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Behzad Shahin-Kaleybar, A. Niazi, A. Afsharifar, G. Nematzadeh, R. Yousefi, Bernhard Retzl, Roland Hellinger, Edin Muratspahić et al.

The plant Citrullus colocynthis, a member of the squash (Cucurbitaceae) family, has a long history in traditional medicine. Based on the ancient knowledge about the healing properties of herbal preparations, plant-derived small molecules, e.g., salicylic acid, or quinine, have been integral to modern drug discovery. Additionally, many plant families, such as Cucurbitaceae, are known as a rich source for cysteine-rich peptides, which are gaining importance as valuable pharmaceuticals. In this study, we characterized the C. colocynthis peptidome using chemical modification of cysteine residues, and mass shift analysis via matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. We identified the presence of at least 23 cysteine-rich peptides in this plant, and eight novel peptides, named citcol-1 to -8, with a molecular weight between ~3650 and 4160 Da, were purified using reversed-phase high performance liquid chromatography (HPLC), and their amino acid sequences were determined by de novo assignment of b- and y-ion series of proteolytic peptide fragments. In silico analysis of citcol peptides revealed a high sequence similarity to trypsin inhibitor peptides from Cucumis sativus, Momordica cochinchinensis, Momordica macrophylla and Momordica sphaeroidea. Using genome/transcriptome mining it was possible to identify precursor sequences of this peptide family in related Cucurbitaceae species that cluster into trypsin inhibitor and antimicrobial peptides. Based on our analysis, the presence or absence of a crucial Arg/Lys residue at the putative P1 position may be used to classify these common cysteine-rich peptides by functional properties. Despite sequence homology and the common classification into the inhibitor cysteine knot family, these peptides appear to have diverse and additional bioactivities yet to be revealed.

Shahrooz Nasrollahi-Shirazi, D. Szöllösi, Qiong Yang, Edin Muratspahić, Ali El‐Kasaby, S. Sucic, T. Stockner, C. Nanoff et al.

In medium-size, spiny striatal neurons of the direct pathway, dopamine D1- and adenosine A1-receptors are coexpressed and are mutually antagonistic. Recently, a mutation in the gene encoding the A1-receptor (A1R), A1R-G279S7.44, was identified in an Iranian family: two affected offspring suffered from early-onset l-DOPA–responsive Parkinson’s disease. The link between the mutation and the phenotype is unclear. Here, we explored the functional consequence of the G279S substitution on the activity of the A1-receptor after heterologous expression in HEK293 cells. The mutation did not affect surface expression and ligand binding but changed the susceptibility to heat denaturation: the thermodynamic stability of A1R-G279S7.44 was enhanced by about 2 and 8 K when compared with wild-type A1-receptor and A1R-Y288A7.53 (a folding-deficient variant used as a reference), respectively. In contrast, the kinetic stability was reduced, indicating a lower energy barrier for conformational transitions in A1R-G279S7.44 (73 ± 23 kJ/mol) than in wild-type A1R (135 ± 4 kJ/mol) or in A1R-Y288A7.53 (184 ± 24 kJ/mol). Consistent with this lower energy barrier, A1R-G279S7.44 was more effective in promoting guanine nucleotide exchange than wild-type A1R. We detected similar levels of complexes formed between D1-receptors and wild-type A1R or A1R-G279S7.44 by coimmunoprecipitation and bioluminescence resonance energy transfer. However, lower concentrations of agonist were required for half-maximum inhibition of dopamine-induced cAMP accumulation in cells coexpressing D1-receptor and A1R-G279S7.44 than in those coexpressing wild-type A1R. These observations predict enhanced inhibition of dopaminergic signaling by A1R-G279S7.44 in vivo, consistent with a pathogenic role in Parkinson’s disease. SIGNIFICANCE STATEMENT Parkinson’s disease is caused by a loss of dopaminergic input from the substantia nigra to the caudate nucleus and the putamen. Activation of the adenosine A1-receptor antagonizes responses elicited by dopamine D1-receptor. We show that this activity is more pronounced in a mutant version of the A1-receptor (A1R-G279S7.44), which was identified in individuals suffering from early-onset Parkinson’s disease.

