CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology.

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state.

Broccoli, Amaranth, and Red Beet Microgreen Juices: The Influence of Cold-Pressing on the Phytochemical Composition and the Antioxidant and Sensory Properties.

The aim of this study was to analyze in detail the phytochemical composition of amaranth (AMJ), red beet (RBJ), and broccoli (BCJ) microgreens and cold-pressed juices and to evaluate the antioxidant and sensory properties of the juices. The results showed the presence of various phenolic compounds in all samples, namely betalains in amaranth and red beet microgreens, while glucosinolates were only detected in broccoli microgreens. Phenolic acids and derivatives dominated in amaranth and broccoli microgreens, while apigenin C-glycosides were most abundant in red beet microgreens. Cold-pressing of microgreens into juice significantly altered the profiles of bioactive compounds. Various isothiocyanates were detected in BCJ, while more phenolic acid aglycones and their derivatives with organic acids (quinic acid and malic acid) were identified in all juices. Microgreen juices exhibited good antioxidant properties, especially ABTS•+ scavenging activity and ferric reducing antioxidant power. Microgreen juices had mild acidity, low sugar content, and good sensory acceptability and quality with the typical flavors of the respective microgreen species. Cold-pressed microgreen juices from AMJ, RBJ, and BCJ represent a rich source of bioactive compounds and can be characterized as novel functional products.

Current rates of purchasing of antibiotics without a prescription across sub-Saharan Africa; rationale and potential programmes to reduce inappropriate dispensing and resistance.

INTRODUCTION: Antimicrobial resistance (AMR) is a global concern. Currently, the greatest mortality due to AMR is in Africa. A key driver continues to be high levels of dispensing of antibiotics without a prescription. AREAS COVERED: A need to document current rates of dispensing, their rationale and potential ways forward including antimicrobial stewardship programmes (ASPs). A narrative review was undertaken. The highest rates of antibiotic purchasing were in Eritrea (up to 89.2% of antibiotics dispensed), Ethiopia (up to 87.9%), Nigeria (up to 86.5%), Tanzania (up to 92.3%) and Zambia (up to 100% of pharmacies dispensing antibiotics without a prescription). However, considerable variation was seen with no dispensing in a minority of countries and situations. Key drivers of self-purchasing included high co-payment levels for physician consultations and antibiotic costs, travel costs, convenience of pharmacies, patient requests, limited knowledge of antibiotics and AMR and weak enforcement. ASPs have been introduced in some African countries along with quality targets to reduce inappropriate dispensing, centering on educating pharmacists and patients. EXPERT OPINION: ASP activities need accelerating among community pharmacies alongside quality targets, with greater monitoring of pharmacists' activities to reduce inappropriate dispensing. Such activities, alongside educating patients and healthcare professionals, should enhance appropriate dispensing of antibiotics and reduce AMR.

Eleven-Year Trends in Lipid-Modifying Medicines Utilisation and Expenditure in a Low-Income Country: A Study from the Republic of Srpska, Bosnia and Herzegovina.

Background: In last two decades, there have been substantial changes in the pattern of lipid-modifying medicines utilisation following the new treatment guidelines based on clinical trials. The main purpose of this study was to analyse the overall utilisation and expenditure of lipid-modifying medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-year follow-up period and to express its share in relation to the total cardiovascular medicines (C group) utilisation. Methods: In this retrospective, observational study, medicines utilisation data were analysed between 2010 and 2020 period using the ATC/DDD methodology and expressed as the number of DDD/1000 inhabitants/day (DDD/TID). The medicines expenditure analysis was used to estimate the annual expenditure of medicines in Euro based on DDD. Results: During the analysed period, the use of lipid-modifying medicines increased almost 3-times (12.82 DDD/TID in 2010 vs 34.32 DDD/TID in 2020), with a rise in expenditure from 1.24 million Euro to 2.15 million Euro in the same period. This was mainly driven by an increased use of statins with 163.07%, and among these, rosuvastatin increased more than 1500-fold, and atorvastatin with 106.95% increase. With the appearance of generics, simvastatin showed a constant decline, while the other lipid-modifying medicines in relation to the total utilisation had a neglecting increase. Conclusion: The use of lipid-modifying medicines in the Republic of Srpska has constantly increased and strongly corresponded to the adopted treatment guidelines and the positive medicines list of health insurance fund. The results and trends are comparable with other countries, but still the utilisation of lipid-lowering medicines represents the smallest share of total medicines use for the treatment of cardiovascular diseases, compared to high-income countries.

