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Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ9-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.

Ketamine is a dissociative anaesthetic used to induce general anaesthesia in humans and laboratory animals. Due to its hallucinogenic and dissociative effects, it is also used as a recreational drug. Anaesthetic agents can cause toxic effects at the cellular level and affect cell survival, induce DNA damage, and cause oxidant/antioxidant imbalance. The aim of this study was to explore these possible adverse effects of ketamine on hepatocellular HepG2 and neuroblastoma SH-SY5Y cells after 24-hour exposure to a concentration range covering concentrations used in analgesia, drug abuse, and anaesthesia (0.39, 1.56, and 6.25 µmol/L, respectively). At these concentrations ketamine had relatively low toxic outcomes, as it lowered HepG2 and SH-SY5Y cell viability up to 30 %, and low, potentially repairable DNA damage. Interestingly, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) remained unchanged in both cell lines. On the other hand, oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] pointed to ketamine-induced oxidant/antioxidant imbalance.

Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.

Existing research on the education of refugee children has been conducted in countries with a longstanding tradition of refugee integration. The aim of this study was to gain insight into the integration process of refugee children in Croatian schools. Croatia is a small EU country with limited experience in refugee integration. The phenomenological approach was used to examine the experiences and perspectives of the relevant actors. Interviews and focus group discussions were conducted with refugee children (N = 15), their parents (N = 5), classmates (N = 50), and school staff (N = 54) from six elementary schools in Zagreb. Data analyses suggested three general needs: educational, language, and social, each of them connected to more specific needs, challenges, and suggestions. The results of the study are discussed within the Schachner et al. (2017) framework of immigrant adolescents' acculturation.

Early-life stages play a key role in the dynamics of bipartite life cycle marine fish populations. Difficult to monitor, observations of these stages are often scattered in space and time. While Mediterranean coastlines have often been surveyed, no effort has been made to assemble historical observations. Here we build an exhaustive compilation of dispersal traits for coastal fish species, considering in situ observations and growth models (Di Stefano et al., 2023; https://doi.org/10.17882/91148). Our database contains over 110 000 entries collected from 1993 to 2021 in various subregions. All observations are harmonized to provide information on dates and geolocations of both spawning and settlement, along with pelagic larval durations. When applicable, missing data and associated confidence intervals are reconstructed from dynamic energy budget theory. Statistical analyses allow traits’ variability to be revisited and sampling biases to be revealed across taxa, space and time, hence providing recommendations for future studies and sampling. Comparison of observed and modelled entries provides suggestions to improve the feed of observations into models. Overall, this extensive database is a crucial step to investigate how marine fish populations respond to global changes across environmental gradients.

There is growing evidence that arbutin and plant extracts rich in arbutin, such as extracts of the strawberry tree (Arbutus unedo L.), exert a range of beneficial effects, including cyto- and genoprotective properties. This study evaluated the effects of strawberry tree water leaf extract (STE) and arbutin in the brain tissue of Lewis rats. STE or arbutin were administered per os to male and female rats at a dose of 200 mg/kg body weight/day for 14 or 28 days. Treatment outcomes were evaluated using biochemical markers (lipid peroxidation and the activities of the antioxidative enzymes catalase and superoxide dismutase). The effects of the tested substances on DNA integrity in brain cells were evaluated using the alkaline comet assay. The results suggest a high biocompatibility of both tested substances with rat brain tissue. No significant harmful disturbances were observed in the oxidative/antioxidative status or impairments of DNA integrity in the rat brain cells. Nearly all post-treatment values were within tolerable limits as compared to the matched control rats. Such encouraging findings support further research using other subtle biomarkers to clarify the safety aspects of arbutin and STE prior to the development of specific nutraceutical products.

