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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.

Background: The innovativeness of founders and their heirs and family businesses (FBs) is a relatively unexplored field of research, and its understanding is incomplete and inconsistent.

Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer (BC) best practices. A new targetable category termed 'HER2-low' has been identified in tumors previously classified as 'HER2-negative'. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries. [ABSTRACT FROM AUTHOR]

There is a dearth of published literature on the organisation of family medicine/general practice undergraduate teaching in the former Yugoslavia.

Introduction. Lipid profile is one of the main determinants of cardiovascular health status. Moderate and vigorous physical activity can positively influence lipid profile, and one such activity is sport climbing. The main aim of this study was to determine the lipid profile and to investigate the influence of training experience on the lipid profile of youth climbers. Material and Methods. This research included 12 youth climbers aged 15.33 ± 1.30 years (6 males, 6 females), who were tested on anthropo-metric indices and lipid profile (total cholesterol, high-density lipoproteins, low-density lipoproteins, triglycerides) using the point-of-care testing. Variables of lipid profile were correlated with years of climbing experience by Spearman's rank correlation coefficients, while the differences between females and males were checked by the Mann-Whitney U test. Results. Youth climbers had acceptable levels of all measured lipid parameters. Training experience was significantly positively correlated with body mass index (R = 0.76, p < 0.01) and significantly negatively correlated with cholesterol (R = -0.80, p < 0.01). Conclusions. Results support that climbing as a vigorous and enjoyable physical activity might be advertised as a proxy for reaching recommended amounts of physical activity among adolescents, which is associated with improved lipid profile. However, this is only a preliminary investigation advocating that determinants of health status related to climbing practice should be further investigated. [ABSTRACT FROM AUTHOR]

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Lifelong education includes formal and nonformal forms of learning during an individual's life cycle for the conscious and continuous development of one's quality and the quality of life in society. The goal of the research is to identify the most frequent research topics related to lifelong education in economics, business, and management research using a systematic literature review. The study analysed 272 lifelong education papers in Business, Management, and Economics journals using bibliometric analysis, text mining, and Provalis Wordstat content analysis, identifying frequent journals, authors, nations, and funding entities. Research on lifelong education, focusing on older adults, critical thinking, quality of life, poverty reduction, professional training, and human capital, is primarily published in the International Journal of Lifelong Education. Four clusters have been identified. The number of lifelong education papers is increasing, primarily published in educational journals. The most common keywords highlight its focus on human capital, supporting economic and social development. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Terrorist attacks on critical infrastructures can cause problems to a national stability and functioning. Food and water supply chains are some of the most important infrastructures, and it is the country's (government's) obligation to provide sufficient quantities of food and water to its population. Intentional food contamination can, among other motives, originate from an act of terrorism (with political or ideological motives) with the aim of causing fear (terror) among people. Food defence systems can help assess vulnerabilities, determine mitigation strategies for terrorist attack, estimate risks, and prevent a terrorist attack. Risk assessment and prevention also include control over the production and distribution of potential chemical, biological, radiological or nuclear (CBRN) agents or their related materials. When a terrorist attack occurs, rapid and organised response is essential in terms of determining the type of agent used, managing the diseased, ensuring the functioning of the food and water supply, and the recovery of the infrastructure system under attack. Food defence planning as part of a food counterterrorism strategy should include considerations regarding the global food market and the fact that ingredients are supplied from all over the world (vendor certificates). Preventing terrorist attacks on sources of food and water is a far better option than crisis management once an attack had already been committed, but governments should have a response to any scenario. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cheeses as ready-to-eat food should be considered as a potential source of foodborne pathogens, primarily Listeria monocytogenes. The aim of present study was to determine the microbiological quality of soft, semi-hard and hard cheeses during the shelf-life, with particular reference to L. monocytogenes. Five types of cheeses were sampled at different time-points during the cold storage and analyzed for presence of Salmonella and L. monocytogenes, as well as lactic acid bacteria, Escherichia coli, coagulase-positive staphylococci, yeasts, molds, sulfite-reducing clostridia and L. monocytogenes counts. Water activity, pH and NaCl content were monitored in order to evaluate the possibility of L. monocytogenes growth. Challenge test for L. monocytogenes was performed in soft whey cheese, to determine the growth potential of pathogen during the shelf-life of product. All analyzed cheeses were compliant with microbiological criteria during the shelf-life. In soft cheeses, lactic acid bacteria increased in the course of the shelf-life period (1.2-2.6 log increase), while in semi-hard and hard cheeses it decreased (1.6 and 5.2 log decrease, respectively). Soft cheeses support the growth of L. monocytogenes according to determined pH values (5.8-6.5), water activity (0.99-0.94), and NaCl content (0.3-1.2%). Challenge test showed that L. monocytogenes growth potential in selected soft cheese was 0.43 log10 cfu/g during 8 days at 4°C. Water activity in semi-hard and hard cheeses was a limiting factor for Listeria growth during the shelf-life. Soft, semi-hard and hard cheeses were microbiologically stable during their defined shelf-life. Good manufacturing and hygienic practices must be strictly followed in the production of soft cheeses as Listeria-supporting food and be focused on preventing (re)contamination. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nerve agents are highly toxic organophosphorus (OP) compounds. They inhibit acetylcholinesterase (AChE), an enzyme that hydrolyses acetycholine (ACh) in the nervous system. Pathophysiological changes caused by OP poisonings are primarily the consequence of surplus ACh on cholinergic receptors and in the central nervous system. Standard treatment of OP poisoning includes combined administration of carbamates, atropine, oximes and anticonvulsants. In order to improve therapy, new compounds have been synthesised and tested. Tenocyclidine (TCP) and its adamantane derivative 1-[2-(2-thienyl)-2-adamantyl] morpholine (TAMORF) have shown interesting properties against soman poisoning. In this study, we developed a qualitative GC-MS method to measure elimination of TCP and TAMORF through rat urine in order to learn more about the mechanisms through which TCP protects an organism from OP poisoning and to determine the duration of this protective effect. GC-MS showed that six hours after treatment with TCP, rat urine contained only its metabolite 1-thienylcyclohexene, while urine of rats treated with TAMORF contained both TAMORF and its metabolites. [ABSTRACT FROM AUTHOR]

