mon, 02 Nov 2020 00:00:00 +0100 Clinical Nocardia species: Identification, clinical characteristics, and antimicrobial susceptibility in Shandong, China <p><em>Nocardia</em> is a pathogen responsible for a variety of clinical infections. Here, we aimed to investigate the species distribution, clinical manifestations, and antimicrobial susceptibility of <em>Nocardia</em> species over 3 years in two tertiary general hospitals in China. In this retrospective study, a total of 27 <em>Nocardia</em> species were isolated from 27 individuals between January 2017 and December 2019. <em>Nocardia</em> isolates were identified to species level by mass spectrometry and 16S rRNA PCR sequencing. Clinical data were collected from medical records. Antimicrobial susceptibility was determined by the standard Broth microdilution method. The 27 patients with <em>Nocardia</em> infection included 12 males and 15 females with a mean age of 60.11 years. Among 27 <em>Nocardia</em> isolates, 7 species were identified, with the most common species being <em>Nocardia otitidiscaviarum</em> (40.7%). The antimicrobial susceptibility profiles varied between different <em>Nocardia</em> species. Notably, all<em> Nocardia</em> isolates were linezolid susceptible. The majority of <em>Nocardia</em> isolates were collected from a department of respiratory medicine (55.56%) and sputum specimen (44.44%). Pulmonary region was the most involved body site (70.37%) followed by skin (7.4%) and pleural cavity (7.4%). Most patients with <em>Nocardia</em> infection needed combination antibiotic therapy. Two deaths were reported during the treatment period and 24 patients achieved improvement after antibiotic therapy. The clinical manifestations of <em>Nocardia</em> infection and antimicrobial susceptibility profiles varied with diverse <em>Nocardia</em> species. Thus, the accurate identification of these species is crucial for the diagnosis and the selection of antibiotic treatment.</p> Shu-Hua Lu, Zhen-Wen Qian, Pei-Pei Mou, Lian Xie Copyright (c) 2020 Shu-Hua Lu, Zhen-Wen Qian, Pei-Pei Mou, Lian Xie Mon, 02 Nov 2020 00:00:00 +0100 Chronic maxillary sinusitis of dental origin and oroantral fistula: The results of combined surgical approach in an Italian university hospital <p>Unilateral chronic maxillary sinusitis is a possible complication of odontogenic disease or dental treatment and is mainly due to the development of an oroantral fistula (OAF). The management of chronic maxillary sinusitis of dental origin (CMSDO) requires a combined treatment via endoscopic sinus surgery (ESS) and intraoral surgical treatment of the odontogenic source. The aim of this study is to present the results of our university hospital unit in the treatment and follow-up of a case series of 34 patients treated with a combined surgical approach for CMSDO due to OAF. All patients were treated with ESS combined with an intraoral approach. No intraoperative or immediate postoperative complications were observed; nasal synechia was found in 3 patients (8.82%). The overall success rate after the primary intervention was 94.12%; recurrence was observed in 2 cases (5.88%), both were suffering from diabetes mellitus and were tobacco smokers. Our results confirm that simultaneous surgery with a combination of an intraoral and endoscopic approach can be considered the best strategy for the long-term restoration of normal sinonasal homeostasis in selected patients with chronic odontogenic sinusitis and OAF, guaranteeing an effective treatment with minimal complications in the short and long term.