Background/Aim: In addition to well-established central effects, benzodiazepines, but also some other allosteric modulators of gamma-amino-butyric acid (GABA) receptor exhibit significant vascular effects. However, there are currently no elucidated mechanisms for manifested vasodilatory properties and very little is known about GABA gamma-amino-butyric acid function and GABAA receptor expression within peripheral blood vessels. Methods: In the present study, we demonstrated the vasorelaxant properties of diazepam, GABA and novel imidazobenzodiazepine amide ligands GL-II-73 and GLII-74, which are characterized as positive allosteric modulators of α5containing GABAA receptor. Using isometric organ bath system, we examined the vascular responses to phenylephrine, in the presence and absence of various ligands, in the rat thoracic aorta. Results: The observed significant and strong attenuation of the maximal contractile response of phenylephrine indicates a non-competitive antagonism of diazepam, GL-II-73 and GL-II-74 (p < 0.001), whereas GABA does not affect phenylephrine contraction. Since the strongest inhibitory effect was observed with compound GL-II-74, that, compared to other tested ligands, exhibited a higher potentiation at α5 GABAARs, it could be assumed that the α5 subunit plays a significant role in the structure of putatively present “vascular” GABAARs. Conclusion: This work emphasizes the importance of GABAARs research in the periphery and also points to the possibility of using α5 selective GABAAR modulators as potential therapeutic targets for novel vasodilators.

Primary Healthcare Centre Modriča, Modriča, the Republic of Srpska, Bosnia and Herzegovina; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, the Republic of Srpska, Bosnia and Herzegovina. Emergency Department, Primary Healthcare Centre Banja Luka, the Republic of Srpska, Bosnia and Herzegovina. Department of Emergency Medicine, Faculty of Medicine, University of Banja Luka, Banja Luka, the Republic of Srpska, Bosnia and Herzegovina.

Introduction: Acute coronary syndrome (ACS) is one of the m ost common and most dramatic manifestations of ischaemic h eart disease and distinguishing of ACS from non-cardiac chest pain represents a diagnostic challenge. Objective: Determine the frequency of ACS types: NSTEMI, STEMI and unstable angina pectoris (UAP) and examine the frequency and significance of risk factors and cardiospecific enzymes in patients with ACS. Methods: The analysis included patients who were referred from the prehospital level of the Banja Luka Primary Healthcare Centre (Emergency Department and Family Medicine Department) and treated under the ACS diagnosis in the coronary unit of the Cardiovascular Diseases Clinic of the Banja Luka University Clinical Centre of the Republic of Srpska (UCCRS) in the first 6 months of 2011. The study included patients older than 18, with recorded information on their gender, age, smoking status, hypertension, diabetes, obesity and family burden. Values of cholesterol, triglycerides, serum potassium, creatine kinase (CK), CK-MB, cardiac tro - ponin T (cTnT) were measured. Results: The total of 192 patients were referred under the referral diagnosis of ACS and treated in the coronary unit of the CVD Clinic of the Banja Luka UCCRS. At the same time, ACS was confirmed in 178 cases. STEMI was confirmed in 86 patients (48.31 %), NSTEMI in 55 (30.90 %) and UAP in 37 (20.79 %). ACS was statistically significantly more common in men (112 men and 66 women), in particular younger men (average age for men was 62.7 and 69.2 for men and women, respectively) (U = 2.472 x 103, p NSTEMI > UAP. Conclusion: Half of patients with ACS did not have STEMI (which is presumably easy to diagnose). Third of patients with ACS reported atypical symptoms, which further complicates the early recognition of MI without ST elevation. Precaution is needed in women and in elderly. Determination of cTnT should be available in every examination room.