We studied bispyridinium oxime K203 [(E)-1-(4-carbamoylpyridinium) -4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide] with tabun-inhibited human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and its antidotal effect on tabun-poisoned mice and rats in vivo. We compared it with oximes K048 and TMB-4, which have proven the most efficient oxime antidotes in tabun poisoning by now. Tabun-inhibited AChE was completely reactivated by K203, with the overall reactivation rate constant of 1806 L mol-1 min-1. This means that K203 is a very potent reactivator of tabun-inhibited ACHE. In addition, K203 reversibly inhibited AChE (Ki 0.090 mmol L-1) and BChE (Ki = 0.91 mmol L-1), and exhibited its protective effect against phosphorylation of AChE by tabun in vitro. hi vivo, a quarter of the LD50 K203 dose insured survival of all mice after the application of as many as 8 LD50 doses of tabun, which is the highest dosage obtained compared to K048 and TMB-4. Moreover, K203 showed high therapeutic potency in tabun-poisoned rats. preserving cholinesterase activity in rat plasma up to 60 rain after poisoning. This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development. [ABSTRACT FROM AUTHOR]

Study aim: The increase in the number of professional climbers led to the development of climbers since early age. Therefore, the average age of elite climbers has decreased over the last decade. Consequently, age and maturity specifics should be investigated with the influential factors in climbing. This research aimed to investigate the forearm muscle strength in youth sport climbers and determine the gender, age, and maturity status as factors of influence on forearm muscle performance in elite youth climbers.

The paper describes the effect of glucocorticoid dexamethasone (DM) given intraperitoneally on the catalytic activity of butyrylcholinesterase (BuChE) measured in plasma, liver and white adipose tissue of rats of both sexes. Effects of DM on the concentration of plasma lipids and lipoproteins were also tested. Rats were given multiple (2 and 4) pharmacological doses (0.4 and 3.0 mg kg(-1) body mass) of DM. All animals were sacrificed 48 hours after the last dose. Administration of DM significantly decreased the catalytic activity of BuChE in plasma and liver of all treated groups regardless of sex. BuChE catalytic activity in white adipose tissue differed depending on the dose and frequency of administration. In contrast to liver where both doses caused significant BuChE inhibition, the lower DM dose did not inhibit BuChE activity in adipose tissue, and the inhibition achieved by the higher dose was not as strong as in liver. This result corroborates an earlier hypothesis that BuChE is also synthesized in the adipose tissue. DM significantly increased plasma concentrations of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol and decreased the low-density lipoprotein (LDL) cholesterol concentration. Neither positive correlation between BuChE and triglycerides nor negative correlation between BuChE and HDL was found. Changes in lipid profile during DM treatment were not sex- and time-dependent.