Bosnian Journal of Basic Medical Sciences <p>The Bosnian Journal of Basic Medical Sciences (BJBMS) is an international, English-language, peer-reviewed journal, publishing articles in different disciplines of basic medical sciences. BJBMS welcomes original research and comprehensive reviews as well as short research communications in the field of molecular biology, biochemistry, genetics, immunology, microbiology, pathology, pharmacology, pharmaceutical sciences, physiology and translational research.</p> en-US <p>© Association of Basic Medical Sciences of FBIH.</p> (Faruk Skenderi) (Faruk Skenderi) Tue, 12 Feb 2019 23:38:59 +0100 OJS 60 Enhancement of bone consolidation using high-frequency pulsed electromagnetic fields (HF-PEMFs): An experimental study on rats <p><em>In vitro</em> studies showed that high-frequency pulsed electromagnetic fields (HF-PEMFs) increase the activity/expression of early and late osteogenic markers and enhance bone mineralization. The main aim of this study was to investigate the <em>in vivo</em> effects of HF-PEMFs on fracture healing using a rat model. A femur fracture was established by surgery in 20 male Wistar rats. Titanium nails were implanted to reduce and stabilize the fracture. After surgery, 20 rats were equally divided into untreated control and treated group (from the first postoperative day HF-PEMFs at 400 pulses/sec [pps] were applied for 10 minutes/day, for two weeks). Quantitative and qualitative assessment of bone formation was made at two and eight weeks following surgery and included morphological and histological analysis, serological analysis by ELISA, micro-computed tomography (micro-CT), and three-point bending test. At two weeks in HF-PEMF group, soft callus was at a more advanced fibrocartilaginous stage and the bone volume/total tissue volume (BV/TV) ratio in the callus area was significantly higher compared to control group (<em>p</em> = 0.047). Serum concentration of alkaline phosphatase (ALP) and osteocalcin (OC) was significantly higher in HF-PEMF group (ALP <em>p</em> = 0.026, OC <em>p</em> = 0.006) as well as the mechanical strength of femurs (<em>p</em> = 0.03). At eight weeks, femurs from HF-PEMF group had a completely formed woven bone with dense trabeculae, active bone marrow, and had a significantly higher BV/TV ratio compared to control (<em>p</em> = 0.01). HF-PEMFs applied from the first postoperative day, 10 minutes/day for two weeks, enhance bone consolidation in rats, especially in the early phase of fracture healing.</p> Daniel Oltean-Dan, Gabriela Bombonica Dogaru, Dragos Apostu, Alexandru Mester, Horea Rares Ciprian Benea, Mihai Gheorghe Paiusan, Catalin Ovidiu Popa, Elena Mihaela Jianu, Gyorgy Istvan Bodizs, Cristian Berce, Alina Mihaela Toader, Gheorghe Tomoaia ##submission.copyrightStatement## Wed, 20 Feb 2019 13:51:44 +0100 Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM) <p>Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several <em>VEGF</em>-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between <em>VEGF</em>-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of &gt;10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 – 2.86, <em>p</em> = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR.</p> Jana Sajovic, Ines Cilenšek, Sara Mankoč, Špela Tajnšek, Tanja Kunej, Daniel Petrovič, Mojca Globočnik Petrovič ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 The association of early postoperative lactate levels with morbidity after elective major abdominal surgery <p>Lactate levels are widely used as an indicator of outcome in critically ill patients. We investigated the prognostic value of postoperative lactate levels for postoperative complications (POCs), mortality and length of hospital stay after elective major abdominal surgery. A total of 195 patients were prospectively evaluated. Lactate levels were assessed on admission to the intensive care unit (ICU) [L<sub>0</sub>], at 4 hours (L<sub>4</sub>), 12 hours (L<sub>12</sub>), and 24 hours (L<sub>24</sub>) after the operation. Demographic and perioperative clinical data were collected. Patients were monitored for complications until discharge or death. Receiver operating characteristic (ROC) curves were used to determine the predictive value of lactate levels for postoperative outcomes. The best cut-off lactate values were calculated to differentiate between patients with and without complications, and outcomes in patients with lactate levels above and below the cut-off thresholds were compared. Univariate and multivariate analyses were used to identify variables associated with