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Amela Bostandzic, V. Beslic, I. Šurković, Šefkija Balić, T. Dujić, Z. Ašimi, Azra Bureković

Background: IDegLira( fixed combination of GLP 1 receptor agonist and insulin) has been shown to be effective in improving the glucoregulation in patients previously treated with oral therapy as well as individual components, GLP-1 receptor agonist or basal insulin. Objective: The aim of this study is to examine the parameters of metabolic control in patients treated with IDegLira who were previously treated with premix insulin in several daily doses and to compare them with patients whose premix insulin dose was increased. Methods: The study included 100 patients who had been previously treated with two or three daily doses of premix insulin. Half of the patients were switched to IdegLira( group I), and half (group II) had their insulin dose increased according to the clinical assessment of the physician. Fasting glucose, 2h postprandial glucose, HbA1c, BMI and insulin dose were determined at baseline and at follow-up after 6 months. Results: Patients treated with IDegLira compared to patients whose insulin dose was increased achieved significantly lower fasting glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p <0.001), BMI (p <0.001) with a significantly lower insulin dose (p <0.001). Comparison of the same parameters within the groups of patients at the beginning and after 6 months showed that patients who were switched from insulin premix to IDegLira achieved significantly lower fasting blood glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p < 0.001), BMI (p <0.001) with significantly lower insulin dose within the fixed combination (p <0.001). Patients with gradually increased insulin dose achieved significant reduction in fasting glucose (p = 0.021) and postprandial glucose (p = 0.036),but with a significantly higher insulin dose (p = 0.005). There was also a slight increase in BMI that was not statistically significant (p = 0.267). Conclusion: The obtained data suggest that switching patients from a complex insulin regimen to a fixed combination of basal insulin and GLP 1 receptor agonist in comparison to increases in insulin dose results in a significant improvement in fasting glucose, postprandial glucose, HbA1c, and BMI. The results were achieved with a significantly lower daily insulin dose.

B. Miletić, Branislava Drašković, T. Đorem, Stefan Bojić, B. Matović, D. Stojanović

As forests in Bosnia and Herzegovina cover 2,904,600 ha or 56.7 % of its total area, and since the meteorological data analysis for the period 1961–2014 shows that the mean annual temperature maintains a continuous rise, сlose attention should be paid to these fragile ecosystems. It is important to note that one of the most economically valuable species for forestry in Bosnia and Herzegovina, Norway spruce, is particularly endangered due to its very low drought resistance and spread of various diseases. Comparing the last climate sequence (1991–2019) with the previous one (1961–1990) we found that the spruce-inhabited areas showed an average increase in the values of the Forest Aridity Index of 0.929. As for the Ellenberg’s climate quotient, it is noticeable that climate change is not as strong as in the case of the Forest Aridity Index. Based on projections for the mid- (2041–2070) and late-century (2071–2100) under the RCP 4.5, there will be no change that is likely to significantly affect the distribution of spruce. The predicted rates of decline and altitudinal shifts of favorable habitats are negligible. On the contrary, projections under the RCP 8.5 predict a significant reduction of suitable habitats, both for the existing range of Norway spruce and the entire territory of Bosnia and Herzegovina. Particularly, late-century projection under the RCP 8.5 predicts an almost complete reduction of suitable habitats, while small areas of suitable habitats at higher elevations will remain intact.

M. Ivanović, D. Grujić, J. Cerar, Maša Islamčević Razboršek, L. Topalić-Trivunović, A. Savić, D. Kočar, M. Kolar

In this study, the extraction efficiency of natural deep eutectic solvents (NADES) based on choline chloride as a hydrogen bond acceptor (HBA) and five different hydrogen bond donors (HBD; lactic acid, 1,4-butanediol, 1,2-propanediol, fructose and urea) was evaluated for the first time for the isolation of valuable bioactive compounds from Achillea millefolium L. The phytochemical profiles of NADES extracts obtained after ultrasound-assisted extraction were evaluated both spectrophotometrically (total phenolic content (TPC) and antioxidant assays) and chromatographically (UHPLC-MS and HPLC-UV). The results were compared with those obtained with 80% ethanol, 80% methanol, and water. The highest TPC value was found in the lactic acid-based NADES (ChCl-LA), which correlated with the highest antioxidant activity determined by the FRAP analysis. On the other hand, the highest antiradical potential against ABTS+• was determined for urea-based NADES. Phenolic acids (chlorogenic acid and dicaffeoylquinic acid isomers), flavones (luteolin and apigenin), and their corresponding glucosides were determined as the dominant individual phenolic compounds in all extracts. The antibacterial and antifungal properties of the extracts obtained against four bacterial cultures and two yeasts were evaluated using two methods: the agar dilution method to obtain the minimum inhibitory concentration (MIC) and the minimum bactericidal or fungicidal concentration (MBC or MFC), and the disc diffusion method. ChCl-LA had the lowest MIC and MBC/MFC with respect to all microorganisms, with an MIC ranging from 0.05 mg mL−1 to 0.8 mg mL−1, while the water extract had the weakest inhibitory activity with MIC and MBC/MFC higher than 3.2 mg mL−1.