S. Siddiqi, Wafa Aftab, F. Siddiqui, L. Huicho, R. Mogilevskii, P. Friberg, Johanna Lindgren-Garcia, S. Causevic et al.

Evidence on early achievements, challenges and opportunities would help low-income and middle-income countries (LMICs) accelerate implementation of health and health-related sustainable development goals (HHSDGs). A series of country-specific and multicountry consultative meetings were conducted during 2018–2019 that involved 15 countries across five regions to determine the status of implementation of HHSDGs. Almost 120 representatives from health and non-health sectors participated. The assessment relied on a multidomain analytical framework drawing on existing public health policy frameworks. During the first 5 years of the sustainable development goals (SDGs) era, participating LMICs from South and Central Asia, East Africa and Latin America demonstrated growing political commitment to HHSDGs, with augmentation of multisectoral institutional arrangements, strengthening of monitoring systems and engagement of development partners. On the other hand, there has been limited involvement of civic society representatives and academia, relatively few capacity development initiatives were in place, a well-crafted communication strategy was missing, and there is limited evidence of additional domestic financing for implementing HHSDGs. While the momentum towards universal health coverage is notable, explicit linkages with non-health SDGs and integrated multisectoral implementation strategies are lacking. The study offers messages to LMICs that would allow for a full decade of accelerated implementation of HHSDGs, and points to the need for more implementation research in each domain and for testing interventions that are likely to work before scale-up.

A. Novo, H. Pandza

Introduction: High educational and teaching standards were the main reason why from the begging student satisfaction surveys and assessments of the students’ knowledge, attitudes and opinions were paramount in the educational process at the Cathedra for Medical Informatics at the Medical Faculty University of Sarajevo. Aim: The aim of this study was to evaluate general knowledge of the fourth semester students about informatics and medical informatics and compare it with previous generations. Methods: Students at the beginning of the fourth semester and before second planned lectures receive “Questionnaire for biomedical students about use and knowledge of information technologies”. Collected data was retrospectively used for this study. The scientific study committee of the Cathedra for Medical Informatics reviewed and approved the database for using this study. At the beginning of the survey, all students were informed that their data could be tracked. Also, all students were informed and got lectures on surveys, development and use of questionnaires for the examination of the patient/student satisfactions and how results of the survey and analysis could help continuously improving quality of the teaching process. Discussion and Conclusion: Medical students come to the faculty with significant IT knowledge and skills. It can even be argued that students rank their knowledge in some way lower than we as teachers estimate based on their practical work. They organize groups on social networks where they exchange information about lectures and exams. It is common for each study year to have its own group. Through this group, information and presentations that teachers send to students are exchanged. One of the goals of teaching medical informatics is the method of searching for medical information on the Internet. The skills learned in medical informatics classes complement those learned earlier and provide a solid base for physicians who are able to supplement their knowledge using IT technologies when they need it.

S. Rusinovci, Xhevdet Aliu, T. Jukić, D. Štubljar, N. Haliti

SUMMARY The purpose of the study was to retrospectively analyze the prevalence of oral cavity, neck and head tumors recorded at our department over a period of 3 years. Retrospective analysis included archival data on cancer patients treated at our department during the 2015-2017 period. A total of 1005 patients with proven carcinomas were selected for final analysis. Cancers were detected by ultrasound, x-ray, biopsy and clinical diagnosis. The mean age of patients was 58.4±19.3 years. The majority of cases (n=264; 26.3%) were detected in the 7th decade of life. The most common cancers were basal cell carcinoma in 374 (37.2%) and squamous cell carcinoma in 228 (22.7%) cases. The male-to-female ratio was 1.7:1. There was no statistically significant age difference between genders. Recurrence of tumor occurred in 31 patients. The most common risk factor in both groups was sun exposure. The most common sites were lower lip, cheek and frontal region in men, and cheek region and nose in women (p<0.001). Men were found to be more susceptible to cancer development. This study showed differences between age groups, i.e. elderly patients had a much higher probability of developing cancer as compared to younger patients.

Abstract This research includes all banks in Bosnia and Herzegovina (B&H) and testing internal and external variables on bank profitability indicators. The primary goal of this paper is to determine, through correlation and regression analysis, the strength and significance of the external and internal variables on bank profitability in Bosnia and Herzegovina. Likewise, data were collected from quarterly reports of the Banking Agency of the Federation of B&H and the Banking Agency of the Republika Srpska for the period 2008 Q1 to 2019 Q4. The following dependent variables were used: ROA, ROE and independent variables: GRNGL, GRNPL, GRGDP, concentration ratio of loans of the largest banks in the system (CR Loans), concentration ratio of deposits of the largest banks in the system (CR Deposits), CAR and loan-to-deposit ratio. The study found that there is a significant statistical impact of the variables on ROA and ROE. In addition, this study points out the need for banks to properly select debtors, and control costs, toxic loans and provisions in order to increase profits and reduce costs.