POCs and mortality. Seventy-six patients developed 184 complications (18 deaths), while 119 had no complications. Serum lactate levels were higher in patients with complications at all time points compared to those without complications (<em>p</em> &lt; 0.001). L<sub>12</sub> had the highest predictive value for complications (AUROC<sub>12</sub> = 0.787; 95% CI: 0.719–0.854; <em>p</em> &lt; 0.001) and mortality (AUROC<sub>12</sub> = 0.872; 95% CI: 0.794–0.950; <em>p</em> &lt; 0.001). The best L<sub>12 </sub>cut-off value for complications and mortality was 1.35 mmol/l and 1.85 mmol/l, respectively. Multivariate analysis revealed that L<sub>12</sub> ≥ 1.35 mmol/l was an independent predictor of postoperative morbidity (OR 2.58; 95% CI 1.27–5.24, <em>p</em> = 0.001). L<sub>24 </sub>was predictive of POCs after major abdominal surgery. L<sub>12</sub> had the best power to discriminate between patients with and without POCs and was associated with a longer hospital stay.</p> Jelena Veličković, Ivan Palibrk, Biljana Miličić, Dejan Veličković, Bojan Jovanović, Goran Rakić, Milorad Petrović, Vesna Bumbaširević ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Delirium following total joint replacement surgery <p>Postoperative delirium (POD) is a common complication associated with increased resource utilization, morbidity and mortality. Our institution screens all postsurgical patients for postoperative delirium. The study aim was to perform an automated interrogation of the electronic health records to estimate the incidence of and identify associated risk factors for POD following total joint arthroplasty (TJA). Adult patients who underwent TJA with a multimodal analgesia protocol, including peripheral nerve blockade, from 2008 through 2012, underwent automated chart review. POD was identified by routine nursing assessment and administrative billing codes. Of 11,970 patients, 181 (1.5%) were identified to have POD. Older age (odds ratio, 95% CI 2.20, 1.80–2.71 per decade, <em>p</em> &lt; 0.001), dementia (7.44, 3.54–14.60, <em>p</em> &lt; 0.001), diabetes mellitus (1.70, 1.1.5–2.47, <em>p</em> = 0.009), renal disease (1.68, 1.03–2.65, <em>p</em> = 0.039), blood transfusions (2.04, 1.14–3.52, <em>p</em> = 0.017), and sedation during anesthesia recovery (1.76, 1.23–2.51, <em>p</em> = 0.002) were associated with POD. Anesthetic management was not associated with POD risk. Patients who developed POD required greater healthcare resources. Dementia is strongly associated with POD. The association between POD and transfusions may reflect higher acuity patients or detrimental effect of blood. Postoperative sedation should be recognized as a warning sign of increased risk.</p> Jeffrey Huang, Juraj Sprung, Toby N. Weingarten ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Decreased heart rate recovery may predict a high SYNTAX score in patients with stable coronary artery disease <p>An impaired heart rate recovery (HRR) has been associated with increased risk of cardiovascular events, cardiovascular, and all‐cause mortality. However, the diagnostic ability of HRR for the presence and severity of coronary artery disease (CAD) has not been clearly elucidated. Our aim was to investigate the relationship between HRR and the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score in patients with stable CAD (SCAD). A total of 406 patients with an abnormal treadmill exercise test and ≥50% coronary stenosis on coronary angiography were included. The HRR was calculated by subtracting the HR in the first minute of the recovery period from the maximum HR during exercise. The SYNTAX score ≥23 was accepted as high. Correlation of HRR with SYNTAX score and independent predictors of high SYNTAX score were determined. A high SYNTAX score was present in 172 (42%) patients. Mean HRR was lower in patients with a high SYNTAX score (9.8 ± 4.5 vs. 21.3 ± 9, <em>p</em> &lt; 0.001). The SYNTAX score was negatively correlated with HRR (r: -0.580, <em>p</em> &lt; 0.001). In multivariate logistic regression analysis, peripheral arterial disease (OR: 13.3; 95% CI: 3.120–34.520; <em>p</em> &lt; 0.001), decreased HRR (OR: 0.780; 95% CI: 0.674–0.902; <em>p</em> = 0.001), peak systolic blood pressure (OR: 1.054; 95% CI: 1.023–1.087; <em>p</em> = 0.001), and peak HR (OR: 0.950; 95% CI: 0.923–0.977; <em>p</em> &lt; 0.001) were found to be independent predictors of a high SYNTAX score. Our results showed that HRR is significantly correlated with the SYNTAX score, and a decreased HRR is an independent predictor of a high SYNTAX score in patients with SCAD.