</p> Massimo Galli, Giulia De Soccio, Fabrizio Cialente, Francesca Candelori, Francesca Romana Federici, Massimo Ralli, Marco de Vincentiis, Antonio Minni Copyright (c) 2020 Massimo Galli, Giulia De Soccio, Fabrizio Cialente, Francesca Candelori, Francesca Romana Federici, Massimo Ralli, Marco de Vincentiis, Antonio Minni Mon, 02 Nov 2020 00:00:00 +0100 Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1 <p>Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified <em>ZFP36L1</em> as the target of miR-129-5p. UALCAN dataset analysis found that <em>ZFP36L1</em> was significantly upregulated in GBM vs. normal brain tissues, and high <em>ZFP36L1</em> expression was positively associated with poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of <em>ZFP36L1</em> expression in GBM, suggesting new candidates for targeted therapy in GBM patients.</p> Xu Guo, Haozhe Piao, Ye Zhang, Peixin Sun, Bing Yao Copyright (c) 2019 Xu Guo, Haozhe Piao, Ye Zhang, Peixin Sun, Bing Yao Mon, 02 Nov 2020 00:00:00 +0100 High MTHFR promoter methylation levels in men confer protection against ischemic stroke <p>The <em>MTHFR</em> gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the <em>MTHFR</em> promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect <em>MTHFR</em> promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, <em>MTHFR</em> promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether <em>MTHFR</em> promoter methylation levels can predict IS. The mean <em>MTHFR</em> methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; <em>p &lt;</em> 0.05). <em>MTHFR</em> promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels &lt;15 μmol/L (16.74 ± 4.26, <em>p &lt;</em> 0.001). Finally, we found that <em>MTHFR</em> hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; <em>p </em>&lt; 0.001). Further, sex and <em>MTHFR</em> promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that <em>MTHFR</em> promoter methylation status might have diagnostic value in IS.</p> Shan Xu, Qianping Shi, Bo Li, Liyuan Han, Guodong Xu, Xiaolin Peng, Hongen Chen, Shuhong Dai, Wancheng Ma, Changyi Wang, Jianping Ma Copyright (c) 2020 Shan Xu, Qianping Shi, Bo Li, Liyuan Han, Guodong Xu, Xiaolin Peng, Hongen Chen, Shuhong Dai, Wancheng Ma, Changyi Wang, Jianping Ma Mon, 02 Nov 2020 00:00:00 +0100 DNA methylation of AHCY may increase the risk of ischemic stroke <p>Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (<em>AHCY</em>) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of <em>AHCY</em> was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in <em>AHCY</em> methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), <em>p</em> &lt; 0.0001], and these associations remained significant in both male (<em>p</em> = 0.003) and female (<em>p</em> = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated <em>AHCY</em> in the case group than the control group in all age groups (age &lt; 60 years, <em>p</em> = 0.007; age ≥ 60 years, <em>p</em> &lt; 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for <em>AHCY</em> methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, <em>p</em> = 0.0001], male patients (AUC = 0.67, <em>p</em> = 0.004), and female patients (AUC = 0.75, <em>p</em> = 0.0002). Our study confirmed a significant association between the <em>AHCY</em> DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.</p> Lei Zhao, Xiaosheng Chen, Shengjun Zhou, Zhiqing Lin, Xi Yu, Yi Huang Copyright (c) 2020 Lei Zhao, Xiaosheng Chen, Shengjun Zhou, Zhiqing Lin, Xi Yu, Yi Huang Mon, 02 Nov 2020 00:00:00 +0100 Monomeric C-reactive protein affects cell injury and apoptosis through activation of p38 mitogen-activated protein kinase in human coronary artery endothelial cells <p>C-reactive protein (CRP) is an important predictor of cardiovascular events and plays a role in vascular inflammation and vessel damage. The aim of this study was to investigate the effect of pentameric CRP (pCRP) and monomeric CRP (mCRP) on the production of atherosclerosis-re­lated factors in cultured human coronary artery endothelial cells (HCAECs). HCAECs were treated with pCRP, mCRP, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, or transfected with p38 MAPK siRNA. Western blotting was performed to detect the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-2 (ICAM-2) and vascular cell adhe­sion molecule-1 (VCAM-1). Proliferation, damage, and