Food nanoemulsions: how simulated gastrointestinal digestion models, nanoemulsion, and food matrix properties affect bioaccessibility of encapsulated bioactive compounds.

Food nanoemulsions are known as very effective and excellent carriers for both lipophilic and hydrophilic bioactive compounds (BCs) and have been successfully used for controlled delivery and protection of BCs during gastrointestinal digestion (GID). However, due to sensitive and fragile morphology, BCs-loaded nanoemulsions have different digestion pathways depending on their properties, food matrix properties, and applied models for testing their digestibility and BCs bioaccessibility. Thus, this review gives a critical review of the behavior of encapsulated BCs into food nanoemulsions during each phase of GID in different static and dynamic in vitro digestion models, as well as of the influence of nanoemulsion and food matrix properties on BCs bioaccessibility. In the last section, the toxicity and safety of BCs-loaded nanoemulsions evaluated on in vitro and in vivo GID models have also been discussed. Better knowledge of food nanoemulsions' behavior in different models of simulated GI conditions and within different nanoemulsion and food matrix types can help to standardize the protocol for their testing aiming for researchers to compare results and design BCs-loaded nanoemulsions with better performance and higher targeted BCs bioaccessibility.

Food nanoemulsions are effective and excellent carriers for bioactive compounds (BCs).Nanoemulsions are often subject to morphological and structural changes during digestion.BC-s loaded nanoemulsions have different digestion pathways in different digestion models.BC-s have different bioaccessibility in different nanoemulsion models.Food matrix can affect the bioaccessibility of BCs entrapped in nanoemulsions.

Antibiotic Utilization during COVID-19: Are We Over-Prescribing?

The aims of this study were to analyze the utilization of antibiotics before (2018, 2019) and during the COVID-19 pandemic (2020) and the practice of prescribing antibiotics in outpatient settings for COVID-19 patients during the 2020-2022 period. The Anatomical Therapeutic Chemical Classification/Defined Daily Dose methodology was used for the analysis of outpatient antibiotic utilization in the Republic of Srpska. The data was expressed in DDD/1000 inhabitants/day. The rate of antibiotics prescribed to COVID-19 outpatients was analyzed using medical record data from 16,565 patients registered with B34.2, U07.1, and U07.2 World Health Organization International Classification of Diseases 10th revision codes. During 2020, outpatient antibiotic utilization increased by 53.80% compared to 2019. At least one antibiotic was prescribed for 91.04%, 83.05%, and 73.52% of COVID-19 outpatients during 2020, 2021, and the first half of 2022, respectively. On a monthly basis, at least one antibiotic was prescribed for more than 55% of COVID-19 outpatients. The three most commonly prescribed antibiotics were azithromycin, amoxicillin/clavulanic acid, and doxycycline. The trend of repurposing antibiotics for COVID-19 and other diseases treatment might be a double-edged sword. The long-term effect of this practice might be an increase in antimicrobial resistance and a loss of antibiotic effectiveness.

Characteristics and Patterns of Proton Pump Inhibitors Prescribing at the Primary Health Care.