</p> Sadık Volkan Emren, Rahman Bilal Gediz, Oktay Şenöz, Uğur Karagöz, Ersin Çağrı Şimşek, Fatih Levent, Emre Özdemir, Mustafa Ozan Gürsoy, Cem Nazlı ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Predictors of acute kidney injury (AKI) in high-risk ST-elevation myocardial infarction (STEMI) patients: A single-center retrospective observational study <p>Acute kidney injury (AKI) is a frequent complication in ST-elevation myocardial infarction (STEMI) patients. Factors other than contrast exposure have been suggested as major contributors to renal dysfunction in patients undergoing primary percutaneous coronary intervention (PPCI). Our aim was to assess the incidence and risk factors of AKI in high-risk STEMI patients, mostly treated by PPCI with implemented measures to prevent contrast-induced AKI. We retrospectively analyzed data of 245 STEMI patients (165 men, mean age 63.9 ± 11.9 years) admitted to the Department of Medical Intensive Care Unit. Demographic, clinical, and mortality data were compared between AKI and non-AKI group. AKI was defined as a 1.5-fold increase in serum creatinine from baseline level within 24–48 hours. AKI developed in 34/245 (13.9%) patients. PPCI was performed in 226/245 (92.2%) of all STEMI cases, with no difference between AKI and non-AKI group. There were significant differences between AKI and non-AKI group in diabetes mellitus (41.2% vs. 20.9%), prior MI (26.5% vs. 11.8%), prior resuscitation (38.2% vs. 12.4%), admission acute heart failure [AHF] (44.1% vs. 12.8%), in-hospital AHF (70.6% vs. 17.5%), and hospital-acquired infection [HAI] (79.4% vs. 18.0%). Significantly more AKI patients had increased admission CRP ≥25 mg/L (38.2% vs. 11.8%), peak CRP ≥50 mg/L (91.2% vs. 36%), admission troponin I ≥10 mg/L (44.1% vs. 24.6%), peak troponin I ≥50 mg/L (64.7% vs. 44.1%), peak NT-proBNP ≥400 pmol/L (82.4% vs. 27.5%), and ejection fraction &lt;45% (76.5% vs. 33.6%). Mortality was significantly increased in AKI group, including in-hospital (52.9% vs. 7.1%), 30-day (64.7% vs. 10.7%) and 6-month mortality (70.6% vs. 13.7%). Significant independent predictors of AKI were prior resuscitation (OR 4.171, 95% CI 1.088–15.998), HAI (OR 7.974, 95% CI 1.992–31.912), and peak NT-proBNP (OR 21.261, 95% CI 2.357–191.795). To reduce the risk of AKI in STEMI patients, early diagnosis and treatment of AHF and HAIs are advisable.</p> Andreja Sinkovič, Klara Masnik, Matic Mihevc ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Analysis of multidrug-resistant bacteria in 3223 patients with hospital-acquired infections (HAI) from a tertiary general hospital in China <p align="left">The frequency of antimicrobial resistance has increased globally due to misuse and overuse of antibiotics, and multi-drug resistant (MDR) bacteria are now recognized as a major cause of hospital-acquired infections (HAI). Our aim was to investigate the prevalence, distribution, and antimicrobial susceptibility rates of MDR bacteria in patients with HAI from a tertiary hospital in China. We retrospectively evaluated all patients with a confirmed diagnosis of bacterial infection at a tertiary general hospital in Jining, for the period between January 2012 and December 2014. The following clinical and demographic data were collected: age, sex, specimens, treatment, microbiology results, and antibiotic resistance patterns of isolates. Bacterial identification and susceptibility testing were performed using VITEK 2 COMPACT system. We screened a total of 15,588 patients, out of which 7579 (48.6%) had an HAI. MDR showed 3223 out of 7579 isolates (42.5%). The most frequently isolated MDR bacteria in patients with HAI were extended-spectrum beta-lactamase (ESBL)-producing <em>Escherichia coli</em> (n = 1216/3223, 37.7%), MDR <em>Pseudomonas aeruginosa </em>(n = 627/3223, 19.5%) and MDR <em>Acinetobacter baumannii </em>(n = 588/3223, 18.2%). MDR-HAI were more common in males (2074/3223, 64.4%) and in elderly patients (≥60 years; 1196/3223, 37.1%). Sputum was the main source of MDR isolates (2056/3223, 63.8%). Patients with MDR-HAI were predominantly distributed in different types of intensive care units. MDR strains in our study showed resistance to most current antibiotics. Overall, patients with HAI infections attributed to MDR bacteria were widely distributed in our hospital. Enhanced surveillance of MDR bacteria is critical for guiding the rational use of antibiotics and reducing the incidence of HAI.