The aim of this study was to examine the relations of academic achievement, self-efficacy, and perfectionism with procrastination in University students, and to examine whether procrastination can be predicted by academic achievement, self-efficacy, and perfectionism dimensions. 227 University students from different faculties completed Tuckmans' procrastination scale, Almost Perfect Scale--Revised (APS-R; Slaney Rice, Mobley, Trippi, & Ashby, 2001) and General self-Efficacy Scale (GSE; Schwarzer & Jerusalem, 1995), as well as data about academic achievement at the end of last academic year. Results have shown negative correlations of academic achievement, self-efficacy and adaptive perfectionism with procrastination, and a positive correlation between maladaptive perfectionism and procrastination. Results have also shown that self-efficacy is positively correlated with adaptive perfectionism and negatively with maladaptive perfectionism. Maladaptive perfectionism was a positive predictor of procrastination, while academic achievement, self-efficacy and adaptive perfectionism were all negative predictors. Finally, we used Hayes bootstrapping method to examine possible mediations. The results have shown that self-efficacy, by its self, is not a significant mediator, while paths containing self-efficacy and adaptive or maladaptive perfectionism mediate the relation between academic achievement and procrastination. Furthermore, both adaptive and maladaptive perfectionism mediated the relation between self-efficacy and procrastination.

Uterine cancer, according to the latest data from the 2017 Croatian Cancer Registry, is the fourth most common cancer in women in Croatia and ranking eighth in mortality. Most commonly, it is diagnosed in postmenopausal women at the age 50–79. Endometrial cancer diagnosis is determined by pathohistological analysis of curettage or biopsy and the stage of the disease by radiological imaging. In most patients, the disease is diagnosed in the localized stage and is successfully treated surgically; depending on the pathohistological finding, appropriate adjuvant therapy could be applied. Locally advanced disease is most commonly treated surgically with adjuvant therapy, and metastatic with chemotherapy or hormone therapy. Mesenchymal tumors of the uterine body are treated surgically with the addition of systemic adjuvant therapy, or only systemic therapy in the case of metastatic disease. The following manuscript presents clinical guidelines to standardise procedures for the diagnosis, treatment and follow-up of patients with malignant tumors of the uterus in the Republic of Croatia.

Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented through educational programs, vaccination, screening and early detection. In early stages it can also be effectively treated. Treatment modalities include surgery, radiotherapy and systemic therapy according to stage of the disease and patient condition. Treatment decisions should be made through multidisciplinary team meetings that consist of gynecologists, radiologists, clinical oncologists, pathologists, cytologists and if necessary surgeons and urologists. The success rate of the treatment depends significantly on their good and thorough communication and cooperation. Due to the significance and impact of this disease it is important to define and implement a standardized algorithm and approach for diagnostics, treatment and monitoring. The following text presents up-dated and supplemented clinical guidelines for the standardization of the diagnostic criteria, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.

Aim: To evaluate the treatment outcomes, with emphasis on the efficacy and safety of olaparib, in patients with platinum-sensitive, BRCA-mutated, recurrent ovarian cancer treated at the University Hospital Center Split in the period from June 2016 to April 2021. Methods: Data were collected retrospectively from a medical history of 28 patients with platinum-sensitive, BRCAmutated, recurrent ovarian cancer. Medical records were reviewed for clinico-pathological characteristics, number of previous chemotherapy lines and platinum-free interval before olaparib, response to olaparib, survival outcomes (time to disease progression, time from first cycle of olaparib to the first cycle of chemotherapy for the first and second relapse / progression, overall survival) and safety. Median follow up time was 27 months. Results: All patients were BRCA mutated, with a 75% predominance of BRCA1 mutation. The median platinum-free interval was 13 months. Most patients were treated after the first relapse (64%) with a three weekly TC protocol (68%). Olaparib maintenance therapy provided clinical control rate in 43% of cases. The median progression free survival was 24 months. Discontinuation of olaparib treatment was reported due to disease progression in 16 patients. The median time to first subsequent chemotherapy was 31 months and time to second subsequent chemotherapy was 38 months. The tolerability of olaparib was good and the side effects were low intensity. The median overall survival is not reached. Conclusion: This retrospective analysis of patients with platinum-sensitive, BRCA-mutated, recurrent ovarian cancer showed that the treatment outcomes, ie efficacy and tolerability of olaparib after platinum based chemotherapy in everyday clinical practice, are comparable to those observed in clinical trials with olaparib in the same indications.

