Atrial fibrillation is the most commonly experienced type of cardiac arrhythmia and is the most associated with substantial clinical occurrences and expenses. This arrhythmia often occurs in its "silent" asymptomatic form, revealed only after complications such as a stroke or congestive heart failure have transpired. New smart devices confer effective advantages in the detection of this heart arrhythmia, of which photoplethysmography-based smart devices have shown great potential, according to previous research. However, the solution becomes a problem as widespread use and high availability of various applications and smart devices may lead to substantial amounts of false and misleading recordings and information, causing unnecessary anxiety regarding arrhythmic occurrences diagnosed by the devices but not professionally confirmed. Thus, with most of the devices being photoplethysmography based for detection of atrial fibrillation, it is important to research devices studied up to this point to find the best smart device to detect the aforementioned arrhythmias.

In the present review, we briefly discuss the breakthrough advances in precision medicine using a tumor-agnostic approach and focus on BRAF treatment modalities, the mechanisms of resistance and the diagnostic approach in cancers with BRAF mutations. Tumor-type agnostic drug therapies work across cancer types and present a significant novel shift in precision cancer medicine. They are the consequence of carefully designed clinical trials that showed the value of tumor biomarkers, not just in diagnosis but in therapy guidance. Six tumor-agnostic drugs (with seven indications) have been approved through October 2022 by FDA. The first tumor-agnostic treatment modality was pembrolizumab for MSI-H/dMMR solid tumors, approved in 2017. This was followed by approvals of larotrectinib and entrectinib for cancers with NTRK fusions without a known acquired resistance mutation. In 2020, pembrolizumab was approved for all TMB-high solid cancers, while a PD-L1 inhibitor dostarlimab-gxly was approved for dMMR solid cancers in 2021. A combination of BRAF/MEK inhibitors (dabrafenib/trametinib) was approved as a tumor-agnostic therapy in June 2022 for all histologic types of solid metastatic cancers harboring BRAFV600E mutations. In September 2022, RET inhibitor selpercatinib was approved for solid cancers with RET gene fusions. Conclusion. Precision cancer medicine has substantially improved cancer diagnostics and treatment. Tissue type-agnostic drug therapies present a novel shift in precision cancer medicine. This approach rapidly expands to provide treatments for patients with different cancers harboring the same molecular alteration.

Background: Zearalenone is a widely spread mycotoxin, contaminant of most cereal grains. It has uterotropic, estrogenic and anabolic activity in farm animals. The results are hormonal disbalances as hyperestrogenism, Zearalenone inhibits follicle-stimulating hormone production, thus supressing ovarian follicle development and ovulation. Also, it induces oxidative stress. Melatonin acts as a potent natural antioxidant and regulates the reproductive function by modification of steroidogenesis. Objective: The present study was conducted to provide detailed qualitative histological analysis of uterus of female rats treated with zearalenone and melatonin and contribute to better understanding of the topic. Methods: Forty adult, female Wistar rats were equally divided into five groups: Z group – zearalenone, 0,3 mg/kg, i.g.; M group – melatonin, 10 mg/kg, i.p.; ZM group –concomitant application of zearalenone and melatonin in the same dosing regimen, VZ group–zearalenone vehiculum/sunflower oil, i.g. and MZ group–melatonin vehiculum/5% ethanol in Ringer, i.p. Animals were treated daily for 28 consecutive days. After that period, all animals were sacrificed to obtain samples for qualitative histological analysis using the light microscope. Results: Zearalenone led to the alterations of the uterine structures, predominantly in the endometrium that were characterized by metaplasia and hypertrophy of the epithelial cells and hypercellularity of the stroma. In the myometrium, zearalenone induced hypertrophy and hyperplasia of the myocytes. Conclusion: Melatonin, when applied together with zearalenone, blocked the adverse effects of the zearalenone.