apoptosis of HCAECs were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and flow cytometry, respectively. mCRP suppressed VEGF and COX-2 expression and enhanced ICAM-2 and VCAM-1 expression in HCAECs, in both dose-dependent and time-dependent manner. Except at 100 μg/ml concen­tration and 20-hour or 24-hour incubation, pCRP had no apparent effects. mCRP but not pCRP induced HCAEC injury and phosphorylation of p38 MAPK, and the inhibitor SB203580 reversed the effects of mCRP. mCRP promotes injury and apoptosis of HCAECs through a p38 MAPK-dependent mechanism, which provides a new therapy for the injury of HCAECs in atherosclerosis.</p> Yong Zhang, Hongxia Cao Copyright (c) 2020 Yong Zhang, Hongxia Cao Mon, 02 Nov 2020 00:00:00 +0100 Human brucellosis in pregnancy – an overview <p>Human brucellosis during pregnancy is characterized by significantly less pronounced adverse obstetric outcomes than in animals, but with remarkably more adverse obstetric outcomes when compared to healthy pregnant women. Seroprevalence of brucellosis in pregnancy and cumulative incidence of brucellosis cases per 1000 delivered obstetrical discharges in endemic regions were reported to be 1.5–12.2% and 0.42–3.3, respectively. Depending on the region, the frequency of pregnant women in the cohorts of patients with brucellosis was from 1.5% to 16.9%. The most common and the most dramatic unfavorable outcomes during brucellosis in pregnancy are the obstetric ones, manifested as abortions (2.5–54.5%), intrauterine fetal death (0–20.6%), or preterm deliveries (1.2–28.6%), depending on the stage of pregnancy. Other unfavorable outcomes due to brucellosis are addressed to infant (congenital/neonatal brucellosis, low birth weight, development delay, or even death), the clinical course of disease in mother, and delivery team exposure. When diagnosed in pregnant women, brucellosis should be treated as soon as possible. Early administration of adequate therapy significantly reduces the frequency of adverse outcomes. Rifampicin in combination with trimethoprim-sulfamethoxazole for 6 weeks is the most commonly used and recommended regimen, although monotherapies with each of these two drugs are also widely used while waiting for the results from prospective randomized therapeutic trials. As no effective human vaccine exists, screening of pregnant women and education of all women of childbearing age about brucellosis should be compulsory preventive measures in endemic regions.</p> Mile Bosilkovski, Jurica Arapović, Fariba Keramat Copyright (c) 2019 BJBMS Mon, 02 Nov 2020 00:00:00 +0100 Can telomere length predict bone health? A review of current evidence <p>Telomeres are repetitive DNA sequences located at the end of chromosomes that serve as a protective barrier against chromosomal deterioration during cell division. Approximately 50–200 base pairs of nucleotides are lost per cell division, and new repetitive nucleotides are added by the enzyme telomerase, allowing telomere maintenance. Telomere shortening has been proposed as an indicator for biological aging, but its relationship with age-related osteoporosis is ambiguous. We summarize the current evidence on the relationship between telomere length and bone health in experimental and epidemiological studies, which serve as a scientific reference for the development of novel diagnostic markers of osteoporosis or novel therapeutics targeting telomere and telomerase of bone cells to treat osteoporosis.