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The National Colorectal Cancer Early Detection Program was launched towards the end of 2007. The Croatian Society for Oncology contributed signifi cantly to the development of the National Colorectal Cancer Early Detection Program. The Program aims to decrease colorectal cancer (CRC) mortality by 15% in the fi rst fi ve years of the Program’s implementation, by covering 75% of the population aged 50-74 years by 2015. The Program is based on fecal occult blood test (FOBT) screening every two years. Program coordinators are the Croatian Institute of Public Health (CIPH) and regional Institutes for Public Health. The proportion of screened persons is 25% and is insuffi cient for achieving the goals of the National Program. It is considered that family medicine doctors and community health nurses need to get involved more actively in the Program by motivating the persons invited for screening.

Traumatic brain injury (TBI), which is a global public health concern, can take various forms, from mild concussions to blast injuries, and each damage type has a particular mechanism of progression. However, TBI is a condition with complex pathophysiology and heterogenous clinical presentation, which makes it difficult to model for in vitro and in vivo studies and obtain relevant results that can easily be translated to the clinical setting. Accordingly, the pharmacological options for TBI management are still scarce. Since a wide spectrum of processes, such as glucose homeostasis, food intake, body temperature regulation, stress response, neuroprotection, and memory, were demonstrated to be modulated after delivering glucagon-like peptide 1 (GLP-1) or GLP-1 receptor agonists into the brain, we aimed to speculate on their potential role in TBI management by comprehensively overviewing the preclinical and clinical body of evidence. Based on promising preclinical data, GLP-1 receptor agonists hold the potential to extend beyond metabolic disorders and address unmet needs in neuroprotection and recovery after TBI, but also other types of central nervous system injuries such as the spinal cord injury or cerebral ischemia. This overview can lay the basis for tailoring new research hypotheses for future in vitro and in vivo models in TBI settings. However, large-scale clinical trials are crucial to confirm their safety and efficacy in these new therapeutic applications.

AbstractThe aim of this study was to determine the influence of joining university on dietary habits, intake of food, and physical activity of students at the Biotechnical Faculty of the University of Ljubljana. Overall, 226 students (82.3% female) self-evaluated their dietary habits and their physical activity before and after starting university. A change in dietary habits was evident for the majority of the students (female: 74.7%; male: 67.5%). After starting their studies, ~20% of students consumed less fruits and vegetables, and only 28.8% and 15.5% of the students consumed fresh fruit and fresh vegetables, respectively, more than once a day. Female students were more likely to prepare home-cooked meals (almost 50%; at least 4 times a week), while male students were more likely to eat in restaurants with subsidised meals. Approximately 70% of the students reported negative changes in their motor skills after starting university and of these, 90% also reported negative change in their dietary habits, as evidenced by higher consumption of savoury snacks and lower consumption of fresh vegetables. Since our results show a negative influence of joining university on dietary habits and physical activity, more attention needs to be paid to the critical factors involved.

“Basal-like” (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy.

To present the response rate results of the Colorectal Cancer Early Detection Program that is part of the project Colorectal Cancer Early Detection Model Integrated in the Practice of Family Medicine, carried out by the Department of Family Medicine of the Osijek University School of Medicine and the Osijek Health Center in the Osijek-Baranja County. Those response rate results were compared with those obtained by the National Colorectal Cancer Early Detection Program. The Project’s strategy is based on the central role of family physicians in implementing early cancer detection programs. The Project started in the year 2007, and by the end of 2009, a total of 1850 cards on an occult fecal blood test (FOBT) were delivered to subjects from two target groups (aged 45-49 and 75-79), i.e., to age groups not covered by the National Colorectal Cancer Early Detection Program. A relatively high response rate of 1083 tested subjects (58.5%) was recorded for both target groups, which is an advantage in comparison with the relatively low response rate of 19.9% obtained by the end of 2010 by the Croatian National Program. The Project revealed positive FOBT results in 54 subjects (4.9%). Of these subjects, 28 underwent colonoscopies, and two had colon cancer detected. The results indicate that family physicians should actively participate in the National Colorectal Cancer Early Detection Program.