J. Pavlović, M. Maksimovic, Olha V Klopanović, Zoran S Vasilić, N. Ivković, M. Račić

Abstract Objective: The aim of the current study is to compare Seniors in the Community: Risk Evaluation for Eating and Nutrition, version II (SCREEN II) and Mini Nutritional Assessment – Short Form (MNA-SF), where each is used to identify nutritional risk prevalence among community-dwelling people aged 65 years and above in Bosnia and Herzegovina. Design: A cross-sectional study. Nutritional risk assessed using the nutritionist’s risk rating, anthropometric measurements, functional indicators, cognitive parameters, SCREEN II and MNA-SF. Setting: The municipalities of Foca, East Sarajevo and Bijeljina, Bosnia and Herzegovina. Participants: Eight hundred twenty-one community-dwelling individuals aged ≥65 years. Results: The prevalence of high nutritional risk per nutritionist’s risk rating, SCREEN II and MNA-SF was 26, 60, and 7 %, respectively. With the nutritionist’s rating score ≥5 as the criterion, the MNA-SF cut-off point of ≤11 (indicating any possible risk) had poor sensitivity (55·7 %), specificity (46·6 %) and AUC (0·563; P = 0·024). When the criterion of >7 was applied, good sensitivity (95·3 %) and specificity (88·9 %) were obtained for the MNA-SF cut-off score of ≤7. AUC for this comparison was 0·742 (considered fair). Cut-off points of <54 (AUC = 0·816) and <50 (AUC = 0·881) for SCREEN II (indicating moderate to high risk) corresponded with good sensitivity (82·2 %; 80·9 %) and fair specificity (72·1 %; 75·0 %). Conclusion: MNA-SF may have a limited role in nutritional risk screening among community-dwelling seniors in Bosnia and Herzegovina. SCREEN II has promising results in regard to validity, but further studies are warranted.

Aida Šehanović, D. Smajlović, E. Tupković, O. Ibrahimagić, S. Kunić, Z. Dostović, Emina Zoletić, Z. Pašić

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, (auto) immune disease of the central nervous system (CNS). Cognitive disorders are found in over 50% of patients. Aim: The aim of the study was to determine the distribution of cognitive disorders in people with MS. Methods: The prospective study included 135 respondents with MS and 50 healthy respondents. The respondents were divided into three groups: the first group consisted of 85 respondents where the disease lasted longer than one year, the second group consisted of 50 respondents with newly diagnosed MS, the third group consisted of 50 healthy respondents. Clinical assessment instruments were: Extended Disability Score in Multiple Sclerosis Patients, Mini Mental Status, Battery of Tests to Assess Cognitive Functions: Wechsler Intelligence Scale, Revised Beta Test, Raven Colored Progressive Matrices, Wechsler Memory Scale, Rey Audio Verbal Learning Test -Osterriecht’s complex character test, verbal fluency test. Results: Cognitive disorders were present in 40-60% of respondents with MS. Visuospatial, visuoconstructive and visuoperceptive functions are worse in the first group. Mnestic functions (learning process, short-term and long-term memory, recollection, verbal-logical memory) were most affected in both groups of respondents, ranging from 30-60%. Poorer cognitive domains are in the first groups of respondents. Immediate working process memory (current learning), memory, attention, short-term and logical memory is worse in the examinees of the first group. At the beginning of the disease, 16% had verbal fluency difficulties, and as the disease progresses, the difficulties become more pronounced. Conclusion: Cognitive disorders are heterogeneous, they can be noticed in the early stages of the disease. They refer to impairments of working memory, executive functions and attention, while global intellectual efficiency is later reduced.

It is well-known that determining the optimal number of guards which can cover the interior of a simple nonconvex polygon presents an NP-hard problem. The optimal guard placement can be described as a problem which seeks for the smallest number of guards required to cover every point in a complex environment. In this paper, we propose an exact twophase method as well as an approximate method for tackling the mentioned issue. The proposed exact approach in the first phase maps camera placement problem to the set covering problem, while in the second phase it uses famous state-of-the-art CPLEX solver to address set covering problem. The performance of our combined exact algorithm was compared to the performance of the approximate one. According to the results presented in the experimental analysis, it can be seen that the exact approach outperforms the approximate method for all instances.

