Motivational Factors Influencing the Choice of Medical Studies and Future Career Plans among Montenegrin Students.

Introduction: There is a concerning trend of emigration among highly educated individuals in Montenegro. This includes medical professionals who seek better job opportunities abroad. The aim of the present study was to identify the primary motivational factors driving Montenegrin medical students to pursue a career in medicine, and whether these factors undergo changes over the course of their studies. Methods: A cross-sectional study included 210 medical students in Montenegro, 27.62% were males, and 72.38% were females. The mean age of the students was 21.90 years (SD=3.05) (range 19-39). Their academic motivation was analysed using the Academic Motivation Scale, previously validated in various cultural contexts. Results: The results showed that autonomous motivation levels were higher than controlled motivation levels (p<0.001) among students in Montenegro, which has been previously associated with better learning outcomes. Students with medical doctors among their family members had higher extrinsic motivation related to rewards and punishments (extrinsic motivation with external regulation p=0.018). Amotivation showed a trend of increasing as the students got closer to graduation (p=0.057). Only 8.1% of students planned a career in primary healthcare, and 1% wished to specialize in family medicine. Conclusions: This study's findings, which indicate high levels of autonomous motivation among medical students, are of significant importance. They contribute to a comprehensive understanding of the motivation factors among medical students and young healthcare professionals in Montenegro. Moreover, they provide a basis for the implementation of strategic interventions to retain highly skilled medical professionals within the country's workforce, thereby addressing the concerning trend of emigration among this group.

The Formulation of Curcumin: 2-Hydroxypropyl-ß-cyclodextrin Complex with Smart Hydrogel for Prolonged Release of Curcumin.

Curcumin comes from the plant species Curcuma longa and shows numerous pharmacological activities. There are numerous curcumin formulations with gels or cyclodextrins in order to increase its solubility and bioavailability. This paper presents the formulation of complex of curcumin with 2-hydroxypropyl-ß-cyclodextrin in a thermosensitive hydrogel, based on N-isopropylmethacrylamide and N-isopropylacrylamide with ethylene glycol dimethacrylate as a crosslinker. The product was characterized by chemical methods and also by FTIR, HPLC, DSC, SEM, XRD. The results show that synthesis was successfully done. With an increase in the quantity of crosslinker in the hydrogels, the starting release and the release rate of curcumin from the formulation of the complex with hydrogels decreases. The release rate of curcumin from the gel complex formulation is constant over time. It is possible to design a formulation that will release curcumin for more than 60 days. In order to determine the mechanism and kinetics of curcumin release, various mathematical models were applied by using the DDSolver package for Microsoft Excel application. The Korsmeyer-Peppas model best describes the release of curcumin from the gel formulation of the complex, while the values for the diffusion exponent (0.063-0.074) shows that mechanism of the release rate is based on diffusion.

Development of Novel Therapeutics for Schizophrenia Treatment Based on a Selective Positive Allosteric Modulation of α1-Containing GABAARs-In Silico Approach.

For the development of atypical antipsychotics, the selective positive allosteric modulation of the ionotropic GABAA receptor (GABAAR) has emerged as a promising approach. In the presented research, two unrelated methods were used for the development of QSAR models for selective positive allosteric modulation of 1-containing GABAARs with derivatives of imidazo [1,2-a]-pyridine. The development of conformation-independent QSAR models, based on descriptors derived from local molecular graph invariants and SMILES notation, was achieved with the Monte Carlo optimization method. From the vast pool of 0D, 1D, and 2D molecule descriptors, the GA-MLR method developed additional QSAR models. Various statistical methods were utilised for the determination of the developed models' robustness, predictability, and overall quality, and according to the obtained results, all QSAR models are considered good. The molecular fragments that have a positive or negative impact on the studied activity were obtained from the studied molecules' SMILES notations, and according to the obtained results, nine novel compounds were designed. The binding affinities to GABAAR of designed compounds were assessed with the application of molecular docking studies and the obtained results showed a high correlation with results obtained from QSAR modeling. To assess all designed molecules' "drug-likeness", their physicochemical descriptors were computed and utilised for the prediction of medicinal chemistry friendliness, pharmacokinetic properties, ADME parameters, and druglike nature.