Objective. The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. Patients and Methods. The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥140/90 mmHg at baseline. On the basis of the investigator’s decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). Results. The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. Conclusion. A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

Background: In the academic world, the debate continues on the subject of how far a lack of vitamin D can affect the healing of various wounds. Objective: To determine if basal serum levels of vitamin D significantly influence clinical parameters linked to post-extraction wound healing after surgical removal of impacted/semi-impacted third molars. Methods: A total of 23 patients were included in this study. Clinical outcome parameters were: edema, trismus, pain, soft tissue healing, and dry socket signs. The research was divided into four stages. Results: Due to the high prevalence of hypovitaminosis D (91%), patients were classified into an insufficient (≥ 20 ng/ml) or a deficient group (<20 ng/ml). The results showed no statistically significant differences in pain, edema, trismus, or soft tissue healing between those two groups. A slight statistical interaction was observed in the clinical parameters related to edema and trismus assessment, but not statistically significant. We did not notice signs of “dry socket” on any of the patients. Conclusion: Within its limitations (low number of patients, high prevalence of vitamin D deficiency), this pilot study failed to find a significant influence of serum vitamin D concentrations in wound healing or post-surgery symptom (pain, edema, trismus) development after third molar extraction. Further clinical investigations are necessary to elaborate on this function of vitamin D more precisely.

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Objectives Oral health in children is additionally burdened with the presence of dental fear and anxiety (DFA). These clinical psychologic entities in their progressive stages inevitably lead to avoidance of dental appointments, which makes prevention and therapy of oral diseases more difficult. Upon the onset of DFA in general, as one of the emotional outcomes of stress in a dental office, most children patients could define the specific stressors that were most intense for them, which could predict the presence of DFA. Aim To examine the predictors of DFA presence in 9-12-year-old children, and investigate how they could explain the DFA occurrence in study participants. Material and Methods The sample consisted of 200 children aged from 9 to 12 years. The DFA presence was determined by the modified version of the CFSS-DS scale. The child's behavior in the dental office during the treatment was evaluated by the trained observer using Venham anxiety and behavior rating scales. Socioeconomic status, characteristics of dental office visits, and previous caries experience were also analyzed. Results The main DFA predictors were related to invasive dental treatments, where the behavior during dental treatment was the most accurate expression of the DFA appearance. Conclusions Invasive dental procedures are the main stressful factor for DFA occurrence. Predisposing factors could strengthen the DFA occurrence.

ABSTRACT Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.

Objective. The aim of this study was to carry out the cultural adaptation and validation of the Assessment of Chronic Illness Care questionnaire (ACIC) in the Republika Srpska, Bosnia and Herzegovina. Methods. A validation study was conducted in two randomly selected primary health care centers in the Republika Srpska, Bosnia and Herzegovina, during March and April 2016. The study participants were all physicians working in family medicine departments during the study. Translation of the ACIC questionnaire version 3.5 was performed following the guidelines of the World Health Organization. The validity and reliability of the questionnaire were tested with face validity, construct validity, and internal consistency. Results. The questionnaire was distributed to 66 family physicians. Missing values were negligible, therefore the criteria for factor analysis were met. Exploratory factor analysis confirmed that the questionnaire measured one factor. The Cronbach alpha coefficient (0.970) showed the excellent level of internal consistency of the questionnaire. The intraclass correlation coefficient (0.802) confirmed the good reliability of the questionnaire. Conclusion. The ACIC questionnaire can be used to assess the quality of chronic care in family medicine practice in Bosnia and Herzegovina. Further research is needed to explore how changes in healthcare care delivery impact changes in the Chronic Care Model domain.

Introduction Menopause is the last physiological menstrual period and is a complex process involving the following: endocrine, genitourinary, cardiovascular, and locomotor system, and it leads to vasomotor symptoms and psychological complaints. This study aims to investigate the influence of smoking and body mass index (BMI) as risk factors on the age of onset of menopause in women in Bosnia and Herzegovina. Material and methods This study included 460 women in natural menopause. The study was conducted in 2 phases: interview and measurement of BMI. Each patient underwent an interview based on the questionnaire, following the verbal consent of the patient, who had previously been explained the nature of the research. Results The age at which menopause occurs increases with the BMI increase, and it can be described by the regression equation: age = 0.096 × BMI + 45.7, which has statistical significance. The mean age of menopause occurrence in current smokers was lower (47.5 ±0.4 years) than in non-smokers (48.8 ±0.2 years) (p = 0.010). Conclusions Our study confirmed the statistically significant correlation between smoking, BMI, and age of onset of menopause.

