The pandemic of COVID-19 has brought many changes in health care systems at all levels of health care. The increase in the number of cases of COVID-19 has led to overuse and misuse of antibiotics.The aim of this study was to compare the consumption of antibiotics for systemic use in outpatients in the Republic of Srpska (RS), before and during the first year of the COVID-19 pandemic, as well as the association between antibiotic consumption and the rate of incidence and mortality of COVID-19. The total consumption of the antibiotics for systemic use (J01) in outpatients in the Republic of Srpska during 2019 was 19.40 DDD/TID, with an increase to 30.80 DDD/TID in 2020.Significantly higher use of penicillin (10.58 ± 11.01 DDD/TID in 2019 vs. 17.10 ± 13.63 DDD/TID in 2020), cephalosporins (2.68 ± 1.90 DDD/TID in 2019 vs. 5.93 ± 2.77 DDD/TID in 2020) and macrolides (2.14 ± 2.22 DDD/TID in 2019 vs. 3.40 ± 3.44 DDD/TID in 2020) was observed during the pandemic period. It is necessary to improve the prescribing practice of antibiotics at the primary health care level, public awareness about rational use of antibiotics, as well as the current antibiotic stewardship programs and control their implementation.

Antibiotics are often misused, especially for the treatment of upper respiratory tract infections (URTIs) in children, where their use is unnecessary and leads to antimicrobial resistance. This study sought to explore the knowledge, attitudes and practices (KAP) of parents and pediatricians on the use of antibiotics among children and whether the level of education of parents has an impact on their KAP. The research was carried out among 1459 parents of children under 6 years of age and among 18 pediatricians. Sixty percent of pediatricians (61.1%) were prescribed antibiotics daily in their practice. Most of the surveyed parents (98.4%) state that doctors are their main source of information when deciding on the use of antibiotics in the treatment of their children. Parents with a higher level of education use television less often as a source of information when making this decision compared to parents with a lower level of education (p = 0.039, i.e., p = 0.003). The majority of parents (80.7%) knew that Panklav (amoxicillin/clavulanic acid) is an antibiotic, while 52.5% identified Pancef (cefixime) as an antibiotic. Parents with a higher level of education correctly identified antibiotics significantly more often (p < 0.001). This study shows that in the Republic of Srpska, parents have adequate knowledge about antibiotics, especially those with a higher level of education, who show better KAP when it comes to antibiotic use.

Objective To establish optimised diffusion weightings (‘ b -values’) for acquisition of whole-body diffusion-weighted MRI (WB-DWI) for estimation of the apparent diffusion coefficient (ADC) in patients with metastatic melanoma (MM). Existing recommendations for WB-DWI have not been optimised for the tumour properties in MM; therefore, evaluation of acquisition parameters is essential before embarking on larger studies. Methods Retrospective clinical data and phantom experiments were used. Clinical data comprised 125 lesions from 14 examinations in 11 patients with multifocal MM, imaged before and/or after treatment with immunotherapy at a single institution. ADC estimates from these data were applied to a model to estimate the optimum b -value. A large non-diffusing phantom was used to assess eddy current–induced geometric distortion. Results Considering all tumour sites from pre- and post-treatment examinations together, metastases exhibited a large range of mean ADC values, [0.67–1.49] × 10^−3 mm^2/s, and the optimum high b -value ( b _high) for ADC estimation was 1100 (10th–90th percentile: 740–1790) s/mm^2. At higher b -values, geometric distortion increased, and longer echo times were required, leading to reduced signal. Conclusions Theoretical optimisation gave an optimum b _high of 1100 (10th–90th percentile: 740–1790) s/mm^2 for ADC estimation in MM, with the large range of optimum b -values reflecting the wide range of ADC values in these tumours. Geometric distortion and minimum echo time increase at higher b -values and are not included in the theoretical optimisation; b _high in the range 750–1100 s/mm^2 should be adopted to maintain acceptable image quality but performance should be evaluated for a specific scanner. Key Points • Theoretical optimisation gave an optimum high b-value of 1100 (10th–90th percentile: 740–1790) s/mm ^ 2 for ADC estimation in metastatic melanoma. • Considering geometric distortion and minimum echo time (TE), a b-value in the range 750–1100 s/mm ^ 2 is recommended. • Sites should evaluate the performance of specific scanners to assess the effect of geometric distortion and minimum TE.