Phthalates leaching from plastic food and pharmaceutical contact materials by FTIR and GC-MS.

Phthalates are often used as plasticizers in the production of plastic food contact materials (FCMs) and pharmaceutical contact materials (PCMs), and having in mind that they are not bound to plastics, phthalates may easily leach from plastics under certain conditions. The aim of this research is determination of phthalates leaching potential from different plastic materials and quantitative determination of 5 phthalates (dimethyl phthalate (DMP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBP), diethyl hexyl phthalate (DEHP), and di-n-octyl phthalate (DOP)) in 44 different plastic articles of 7 different plastic polymers used as FCMs and PCMs by FTIR, GC-MS, and gravimetric methods. The FTIR technique is shown to be rapid method for determination of phthalate content in PVC articles. Comparing of FTIR method with GC-MS and gravimetric showed that separation and quantitative determination of each phthalate separately favor the GC-MS method, because FTIR method determines the total amount of phthalate content. However, the FTIR method is less expensive and demanding in terms of sample preparation, which is suited for use in pre-screening analysis. The results of GC-MS phthalates determination showed that PVC articles used as PCMs contain DEHP in significant amount, from 5.19 to 28.76% by weight and could be a potential risk to human health.

A Framework for Enhancing and Updating Study Programs in Public Health and Medical Informatics Fields in Montenegro.

Montenegro plans to enhance and modernize the curricula and programs in public health fields in line with EU standards and hence the Erasmus-Phelim project developed a framework to develop, implement, and evaluate the education process. A stepwise approach consisting of three dimensions per step was implemented for workshop development. For the evaluation, a train-the-trainer approach was developed and a self-regulation concept consisting of three phases was applied. Semi-structured interviews with the workshop participants were conducted and results suggested that self-regulation is an understandable concept and can be applied as a training and knowledge transfer method.

Synthesis, spectroscopic and structural characterization of Co(II)-pullulan complexes by UV-Vis, ATR-FTIR, MALDI-TOF/TOF MS and XRD.

Complexes of Co(II) ion with reduced low-molar pullulan (RLMP) (Mw 6000 g/mol) were synthesized in aqueous solutions at boiling temperature in the pH range from 7.5 to 13.5. Obtained Co(II)-RLMP complexes, with cobalt content ∼2-8% (AAS), were characterized by UV-Vis spectrophotometry, FTIR spectroscopy (ATR-FTIR, FT-IRIS), MALDI-TOF/TOF MS, and XRD. Tetragonally distorted Oh coordination of Co(II) ions with O ligand atoms in synthesized complexes is suggested based on the spectrophotometric data. No influence of complexation process on the 4C1 chair conformation of the d-glucopyranose units of pullulan was detected by ATR-FTIR measurements and FT-IRIS showed high homogeneity of synthesized complexes. Some additional depolymerization of pullulan during complex synthesis was indicated by MALDI-TOF/TOF MS but it also revealed good stability of complexes with much weaker binding of Co(II) ion in low molar mass fragments. Even in complexes with highest Co(II) ion content a low degree of crystallinity was detected by XRD analysis.

The Stratified Framework for Enhancement of Study Programs in Public Health in Montenegro.

Montenegro plans to enhance its educational system in the area of health information management, in accordance with well-known EU best practices. Within the Erasmus+ project PH-ELIM, a Stratified Framework was developed to provide education of public health professionals making them highly skilled to support the nation in creating a sustainable and flexible health system, in providing good quality health, in protecting citizens against health threats, all by a cost-effective and straightforward approach. The objective of this presentation is to present the intermediate results of the Framework and lessons learned until now.

Instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue: A review.