Background and objectives: the aim of this study was to analyse the utilisation of proton pump inhibitors (PPIs) during a 12-year period and to show the characteristics and patterns of their prescribing. Materials and methods: firstly, in the pharmacoepidemiological analyses the ATC/DDD methodology was used to assess the utilisation of PPIs in the Republic of Srpska. The annual PPI utilisation was expressed as a number of DDD/1000 inhabitants/year. Secondly, the cross-sectional surveys were used to reveal the characteristics of PPIs prescribing and medicines use, namely the dose, duration and indication, and possible adverse reactions. For the purposes of the surveys, the adapted version of questionnaires related to physicians' and patients' perspectives of medicines prescribing and use were performed. Results: the utilisation of medicines for alimentary tract and metabolism (group A/ATC classification) increased by almost threefold in a 12-year period, which was consistent with the total medicine utilisation. Pantoprazole was the most prescribed medicine among the PPIs. With the exclusion of PPIs in the therapy of Helicobacter pylori eradication, more than half of family physicians prescribed PPIs with antibiotics, and only 53/239 physicians, noticed some adverse reactions of PPIs in their patients. Most of the patients knew how to use PPIs and were taking these medicines in recommended daily doses, but approximately 45% of them were using PPIs for a long period of time (>6 months). Conclusions: the overuse of PPIs is a major concern due to potential serious adverse reactions, especially in elderly patients and in a case of prolonged exposure.

Trends in Antihypertensive Medicine Utilization in the Republic of Srpska, Bosnia and Herzegovina: An Eleven-Year Follow-Up.

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines. Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009-2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing. Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times. Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

Prevalence of Cigarette Smoking and Influence of Associated Factors among Students of the University of Banja Luka: A Cross-Sectional Study.

Background and Objectives: Cigarette smoking among the youth population has increased significantly in developing countries, including Bosnia and Herzegovina. However, no extant literature assesses the prevalence of tobacco use, nor identifies factors associated with smoking. This study determined the prevalence of cigarette smoking among a specific cohort of students and assessed factors related to tobacco use in this population. Materials and Methods: This cross-sectional study included 1200 students at all faculties of Banja Luka University. Data were collected from questionnaires adapted from the Global Youth Tobacco Survey (GYTS) and the Global Health Professional Student Survey (GHPSS) standardized questionnaires and were analyzed using descriptive statistics, Pearson's χ2 test, and logistic regression. Results: When the prevalence of cigarette smoking within the last thirty days was recorded, we found that 34.1% of students smoked within this period. Nearly three-quarters (74.9%) of the student population had smoked or experimented with cigarette smoking. However, medical students were 27.2% less likely to smoke than their counterparts from other faculties. Overall, 87% of all students were aware of the harmful effects of cigarette smoking, 79% were aware of the harmful effects of secondhand smoke, and 65% reported that it was difficult to quit. Increased spending of personal money was associated with a higher probability of smoking, while exposure to secondhand smoke increased the odds of smoking by 62%. Conclusion: Policies, strategies, and action plans should be introduced in order to reduce the prevalence of smoking among university students and to create a smoke-free environment at the various universities involved.

Pharmacists' clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications.

BACKGROUND: Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. PURPOSE OF THE STUDY: To assess pharmacists' clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists' self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. METHODS: A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman's correlation was used to assess the correlation between variables. RESULTS: Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists' real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. CONCLUSION: Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists' capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.

Predictors and Motivation of Preceptors' Interest in Precepting of Pharmacy Interns-Do We Have a Useful Questionnaire?

PURPOSE: To determine the potential value of an adapted questionnaire to discover the predictors of preceptors' higher interest in precepting pharmacy interns and to evaluate preceptors' motivational factors and incentives for teaching as well as their professional satisfaction. METHOD: A link to the survey study of adapted questionnaire (JSAMPPP) was e-mailed to all pharmacists registered with the Pharmaceutical Chamber of the Republic of Srpska. Pharmacists' demographic and work experience characteristics, their attitudes related to motivation for precepting, value of incentives for precepting, job satisfaction, and influence of interns on pharmacists' professional practice were obtained. RESULTS: Half of the preceptors who reported feeling satisfied with their professional life also showed interest in teaching. In addition, teaching pharmacy students positively contributed to the overall job satisfaction of the preceptors. Pharmacy preceptors were found to be most motivated by intrinsic factors. The most valued incentives reported were those related to continuing education. CONCLUSIONS: The adapted questionnaire has potential value and it revealed the following predictors of preceptors' higher interest in precepting: enjoyment of teaching, satisfaction with professional life, satisfaction as a pharmacy preceptor, and interns' influence on preceptors. These identified predictors can be emphasized to improve pharmacy students' internship experiences, thereby reinforcing the pharmacy profession.