Previous studies have revealed the extraordinarily large catalytic efficiency of some enzymes. High catalytic proficiency is an essential accomplishment of biological evolution. Natural selection led to the increased turnover number, kcat, and enzyme efficiency, kcat/KM, of uni–uni enzymes, which convert a single substrate into a single product. We added or multiplied random noise with chosen rate constants to explore the correlation between dissipation and catalytic efficiency for ten enzymes: beta-galactosidase, glucose isomerase, β-lactamases from three bacterial strains, ketosteroid isomerase, triosephosphate isomerase, and carbonic anhydrase I, II, and T200H. Our results highlight the role of biological evolution in accelerating thermodynamic evolution. The catalytic performance of these enzymes is proportional to overall entropy production—the main parameter from irreversible thermodynamics. That parameter is also proportional to the evolutionary distance of β-lactamases PC1, RTEM, and Lac-1 when natural or artificial evolution produces the optimal or maximal possible catalytic efficiency. De novo enzyme design and attempts to speed up the rate-limiting catalytic steps may profit from the described connection between kinetics and thermodynamics.

Traumatic brain injury (TBI), which is a global public health concern, can take various forms, from mild concussions to blast injuries, and each damage type has a particular mechanism of progression. However, TBI is a condition with complex pathophysiology and heterogenous clinical presentation, which makes it difficult to model for in vitro and in vivo studies and obtain relevant results that can easily be translated to the clinical setting. Accordingly, the pharmacological options for TBI management are still scarce. Since a wide spectrum of processes, such as glucose homeostasis, food intake, body temperature regulation, stress response, neuroprotection, and memory, were demonstrated to be modulated after delivering glucagon-like peptide 1 (GLP-1) or GLP-1 receptor agonists into the brain, we aimed to speculate on their potential role in TBI management by comprehensively overviewing the preclinical and clinical body of evidence. Based on promising preclinical data, GLP-1 receptor agonists hold the potential to extend beyond metabolic disorders and address unmet needs in neuroprotection and recovery after TBI, but also other types of central nervous system injuries such as the spinal cord injury or cerebral ischemia. This overview can lay the basis for tailoring new research hypotheses for future in vitro and in vivo models in TBI settings. However, large-scale clinical trials are crucial to confirm their safety and efficacy in these new therapeutic applications. [ABSTRACT FROM AUTHOR]

Tropaeolum majus L. is a traditional medicinal plant with a wide range of biological activities due to the degradation products of the glucosinolate glucotropaeolin. Therefore, the goals of this study were to identify volatiles using gas chromatography–mass spectrometry analysis (GC-MS) of the hydrosols (HYs) isolated using microwave-assisted extraction (MAE) and microwave hydrodiffusion and gravity (MHG). Cytotoxic activity was tested against a cervical cancer cell line (HeLa), human colon cancer cell line (HCT116), human osteosarcoma cell line (U2OS), and healthy cell line (RPE1). The effect on wound healing was investigated using human keratinocyte cells (HaCaT), while the antibacterial activity of the HYs was tested against growth and adhesion to a polystyrene surface of Staphylococcus aureus and Escherichia coli. Antiphytoviral activity against tobacco mosaic virus (TMV) was determined. The GC-MS analysis showed that the two main compounds in the HYs of T. majus are benzyl isothiocyanate (BITC) and benzyl cyanide (BCN) using the MAE (62.29% BITC and 15.02% BCN) and MHG (17.89% BITC and 65.33% BCN) extraction techniques. The HYs obtained using MAE showed better cytotoxic activity against the tested cancer cell lines (IC50 value of 472.61–637.07 µg/mL) compared to the HYs obtained using MHG (IC50 value of 719.01–1307.03 μg/mL). Both concentrations (5 and 20 µg/mL) of T. majus HYs using MAE showed a mild but statistically non-significant effect in promoting gap closure compared with untreated cells, whereas the T. majus HY isolated using MHG at a concentration of 15 µg/mL showed a statistically significant negative effect on wound healing. The test showed that the MIC concentration was above 0.5 mg/mL for the HY isolated using MAE, and 2 mg/mL for the HY isolated using MHG. The HY isolated using MHG reduced the adhesion of E. coli at a concentration of 2 mg/mL, while it also reduced the adhesion of S. aureus at a concentration of 1 mg/mL. Both hydrosols showed excellent antiphytoviral activity against TMV, achieving100% inhibition of local lesions on the leaves of infected plants, which is the first time such a result was obtained with a hydrosol treatment. Due to the antiphytoviral activity results, hydrosols of T. majus have a promising future for use in agricultural production.