The Joint Programming Initiative was originally created as a Member States-led initiative in Europe. It aims to address “grand challenges” to the EU and global society by coordinating national research pro-grammes to increase the impact and effectiveness of research efforts. Neurodegenerative diseases (ND) and dementia in particular, represent one of the world’s most pressing medical and societal challenges and the solutions are likely beyond the scope and resources of any single country. JPND aims to find causes, develop cures and identify better ways of caring for people with neurodegenerative diseases. Although JPND originally a European initiative, it global, 30 countries JPND medicine life each longer life expectancy without is our brain health: neurodegenerative dementia one third of the aging populations 85 years of age, mental health disorders including addictions 12% entire and neurodevelopmental disorders 15% European global mea-surements We analyzed changes in dendritic morphology and spine density on associative layer IIIc cortical projecting neurons and large layer V subcortical projecting pyramidal neurons to establish age-related changes within microcircuitries of the human prefrontal cortex (Brodmann area 9). Postmortem human brain tissue of adults was processed using the rapid Golgi method in two age groups: 38 – 64 years (n = 8) and 72 – 91 years, (n = 7). Neuropathological findings were unre-markable in all analyzed brain specimens. From each layer, the basal dendritic arbor and side dendritic branches from 10 – 15 well-impregnated pyramidal neurons per subject were three-dimensionally recon-structed using Neurolucida software. Soma size, total dendritic length, total segment number, individual segment length and spine density were quantitatively analyzed. Regarding layer V neurons, no significant differences were observed between adults and the elderly, either for dendritic morphology or for the spine density. The interindividual differences in the elderly group were however higher than in adults. Regarding associative layer IIIc pyramidal neurons, the mean values of spine density, on both side branches and basal dendrites, were 20–25% lower in the elderly than in adults (p = 0.07). In two aged cases the spine density was around mean level of adult and in the remaining aged subjects values were lower than in all adult subjects. These data show that the dendritic morphology and synaptic connectivity of the major classes of principal neurons in higher order associative areas are largely preserved in aging, while the connectivity of associative cortico-cortical layers is more prone to regression. is accumulating that in cardiometabolic diseases changes in glycosylation are not only biomarkers, but functional effectors that actively participate in disease is a kinase involved in DNA damage response (DDR), regulation of response to oxidative stress, autophagy and mitophagy. Mutations in the ATM gene in humans result in ataxia-telangiectasia disease (A-T) characterized by a variety of symptoms with neurodegeneration and premature ageing among them. In this study, we have focused on the process of senescence in A-T cells. Given that brain is one of the most affected organs in A-T, we turned our attention to neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts. We observed that A-T NPCs obtained through neural differentiation of iPSCs in 5% oxygen possessed some features of senescence including increased activity of SA-β-gal and secretion of IL6 and IL8 in comparison to control NPCs. This phenotype of A-T NPC was accompanied by elevated oxidative stress resulting in 4-HNE protein modification. A-T NPCs exhibited symptoms of impaired autophagy and mitophagy with lack of response to chloroquine treatment. Additional sources of oxidative stress like increased oxygen concentration and re-spectively aggravated the phenotype of senescence and the process of mitophagy. The by transcriptional analysis of several NPCs reacted to the treatment. We conclude that oxidative stress may be responsible for the phenotype of senescence and impairment of autophagy in A-T NPCs. Our results point to senescent A-T cells as a potential therapeutic target in this disease. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucle-inopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased pha-sic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signalling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early cau-date dysfunction. We will discuss the implication of utilising this window of the opportunity in the disease process to intervene, and to potentially abort, further development of neurodegenerative process. The changes in sleep-wake process over the lifespan are well established. Epidemiological data show that 50–65% of older adults report impaired sleep quality (SQ). This impairment can rather be attributed to health status and various psychosocial factors than to the aging process per se. The results of our previous study showed the expectedly impaired SQ in nursing home residents, best predicted by self-perceived health and functional ability. The aims of the current study were to examine SQ of older adults living in different arrangements and to examine factors contributing to their SQ. Participants were 334 older adults (73% fe-males) from Zagreb. Half were the NH residents and half OH residents. Their dominant age was 78 years, varying between 69 and 100 years. All were ambula-tory, without diagnosis of dementia. Trained inter-viewers collected data individually, through structured interviews in nursing homes and in gerontology center. Questionnaire comprised of general questions, questions to assess self-perceived health and standardized scales to measure social participation, functional ability, life satisfaction, and SQ. SQ was assessed by the Pittsburgh Sleep Quality Index (PSQI). Our results showed PSQI score greater than 5, indicating poor SQ in 60% of older adults. In NH residents the percentage was higher than in OH residents (71% vs. 50%, p < .001). Selected set of predictors explained small but significant proportion of variance in PSQI score and 7 domains. Predictors explained the highest proportion of variance in the use of sleep medication (22.6%) and subjective SQ (21%). Expectedly, women had poorer total PSQI, longer sleep PSQI, sleep functional predicted shorter sleep latency daytime functioning. There is a need to identify reliable predictors of mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD) in normal elderly people to en able timely intervention. The Mini‐Mental State Examination (MMSE) is the best‐known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research, and community settings. However, MMSE is not actually a mental status examination designed to detect dementia as it was originally developed to dif-ferentiate organic from functional psychiatric patients. The MMSE has low sensitivity in detecting dementia as as poor specificity, and low negative (NPV), and positive predictive values (PPV), in ear-ly-stage A recent systematic review not role hidden-goal task (HGT) in the human subject target navigational imaged positive cells counted for each Results correlated to lesion the composition of unknown substances on a molecular basis. Methods. The study included 80 age matched subjects from the Reference Center for Glaucoma, UHC “Sestre milosrdnice”, divided into two groups 1) 40 glaucoma patients and 2) a control group comprising 40 patients with cataracts. For the purpose of molecular analysis, all aqueous humor samples were collected at the start of the glaucoma or cataract surgery. FTIR spectra of the samples dried on transparent silicon windows were obtained in a transmission mode, followed by principal component analysis (PCA) modeling of the recorded spectra. Results. FTIR spectra with vibrational modes specific to glaucoma and cataract were examined. In the chemomet-ric analysis of the spectroscopic data, all 40 (100%) of the cataract eyes were correctly diagnosed as the cataract group and all 40 (100%) glaucoma eyes were diagnosed as the glaucoma group, demonstrating a distinct correlation between studied eye diseases and their FTIR spectra. conclusions. FTIR spectroscopy combined with the chemometrics has proven to be a promising method for molecular analysis of the aqueous humor as the differentiation between eyes with cataract and glaucoma has been achieved. Separation of the two groups of FTIR spectra in the created PCA statistical model also indicates that this method may have a promising role in the discovery of glaucoma biomarkers. possible and have piloted a project to collect DNA and phenotype data of ADR cases using international standardized phenotypic criteria. Patients with ADRs (N=860) and controls were genotyped for pharmacogenes. Univariate and multi-variate prediction of ADRs were carried by means of binary logistic regression in order to identify novel associations or validate findings in cohorts of patients with well-defined phenotypes. Results. We developed a comprehensive knowledge repository of actionable pharmacogenes. HALMED developed a method for informing physicians or pharmacists and their patients about a possible pharmacogenetic involvement in the ADR pathogenesis. An anonymized copy of the test results has been used for the interpretation of possible signals. Several publications from this project have been published, depending on the medication in question (warfarin, statins, clopidogrel, methotrexate, AEDs, psych