</p> Meng Wang, Hongyan Wei, Yaxin Zhao, Linlin Shang, Linlin Di, Chuanfeng Lyu, Jun Liu ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Overexpression of miR-361-5p in triple-negative breast cancer (TNBC) inhibits migration and invasion by targeting RQCD1 and inhibiting the EGFR/PI3K/Akt pathway <p align="left">Triple-negative breast cancer (TNBC) is the leading cause of cancer-related death in women. Previous studies indicated that miR-361-5p was downregulated in breast cancer, however, the exact effect of miR-361-5p on TNBC requires further investigation. In the present study, we investigated whether miR-361-5p can act as a tumor suppressor by targeting required for cell differentiation 1 homolog (RQCD1) and inhibiting epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway in TNBC. The expression of miR-361-5p and RQCD1 was determined by quantitative reverse transcription PCR (qRT-PCR) and/or western blot in TNBC and the adjacent tissues. miR-361-5p mimics were constructed and transfected to TNBC cell line MDA-MB-231. Cells were divided into three groups: blank control group, miRNA mimic negative control (NC) group, and miR-361-5p mimics group. Expression of miR-361-5p, mRNA and protein expression of PI3K, Akt, EGFR, phosphorylated (p)-EGFR/PI3K/Akt, and protein expression of RQCD1 and matrix metallopeptidase 9 (MMP-9) in MDA-MB-231 were measured by qRT-PCR/western blot after transfection. Cell viability was determined by CCK-8 assay. Cell migration and invasion ability were evaluated by scratch and transwell assay, respectively. miR-361-5p target gene was determined by bioinformatics analysis and luciferase reporter assay. RQCD1 was identified as a target of miR-361-5p by TargetScan and confirmed by luciferase reporter assay. Downregulated miR-361-5p and upregulated RQCD1 were observed in TNBC tissues. Expression of EGFR, PI3K, Akt and MMP-9 was inhibited in cells treated with miR-361-5p mimics. Transfection of miR-361-5p mimics also inhibited the phosphorylation of EGFR, PI3K, and Akt. Suppressed cell viability, migration, and invasion was found in miR-361-5p mimics groups. Our results indicated that overexpression of miR-361-5p might act as a suppressor in TNBC by targeting RQCD1 to inhibit the EGFR/PI3K/Akt signaling pathway.</p> Jianjun Han, Jingjing Yu, Yu'na Dai, Jumei Li, Meiyan Guo, Jingzhen Song, Xuefeng Zhou ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Human amniotic fluid stem cells (hAFSCs) expressing p21 and cyclin D1 genes retain excellent viability after freezing with (dimethyl sulfoxide) DMSO <p>Human amniotic fluid stem cells (hAFSCs) have features intermediate between embryonic and adult SCs, can differentiate into lineages of all three germ layers, and do not develop into tumors <em>in vivo</em>. Moreover, hAFSCs can be easily obtained in routine procedures and there is no ethical or legal limitations regarding their use for clinical and experimental applications. The aim of this study was to assess the effect of slow freezing/thawing and two different concentrations of DMSO (10% DMSO + 90% fetal bovine serum [FBS] and 5% DMSO + 95% FBS) on the survival of hAFSCs. hAFSCs were obtained from 5 pregnant women during amniocentesis at 16–22 weeks of gestation. The expression of pluripotency markers (Octamer-binding transcription factor 4 [Oct4] and NANOG) by reverse transcription polymerase chain reaction and cell surface markers (cluster of differentiation [CD31], CD44, CD45, and CD90) by flow cytometry was analyzed before and after the slow-freezing. Cell viability was assessed by trypan blue exclusion or MTT assay. Quantitative mRNA expression of Oct4, NANOG, cyclin D1 and p21 was determined by real-time PCR before and after the slow-freezing. Pluripotency of hAFSCs was confirmed by <em>NANOG</em> and <em>POU5F1</em> (Oct4) gene expression before and after slow-freezing. All hAFSC cultures were positive for CD44 and CD90. A higher viability of hAFSCs was observed after freezing with 90% FBS + 10% DMSO. There was increased expression of <em>NANOG</em> and decreased expression of <em>POU5F1 </em>gene after freezing, compared to control cells (before freezing). DMSO and the process of freezing did not significantly change the expression of p21 and cyclin D1 genes in hAFSCs. Overall, our results indicate the applicability of slow-freezing and DMSO in cryopreservation of SCs.