Introduction The COVID-19 pandemic has threatened the mental health of individuals around the world. Ex-combatants have been repeatedly shown to be increased risk of experiencing social and psychological problems during emergencies. Objectives To compare the severity of overall posttraumatic stress disorder (PTSD) symptoms and PTSD clusters among help-seeking veterans before and during the COVID-19 pandemic. The second aim was to identify coping strategies used and track possible changes during the timeline. Methods Male war veterans receiving outpatient treatment at the Referral Center for PTSD were assessed at baseline (t1=12-18 months before the COVID-19 pandemic), during the first lockdown (March-June 2020) and 12 months after the beginning of the COVID-19 pandemic (March-June 2021). A total of 132 veterans participated in all three measurements. The Life Events Checklist for DSM-5 (LEC-5), PTSD Checklist for DSM-5 (PCL-5), and The Brief COPE were used. Results Exposure to COVID-19 pandemic related stressors increased over time. The great majority of participants (91.0%) followed the preventive measures. The severity of the overall PTSD symptoms significantly decreased during timeline (t1=56.9, 11.15; t2= 47.24, SD=12.87; t3= 44.1, SD=14.09). At t2, all participants still fulfilled the PTSD diagnostic criteria, and at t3, 23 participants (17.42%) did not meet all of the criteria for PTSD. The participants used adaptive coping rather than dysfunctional coping during the pandemic. Conclusions Despite the expectations of worsening the symptoms, help-seeking veterans with PTSD appeared to develop adaptive adjustment to the COVID-19 pandemic stressors, which is in line with the results of the recent longitudinal research and will be discussed. Disclosure No significant relationships.

Pharmaceuticals are characterized by a wide range of physical, chemical, and biological properties and functionalities that contribute to their inherent complexity as compounds. Unfortunately, human carelessness during the production, use, and disposal of these compounds results in their presence in the environment. This study utilized a nanostructured TiO2 film on a glass ring at the bottom of a reactor and simulated a solar radiation lamp as the radiation source for both photocatalytic and photolytic experiments, with the aim of unraveling the mechanism behind the degradation of trimethoprim (TMP), a pharmaceutical compound. This approach provides a novel perspective on the role of TiO2 in the degradation of pharmaceuticals and could pave the way for more efficient and sustainable wastewater treatment methods. Scavenger studies were carried out using isopropanol, ammonium oxalate, and triethanolamine to examine the photocatalytic mechanism. Isopropanol and triethanolamine were found to impede the photocatalytic degradation of TMP, highlighting the significance of hydroxyl radicals and positive holes in the degradation process, while no inhibition was observed in the presence of ammonium oxalate. The complete degradation of TMP through photocatalysis under simulated solar radiation was observed in ultra-pure water in fewer than 3 h, as indicated by the results. Our findings suggest that utilizing natural solar radiation as a source of UV-A radiation in reactor configurations based on this approach holds promise for cost-effective pharmaceutical degradation treatment in wastewater treatment plants. The practical potential of this approach is supported by the results obtained under simulated solar radiation with an irradiation intensity in the UV-A region of 33 ± 2 W/m2.

Increase in body fat contributes to loss of function and changes in skeletal muscle, accelerating sarcopenia, a phenomenon known as sarco-obesity or sarcopenic obesity. Studies suggest that obesity decreases the skeletal muscle (SM)’s ability to oxidize glucose, increases fatty acid oxidation and reactive oxygen species production, due to mitochondrial dysfunction. Exercise improves mitochondrial dysfunction in obesity; however, it is not known if exercise regulates the mitochondrial unfolded protein response (UPRmt) in the SM. Our study aimed to determine the mito-nuclear UPRmt in response to exercise in a model of obesity, and how this response is associated with the improvement in SM functioning after exercise training. C57BL/6 mice were fed a normal diet and high-fat diet (HFD) for 12 weeks. After 8 weeks, animals were subdivided into sedentary and exercised for the remaining 4 weeks. Grip strength and maximal velocity of mice submitted to HFD improved after training. Our results show an increase in the activation of UPRmt after exercise while in obese mice, proteostasis is basally decreased but shows a more pronounced increase with exercise. These results correlate with improvement in the circulating triglycerides, suggesting mitochondrial proteostasis could be protective and could be related to mitochondrial fuel utilization in SM.