Introduction: Stress is currently ubiquitous in the modern world and dentists are very susceptible to stress. Objectives: The aim of this study was to evaluate subjective perception of stress in dentists, confirm known correlations between stress and various factors, such as gender, age, socioeconomic level, work seniority, and specialization. Material and methods: The research was conducted through an electronic survey, which was sent via email to 800 addresses of actively working dentists in the Republic of Croatia. The survey was completed by 432 respondents. Results: 91.9% of participants considered dentistry a stressful occupation, 46.1% of respondents believed that practicing dentistry may cause problems in mental health, 93% of participants thought that practicing dentistry can endanger their general health. Regarding working experience, the participants’ group with less than 10 years of experience identified fear of unsuccessful outcomes more frequently compared to their colleagues with more experience. Specialists perceived their health risks as lesser than expected. We found that 77.1% of participants were smokers. Conclusions: Chronic stress remains one of the principal factors contributing to the decline in overall health and mental health among dental professionals. No association was found between gender and stress, or stressor perceptions. In regard to working experience, we found that younger dentists with up to 10 years of experience presented with more fear from unsuccessful outcomes. It was also found that general dentists perceived health risks as greater in contrast to specialists. Male participants reported a much greater frequency of consumption of alcoholic beverages than female counterparts. Also, specialists reported consuming strong alcoholic beverages more than expected.

The aim of the work was to carry out a modal analysis of a multiple structure. Own forms of oscillation of the structure for five tones were obtained through the vector iteration process and were presented in table and graphic form. Using the different methods (Time history, SRSS and CQC), a calculation of the displacements was performed. Theoretically, all three methods are described and the results of the calculation for each of them are obtained. A comparison of the results, for the three methods in a given time interval, is graphically shown. Also, the results are compared which are all the same in all three methods. The modal seismic analysis of Spectral Theory was also performed. It can be concluded that by comparing the method of Time history and Spectral theory their results correspond to the maximum modal displacement.