S. Karakas, Dženana Huduti, M. Mehić, A. Šukalo, Jasna Džananović Jaganjac, A. Avdić, A. Skopljak, Azra Dupovac et al.

Objective. This study aimed to evaluate the efficacy and safety of lysozyme-based oral antiseptic in the therapy of non-infectious sore throat in teachers. Materials and Methods. A non-interventional, prospective, pilot study was conducted with two examinations. The first was performed as part of a general medical examination. If a non-infectious sore throat was confirmed by clinical checkup and all other inclusion and non-exclusion criteria confirmed, patients were offered to be enrolled in the study. After signing the informed consent form, patients were advised to use lysozyme-based lozenges, six times a day, for a period of five days. A telephone call follow-up examination was performed within 24 hours from the therapy completion. Results. This was a pilot study involving 25 adult patients of both genders. Lysozyme-based lozenges showed positive effects in relieving the symptoms of non-infectious sore throat in teachers. At the same time, the lozenges showed excellent tolerability, and no side effects were reported during the study. 92% of patients confirmed they would take the same medicine again due to the same problem. Conclusion. The results of this “proof-of-concept” study indicated that lysozyme-based antiseptic could be effective and safe in the treatment of non-infectious sore throat in teachers and should be further evaluated as treatment option in this condition.

S. Abdovic, M. Colic, Lorna Stemberger Marić, M. Cuk, I. Hizar, M. Milošević

INTRODUCTION Reports showed that observing detrusor overactivity (DO) and maximum cystometric capacity (MCC) may guide rational pharmacotherapy. Since urodynamic studies (UDS) are challenging for both patients and the healthcare system, a non-invasive objective prognostic marker is preferable. OBJECTIVES To investigate the value of the overactivity index (OI), a non-invasive measure calculated from the frequency-volume chart (FVC), for predicting the presence of symptoms and abnormal UDS in children with non-neurogenic OAB. STUDY DESIGN This was a prospective interventional study on a consecutive sample of 92 children with urgency treated with anticholinergics and standard urotherapy. Data from history, physical examination, bladder diaries, kidneys and bladder ultrasonography, uroflow, urinalysis, urine culture, and UDS was collected at baseline, and after 3 and 6 months. Binary logistic regression was used to evaluate noninvasive parameters as predictors of Overactive Bladder Symptom Score (OABSS) total score >2 and DO and/or small MCC defined as <65% of expected bladder capacity (EBC) for age. OI was calculated as (1 - (median (all voided volumes in FVC in ml))/(0.65 ∗ EBC in ml)) ∗ 100. RESULTS At baseline, 26 patients (36.1%) had DO and small MCC, while 21 patients (29.2%) only had DO. In 18 patients (25.0%) only small MCC was found. Seven patients had normal findings and 20 did not perform a urodynamic study. OI ≥ 23 returned as a single significant predictor of OABSS >2 (OR 7.97, 95% 1.97-32.22, p = 0.004) in multivariate regression (R2 = 30.8%; AUC = 0.86). OI correlated with "urgency episodes over two weeks" and MCC/EBC with medium (r = 0.45) and large effect (r = -0.56), respectively, p = 0.001. DISCUSSION A strong correlation of OI and MCC/EBC ratio is useful, as rise in MCC is predictive of a positive outcome. Also, calculating the OI is more practical than performing UDS. This could contribute to the use of OI as a predictive marker for starting (or continuing) anticholinergic treatment (when OI ≥ 23) or for maintaining urotherapy alone (when OI < 23) in children with OAB. The limitations were lack of external validation of OI, a 37-49% drop-off rate for follow-up visits at 3 and 6 months, respectively, and not performing UDS on all participants at every follow-up visit. CONCLUSIONS OI was found to be a significant predictor of the presence of OAB symptoms and correlated with the number of urgency episodes. It could estimate how much MCC differs from EBC.

Background: Acute kidney injury (AKI) is the result of various causes and is associated with significant morbidity and mortality as well as long-term renal sequelae in pediatric patients. Objectives: The aim of the study is to determine the causes of AKI in pediatric patients who needed renal replacement therapy (RRT) and were admitted to the Pediatric and Neonatal Intensive Care Unit (PICU and NICU) at the Pediatric Clinic, University Clinical Center Sarajevo (UCCS). Methods: Our research included 81 children with AKI who needed RRT. We used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI. Severe acute kidney injury was defined as stage 2 or 3 of AKI when plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours. Other laboratory findings and imaging tests were made depending on their primary disease that led to the AKI and its complications. Results: Our research analyzed 81 children with AKI who needed RRT 38 girls and 43 boys ages from birth to 18 years. Mean age of presentation was 6.28 years. Male female ratio in this study was 1.1:1. Non-olyguric AKI was diagnosed in 12 (14.8%) of children with AKI, while the rest 69 (85.2%) had the olyguric type. Patients with AKI were analyzed after a rough division on prerenal in 57 (70.4%) children, intrarenal in 23 (28.4%) and post-renal in 1 (1.2%) patient. Conclusion: As the AKI plays a key role in the mortality and morbidity in pediatric patients, especially in infants, it is important to recognise and treatment on time different etiologies of this serious condition. Some causes of AKI in our country can be prevented by better organization of primary and secondary health care, which would also reduce mortality and morbidity from AKI.

