ABSTRACT Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above. Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics. Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.

Exhaled breath analysis has become a promising monitoring tool for various ailments by identifying volatile organic compounds (VOCs) as indicative biomarkers excreted in the human body. Throughout the process of sampling, measuring, and data processing, non-biological variations are introduced in the data leading to batch effects. Algorithmic approaches have been developed to cope with within-study batch effects. Batch differences, however, may occur among different studies too, and up-to-date, ways to correct for cross-study batch effects are lacking; ultimately, cross-study comparisons to verify the uniqueness of found VOC profiles for a specific disease may be challenging. This study applies within-study batch-effect-correction approaches to correct for cross-study batch effects; suggestions are made that may help prevent the introduction of cross-study variations. Three batch-effect-correction algorithms were investigated: zero-centering, combat, and the analysis of covariance framework. The breath samples were collected from inflammatory bowel disease (n=213), chronic liver disease (n=189), and irritable bowel syndrome (n=261) patients at different periods, and they were analysed via gas chromatography-mass spectrometry. Multivariate statistics were used to visualise and verify the results. The visualisation of the data before any batch-effect-correction technique was applied showed a clear distinction due to probable batch effects among the datasets of the three cohorts. The visualisation of the three datasets after implementing all three correction techniques showed that the batch effects were still present in the data. Predictions made using partial least squares discriminant analysis and random forest confirmed this observation. The within-study batch-effect-correction approaches fail to correct for cross-study batch effects present in the data. The present study proposes a framework for systematically standardising future breathomics data by using internal standards or quality control samples at regular analysis intervals. Further knowledge regarding the nature of the unsolicited variations among cross-study batches must be obtained to move the field further.

Temperature-stable dissolving film eliminates cold-chain storage and successfully immunizes mice sublingually and buccally. A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an amorphous solid with a glass transition above room temperature and nitrogen-hydrogen bonding between virus and film components are critical determinants of stability. Administration of live influenza virus in the optimized film by the sublingual and buccal routes induced antibody-mediated immune responses as good as or better than those achieved by intramuscular injection. This work introduces the possibility of improving global access to a variety of medicines by offering a technology capable of reducing costs of production, distribution, and supply chain maintenance.

Introduction: Ramadan is the holy month of Muslims including fasting sometimes more than 20 hours. Even diabetes patients can be exempted from fasting it has been shown that almost 80% of diabetes type 2 patients intend and do fasting. To avoid acute complications during fasting, different recommendations on diabetes management are available. Considering the fact that there are more than 226 thousand diabetics in Bosnia and Herzegovina, it is important to provide structured support and healthcare service to those who are practicing fast during Ramadan. Aim: To evaluate knowledge, practice and attitudes of physicians treating diabetes (diabetologists and endocrinologists) in Bosnia and Herzegovina regarding management of diabetes in fasting patients during Ramadan. Methods: A 32 questions survey has been developed, validated and disseminated to the 27 specialists treating diabetes in Bosnia and Herzegovina through online form examining demographic characteristics, current practices and attitudes and knowledge on diabetes management during Ramadan. Results: All surveyed physicians deal with patients who are fasting during Ramadan. The majority of surveyed physicians 23 (85,2%) proactively initiate a discussion about planned fasting. More than 63,0% are following their experience and only 18,5% ADA/EASD guidelines on diabetes management during Ramadan. There are no significant differences between gender of the physicians, place of work and specialization when it comes to specific knowledge related to treatment guidelines, but some differences are observed. Conclusion: Although overall physicians` knowledge of diabetes management during Ramadan is satisfying there is opportunity in additional specialized education and measures introduction into the practice in order to improve treatment outcomes and standards of care.

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

Before even opening the book, Democracy by Decree: Prospects and Limits of Imposed Consociational Democracy in Bosnia and Herzegovina captures the reader’s attention with its intriguing and provocative title. But what author Adis Merdzanovic delivers in its pages is equally engaging. Merdzanovic illustrates how the consociational power-sharing arrangements in Bosnia and Herzegovina were imposed by the international community following the wars in the 1990s, rather than genuinely initiated from inside a country, and have, perhaps unsurprisingly, largely failed.

The Internet of Things (IoT) is a concept of the modern, interconnected world. Over 50 billion devices, globally-connected, make up the largest network that is stepping towards the fourth industrial revolution, and which will significantly change the system of values and business systems. In the world of heterogeneous communication technologies, choosing the optimal one is a challenge for system architects, which is not an easy task often. The paper presents a comparative analysis of widespread communication technologies in the domain of IoT, and the conclusions presented based on the performed analysis, provide a better insight into the choice of the optimal solution depending on the problem domain and therefore better quality of solutions based on the concept of IoT.