Grazing-incidence small-angle X-ray scattering (GISAXS) is a powerful method for the structural analysis of ordered arrays of nanoparticles, quantum dots, or similar objects. However, for the correct interpretation of the measured GISAXS intensity distributions, a proper data analysis, including a suitable model, is required. Here, we demonstrate a software platform, GisaxStudio, aimed at the analysis and simulation of 2D GISAXS intensity distributions from ordered lattices of different nanoparticles. It contains several models that satisfactorily describe the GISAXS from 3D lattices or crystals of nanoparticles prepared by the self-assembly processes, pre-pattering, or ion-beam interaction with the material within their tracks. It also supports different shapes of nanoparticles, including core-shell structure with the center of core possibly displaced from the center of the shell. The software is very useful for fast and accurate GISAXS data analysis.

The self-rooted plum genotype ‘Mrkosljiva’ was first selected as it was devoid of Sharka leaf symptoms during the 5‑year study (2009–2014), which was subsequently confirmed by negative ELISA test results. Hence, the aim of the study was to investigate the biochemical variability of the autochthonous ‘Mrkosljiva’ plum genotype, based on its sugar, acid and phenolic compounds content during 3 years. In 2010 and 2011, the plums tasted sweet with favourable sugar:acid ratios of 55:1 to 65:1. These plum fruits were collected at the full ripeness stage from an extensive orchard located in northeastern Bosnia and Herzegovina (45 °N). Analysis by HPLC identified the following polyphenolic compounds—chlorogenic acid, cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, neochlorogenic acid, quercetin-3-O-galactoside and quercetin-3-O-rutinoside—in all 3 years that were evaluated (2009–2011), but in different amounts, depending on the environmental conditions of each year. In 2009, the plums were healthier with a threefold greater phenol content than during the other 2 years of growth. In 2009, protocatechuic acid was detected, whereas catechin, procyanidin B1, procyanidin B2 and quercetin-3‑O-rhamnoside were not detected. The combination of high phenol and sugar content in ‘Mrkosljiva’ provides healthy and tasty plums suitable primarily for processing, and to a lesser extent, due to their size, for fresh fruit marketing.

One of the most common tools for achieving optimization and adequate production process management is linear programming (LP) in various forms. However, there are specific cases of the application of linear programming when production optimization implies several potential solutions instead of one. Exactly such a problem is solved in this paper, which integrates linear programming and a Multi-Criteria Decision-Making (MCDM) model. First, linear programming was applied to optimize production and several potential solutions lying on the line segment AB were obtained. A list of criteria was created and evaluated using the Improved Fuzzy Stepwise Weight Assessment Ratio Analysis (IMF SWARA). To obtain the final solution, a novel Rough compromise ranking of alternatives from distance to ideal solution (R-CRADIS) method was developed and verified through comparative analysis. The results show that the integration of linear programming and a Fuzzy-Rough MCDM model can be an exceptional solution for solving specific optimization problems.

The emergence of blockchain technologies, including smart contracts, enables the decentralization of applications that were previously controlled by a single entity. In many cases, however, smart contracts still need to distinguish between different user roles according to their assigned duties. To ensure security, smart contracts often apply a simple form of role-based access control (RBAC), where a dedicated administrator assigns users to roles that are authorized to invoke specific smart contract functions. As this solution contradicts the blockchain principles of decentralization and democratic decision making, smart contracts may also form decentralized autonomous organizations where governance decisions are based on voting by all participants. Many applications would benefit from a hybrid approach that involves roles with different permissions while still allowing for collaborative management. Therefore, we propose a novel mechanism for RBAC administration in smart contracts based on hierarchical roles and configurable administration rules for each role. Any change in the user-role relation requires joint approval by members of selected roles according to the associated rule. This enables decentralized organizational charts with flexible administration constraints, where each role corresponds to specific permissions in the decentralized application and any change is transparently and securely recorded on the blockchain. The practical feasibility of the approach is demonstrated by means of a prototypical implementation for the Ethereum blockchain. Several benchmarks are performed to analyze the potential overhead of different solution variants.