</p> Sok Kuan Wong, Soelaiman Ima-Nirwana, Kok-Yong Chin Copyright (c) 2020 Sok Kuan Wong, Soelaiman Ima-Nirwana, Kok-Yong Chin Mon, 02 Nov 2020 00:00:00 +0100 Clinical applications of avian eggshell-derived hydroxyapatite <p>The search for bone reconstruction materials and methods is an ongoing challenge. The aim of this review is to systemically search the available literature concerning the clinical performance of eggshell as a substitute material in guided bone regeneration in oral surgery. Five databases (PubMed, Cochrane, Web of Science, Scopus, and Embase) were searched up to February 2020. Clinical trials that used eggshell as a bone substitute material were included in the review. Animal and <em>in vivo</em> studies were excluded from the review. ROBINS-I was used to evaluate the risk of bias. A total of 840 studies were retrieved, out of which 55 full-text articles were screened. Five studies were finally included: one study showed critical and four serious risk of bias. A total of 74 patients and 88 intervention sites were included in the five studies. Clinical and radiological evaluation showed complete healing during the follow-ups. Statistically significant radiological and clinical evidence of new bone formation was achieved for socket preservation, grafting after third molar extraction, and cystic/apicectomy grafting. One patient with complications was reported. Histological analysis and micro computed tomography confirmed that it promotes bone regeneration. A comparison with synthetic hydroxyapatite showed similar healing characteristics. Within the limitations of the included studies, the eggshell can be safely and efficiently used in guided bone regeneration procedures, but more research is needed to completely evaluate the full potential of this material.</p> Horia Opris, Simion Bran, Cristian Dinu, Mihaela Baciut, Daiana Antoaneta Prodan, Alexandru Mester, Grigore Baciut Copyright (c) 2020 Horia Opris, Simion Bran, Cristian Dinu, Mihaela Baciut, Daiana Antoaneta Prodan, Alexandru Mester, Grigore Baciut Mon, 02 Nov 2020 00:00:00 +0100 Upper limb principal arteries variations: A cadaveric study with terminological implication <p>Although the variability of the upper limb arteries is a clinically important problem, the prevalence is varying across the existing studies and classification is rather complicated, not well established and sometimes even unclear for simple and direct understanding and usage. Multiple case reports appearing in the last years apply incorrect, inappropriate, and sometimes misleading terminology. We performed an anatomical cadaveric study of the variability of the arteries of the upper limb, namely, the axilla, arm, and forearm, in 423 upper limbs embalmed with classical formaldehyde method (Central European population). We proposed to apply the Equality system based on the common trunks for denomination of the axillary artery branches principal variations: <em>Truncus subscapulocircumflexus </em>(22.9%), <em>truncus profundocircumflexus </em>(13.75%)<em>, </em>and<em> truncus bicircumflexus </em>(13.95%). Further, we proposed the terminology system developed by Rodríguez-Niedenführ et al. for the free upper limb principal arterial trunk variations based on the origin, location (in the arm only, or in the arm and forearm), and course (related to the forearm flexor muscles) of the involved artery: <em>Arteria brachialis superficialis </em>(9.5%), <em>arteria brachioradialis superficialis </em>(6.4%), <em>arteria brachioulnaris superficialis</em> (1.9%), <em>arteria brachiomediana superficialis </em>(0.5%), and <em>arteria comitans nervi mediani manus </em>(3.3%). Extensive development of the catheterization methods via the <em>arteria radialis et ulnaris</em> as well as surgical procedures using flaps based on perforating branches of these arteries (including <em>arteria brachioradialis superficialis et brachioulnaris superficialis</em>) necessitate thorough data on prevalence of the variant vessels for safe performance of these procedures to prevent any unexpected situations or to react adequately in such.