A review of recent advances in instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue is presented in this paper. In recent years, biomaterials attracted great attention primarily because of the wide range of biomedical applications. This paper focuses on the practical aspects of instrumental methods and techniques that were most often applied (X-ray methods, vibrational spectroscopy (IR and Raman), magnetic-resonance spectroscopy (NMR and ESR), mass spectrometry (MS), atomic absorption spectrometry (AAS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES), thermogravimetry (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM)) in the structural investigation and physicochemical characterization of biomaterials and bone tissue. The application of some other physicochemical methods was also discussed. Hands-on information is provided about these valuable research tools, emphasizing practical aspects such as typical measurement conditions, their limitations and advantages, interpretation of results and practical applications.

Essential Oils of Morus alba and M. nigra Leaves: Effect of Drying on the Chemical Composition.

Detailed GC and GC/MS analyses of essential-oil samples obtained by hydrodistillation of Morus alba L. and M nigra L. leaves (four samples) allowed the identification of 131 constituents representing 95.1 - 96.4% of the total GC peak areas. The most abundant compounds classes were alkanes, diterpenoids, carotenoid-derived compounds and fatty acid-related constituents with trans-phytol (7.9 - 71.2%), (E,E)-geranyl linalool (0.2 - 8.0%), (Z)-bovolide (8.1/) and n-chain alkanes (in total, 17.5 - 52.4%) as the major constituents of the analyzed samples. In general, there were only quantitative differences noted between M nigra essential oils from fresh and dry leaves. The most discernable changes included a variation in the content of the major constituents (e.g. the relative amount of trans-phytol and the total amount of alkanes decreased by 5.8% and ≈ 2%, respectively, while that of (E,E)-geranyl linalool increased by 7.8%). On the other hand, the composition of M. alba essential oil was much more significantly affected by the drying process. The highest quantitative differences were noted for trans-phytol, geranyl acetone, and all isomers of 4,6,8-megastigmatrien-3-one. Also, a rare plant metabolite, (Z)-bovolide, characteristic of leaf senescence, was only identified (8.1%) in the essential oil of M alba dried leaves.

Faecal occult blood screening for colorectal cancer in Serbia: a pilot study.

Colorectal cancer (CRC) is becoming a major public health problem in the Republic of Serbia. Organized mass screening has been shown to decrease CRC mortality and even its incidence. The aim of this study was to assess the acceptability of a faecal immunochemical test for haemoglobin proposed by primary care physicians. From August to November 2013, a pilot study for CRC screening was organized in individuals aged 50 to 74 years. The study included 50 primary healthcare centres from all 25 administrative regions of Serbia. A qualitative immunochromatographic faecal immunochemical test for human haemoglobin detection was used. Overall, 50 894 individuals were invited. The participation rate was 67.8 and 3.4% of the tests were positive. Among individuals with a positive test, 69.7% agreed to undergo colonoscopy. The positive predictive value was 27.1% for adenoma and 14.6% for carcinoma. This was the first CRC screening project encompassing approximately one-third of primary healthcare facilities in all regions across the country. It showed a good response of the target population and satisfactory cooperation of the healthcare professionals involved.

In silico prediction of the ß-cyclodextrin complexation based on Monte Carlo method.

In this study QSPR models were developed to predict the complexation of structurally diverse compounds with ß-cyclodextrin based on SMILES notation optimal descriptors using Monte Carlo method. The predictive potential of the applied approach was tested with three random splits into the sub-training, calibration, test and validation sets and with different statistical methods. Obtained results demonstrate that Monte Carlo method based modeling is a very promising computational method in the QSPR studies for predicting the complexation of structurally diverse compounds with ß-cyclodextrin. The SMILES attributes (structural features both local and global), defined as molecular fragments, which are promoters of the increase/decrease of molecular binding constants were identified. These structural features were correlated to the complexation process and their identification helped to improve the understanding for the complexation mechanisms of the host molecules.

Monte Carlo method based QSAR modeling of maleimide derivatives as glycogen synthase kinase-3ß inhibitors.