With the progress of medicine, especially in the last century, life expectancy increased considerably. As a result, age-related diseases also increased, especially malignancies and degenerative diseases of the central nervous system. The incidence and prevalence of neurodegenerative diseases steadily increased over the years, but despite efforts to uncover the pathophysiological processes behind these conditions, they remain elusive. Among the many theories, oxidative stress was proposed to be involved in neurodegenerative processes and to play an important role in the morbidity and progression of various neurodegenerative disorders. Accordingly, a number of studies discovered the potential of natural plant constituents to have significant antioxidant activity. This review focused on several plant-based antioxidants that showed promising results in the prevention and treatment of neurodegenerative diseases. Laurus nobilis, Aronia melanocarpa, and celastrol, a chemical compound isolated from the root extracts of Tripterygium wilfordii and T. regelii, are all known to be rich in antioxidant polyphenols.

No alternatives are currently available to operate industrial furnaces, except for hydrocarbon fuels. Plant managers, therefore, face at least two challenges. First, environmental legislation demands emission reduction. Second, changes in the origin of the fuel might cause unforeseen changes in the heat release. This paper develops the hypothesis for the detailed control of the combustion process using computational fluid dynamic models. A full-scale mock-up of a rotary cement kiln is selected as a case study. The kiln is fired by the non-premixed combustion of Dutch natural gas. The gas is injected at Mach 0.6 via a multi-nozzle burner located at the outlet of an axially mounted fuel pipe. The preheated combustion air is fed in (co-flow) through a rectangular inlet situated above the attachment of the fuel pipe. The multi-jet nozzle burner enhances the entrainment of the air in the fuel jet. A diffusion flame is formed by thin reaction zones where the fuel and oxidizer meet. The heat formed is transported through the freeboard, mainly via radiation in a participating medium. This turbulent combustion process is modeled using unsteady Favre-averaged compressible Navier–Stokes equations. The standard k-ϵ equations and standard wall functions close the turbulent flow description. The eddy dissipation concept model is used to describe the combustion process. Here, only the presence of methane in the composition of the fuel is accounted for. Furthermore, the single-step reaction mechanism is chosen. The heat released radiates throughout the freeboard space. This process is described using a P1-radiation model with a constant thermal absorption coefficient. The flow, combustion, and radiative heat transfer are solved numerically using the OpenFoam simulation software. The equations for flow, combustion, and radiant heat transfer are discretized on a mesh locally refined near the burner outlet and solved numerically using the OpenFoam simulation software. The main results are as follows. The meticulously crafted mesh combined with the outlet condition that avoids pressure reflections cause the solver to converge in a stable manner. Predictions for velocity, pressure, temperature, and species distribution are now closer to manufacturing conditions. Computed temperate and species values are key to deducing the flame length and shape. The radiative heat flux to the wall peaks at the tip of the flame. This should allow us to measure the flame length indirectly from exterior wall temperature values. The amount of thermal nitric oxide formed in the flame is quantified. The main implication of this study is that the numerical model developed in this paper reveals valuable information on the combustion process in the kiln that otherwise would not be available. This information can be used to increase fuel efficiency, reduce spurious peak temperatures, and reduce pollutant emissions. The impact of the unsteady nature of the flow on the chemical species concentration and temperature distribution is illustrated in an accompanying video.

Nature’s way for bioactive peptides is to provide them with several related functions and the ability to cooperate in performing their job. Natural cell-penetrating peptides (CPP), such as penetratins, inspired the design of multifunctional constructs with CPP ability. This review focuses on known and novel peptides that can easily reach intracellular targets with little or no toxicity to mammalian cells. All peptide candidates were evaluated and ranked according to the predictions of low toxicity to mammalian cells and broad-spectrum activity. The final set of the 20 best peptide candidates contains the peptides optimized for cell-penetrating, antimicrobial, anticancer, antiviral, antifungal, and anti-inflammatory activity. Their predicted features are intrinsic disorder and the ability to acquire an amphipathic structure upon contact with membranes or nucleic acids. In conclusion, the review argues for exploring wide-spectrum multifunctionality for novel nontoxic hybrids with cell-penetrating peptides.