</p> Shiva Gholizadeh-Ghaleh Aziz, Zahra Fardyazar, Fatima Pashaei-Asl, Mohammad Rahmati-Yamchi, Khodadad Khodadadi, Maryam Pashaiasl ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers <p>Spermatogenesis is a tightly controlled, multi-step process in which mature spermatozoa are produced. Disruption of regulatory mechanisms in spermatogenesis can lead to male infertility, various diseases of male reproductive system, or even cancer. The spermatogenic impairment in infertile men can be associated with different etiologies, and the exact molecular mechanisms are yet to be determined. MicroRNAs (miRNAs) are a type of non-protein coding RNAs, about 22 nucleotides long, with an essential role in post-transcriptional regulation. miRNAs have been recognized as important regulators of various biological processes, including spermatogenesis. The aim of this review is to summarize the recent literature on the role of miRNAs in spermatogenesis, male infertility and reproductive cancers, and to evaluate their potential in diagnosis, prognosis and therapy of disease. Experimental evidence shows that aberrant expression of miRNAs affects spermatogenesis at multiple stages and in different cell types, most often resulting in infertility. In more severe cases, dysregulation of miRNAs leads to cancer. miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and reproductive system diseases. However, to exploit this potential fully, we need a better understanding of miRNA-mediated regulation of spermatogenesis, including the characterization of yet unidentified miRNAs and related regulatory mechanisms.</p> Muhammad Babar Khawar, Rabia Mehmood, Nabila Roohi ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 A plea for an extension of the anatomical nomenclature: Organ systems <p>This article is the third part of a series aimed at correcting and extending the anatomical nomenclature. Communication in clinical medicine as well as in medical education is extensively composed of anatomical, histological, and embryological terms. Thus, to avoid any confusion, it is essential to have a concise, exact, perfect and correct anatomical nomenclature. The Terminologia Anatomica (TA) was published 20 years ago and during this period several revisions have been made. Nevertheless, some important anatomical structures are still not included in the nomenclature. Here we list a collection of 156 defined and explained technical terms related to the anatomical structures of the human body focusing on the digestive, respiratory, urinary and genital systems. These terms are set for discussion to be added into the new version of the TA.</p> Vladimir Musil, Alzbeta Blankova, Vlasta Dvorakova, Radovan Turyna, Vaclav Baca ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Cannabinoids in cancer treatment: Therapeutic potential and legislation <p align="left">The plant <em>Cannabis sativa</em> L. has been used as an herbal remedy for centuries and is the most important source of phytocannabinoids. The endocannabinoid system (ECS) consists of receptors, endogenous ligands (endocannabinoids) and metabolizing enzymes, and plays an important role in different physiological and pathological processes. Phytocannabinoids and synthetic cannabinoids can interact with the components of ECS or other cellular pathways and thus affect the development/progression of diseases, including cancer. In cancer patients, cannabinoids have primarily been used as a part of palliative care to alleviate pain, relieve nausea and stimulate appetite. In addition, numerous cell culture and animal studies showed antitumor effects of cannabinoids in various cancer types. Here we reviewed the literature on anticancer effects of plant-derived and synthetic cannabinoids, to better understand their mechanisms of action and role in cancer treatment. We also reviewed the current legislative updates on the use of cannabinoids for medical and therapeutic purposes, primarily in the EU countries. <em>In vitro</em> and <em>in vivo</em> cancer models show that cannabinoids can effectively modulate tumor growth, however, the antitumor effects appear to be largely dependent on cancer type and drug dose/concentration. Understanding how cannabinoids are able to regulate essential cellular processes involved in tumorigenesis, such as progression through the cell cycle, cell proliferation and cell death, as well as the interactions between cannabinoids and the immune system, are crucial for improving existing and developing new therapeutic approaches for cancer patients. The national legislation of the EU Member States defines the legal boundaries of permissible use of cannabinoids for medical and therapeutic purposes, however, these legislative guidelines may not be aligned with the current scientific knowledge.