New resveratrol–thiophene and resveratrol–maltol hybrids were synthesized as cholinesterase inhibitors and antioxidants. As with photostability experiments, biological tests also found remarkable differences in the properties and behavior of thiophene and maltol hybrids. While resveratrol–thiophene hybrids have excellent inhibitory and antioxidant properties (similar to the activity of reference drug galantamine), maltols have been proven to be weaker inhibitors and antioxidants. The molecular docking of selected active ligands gave insight into the structures of docked enzymes. It enabled the identification of interactions between the ligand and the active site of both cholinesterases. The maltols that proved to be active cholinesterase inhibitors were able to coordinate Fe3+ ion, forming complexes of 1:1 composition. Their formation constants, determined by spectrophotometry, are very similar, lgK = 11.6–12.6, suggesting that Fe3+ binds to the common hydroxy-pyranone moiety and is hardly affected by the other aromatic part of the ligand. Accordingly, the characteristic bands in their individual absorption spectra are uniformly red-shifted relative to those of the free ligands. The crystal structures of two new resveratrol–maltol hybrids were recorded, giving additional information on the molecules’ intermolecular hydrogen bonds and packing. In this way, several functionalities of these new resveratrol hybrids were examined as a necessary approach to finding more effective drugs for complicated neurodegenerative diseases.

Aims: To evaluate the efficacy of metronidazole monotherapy and modified therapy with metronidazole + nifuroxazidefor the for treatment of a mild form of Clostridium difficile infection (CDI). Study Design: A prospective, randomized, controlled clinical trial. Place and Duration of Study: University of Applied Sciences Tuzla in the period from June 2018 to June 2019. Methodology: Sixty patients were included in the study, divided into two groups. One group received standard therapy (metronidazole) for the treatment of a mild form of CDI, while the other group was treated with modified therapy (metronidazole + nifuroxazide). Subjects with a developed clinical picture and a positive toxin test for Clostridium difficile were surveyed on the day of admission, then on the 4th, 10th, 14th and 30th days from the start of therapy. The goal of the research was to determine the impact of the modified therapy protocol on the number of stools and the presence of pain compared to standard therapy. Results: The modified therapy with metronidazole + nifuroxazide showed better pharmacological efficacy in the treatment of CDI compared to the standard therapy with metronidazole alone. The group of subjects who were treated with modified therapy reported a significantly lower number of stools (P=.001) and the absence of pain at the first and second check-ups. Conclusion: Nifuroxazide and metronidazole represent a combination of drugs that reduce the number of stools in the shortest possible time and result in the absence of abdominal pain in patients diagnosed with a mild form of CDI.

Smoking is a widely recognized risk factor in the emergence of cancers and other lung diseases. Studies of non-cancer lung diseases typically investigate the role that smoking has in chronic changes in lungs that might predispose patients to the diseases, whereas most cancer studies focus on the mutagenic properties of smoking. Large-scale cancer analysis efforts have collected expression data from both tumor and control lung tissues, and studies have used control samples to estimate the impact of smoking on gene expression. However, such analyses may be confounded by tumor-related micro-environments as well as patient-specific exposure to smoking. Thus, in this paper, we explore the utilization of mutational signatures to study environment-induced changes of gene expression in control lung tissues from lung adenocarcinoma samples. We show that a joint computational analysis of mutational signatures derived from sequenced tumor samples, and the gene expression obtained from control samples, can shed light on the combined impact that smoking and tumor-related micro-environments have on gene expression and cell-type composition in non-neoplastic (control) lung tissue. The results obtained through such analysis are both supported by experimental studies, including studies utilizing single-cell technology, and also suggest additional novel insights. We argue that the study provides a proof of principle of the utility of mutational signatures to be used as sensors of environmental exposures not only in the context of the mutational landscape of cancer, but also as a reference for changes in non-cancer lung tissues. It also provides an example of how a database collected with the purpose of understanding cancer can provide valuable information for studies not directly related to the disease.

Purpose Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

Noise represents any unwanted sound that interferes with a person's work, psychological and health condition, and their rest time. Numerous studies indicate that noise affects changes in human behavior (aggression, social conflicts) and causes stress reactions associated with physiological reactions. It also affects the central and neurovegetative system, reduces attention and concentration ability, reduces work ability, and reduces work productivity. Noise pollution is a major environmental health problem in Europe, with the transport sector being its main cause. The noise level is mostly affected by the number of vehicles, traffic flow, relative share of passenger and freight vehicles, their speed, types and characteristics of the road, whether the traffic is one-way or two-way, intersections, weather conditions, etc. In order to adequately protect against the negative effects of traffic noise, it is necessary to take various measures to reduce it. This paper provides a comprehensive review of the literature with special measures for the protection, monitoring and reduction of the negative impact of traffic noise. Keywords: traffic, traffic noise, protection measures, noise barriers