The Monte Carlo method was used for QSAR modeling of maleimide derivatives as glycogen synthase kinase-3ß inhibitors. The first QSAR model was developed for a series of 74 3-anilino-4-arylmaleimide derivatives. The second QSAR model was developed for a series of 177 maleimide derivatives. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system. Two splits have been examined: one split into the training and test set for the first QSAR model, and one split into the training, test and validation set for the second. The statistical quality of the developed model is very good. The calculated model for 3-anilino-4-arylmaleimide derivatives had following statistical parameters: r(2)=0.8617 for the training set; r(2)=0.8659, and r(m)(2)=0.7361 for the test set. The calculated model for maleimide derivatives had following statistical parameters: r(2)=0.9435, for the training, r(2)=0.9262 and r(m)(2)=0.8199 for the test and r(2)=0.8418, r(av)(m)(2)=0.7469 and ∆r(m)(2)=0.1476 for the validation set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new potential glycogen synthase kinase-3ß inhibitors has been presented by using defined structural alerts.

Anismus as a cause of functional constipation--experience from Serbia.

UNLABELLED: BACKROUND/AIM: Anismus is paradoxal pressure increase or pressure decrease less than 20% of external anal sphincter during defecation straining. This study analyzed the presence of anismus as within a group of patients with the positive Rome III criteria for functional constipation. We used anorectal manometry as the determination method for anismus. METHODS: We used anorectal water-perfused manometry in 60 patients with obstructive defecation defined by the Rome III criteria for functional constipation. We also analyzed anorectal function in 30 healthy subjects. RESULTS: The presence of anismus is more frequent in the group of patients with obstructive defecation compared to the control group (a highly statistically significant difference, p < 0.01). Furthermore, we found that the Rome III criteria for functional constipation showed 90% accuracy in predicting obstructive defecation. We analyzed the correlation of anismus with the presence of weak external anal sphincter, rectal sensibility disorders, enlarged piles, diverticular disease and anatomic variations of colon. We found no correlation between them in any of these cases. CONCLUSION: There is a significant correlation between anismus and positive Rome III criteria for functional constipation. Anorectal manometry should be performed in all patients with the positive Rome III criteria for functional constipation.

Application of SMILES Notation Based Optimal Descriptors in Drug Discovery and Design.

SMILES notation based optimal descriptors as a universal tool for the QSAR analysis with further application in drug discovery and design is presented. The basis of this QSAR modeling is Monte Carlo method which has important advantages over other methods, like the possibility of analysis of a QSAR as a random event, is discussed. The advantages of SMILES notation based optimal descriptors in comparison to commonly used descriptors are defined. The published results of QSAR modeling with SMILES notation based optimal descriptors applied for various pharmacologically important endpoints are listed. The presented QSAR modeling approach obeys OECD principles and has mechanistic interpretation with possibility to identify molecular fragments that contribute in positive and negative way to studied biological activity, what is of big importance in computer aided drug design of new compounds with desired activity.

Selected 4-phenyl hydroxycoumarins: in vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study.

A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.

Monte carlo method-based QSAR modeling of penicillins binding to human serum proteins.

The binding of penicillins to human serum proteins was modeled with optimal descriptors based on the Simplified Molecular Input-Line Entry System (SMILES). The concentrations of protein-bound drug for 87 penicillins expressed as percentage of the total plasma concentration were used as experimental data. The Monte Carlo method was used as a computational tool to build up the quantitative structure-activity relationship (QSAR) model for penicillins binding to plasma proteins. One random data split into training, test and validation set was examined. The calculated QSAR model had the following statistical parameters: r(2) = 0.8760, q(2) = 0.8665, s = 8.94 for the training set and r(2) = 0.9812, q(2) = 0.9753, s = 7.31 for the test set. For the validation set, the statistical parameters were r(2) = 0.727 and s = 12.52, but after removing the three worst outliers, the statistical parameters improved to r(2) = 0.921 and s = 7.18. SMILES-based molecular fragments (structural indicators) responsible for the increase and decrease of penicillins binding to plasma proteins were identified. The possibility of using these results for the computer-aided design of new penicillins with desired binding properties is presented.

QSAR Models for the Reactivation of Sarin Inhibited AChE by Quaternary Pyridinium Oximes Based on Monte Carlo Method.

