Abstract Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Through the use of hydrogen bond driven solid-state synthesis, mononuclear complexes are transformed into crystalline materials.

We propose a simple $SU(5)$ model that connects the neutrino mass generation mechanism to the observed disparity between the masses of charged leptons and down-type quarks. The model is built out of $5$-, $10$-, $15$-, $24$-, and $35$-dimensional representations of $SU(5)$ and comprises two (three) $3 \times 3$ ($3 \times 1$) Yukawa coupling matrices to accommodate all experimentally measured fermion masses and mixing parameters. The gauge coupling unification considerations, coupled with phenomenological constraints inferred from experiments that probe neutrino masses and mixing parameters and/or look for proton decay, fix all relevant mass scales of the model. The proposed scenario places several multiplets at the scales potentially accessible at the LHC and future colliders and correlates this feature with the gauge boson mediated proton decay signatures. It also predicts that one neutrino is massless.

At university, you are continually engaged with other people’s ideas: You read them in texts, hear them in lectures and seminars, discuss them in class, and incorporate them into your own writing. Not least, you build on other people’s ideas in developing your own ideas. As a consequence, it is very important that you give credit where it is due. If you do not do that, you plagiarize. Plagiarism is using others’ ideas and words without clearly acknowledging these sources.

Rapid population growth and urbanisation has entailed a strong motivation to develop more sustainable construction solutions in line with the 7th basic requirement for construction works sustainable use of natural resources. One of the strategies is to use materials available in abundant quantities as partial replacement for cement, or to create alternative binders for concrete. The aim of the paper is to provide an overview of the current state of the art in the field of alternative binders for concrete, and to point to the opportunities and challenges for their more systematic application in engineering practice. The state of the art review is connected to scientific projects currently undertaken at the Department of Materials, Faculty of Civil Engineering University of Zagreb, Croatia.

Feohromocitom je neuroendokrini tumor, čija je glavna karakteristika sekrecijakateholamina sa posljedičnom hipertenzijom. Vrlo je rijedak u pedijatrijskoj populaciji,uobičajeno se javlja u bolesnika srednje životne dobi. Klinička slika podrazumijevaparoksizmalne napade glavobolje, bljedila, palpitacije i znojenja. Cilj rada je prikazslučaja feohromocitoma kod desetogodišnjeg dječaka, kao rijetkog tumora u pedijatrijskojpopulaciji.

In this paper, the room temperature mechanical properties, as well as the microstructure of HK 30 Nb steel, were tested in the initial as-cast and solution annealed condition. Results show that tensile properties after the solution annealing have a slightly lower value than as-cast samples. Microstructural analysis of samples after solution annealing showed dissolution of primary carbides present in the initial as-cast condition. The morphology and composition of carbides were changed during a solution annealing. Analysis of microstructure was done by optical microscopy (OM) and scanning electron microscope (SEM), whereas hardness and tensile tests were performed for characterization of mechanical properties.

In an open letter more than five years ago, a group of scientists called for adopting Registered Reports in all journals of the life sciences. This letter and subsequent efforts have yielded some notable success. At time of writing, 207 journals support the Registered Reports format, with many more currently considering its implementation. However, these numbers are still small in comparison to the many journals that rely exclusively on the traditional way of evaluating scientific quality. We, a group of over 250 scientists, want to emphatically reiterate the importance of accepting studies before the results are in. We call for all empirical journals in the social and life sciences to offer Registered Reports, alongside the traditional publication formats.

Abstract Vancomycin is a tricyclic glycopeptide antibiotic, mostly used in the treatment of severe staphylococcal and enterococcal infections, especially in orthopedic surgery. The purpose of this analysis was to develop a population pharmacokinetic (PPK) model of vancomycine in hospitalized patients with bone fractures and identify important factors which influence its clearance (CL). A total of ninety-nine measurements of vancomycin serum concentrations were used in our population modeling. A two-compartment model was applied to describe the pharmacokinetics of vancomycin using subroutines ADVAN3 and TRANS4. The study population included patients of both sexes, with the mean age of 62.12±14.69 years and body weight of 80.32±12.44kg. Vancomycin was administered as intravenous infusion with average daily dose of 1772.73±521.34mg. Out of twenty different factors evaluated in the study (including demographic, clinical and laboratory data), only daily dose of vancomycin (DD) and co-medication with piperacillin/tazobactam (PT) showed significant effect on clearance of vancomycin. The final model was described by the following equation: CL (l/h) = 0.03 + 0.000468 x DD + 0.675 x PT. Bootstrapping was used for validation of the final model. In conclusion, the main causes of variability in the clearance of vancomycin among adult patients with bone fractures are daily dose of vancomycin and co-medication with piperacillin/tazobactam.

Continuous progress in the nursing profession has a significant impact on the quality in the process of clinical care, which brings about new challenges and tasks for nurses to invest in new knowledge and skills. The healthcare process requires a systematic team approach in the design of evidence-based tasks, good clinical practice and clinical guidelines, documented standardized phenomena and evaluated measurements and tests. Measurement instruments and statistical tests of treatment effectiveness are used to assess the quality of health care provided. For a successful measurement and analysis of the quality of clinical care, it is necessary to have standardized healthcare documentation that allows treatment and outcomes monitoring. Qualitative and safety indicators are used to assess the quality of clinical health care, which represent a means of measurement, screening or warning. Monitoring Quality and Safety Indicators in Health Care Services is used as a guide to monitoring, evaluating and improving the quality of health care, and supporting services and organizational functions. In the field of health care, we measure the total treatment, outcome of the healthcare process, patient satisfaction, unwanted events,quality of life, etc.

Mastitis is frequent and costly disease in dairy farming, while antimicrobial resistance is an important public health threat. Increasing resistance among zoonotic pathogens led to more investigation among animal pathogens. Study, conducted on dairy farms in Canton Sarajevo, aimed to establish mastitis prevalence in dairy cows, causative bacteria and investigate antimicrobial resistance. Lactating animals (n=1214) were tested using the California Mastitis Test during November 2017. Milk from positive animals was microbiologically cultivated. The overall prevalence of mastitis was 9.9 %, while 19 out of 180 dairy farms had at least one mastitis case. In 49.2% of samples, we identified S. aureus, 2.5% contained E. coli, 0.8% contained Enterobacteriaceae, 13.3 % had mixed infection and 34.2% samples had no growth. Using disk diffusion test highest resistances were observed to bacitracin (E. coli), trimethoprim/sulfamethoxazole (Enterobacteriaceae) and penicillin (S. aureus). Since oversight on antimicrobial use in farm animals is sporadic in the country, additional investigations of antimicrobial usage and trends in antimicrobial resistance causing agents are needed. Reducing mastitis rates on farms requires compliance with preventive measures alongside early detection, isolation of cases, culling of repeated cases, microbiological monitoring and testing for antimicrobial resistance before treatment.

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.