</p> Marek Konarik, Vladimir Musil, Vaclav Baca, David Kachlik Copyright (c) 2020 Marek Konarik, Vladimir Musil, Vaclav Baca, David Kachlik Mon, 02 Nov 2020 00:00:00 +0100 Association of polymorphisms in TP53 and the promoter region of IL10 with gastric cancer in a Kazakh population <p>The emerging evidence indicates that single nucleotide polymorphisms (SNPs) of the tumor necrosis factor (<em>TNF</em>), interleukin 10 (<em>IL10</em>), tumor protein p53 (<em>TP53</em>), and cluster of differentiation 14 (<em>CD14</em>) genes may determine individual susceptibility to gastric cancer (GC). We aimed to investigate the associations for polymorphisms of the <em>TNF</em>, <em>IL10</em>, <em>TP53</em>, and <em>CD14</em> genes in a population of Kazakhs, to identify potential risk or protective associations of the SNPs with GC. A case group of 143 patients hospitalized for GC was enrolled. Controls were 355 volunteers with no history of any cancer and frequency matched with cases by age. Differences in proportions for categorical variables and the assessment of genotypic frequencies conforming to the Hardy–Weinberg equilibrium law were evaluated by the Chi-square test. Associations between genetic polymorphisms and the risk of GC were estimated by regression analysis. For genetic analysis, three genetic models (additive, dominant, and recessive) were used. Four significant associations were found. The SNPs rs1042522 of <em>TP53</em> and rs1800896 of <em>IL10</em> were risk factors for GC by the additive model. Two polymorphisms of <em>IL10</em> were protective of GC, namely, rs1800872 by additive model and rs1800871 by recessive model. No significant associations were observed between the <em>TNF</em> and <em>CD14</em> polymorphisms and GC. The polymorphisms <em>TP53</em> rs1042522 and <em>IL10</em> rs1800896 are associated with GC risk, while the polymorphisms <em>IL10</em> rs1800872 and rs1800871 are protective of GC in the population of Kazakhs.</p> Gulmira Kulmambetova, Ivan Shtefanov, Akbota Aitkulova, Meruyert Imanbekova, Aisha Iskakova, Abay Makishev, Yerlan Ramankulov Copyright (c) 2020 Gulmira Kulmambetova, Ivan Shtefanov, Akbota Aitkulova, Meruyert Imanbekova, Aisha Iskakova, Abay Makishev, Yerlan Ramankulov Mon, 02 Nov 2020 00:00:00 +0100 SARS-CoV-2 virus outbreak and the emergency public health measures in Bosnia and Herzegovina: January – July, 2020 <p>Between March 5 and July 25, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10 090 corresponding to a cumulative incidence rate of 285.7 per 100 000 population. Demographic and clinical information on all the cases along with exposure and contact information was collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number R<sub>t</sub> and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0 % (790/5646) in Federation of Bosnia and Herzegovina (FBH) and 6.2 % (267/4299) in Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the basic reproduction number increased from 1.13 on May, the 20th to 1.72 on May the 31st.&nbsp;The outbreak concerns both entities, Federation of Bosnia and Herzegovina and Republika Srpska, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.</p> Mirsada Hukic, Mirza Ponjavic, Emin Tahirovic, Almir Karabegovic, Elvir Ferhatbegovic, Maja Travar, Fadila Serdarevic Copyright (c) 2020 Mirsada Hukic, Mirza Ponjavic, Emin Tahirovic, Almir Karabegovic, Elvir Ferhatbegovic, Maja Travar, Fadila Serdarevic Wed, 21 Oct 2020 14:40:50 +0200 The Ki-67 proliferation index predicts recurrence-free survival in patients with dermatofibrosarcoma protuberans <p>Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2−412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019−1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.