Background/Aim: Pulmonary embolism (PE) is a diagnostic challenge, particularly in prehospital care. The aim of this study was to determine to what extent the evaluation of D-dimer value helps physicians with differentiation of PE and whether D-dimer values are in correlation with the values of revised Geneva score. Methods: Data have been collected for the patients whose D-dimer has been evaluated at the Emergency Care Department of the City of Banja Luka in 2018. Gender, age, symptoms, working diagnosis and D-dimer value have all been recorded and also the fact whether the patient was referred to hospital treatment or not. For each patient the revised Geneva score was determined. Results: Sixty-eight tests were done in 2018. Out of 68 tests, 41 were negative (60.3 %). D-dimer results helped in making decisions about referring patients to the hospital or not (ch2 = 36.32, p < 0.001). Patients with elevated D-dimer levels, especially where the values were four times higher than the reference ones typically were referred to hospital treatment, whereas 67.5% patients with negative D-dimer results were sent home after giving a treatment and advice. In the elderly patients D-dimer was statistically more positive (F = 10.82, p < 0.001). Values of D-dimer were not significantly different regarding gender (ch2 = 2.19, p = 0.33). According to the results of the revised Geneva score, 5.1 % of patients had high risk of PTE, while moderate and low risk had 47.5 % each. Although it has been found that the values of D-dimer were slightly more elevated at higher values of the revised Geneva score and that the difference was not statistically significant (ch2 = 7.71, p = 0.10). Conclusion: Values of D-dimer considerably helped in differentiation of PE in the Emergency Care Department. D-dimer has a high negative predictive value and should be used to exclude PE diagnosis for patients with low clinical probability of PE.

In diagnosing COVID-19, false negative findings from the biological sample taken from a mucosal swab of the upper respiratory tract and tested with the real-time reverse-transcription polymerase chain reaction (RT-PCR) technique have been reported. This patient has had a proven contact with an infected person, clear symptoms of viral respiratory disease, yet negative test results on the fifth day of self-isolation. On repeated test after 48 hours, on the 7th day of isolation, due to persistence of some symptoms, he tested positive for SARS-CoV-2. The existence of symptoms and characteristic sings after laboratory and radiological analysis of the patient prompted the repetition of the tests, which at the end led to the confirmed diagnosis and the possibility for adequate treatment of the patient as well.

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This article should be cited as follows: Igić R. Pharmacologist's view of the new corona virus. Scr Med 2020;51(1):6-8. Despite many advances in the prevention and treatment of infectious diseases, the global spread of infections is accelerated by close contact among concentrated populations. A pandemic caused by a new type of coronavirus (SARS-CoV-2) continues to spread across the globe. This new disease attributed to COVID-19 emerged a century after the Spanish flu pandemic, which affected one-third of the world's population, killing more than 50 million people.1 The disease, caused by the H1N1 virus, has been around for less than two years and it is still unclear what contributed to its termination; possibly a mutation of the virus reduced its viral strength. Since information about biological sciences and human medicine is far more advanced today than at the beginning of the 20th century, it is expected that the current pandemic will be contained, regardless of the potential for viral mutation. Scientists and doctors now face an urgent task how to treat numerous sick people and stop the spread of this infection. The pandemic urgently requires identification of preventive measures, along with optimum means of diagnosis and treatment and data on dissemination of the infection, duration of incubation, clinical features of the disease, along with the best means of diagnosis and treatment for a very large number of people, and ultimately the long lasting consequences of the disease. In addition, we must identify pathways for the spread of the virus, its persistence on various surfaces and means of its inactivation.2

In general, polynomial difference equations and polynomial maps in the plane have been studied in both the real and complex domains (see [8, 9]). First results on quadratic polynomial difference equation have been obtained in [1, 2] but these results gave us only a part of the basins of attraction of equilibrium points and period-two solutions. In [4], the general second order difference equation is completely investigated and described the regions of initial conditions in the first quadrant for which all solutions tend to equilibrium points, period-two solutions, or the point at infinity, except for the case of infinitely many period-two solutions. In [3], case of infinitely many period-two solutions is completely investigated. Our results are based on the theorems which hold for monotone difference equations. Our principal tool is the theory of monotone maps, and in particular cooperative maps, which guarantee the existence and uniqueness of the stable and unstable invariant manifolds for the fixed points and periodic points (see [5]). Consider the difference equation