SUMMARY The aim of the study was to investigate if preoperative blood flow velocity in femoral vein in different positions of the hip during total hip arthroplasty (THA) is a predictor of postoperative deep vein thrombosis (DVT). In patients undergoing THA, blood flow velocity and diameter of proximal femoral vein on THA side were measured preoperatively in four flexion positions of the hip. After THA, patients were followed up for 42 days for DVT occurrence, and clinical features of patients with and without postoperative DVT were compared. The mean blood flow velocity in maximal flexion (90º+) preoperatively was significantly lower in patients with postoperative DVT (19/103) compared to patients without it (8.4±2 cm/s vs. 10.6±2.3 cm/s; p<0.001). Using the receiver operating characteristic curve analysis, the cut-off value for blood flow velocity during maximal flexion was 8.24 cm/s. In addition, anesthesia duration, duration of surgical position of the patient, body mass index, amount of blood transfused after surgery, and clinical signs of DVT were markedly different between patients with and those without postoperative DVT. Blood flow velocity in femoral vein in maximal flexion of the hip (90º+) measured prior to THA is an independent predictor of postoperative DVT.

Abstract The goal of the present study was to examine the predictors of reading speed and reading comprehension in third-grade students from Bosnia and Herzegovina (BIH). The sample consisted of 168 third-grade students (86 boys, 82 girls) attending regular schools in Canton Sarajevo, BIH. We examined the effects of phonological awareness (phoneme deletion and rhyming), rapid automatized naming (RAN) of letters and objects, semantic fluency, working memory, and processing speed, on three reading speed tasks and a reading comprehension task. For the reading speed tasks, total amount of explained variance was 33% for reading a text passage, 40% for word reading and 36% for pseudoword reading. The most important predictors of reading speed tasks were phoneme deletion task and RAN: Letters. On the other hand, the model explaining reading comprehension was much less predictive and explained about 11% of variance. Significant predictors of reading comprehension were working memory and processing speed. The results of this study are very informative in creating better models of reading. This in turn will help create better reading intervention programs and potentially reduce the number of children with reading disabilities.

Vehicle routing problem as the generalization of the Travelling Salesman Problem (TSP) is one of the most studied optimization problems. Industry itself pays special attention to this problem, since transportation is one of the most crucial segments in supplying goods. This paper presents an innovative cluster-based approach for the successful solving of real-world vehicle routing problems that can involve extremely complex VRP problems with many customers needing to be served. The validation of the entire approach was based on the real data of a distribution company, with transport savings being in a range of 10-20 %. At the same time, the transportation routes are completely feasible, satisfying all the realistic constraints and conditions.

Introduction The liver is the largest gland in the human body, and serves to store nutrients and neutralize harmful compounds. The liver plays a very important role in a number of metabolic, both catabolic and anabolic processes, and is therefore called the "central laboratory" of the organism. If liver disease occurs, they can affect all its parts-liver cells, bile ducts, blood and lymph vessels. The liver is damaged by various toxins, drugs, infections, disturbances in the blood supply and other disorders. Diet therapy has been a part of the process in the treatment of liver disease for a while. The therapeutic principle is better known as the "liver diet". The liver diet not only means the replenishment of calories and nutrients, but it significantly affects the course of the disease. Aim The aim of the research is to show that diet therapy plays an important role in the treatment of liver disease as a component for faster recovery of the liver and restoration of its normal function, as well as protecting the liver after overcoming the disease. Results Among the respondents, there were 39 men (64%) and 22 women (36%) who had liver disease as a chronic condition. Most respondents are between 51 and 65 years old (28 and 46%, respectively), while the least number of respondents are in the 20 to 30 age group. The largest number of respondents cited alcohol as the cause of the disease, 31 of them (50.8%), while the virus was the cause of the disease in 15 respondents (24.5%). Of the total sample, most respondents answered that they sometimes (45.9%) or often (47.5%) overeat. The results of the questionnaire showed that 85.2% of the respondents were smokers before the diagnosis of the disease. In most respondents, the food they ate before diagnosis was moderately fatty (52.5%). Using chi-square tests, it was found that there are statistically significant differences in the consumption of almost all foods before the diagnosis of the disease and after the obtained dietary recommendations (p<0.05). Conclusions The aim of the research was confirmed that diet therapy plays an important role in the treatment of liver disease as a component for faster recovery of the liver and restoration of its normal function, and after overcoming the disease it still protects the liver. The main purpose of creating a diet therapy program and plan proved to be significant and necessary because more than half of the respondents rated our advice as excellent. As most causes of liver disease can be prevented, it is necessary to work on familiarizing the population with risk factors, promote a healthy lifestyle and proper nutrition, and identify at-risk patients who must enter the monitoring system for early detection of liver disease.

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