</p> Barbara Dariš, Mojca Tancer Verboten, Željko Knez, Polonca Ferk ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Review of first clinical experiences with a 1.5 Tesla ceiling-mounted moveable intraoperative MRI system in Europe <p>High-field intraoperative MRI (iMRI) systems provide excellent imaging quality and are used for resection control and update of image guidance systems in a number of centers. A ceiling-mounted intraoperative MRI system has several advantages compared to a conventional iMRI system. In this article, we report on first clinical experience with using such a state-of-the-art, the 1.5T iMRI system, in Europe. A total of 50 consecutive patients with intracranial tumors and vascular lesions were operated in the iMRI unit. We analyzed the patients’ data, surgery preparation times, intraoperative scans, surgical time, and radicality of tumor removal.</p> <p>Patients’ mean age was 46 years (range 8 to 77 years) and the median surgical procedure time was 5 hours (range 1 to 11 hours). The lesions included 6 low-grade gliomas, 8 grade III astrocytomas, 10 glioblastomas, 7 metastases, 7 pituitary adenomas, 2 cavernomas, 2 lymphomas, 1 cortical dysplasia, 3 aneurysms, 1 arterio-venous malformation and 1 extracranial-intracranial bypass, 1 clival chordoma, and 1 Chiari malformation. In the surgical treatment of tumor lesions, intraoperative imaging depicted tumor remnant in 29.7% of the cases, which led to a change in the intraoperative strategy.</p> <p>The mobile 1.5T iMRI system proved to be safe and allowed an optimal workflow in the iMRI unit. Due to the fact that the MRI scanner is moved into the operating room only for imaging, the working environment is comparable to a regular operating room.</p> Guenther C. Feigl, Stefan Heckl, Marcel Kullmann, Zoltan Filip, Karlheinz Decker, Jan Klein, Ulrike Ernemann, Marcos Tatagiba, Tomaz Velnar, Rainer Ritz ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 The effect of micro-sized titanium dioxide on WM-266-4 metastatic melanoma cell line <p>Titanium dioxide (TiO<sub>2</sub>) is widely used as an inorganic UV-filter in cosmetic products; however, it has been classified as possibly carcinogenic to humans. While numerous studies demonstrated cytotoxic and genotoxic effects of nano-sized TiO<sub>2</sub> in different cell lines, including human skin cells, studies investigating the effects of micro-TiO<sub>2</sub> on human keratinocytes and melanocytes, in healthy and cancer cells, are scarce. Adenosine triphosphate (ATP) binding cassette subfamily B member 5 (ABCB5) is a plasma membrane protein known for its role in the tumorigenicity, progression, and recurrence of melanoma. Here, we investigated the effect of micro-TiO<sub>2</sub> (average particle size ≤5 µm) on the metabolic activity, cytotoxicity and <em>ABCB5</em> mRNA expression in metastatic melanoma cells. Metastatic melanoma cell line WM-266-4 was treated with different concentrations of micro-TiO<sub>2</sub> for different incubation times to obtain dose- and time-dependent responses. Untreated WM-266-4 cells, cultured under the same conditions, were used as control. The cell metabolic activity was determined by MTT assay. Cytotoxicity of micro-TiO<sub>2</sub> was analyzed by lactate dehydrogenase (LDH) cytotoxicity assay. The <em>ABCB5</em> mRNA expression in melanoma cells was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). After 120 hours of exposure to micro-TiO<sub>2</sub> the metabolic activity of melanoma cells decreased, especially at the two highest micro-TiO<sub>2</sub> concentrations. Comparably, the cytotoxicity of micro-TiO<sub>2</sub> on melanoma cells increased after 48 and 120 hours of exposure, in a time-dependent manner. The <em>ABCB5</em> mRNA expression in micro-TiO<sub>2</sub>-treated melanoma cells also decreased significantly after 24 and 48 hours, in a time-dependent manner. Overall, our results suggest inhibitory effects of micro-TiO<sub>2</sub> on the metabolic activity and <em>ABCB5</em> mRNA expression in metastatic melanoma cells, indicating its potential use as an anticancer agent.</p> Tanja Prunk Zdravković, Bogdan Zdravković, Mojca Lunder, Polonca Ferk ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Teucrium Polium Plant Extract Provokes Substantial Cytotoxicity at the Early Stage of Embryonic Development <p>The aim of this study is to explore the outcome of <em>Teucrium polium </em>(TP) medicinal plant consumption on the early stage of fetal development. We used the chicken embryo at 3 days of incubation as a model to evaluate the effect of TP plant extract during embryogenesis. In addition, quantitative polymerase chain reaction (qPCR) was applied to explore the expression of six genes related to cell proliferation, apoptosis, sur­vival, angiogenesis, and migration. Our data