Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration, and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.

Abstract. Current global mitigation ambition up to 2030 under the Paris Agreement, reflected in the National Determined Contributions (NDCs), is insufficient to achieve the agreement's 1.5  ∘ C long-term temperature limit. As governments are preparing new and updated NDCs for 2020, the question as to how much collective improvement is achieved is a pivotal one for the credibility of the international climate regime. The recent Special Report on Global Warming of 1.5  ∘ C by the Intergovernmental Panel on Climate Change has assessed a wide range of scenarios that achieve the 1.5  ∘ C limit. Those pathways are characterised by a substantial increase in near-term action and total greenhouse gas (GHG) emission levels about 50 % lower than what is implied by current NDCs. Here we assess the outcomes of different scenarios of NDC updating that fall short of achieving this 1.5  ∘ C benchmark. We find that incremental improvements in reduction targets, even if achieved globally, are insufficient to align collective ambition with the goals of the Paris Agreement. We provide estimates for global mean temperature increase by 2100 for different incremental NDC update scenarios and illustrate climate impacts under those median scenarios for extreme temperature, long-term sea-level rise and economic damages for the most vulnerable countries. Under the assumption of maintaining ambition as reflected in current NDCs up to 2100 and beyond, we project a reduction in the gross domestic product (GDP) in tropical countries of around 60 % compared to a no-climate-change scenario and median long-term sea-level rise of close to 2 m in 2300. About half of these impacts can be avoided by limiting warming to 1.5  ∘ C or below. Scenarios of more incremental NDC improvements do not lead to comparable reductions in climate impacts. An increase in aggregated NDC ambition of big emitters by 33 % in 2030 does not reduce presented climate impacts by more than about half compared to limiting warming to 1.5  ∘ C. Our results underscore that a transformational increase in 2030 ambition is required to achieve the goals of the Paris Agreement and avoid the worst impacts of climate change.

Muesli bars is a generic term that refers to baked or cold-formed cereal-based snack bars, and may contain other ingredients such as fruit, nuts, seeds, chocolate, yoghurt, and a variety of other fillings and/or toppings. By changing the ingredients nutritional value of muesli bar can be modified. In this research, protein-rich and energy-high muesli bars have been produced, because they contain a higher amount of fat, proteins and sugar. However, fats and sugars were not added but come from specific ingredients (hazelnuts, walnuts, chia seeds, sesame, sunflower and pumpkin seeds, oat flakes, etc.). Four muesli bar formulations were developed, two with hazelnuts and two with walnuts, added in the amount of 25% and 50%, respectively. The other ingredients were added in the same amount. The product was dried at 80°C for several hours. The composition, polyphenolic compounds and antioxidant capacity were determined in the products before and after drying. Also, muesli bars were sensory evaluated.

This paper presents the study that would allow a revision of the currently valid diagnostic reference level in intraoral dental X-ray radiography in Bosnia and Herzegovina. The study was conducted for six procedures that are used to capture incisor, premolar and molar teeth, of both maxilla and mandible, in adults. Measurements were performed on 41 intraoral X-ray devices, 20 of which were systems with digital image receptor and 21 film-based X-ray systems. In this study, incident air kerma (Ki) and air kerma-area product (PKA) were used as patient dose descriptors. The third quartile (Q3) of the measured incident air-kerma values was used to compare with the current national diagnostic reference level (DRL) for intraoral dental procedures. The obtained results of Q3 for both types of devices, with film-based and digital image receptors, have shown that the third quartile values are lower (3.5 and 1.2 mGy, respectively) than the current national DRL (7.0 mGy). Hence, new data can be used to re-establish the diagnostic reference levels in intraoral dental X-ray examinations in Bosnia and Herzegovina.

Background Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV), known oncoviruses, can be co-present and cooperate in the initiation and/or progression of human carcinomas, including head and neck. Based on this fact, we recently reported the prevalence of both HPVs and EBV in cervical and breast cancers. Methods We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology. Results The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of the SCC samples; with a significant correlation between the various HPV types and EBV co-incidence (p = 0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoprotein of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. Additionally, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p < 0.05). More importantly, our data revealed that the co-presence of HPV and EBV is strongly correlated with advanced tumor stage (p = 0.035). Conclusion In this study we show that HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of this cooperation.

Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV), known oncoviruses, can be co-present and cooperate in the initiation and/or progression of human carcinomas, including head and neck. Based on this fact, we recently reported the prevalence of both HPVs and EBV in cervical and breast cancers. We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology. The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of the SCC samples; with a significant correlation between the various HPV types and EBV co-incidence (p = 0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoprotein of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. Additionally, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p < 0.05). More importantly, our data revealed that the co-presence of HPV and EBV is strongly correlated with advanced tumor stage (p = 0.035). In this study we show that HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of this cooperation.

While the increasing penetration of renewable energy resources into the electric power grid improves energy efficiency and reduces greenhouse gas emissions, it may drive the grid towards weak power grid conditions, under which grid stability issues may affect the operation of inverter-based renewable generators. The short-circuit ratio (SCR) with some modifications has been used to analyze power grid strength. However, the existing SCR-based methods for grid strength assessment neglect the impact of the interactions between shunt capacitors interconnected through the power network, which may cause over-optimistic results of grid strength assessment. To account for the impact, a novel method for grid strength assessment is proposed in this paper by theoretical analysis of how the interconnected capacitors affect static voltage stability. The efficacy of the proposed method is demonstrated through numerical simulation case studies on the IEEE 39-bus system.