E. Karalija, Sabina Dahija, A. Demir, R. Bešta-Gajević, S. Ć. Zeljković, P. Tarkowski

This study presents the first report on phenolic composition and bioactivity of ethanolic extracts of three plant species that grow in the western Balkan mountains and are used in traditional folk medicine: Valeriana montana, Salix retusa, and Campanula hercegovina. Phenolics were extracted from different aerial plant parts using 80% ethanol to assess the possibility of sustainable use of these plants as a source of bioactive compounds without disruption to the roots (for V. montana) or destruction of whole habitats (for S. retusa and C. hercegovina). The ethanolic extract of V. montana flower contained noticeable levels of apigenin and quercetin. The branches and bark of S. retusa were significantly rich in catechin, while rutin was the major phenolic found in the leaf extract of C. hercegovina. Furthermore, the flower extract of V. montana revealed the best antioxidant activity, which was comparable to 4-hydroxybenzoic acid and quercetin. Considering antimicrobial activity, the leaf extracts of V. montana and C. hercegovina demonstrated potent activity against all microbes tested, while the extracts of S. retusa were moderately effective. The presented results emphasize the potential of these plants as novel sources of bioactive compounds.

A. Markotic, T. Kelava, Helena Markotić, H. Silovski, A. Mrzljak

Vitamin D has been a focus of attention in liver cancer due to its direct and indirect antineoplastic effects. This review critically evaluates data from recently published basic and clinical studies investigating the role of vitamin D in liver cancer. Basic studies indicate that vitamin D plays an important role in liver cancer development by suppressing the activity of hepatic stellate cells and Kupffer cells. Furthermore, vitamin D has a direct anti-proliferative, anti-angiogenic, proapoptotic, and prodifferentiative effect on liver cancer cells. Recent investigation suggested several interesting mechanisms of these actions, such as inactivation of Notch signaling, p27 accumulation, and tyrosine-protein kinase Met/extracellular signal-regulated kinases inhibition. On the other hand, data from clinical observational studies, although promising, are still inconclusive. Unfortunately, studies on the effect of vitamin D supplementation were generally focused on short-term outcomes of chronic liver diseases (liver enzyme levels or elastographic finding); therefore, there are still no reliable data on the effect of vitamin D supplementation on liver cancer occurrence or survival.

Katy Stokes, Busola Oronti, F. Cappuccio, L. Pecchia

Objective To identify and assess the use of technologies, including mobile health technology, internet of things (IoT) devices and artificial intelligence (AI) in hypertension healthcare in sub-Saharan Africa (SSA). Design Systematic review. Data sources Medline, Embase, Scopus and Web of Science. Eligibility criteria Studies addressing outcomes related to the use of technologies for hypertension healthcare (all points in the healthcare cascade) in SSA. Methods Databases were searched from inception to 2 August 2021. Screening, data extraction and risk of bias assessment were done in duplicate. Data were extracted on study design, setting, technology(s) employed and outcomes. Blood pressure (BP) reduction due to intervention was extracted from a subset of randomised controlled trials. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Results 1717 hits were retrieved, 1206 deduplicated studies were screened and 67 full texts were assessed for eligibility. 22 studies were included, all reported on clinical investigations. Two studies were observational, and 20 evaluated technology-based interventions. Outcomes included BP reduction/control, treatment adherence, retention in care, awareness/knowledge of hypertension and completeness of medical records. All studies used mobile technology, three linked with IoT devices. Short Message Service (SMS) was the most popular method of targeting patients (n=6). Moderate BP reduction was achieved in three randomised controlled trials. Patients and healthcare providers reported positive perceptions towards the technologies. No studies using AI were identified. Conclusions There are a range of successful applications of key enabling technologies in SSA, including BP reduction, increased health knowledge and treatment adherence following targeted mobile technology interventions. There is evidence to support use of mobile technology for hypertension management in SSA. However, current application of technologies is highly heterogeneous and key barriers exist, limiting efficacy and uptake in SSA. More research is needed, addressing objective measures such as BP reduction in robust randomised studies. PROSPERO registration number CRD42020223043.

A. Maslo, Lamija Hatibović

Hamid Hadžibegić spada u red važnijih istraživača prošlosti Bosne i Hercegovine koji su djelovali u drugoj polovini XX. stoljeća. U prvom dijelu rada ponuđene su biografske informacije te je dan osvrt na znanstveni doprinos Hamida Hadžibegića. Drugi dio rada posvećen je Hadžibegićevoj biblioteci, koju su nakon posljednjega rata u Bosni i Hercegovini (1992. – 1995.) i uništenja Orijentalnoga instituta u Sarajevu ovoj instituciji darovali Hadžibegićevi nasljednici. Poseban osvrt napravljen je na posvete drugih autora koje se pojavljuju u knjigama unutar Hadžibegićeve biblioteke.

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