revealed that TP exposure inhibits angiogenesis of the chicken embryo and its chorioallantoic membrane. In addition, we found that TP extract significantly harms the normal development of the embryos since around 95% of TP<em>-</em>exposed embryos died after 1–3 days of treatment. Macroscopic examination did not show any anomalies in these embryos. However, qPCR analysis of activation transcription factor-3, B-cell lymphoma-2, caspase 8, inhibin subunit beta A, vascular endothelial growth factor-C, and Cadherin-6 type-2 genes revealed that these genes are considerably deregulated in heart and brain tissues from TP-exposed embryos in comparison with their matched tissues from unexposed ones. Our study implies that TP plant can have very toxic effects on the early stage of the embryo. Therefore, it is important to alert expectant women to avoid the use of this medicinal plant during pregnancy.</p> Shaikha S. Al-Qahdi, Nada Alzohari, Abrar Y. Alsaid, Anas A. Ashour, Tahar Aboulkassim, Semir Vranic, Ala-Eddin Al Moustafa, Ashraf A. Khalil ##submission.copyrightStatement## Tue, 12 Feb 2019 00:00:00 +0100 Intervertebral disc tissue engineering: A brief review <p>Intervertebral disc (IVD) degeneration (IDD) is associated with low back pain and significantly affects the patient’s quality of life. Degeneration of the IVD alters disk height and the mechanics of the spine, leading to chronic segmental spinal instability. The pathophysiology of IVD disease is still not well understood. Current therapies for IDD include conservative and invasive approaches, but none of those treatments are able to restore the disc structure and function. Recently, tissue engineering techniques emerged as a possible approach to treat IDD, by replacing a damaged IVD with scaffolds and appropriate cells. Advances in manufacturing techniques, material processing and development, surface functionalization, drug delivery systems and cell incorporation furthered the development of tissue engineering therapies. In this review, biomaterial scaffolds and cell-based therapies for IVD regeneration are briefly discussed.</p> Janja Stergar, Lidija Gradisnik, Tomaz Velnar, Uros Maver ##submission.copyrightStatement## Thu, 31 Jan 2019 20:45:59 +0100 Feasibility and accuracy of a voxel-based neuronavigation system with 3D image rendering in preoperative planning and as a learning tool for young neurosurgeons, exemplified by the anatomical localization of the superior sagittal sinus <p>It is essential for a neurosurgeon to know individual anatomy and the corresponding anatomical landmarks before starting a surgery. Continuous training, especially of young neurosurgeons, is crucial for understanding complex neuroanatomy. In this study, we used a neuronavigation system with 3D volumetric image rendering to determine the anatomical relationship between the sagittal suture and the superior sagittal sinus (SSS) in patients with intracranial lesions. Furthermore, we discussed the applicability of such system in preoperative planning, residency training, and research. The study included 30 adult patients (18 female/12 male) who underwent a cranial computed tomography (CT) scan combined with venous angiography, for preoperative planning. The position of the sagittal suture in relation to the SSS was assessed in 3D CT images using an image guidance system (IGS) with 3D volumetric image rendering. Measurements were performed along the course of the sagittal sinus at the bregma, lambda, and in the middle between these two points. The SSS deviated to the right side of the sagittal suture in 50% of cases at the bregma, and in 46.7% at the midpoint and lambda. The SSS was displaced to the left of the sagittal suture in 10% of cases at the bregma and lambda and in 13% at the midpoint. IGSs with 3D volumetric image rendering enable simultaneous visualization of bony surfaces, soft tissue and vascular structures and interactive modulation of tissue transparency. They can be used in preoperative planning and intraoperative guidance to validate external landmarks and to determine anatomical relationships. In addition, 3D IGSs can be utilized for training of surgical residents and for research in anatomy.</p> Guenther C. Feigl, Firas Thaher, Sören Danz, Marcos Tatagiba, Anne K. Hickmann, Antje Fahrig, Tomaz Velnar, Marcel Kullmann ##submission.copyrightStatement## Sun, 27 Jan 2019 18:50:57 +0100 Clinical outcomes after intentional replantation of permanent teeth: A systematic review <p>This study aimed to systematically assess the outcomes of intentional replantation (IR) of teeth and to determine the survival rate, success rate, and prognostic factors related to the treatment.