</p> Deligonul Adem, Serkan Yazici, Mine Ozsen, Sibel Kahraman Cetintas, Ulviye Yalcinkaya, Ahmet Bilgehan Şahin, Ozgur Tanrıverdi, Sibel Oyucu Orhan, Birol Ocak, Erdem Cubukcu, Ramazan Kahveci, Turkkan Evrensel Copyright (c) 2020 Deligonul Adem, Serkan Yazici, Mine Ozsen, Sibel Kahraman Cetintas, Ulviye Yalcinkaya, Ahmet Bilgehan Şahin, Ozgur Tanrıverdi, Sibel Oyucu Orhan, Birol Ocak, Erdem Cubukcu, Ramazan Kahveci, Turkkan Evrensel Tue, 20 Oct 2020 23:02:50 +0200 Alectinib and lorlatinib function by modulating EMT-related proteins and MMPs in NSCLC metastasis <p>Most advanced non-small cell lung cancer (NSCLC) patients are accompanied by brain metastasis which is the major cause of increased mortality. The fusion rearrangement of anaplastic lymphoma kinase (ALK) gene is an important feature of brain metastasis in lung cancer. The novel ALK inhibitors alectinib and lorlatinib are shown to be effective against NSCLC brain metastasis, while their underlying mechanism of action is unclear. Epithelial–mesenchymal transition (EMT) proteins and matrix metalloproteinases (MMPs) play important roles in brain metastasis by regulating the blood-brain barrier (BBB). To reveal the molecular function of alectinib and lorlatinib, we explored their effects on the cellular levels of EMT markers: VIM and FN1 and the matrix metalloproteinases MMP-9 and MMP-7. The mRNA and protein levels of VIM, FN1, MMP-9, and MMP-7 were elevated in H3122 cells. However, upon alectinib and lorlatinib treatment the levels were significantly reduced. Similar results were obtained when these experiments were performed either in a dose dependent or time dependent manner. Furthermore, alectinib and lorlatinib also inhibited the cell viability and migration of H3122 cells. Interestingly, in comparison to individual drugs, the combination of alectinib and lorlatinib was found to be substantially more effective. Overall, these results suggest that alectinib and lorlatinib possibly function via the downregulation of MMPs and EMT in NSCLC metastasis.</p> Xu Feng, En-Shi Xu Copyright (c) 2020 Xu Feng, En-Shi Xu Tue, 20 Oct 2020 17:26:24 +0200 Kawasaki-like disease and acute myocarditis in the SARS-CoV-2 pandemic – reports of three adolescents <p>The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.</p> Stasa Krasic, Sergej Prijic, Predrag Minic, Gordana Petrovic, Dejan Nesic, Aleksandra Paripovic, Milena Vasiljevic, Borko Gobeljic, Vladislav Vukomanovic Copyright (c) 2020 Stasa Krasic, Sergej Prijic, Predrag Minic, Gordana Petrovic, Dejan Nesic, Vladislav Vukomanovic Fri, 16 Oct 2020 20:49:16 +0200 Development and validation of prognostic nomogram for lung cancer patients below the age of 45 years <p>This study aimed to establish a nomogram for the prognostic prediction of patients with early-onset lung cancer (EOLC) in both overall survival (OS) and cancer-specific survival (CSS). We retrieved EOLC patients diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database and further divided them into training and validation sets randomly. The prognostic nomogram for predicting 3-, 5- and 10-years OS and CSS was established based on the relative clinical variables determined by the multivariate Cox analysis results. Furthermore, the predictive performance of the nomogram was assessed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. A total of 1,822 EOLC patients were selected and randomized into a training cohort (1,275, 70%) and a validation cohort (547, 30%). The nomograms were established based on the statistical results of Cox analysis. In training set, the C-indexes for OS and CSS prediction were 0.797 (95% confidence interval [CI]: 0.773-0.818) and 0.794 (95%CI:0.771-0.816). Significant agreement in the calibration curves was noticed in the nomogram models. The results of ROC and DCA indicated nomograms possessed better predict performance compared with TNM-stage and SEER-stage. Furthermore, the areas under the curve (AUC) of the nomogram for OS and CSS prediction in ROC analysis were 0.766 (95%CI:0.745-0.787) and 0.782 (95%CI:0.760-0.804) respectively. In conclusion, the prognostic nomogram provided an accurate prediction of 3-, 5-, and 10-year OS and CSS of EOLC patients which contributed clinicians to optimize individualized treatment plans.&nbsp;</p> Kaixin Qu, Lili Dai, Wei Wang, Qi Liu, Tongjia Xia, Qikui Wang, Qingqing Chen, Ning Zhu, Yu Cheng, Ying Yan, Jun Shu Copyright (c) 2020 Kaixin Qu, Lili Dai, Wei Wang, Qi Liu, Tongjia Xia, Qikui Wang, Qingqing Chen, Ning Zhu, Yu Cheng, Ying Yan, Jun Shu Wed, 14 Oct 2020 19:17:11 +0200