The electric power grid is undergoing significant changes in the mix of generation source types. The increasing penetration of renewable energy resources (RERs), such as wind and solar, is improving energy efficiency, but meanwhile it is also challenging grid planners and operators to maintain reliable electricity services. The high penetration of RERs may drive the power grid toward weak grid conditions, which may cause grid stability and reliability issues. One of ways to address these issues is to select appropriate points of interconnection for integrating RERs into power grids. In previous works, grid stability analysis and grid reliability assessment are evaluated separately for selecting the points of interconnection. This paper presents an integrated method for selecting such points by coordinating grid strength assessment and grid reliability evaluation as well as investment cost. The efficacy of the proposed method is demonstrated on the IEEE reliability test system.

Aim Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which have increased the risk of infection, thus the bacterial resistance to antibiotics. The aim of this study was to analyse the epidemiology of multidrug resistance pathogens as causative agents of neonatal sepsis in the neonatal intensive care unit. Methods A retrospective cohort study conducted at the Intensive care unit of the Paediatric Clinic of Tuzla over a three-year period (2016-2018) analysed epidemiology of neonatal sepsis caused by multidrug resistance pathogens. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results Of the total of 921 treated neonates, multidrug resistance (MDR) pathogens among causative agents of neonatal sepsis were found in 22 neonates (2.38%) with no gender difference. Prematurity and low birth weight were confirmed as the most significant risk factors. From the maternal risk factors a significant difference was found in the first birth and in vitro fertilization. Clinically, MDR sepsis manifested frequently as late onset sepsis, with longer hospital stay and higher mortality. The findings of leukopenia, thrombocytopenia and coagulation disorders were significant. Gram negative bacteria were frequently isolated, in particular Acinetobacter, which showed the greatest resistance to antibiotics. Conclusion Neonatal MDR sepsis is a threat to life, it complicates the treatment, increases costs and mortality. Outcomes can be improved by preventive strategies, earlier and more accurate diagnosis and rational use of antibiotics.

Aim To determine the degree of accuracy in determining the sex of the skull based on classical morphometric analysis of the mastoid process. Morphometric analysis excluded a subjective approach expressed in osteoscopic analysis. Methods The study was conducted on a sample of 100 macerated skulls of known gender and age from the second half of the 20th century, including the Bosnian population. Of the 100 skulls, 50 (50%) were male and 50 (50%) were female. Male skulls were on average 60 (47-71) years old and female 57 (43-76) years old. At each mastoid process, 3 measurements were made: mastoid length, mastoid width (medio-lateral diameter) ML) and anteroposterior diameter (AP) of the mastoid process. Results Using the univariate method, we found a significant difference between length, width, AP diameter and size of mastoid processes as well as between gender (p <0.05). Multivariate binary logistic regression showed statistically significant differences in AP diameter of the mastoid process (p<0.05). Conclusion The created model "P" ("P"=exp [X]/1+exp [X]) for sex determination based on mastoid process showed sensitivity of 82% correct prediction for female skulls and 65% accurate prediction for male skulls. This discourse with respect of population standards grants most effective anthropological proof and as such may be suggested for forensic expertise based on human skull.

Aim To present characteristics of collecting autologous peripheral blood stem cells over a one-year period with an emphasis on efficiency and safety. Methods A retrograde analysis of 24 leukapheresis in 20 adult patients with malignant haematological diseases in the Blood Transfusion Institute of the Federation of Bosnia and Herzegovina in Sarajevo, was done. Cell separators Amicus and Spectra Optia were used for collection procedures. Results The patient's age ranged from 27 to 65 years. Target cells were collected in one procedure in sixteen patients, while in four patients they were collected in two procedures. The mean CD34+ collection efficiency was 57.7%. The median number of CD34+ cells and percentage of CD34+ cells in the products were 5.52x10e6/kg (range 3.28-9.00) and 1.57% (range 0.96-2.91). A strong positive correlation was found between the number of CD34+ cells in peripheral blood on the apheresis day and the amount of CD34+ cells collected in the products (rs =0.73). A total of 95% of patients collected the amount of ≥3x10e6/kg and 55% of ≥5x10e6/kg CD34+ cells for a single transplant. A decrease in platelet count, haemoglobin and haematocrit values after the procedure was not significant. Potassium decrease showed statistical significance (p<0.000). Adverse events occurred during one procedure (4.2%). Conclusion A low number of adverse events and good collection efficiency with adequate patient monitoring, indicate that leukapheresis is a safe procedure that is successfully used in the autologous transplantation process in the treatment of malignant haematological diseases.

Aim Phlebotominae sandflies are primary vectors of phleboviruses, causing the sandfly fever disease. The aim of this study was to detect and report the presence of flaviviruses in Phlebotominae sandflies captured in Bosnia and Herzegovina. Methods After a microscopic and morphometric analysis, the final identification of collected Phlebotomus specimens was confirmed by PCR, using a hemi-nested polymerase chain reaction on extracted and reversely transcribed RNA. Results We obtained a 155 nt long fragment of the viral non-structural protein 5 (NS5) gene (GenBank accession no. MN090154). The acquired nucleotide sequence, provisionally named as Drežnica, showed a maximum of 70-80% identity in 70-88% (110-137 nucleotides) of the query coverage with several Anopheles, Sabethes, Calbertado and Culex flaviviruses. Maximum likelihood phylogenetic analysis showed that the new flavivirus Drežnica clusters together with the flavivirus isolated from Culiseta annulata mosquitos. Conclusion We report the presence of flavivirus in Phlebotominae sandflies, captured in Drežnica, Herzegovina for the first time. The next phase of research will be directed towards virus cultivation, obtaining a longer or complete virus sequence and clarifying the medical and epidemiological importance of the Drežnica virus.