<strong> </strong>A search was conducted for all relevant English language articles published from January 2000 to October 2017. The search terms included "intentional replantation" and "teeth" according to the inclusion criteria. The Methodological Index for Non-randomized Studies (MINORS) was used to assess the methodological quality of included studies.<strong> </strong>Twelve studies were identified as relevant for the systematic review. In total, 896 patients with 905 teeth were examined for intentional teeth replantation. The success rate was greater than 90% in four studies (33.33%) and between 70% and 80% in five studies. At short-term follow-up (&lt;6 months), the survival rate was approximately 90%. At longer-term follow-up (&gt;36 months), the survival rates of teeth were slightly reduced in four studies, and tended to be stable after 48 months. In conclusion, the long-term success and survival rate of IR are likely dependent upon short extraoral time, reduced pocket depth, type of tooth, type of root-end filling material, and the prevention of atraumatic tooth root damage.</p> Lin Wang, Hua Jiang, Yang Bai, Qiang Luo, Hao Wu, Hongchen Liu ##submission.copyrightStatement## Thu, 17 Jan 2019 10:25:25 +0100 Limb-girdle muscular dystrophy due to GMPPB mutations: A case report and comprehensive literature review Mutations in the guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (<em>GMPPB</em>) gene are rare. To date, 72 cases with <em>GMPPB</em> gene mutations have been reported. Herein, we reported a case of a 29-year-old Chinese male presenting with limb-girdle muscular dystrophy (LGMD) who was found to have two heterozygous <em>GMPPB</em> mutations. The patient had a progressive limb weakness for 19 years. His parents and elder brother were normal. On examination he had a waddling gait, and absent tendon reflexes in all four limbs. Electromyography showed myogenic damage. Muscle magnetic resonance imaging (MRI) showed fatty degeneration in the bilateral medial thigh muscles. High throughput gene panel sequencing revealed that the patient carried compound heterozygous mutations in the <em>GMPPB</em> gene, c.553C&gt;T (p.R185C, maternal inheritance) and c.346C&gt;T (p.P116S, paternal inheritance). This case provides additional information regarding the phenotypic spectrum of <em>GMPPB</em> mutations in the Chinese population. LiuQing Sun, DingGuo Shen, Ting Xiong, Zhibin Zhou, Xianghui Lu, Fang Cui ##submission.copyrightStatement## Wed, 16 Jan 2019 15:07:49 +0100 Neurostructural correlates of strength decrease following total knee arthroplasty: A systematic review of the literature with meta-analysis <p>Recent literature suggests that alterations in both neural and structural components of the neuromuscular system are major determinants of knee extensor muscle weakness after total knee arthroplasty (TKA). Therefore, the goal of this study was to investigate the maximal voluntary strength (MVS), voluntary muscle activation (VMA), and the cross-sectional area (CSA) of the muscle, up to 33 months after the TKA.  We searched relevant scientific databases and literature for outcomes of interest, including quadriceps MVS, VMA, and CSA. Ten studies met the inclusion criteria and involved a total of 289 patients. The quality of the studies was evaluated by Methodological Index for Non-Randomized Studies (MINORS). Results showed that quadriceps MVS markedly declines in the early postoperative period, after which it slowly and linearly recovers over time. However, the same phenomenon was not observed for VMA and CSA, which were not significantly altered after the TKA. Furthermore, a meta-regression analysis revealed that the change in VMA accounted for 39% of the relative change in quadriceps strength (R<sup>2</sup>=0.39; p=0.015) in the early postoperative period. Patients treated with TKA had considerable weakness of the quadriceps muscle, which was detectable up to 3 months after surgery. Although the change in VMA largely explains quadriceps weakness, this change and CSA differences were not significant, suggesting that other neural correlates, such as hamstrings coactivation, might alter quadriceps muscle function. Thus, more attention should be paid to address VMA failure and coactivation of antagonist muscles.  More comprehensive rehabilitation approaches may be required to target the whole neural circuit controlling the motor action.</p> Armin H Paravlic, Simon Kovač, Rado Pisot, Uros Marusic ##submission.copyrightStatement## Mon, 14 Jan 2019 10:56:59 +0100