Although around the globe numerous studies have been conducted on the nutritional composition of blueberry/bilberry and its effect on human health, very little is known about the fruit in Bosnia and Herzegovina. This is the first report regarding the physical and chemical characteristics of the cultivated highbush blueberry and bilberry harvested in the same climatic conditions in Bosnia and Herzegovina. In this paper we present the physical weight and chemical soluble solids content, total sugars, titratable acidity, pH, and total phenols properties of the wild bilberry Vaccinium myrtillus L. and cultivated highbush-'Earliblue', 'Bluegold', 'Bluecrop', 'Goldtraube'-blueberry Vaccinium corymbosum L. . Among the highbush blueberry cultivars, 'Bluegold' 2.07-2.11 g and 'Bluecrop' 2.08-2.11 g had the highest weight. 'Bluecrop' had the highest soluble solids content 13.3-13.7 °Brix and total sugars 9.73%?9.94% , but the lowest content of titratable acidity 0.70-0.72 g/100 g , which was highest in 'Goldtraube' 0.92-0.93 g/100 g . This cultivar also had the highest content of total phenols 289-309 mg gallic acid equivalent/100 g of fresh weight . In the case of wild bilberry, the following values were obtained: average weight 0.28-0.32 g, soluble solids content 11.1-11.3 °Brix, total sugars 7.23%-7.37%, titratable acidity 0.99%-1.02%, and total phenols 431-455 mg/100 g. Blueberry and wild bilberry also had a fairly uniform pH 3.2-3.6 . All samples had a valuable composition and so it is advisory to expand their production in Bosnia and Herzegovina in order to increase their consumption.

The steady increase in electricity demand has led to more installed generation capacity in wind farms, which, due to the stochastic nature of their production, may have characteristic and non-standard responses to some occurrences in the grid. The power output from the wind farm changes constantly, depending on the wind speed, so the impact of the network on the wind farm will inversely vary depending on the moment of the short circuit and the wind farm operating mode, since the values of currents and voltages in these fault systems depend on the power flows. Although wind power is known to contribute to the short circuit current / power at the point of its connection, this paper focuses on the response of the wind farm to short circuits in the network and the impact of these phenomena on the grid-wind relation. The aim of the paper is to determine the worst type of short circuit for wind turbine operation in the distribution system.

Abstract The aim of this study was to perform screening for anxiety disorders among children with asthma and to reveal factors associated with general anxiety disorder and its specific forms. This was a cross-sectional study conducted among out-patients with asthma during routine visits to pediatricians. They were screened for anxiety disorders using SCARED self-reported questionnaire. Additional data were collected using specially designed questionnaire as well as the patient files. Statistical analysis was performed by the SPPS software using descriptive statistics and logistic regression. Study population consisted mostly of schoolchildren (n=58), 8-12 years old, and adolescents (13-17 years) (n=13). Approximately 33.8% respondents were positive for general anxiety disorder. The most common were separation anxiety and social anxiety, recorded among 49.3% and 32.4% of patients, respectively. Generalized anxiety and panic/somatic disorder were recorded in the same percentage of patients (21.3%), while avoiding school was the least frequent (14.08%). Influence of numerous factors was tested, but only the following showed significant effects: peak expiratory flow test was associated with general anxiety disorder, patient’s age and gender with PD, and living place, asthma control according to GINA and age on GAD. Parent’s smoking was associated with SAD, age and patient’s weight status with SPH, and GINA asthma control with SA. These findings suggest that anxiety disorders are common among children and adolescents with asthma. Various factors can be associated with general anxiety disorder and its specific forms, but some of them being preventable as avoiding smoking in the family.

New technologies introduce more services which will call for significant advances and changes in IP networks. Networks will have to go in the direction of network programmability, virtualization and cloud-based services. In this paper, Quality of Service (QoS) is configured in two different environments: (i) in traditional IP network using QoS policy-maps and (ii) in Software Defined Network. Two scenarios are compared in order to emphasize the benefits of using SDN technology when providing QoS provisioning mechanisms.

Multiprotocol Label Switching Traffic-Engineering (MPLS TE) is a mechanism for optimizing network performances by using existing routing and resource reservation protocols in order to calculate and establish tunnels used for transporting different traffic flows depending on their destination. Aim of this paper is presenting benefits of using Segment Routing Traffic Engineering (SR-TE) in Software Defined Network (SDN) environment in order to overcome several MPLS TE problems and challenges presented in this paper. In order to present benefits of SR-TE in SDN, two scenarios are compared. In the first scenario SR is implemented in classical IP/MPLS network. In the second scenario, SDN controller is added to a topology and control over paths is delegated to SDN controller.