For three random splits, one-variable models of oximes reactivation of sarin inhibited acetylcholinesterase (logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M) have been calculated with CORAL software. The total number of considered oximes was 42. Simplified molecular input line entry system (SMILES) and hydrogen-suppressed graph (HSG) are used to represent the molecular structure. Using CORAL software by means of the calculation with Monte Carlo optimization of the so called correlation weights for the molecular fragments, optimal SMILES-based descriptors were defined, which are correlated with an endpoint for the training set. The predictability of these descriptors for an external test are estimated. In this study hybrid representation HSG together with SMILES was used. The "classic" scheme (i.e. split data into the training set and test set) of building up quantitative structure-activity relationships was employed. Computational experiments indicated that this approach can satisfactorily predict the desired endpoint. Best model had following statistical characteristics n=32, r2= 0.6012, s= 0.279, F= 45 for training and n=10, r2= 0.9301, s= 0.076, Rm2=0.9206 for test set.

Antioxidant properties of selected 4-phenyl hydroxycoumarins: Integrated in vitro and computational studies.

A study on the structure-activity relationship of three hydroxy 4-phenyl coumarins, carried out by employing a series of different chemical cell-free tests is presented. Different assays involving one redox reaction with the oxidant (DPPH, ABTS, FRAP and CUPRAC) were employed. Further, the measurement of inhibition of oxidative degradation, such as lipid peroxidation, was used to define compound antioxidant activity. Our results confirm the good antioxidant activity of the 7,8-dihydroxy-4-phenyl coumarin and moderate antioxidant activity of 5,7-dihydroxy-4-phenyl coumarin. In this work, quantum chemical calculations based on density functional theory have been employed at B3LYP/6-311++G(d,p) level of theory to study the influence of number and position of hydroxyl groups in coumarin molecules on antioxidant activity. Calculated values for HOMO and LUMO energies, energy gap, stabilization energies and spin density distribution confirmed experimental results and were used for SAR definition. For determination of reaction mechanism in gas phase and selected solvents bond dissociation enthalpy, adiabatic ionization potential, proton dissociation enthalpy, proton affinity, electron transfer enthalpy and gas phase acidity have been calculated. Hydrogen Atom Transfer mechanism in vacuum and Single-Electron Transfer followed by the Proton Transfer mechanism in other studied systems are most probable free radical scavenging pathways. On the basis of these findings, these hydroxy 4-phenyl coumarins may be considered as potential therapeutic candidates for pathological conditions characterized by free radical overproduction.

Bradbury-Eggleston syndrome - an unusual cause of gastroesophageal reflux disease (GERD).

The report presents a case of a 46-year-old male patient, previously treated because of dysphagia, pyrosis, vertigo while standing up and impotency. Manometric and pH-metric analysis showed presence of gastroesophageal reflux disease (GERD) caused by transient relaxation of lower esophageal sphincter (TRLES). Heart-rate variability showed decreased sympathetic function. Electromyoneurography showed a neurological lesion in muscles of upper extremities. The patient received midodrine and clonazepam which resolved this condition. These findings suggest that a neurological disorder can be a cause of GERD.

QSAR models for the reactivation of sarin inhibited acetylcholinesterase by quaternary pyridinium oximes based on Monte Carlo method.

Monte Carlo method has been used as a computational tool for building QSAR models for the reactivation of sarin inhibited acetylcholinesterase (AChE) by quaternary pyridinium oximes. Simplified molecular input line entry system (SMILES) together with hydrogen-suppressed graph (HSG) was used to represent molecular structure. Total number of considered oximes was 46 and activity was defined as logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M. One-variable models have been calculated with CORAL software for one data split into training, calibration and test set. Computational experiments indicated that this approach can satisfactorily predict the desired endpoint. Best QSAR model had the following statistical parameters: for training set r2=0.7096, s=0.177, MAE=0.148; calibration set: r2=0.6759, s=0.330, MAE=0.271 and test set: r2=0.8620, s=0.182, MAE=0.150. Structural indicators (SMILES based molecular fragments) for the increase and the decrease of the stated activity are defined. Using defined structural alerts computer aided design of new oxime derivatives with desired activity is presented.