Introduction. Disease recurrence in patients with the early hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one‐quarter of patients with early‐stage disease will experience disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) gene are highly prevalent (30–40%) in HR+/HER2− advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine the association between and impact of PIK3CA mutation status on disease‐free survival (DFS) in HR+/HER2− early breast cancer patients. Methods. This cohort study was multicentric and retrospective in nature and was conducted at five Croatian institutions from July 2020 to December 2021. The study included initially early and locally advanced operable HR+/HER2− breast cancer patients who were diagnosed with disease recurrence during adjuvant hormonal treatment or within the first six years of follow‐up. Results. A total of 186 patients were included, 40.9% of whom tested positive for the PIK3CA mutation. Primary and adjuvant treatment, particularly adjuvant endocrine treatment, were similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with a positive PIK3CA status and the H1047 PIK3CA mutation had a significantly lower hazard of disease recurrence than patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; false discovery rate, FDR <10%). Conclusions. This study highlights the potential impact of PIK3CA mutations on disease recurrence during or following adjuvant endocrine therapy and potentially opens the door for further investigation of possibly more personalized treatment strategies. [ABSTRACT FROM AUTHOR]

There is growing evidence that arbutin and plant extracts rich in arbutin, such as extracts of the strawberry tree (Arbutus unedo L.), exert a range of beneficial effects, including cyto- and genoprotective properties. This study evaluated the effects of strawberry tree water leaf extract (STE) and arbutin in the brain tissue of Lewis rats. STE or arbutin were administered per os to male and female rats at a dose of 200 mg/kg body weight/day for 14 or 28 days. Treatment outcomes were evaluated using biochemical markers (lipid peroxidation and the activities of the antioxidative enzymes catalase and superoxide dismutase). The effects of the tested substances on DNA integrity in brain cells were evaluated using the alkaline comet assay. The results suggest a high biocompatibility of both tested substances with rat brain tissue. No significant harmful disturbances were observed in the oxidative/antioxidative status or impairments of DNA integrity in the rat brain cells. Nearly all post-treatment values were within tolerable limits as compared to the matched control rats. Such encouraging findings support further research using other subtle biomarkers to clarify the safety aspects of arbutin and STE prior to the development of specific nutraceutical products. [ABSTRACT FROM AUTHOR]

This essay argues that although political thinkers frequently draw on his thought, Friedrich Nietzsche has not been read as a 'thinker of politics' in his own regard because the Euro-American field of political thought owes its very notion of 'politics' to the conceptual heritage Nietzsche's project directly challenges. The first part of the essay traces the prevailing conception of politics to Aristotle, in whose view politics is the quintessentially human (anthropos) activity of organising collective life through reason/speech (logos). The second part presents Nietzsche's project as a novel type of political naturalism, one which replaces the two Aristotelian axioms underpinning standard construals of politics, namely logocentrism and anthropocentrism. For Nietzsche, politics is not a unique, intra-species behaviour of certain bipedal primates, but the relational power dynamics present in all of nature, humans included. Nietzsche's political naturalism thereby gifts us an image of politics befitting the thoroughly entangled, volatile world we urgently have to come to terms with today. [ABSTRACT FROM AUTHOR]

More than two-thirds of the Earth's surface is covered by oceans and yet only a small portion of these oceans has been directly explored in detail, highlighting the need for powerful tools like remote sensing (RS) technology to bridge this gap. International frameworks, the 2030 Agenda for Sustainable Development, and Ocean Decade point out the significance of marine areas for achieving sustainable growth. This study conducts a bibliometric analysis of RS over marine areas for sustainable development to identify key contributors, collaboration networks, and evolving research themes from the beginning of the 21st century until last year. Using the Web of Science Core Collection database, 499 relevant articles published between 2000 and 2023 were identified. The bibliometric analysis showed a significant increase in scientific productivity related to the field. On an international level, China emerges as the most productive country, but international collaboration has played a crucial role, with 36.87% of articles resulting from international co-authorship, pointing to the global nature of research in this field. RS technology has continuously evolved from airborne sensors to the augmentation of Earth Observation missions. Our findings reveal a shift towards automated analysis and processing of RS data using machine learning techniques to integrate large datasets and develop robust scientific solutions. [ABSTRACT FROM AUTHOR]