Currently, blockchain is one of the most innovative emerging digital technologies. As such, it can undermine traditional business models and revolutionize tax administration. This objective of this article is to present the potential of blockchain technology in the administration of specific tax categories such as payroll taxes, value added tax, international taxes, and customs. It also analyses blockchain technology’s strengths, weaknesses, opportunities, and threats (SWOT) with a focus on tax administration. As a generator of a substantial amount of information, tax administration requires reliable and efficient technology for processing and storing the information that is generated. The results of the analysis showed strengths such as a lower cost of fulfilling tax liabilities, a direct connection with taxpayers without the need of third parties. a higher degree of efficiency, and threats such as insufficient funds for modernization, knowledge and skills of employees, and willingness to adapt and high investment costs related to implementation. Moreover, it will modernize accounting and tax payments. Blockchain technology, digitalization, tax administration, SWOT analysis, digital economy, digital services, tax policy

This retrospective cohort study aimed to analyze the clinical manifestations, complications, and maternal-fetal outcomes in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during delivery. The cohort included 61 pregnant women positive for SARS-CoV-2 infection at the time of delivery. Patients were divided into two groups: symptomatic and asymptomatic. We found a significantly higher rate of leukocytosis (p < 0.00078) and lymphopenia (p < 0.0024) in symptomatic women compared with asymptomatic ones. Other laboratory parameters, such as CRP (p = 0.002), AST (p = 0.007), LDH (p = 0.0142), ferritin (p = 0.0036), and D-dimer (p = 0.00124), were also significantly more often increased in the group of symptomatic pregnant women. Overall, symptomatic pregnant women with SARS-CoV-2 infection at the delivery show more often altered laboratory parameters compared with asymptomatic ones; nevertheless, they have a slightly higher but non-significant rate of preterm delivery, cesarean section, as well as lower neonatal birth weight and Apgar score, compared with asymptomatic women.

Introduction The optimal management of distal ureteral stones remains a matter of debate since current guidelines favor ureteroscopy over extracorporeal shock wave lithotripsy (ESWL). We aimed to evaluate the efficiency of ESWL for distal ureteral stones and to identify factors that affect treatment outcomes. Materials and methods The retrospective study included records of 115 patients with distal ureteral stones, 5 mm to 18 mm in size, undergoing 223 ESWL sessions as an outpatient procedure. Early fragmentation and three-month follow-up stone-free rate (SFR) was assessed through radiographic imaging. Treatment was successful if there were no residual fragments or they were ≤4 mm, three months after the last session. Results The mean ±standard deviation (range) stone size was 9.68 ±3.10 (5.00-18.0) mm. The mean body mass index (BMI) was 24.3 ±2.67 (18.4-29.8) kg/m² with a significant correlation between BMI and stone size (r2 =0.324, p <0.001). Patients underwent ESWL an average of 1.7 ±1.36 times (1-5), while 68 patients (59.1%) became stone-free after one session. The overall SFR was 82.6%; for patients with stone sizes ≤10 mm and >10 mm, it was 99% and 9.4%, respectively. Cumulative SFR after the second session was 77%. In 20 (17%) patients the treatment was a failure. Complications occurred in 10.4%, while auxiliary procedures were needed in 8.7% of cases, both significantly affected by the stone size (p <0.001). The efficiency quotient (EQ) was 0.76. Treatment outcome was significantly different depending on stone size, BMI, number of sessions, complications, and auxiliary procedures (p <0.001, p =0.022, p <0.001, p <0.001, p <0.001, respectively). Univariate regression analysis identified stone size and BMI as significant predictors of treatment outcome (odds ratio (OR) 3.84, 95% confidence interval (CI): 2.31-8.97, p =0.001, and OR 1.25, 95% CI: 1.04-1.54, p =0.024, respectively). Conclusions Extracorporeal shock wave lithotripsy continues to be a safe and effective option for managing simple calculi in distal ureters with a diameter of ≤10 mm. The stone size and BMI remain significant predictors of treatment outcome.