The Role of Emerging and Neglected Viruses in the Etiology of Hepatitis.

PURPOSE OF REVIEW: In this review, we present the overview of emerging and neglected viruses associated with liver involvement. RECENT FINDINGS: Hepatitis E virus (HEV) emerged in the last two decades, causing hepatitis in many parts of the world. Moreover, liver involvement was also described in some emerging arboviral infections. Many reports showed dengue-associated liver injury; however, chikungunya, West Nile, tick-borne encephalitis, and Zika virus are rarely associated with clinically manifest liver disease. In addition, some neglected highly prevalent viruses such as adenoviruses and parvovirus B19 are capable of causing hepatitis in specific population groups. Anelloviruses (torque teno virus/torque teno mini virus/torque teno midi virus, SEN virus), human bocavirus, pegiviruses, and lymphocytic choriomeningitis virus have shown a little potential for causing hepatitis, but their role in the etiology of liver disease remains to be determined. In addition to the well-known hepatotropic viruses, many emerging and neglected viruses have been associated with liver diseases. The number of emerging zoonotic viruses has been increasingly recognized. While zoonotic potential of HEV is well documented, the recent identification of new hepatitis-related animal viruses such as HEV strains from rabbits and camels, non-primate hepaciviruses in domestic dogs and horses, as well as equine and porcine pegivirus highlights the possible zoonotic transmission in the context of "One Health." However, zoonotic potential and hepatotropism of animal hepatitis viruses remain to be determined.

[Coarctation of the aorta in children in the 10-year epidemiological study: diagnostic and therapeutic consideration]. / Koarktacija aorte kod djece u 10-godisnjoj klinickoj epidemioloskoj studiji: dijagnosticko i terapijsko razmatranje.

Our study is a clinical epidemiological retrospective analysis of coarctation of the aorta in a 10-year follow-up (2001-2011). The study includes 201 children, 72 (35.82%) girls and 129 (64.18%) boys (1:1,6), with an average age of 28.57-49.37 mo (0.1-204 mo). They are categorized in 4 age groups: <1 month, 1 month - 1 year, 1 year - 6 years, >6 years. Isolated coarctation of the aorta was found in 125 (62.19%) patients; 33 (16.42%) preductal and 92 (45.77%) postductal. Coarctation of the aorta with an additional heart defect was found in 76 (37.81%) patients; 32 (15.32%) with ventricular septal defect, 28 (13.93%) within a complex heart defect, 11 (5.47%) within the Shone syndrome, and 5 (2.49%) with a dilated cardiomyopathy. Tiredness, intense tachypneic and dyspneic difficulties are dominant features in lower age groups (newborns and infants), while claudications, headaches and epistaxis are typical in older children. In the case of as many as 61 (30.35%) patients diagnosis was missed on the previous cardiological examination. In 20 (9.95%) patients coarctation is found within the known syndromes (Turner, Noonan, Williams Beuren, Ellis van Creveld, Down, partial trisomy 18, fetal valproate syndrome). Echocardiography was performed in all patients, and in 45 (22.38%) it was the only diagnos tic procedure. Altogether, 123 heart catheterizations, 38 multislice computed tomography and 15 magnetic resonance imagings were performed. The gradient on the place of coarctation before surgery or emergency procedures measured by catheter in 132 (65.67%) patients was 57.99 +/- 18.68 mmHg (20-100 mmHg). In 82 (40.80%) patients a bicuspid aortic valve was found. Average age at the time of surgery was 27.92 +/- 47.98 months (0.1-204 mo.). In 169 (84.07%) patients a cardiosurgical intervention was performed; 109 (54.23%) T-T anastomoses, 30 (14.29%) therapeutic catheterisations (balloon dilatation or stent implantation). Fatal outcome occurred in 4 (1.99%) children, all newborns or infants.