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Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-β antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.

Abstract Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, and downstream fibrosis. Despite its increasing prevalence, there is no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models for studying this complex disease. Here, we present a 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture of primary human hepatocytes, Kupffer cells, liver endothelial cells and hepatic stellate cells. Upon exposure to defined and clinically relevant lipotoxic and inflammatory stimuli, these microtissues develop key pathophysiological features of NASH within 10 days, including an increase of intracellular triglyceride content and lipids, and release of pro-inflammatory cytokines. Furthermore, fibrosis was evident through release of procollagen type I, and increased deposition of extracellular collagen fibers. Whole transcriptome analysis revealed changes in the regulation of pathways associated with NASH, such as lipid metabolism, inflammation and collagen processing. Importantly, treatment with anti-NASH drug candidates (Selonsertib and Firsocostat) decreased the measured specific disease parameter, in accordance with clinical observations. These drug treatments also significantly changed the gene expression patterns of the microtissues, thus providing mechanisms of action and revealing therapeutic potential. In summary, this human NASH model represents a promising drug discovery tool for understanding the underlying complex mechanisms in NASH, evaluating efficacy of anti-NASH drug candidates and identifying new approaches for therapeutic interventions.

Introduction and objective Drinking alcohol by adolescents and children poses a risk of long-term psychological and sociological consequences, often leading to addiction in adulthood. A steady increase in the number of young people reaching for alcohol is worrying. The study analyzes the age and gender of the children, concentration of alcohol in the blood, depending on the origin of the youth (urban or rural). Material and Methods The study was a retrospective analysis of 402 patients hospitalized due to alcohol intoxication in the Department of Paediatrics at Medical University in Lublin, Poland between 2004 – 2013. Results During the study period a continuous increase in admissions of patients after alcohol consumption was observed: from 27 children in 2004 to 53 in 2012 and 2013. The youngest patient hospitalized after drinking was 7.6 years old and came from the rural environment, the oldest 18 years old and came from the urban environment. In 2004 – 2007, boys dominated among children intoxicated with alcohol; since 2008, a slight prevalence of girls has been observed, especially in the urban environment. Among patients coming from the country, boys always predominated. In the study period there was noted a similar number of children consuming alcohol from rural and urban environments. Conclusions The results suggest the need to introduce appropriate educational programmes in schools to prevent the consumption of alcohol at a young age.

Bacterial cell adhesion onto mineral surfaces is important in a broad spectrum of processes, including bioweathering, bioleaching, and bacterial cell transport in the soil. Despite many research efforts, a detailed explanation is still lacking. This work investigates the role of surface-active compounds, cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and pure rhamnolipid (RH), in the process of bacteria attachment on the schwertmannite surface. The surface energy was calculated based on the wettability of the tested systems, and for bacteria it was 54.8 mJ/m2, schwertmannite-SDS 54.4 mJ/m2, schwertmannite-CTAB 55.4 mJ/m2, and schwertmannite-RH 39.7 mJ/m2. The total energy of adhesion estimated based on thermodynamic data was found to be negative, suggesting favorable conditions for adhesion for all examined suspensions. However, including electrostatic interactions allowed for a more precise description of bacterial adhesion under the tested conditions. The theoretical analysis using the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) approach showed a negative value of total adsorption energy only in bacteria-mineral suspensions, where SDS and rhamnolipid were added. The calculated data were in good agreement with experimental results indicating the significance of electrostatic forces in adsorption.

AbstractBackground Extremely low-frequency (50 Hz) electromagnetic field (ELF-EMF) is produced by electric power transmission lines and electronic devices of everyday use. Some phenomena are proposed as “first effects” of ELF-EMF: the discrete changes in the membrane potential and the increase of the calcium channel activity as well as the intracellular concentration of Ca 2+ . Interaction of the scorpion alpha toxin with the sodium channel depends on the orientation of the charges and may be perturbed by changes in the membrane polarization. The toxin induces overexcitability in the nervous system and an increase in the neurotransmitters released with different consequences, mainly the paralysis of muscles. We assumed that the exposure to ELF-EMF 0.7 mT will change the effects of the insect selective scorpion alpha toxin (recombinant LqhαIT from Leiurus quinquestriatus hebraeus) at the level of the cercal nerve function, the synaptic transmission and on the level of entire insect organism. Taking into account the compensatory mechanisms in organisms, we tested in addition ten times higher ELF-EMF on whole insects.Methods Experiments were performed in vivo on cockroaches (Periplaneta americana) and in vitro – on isolated cockroach abdominal nerve cord with cerci. In biotests, the effects of LqhαIT (10 −8 M) were estimated on the basis of the insect ability to turn back from dorsal to ventral side. Three groups were compared: the control one and the two exposed to ELF-EMF – 0.7 and 7 mT. Bioelectrical activity of the cercal nerve and of the connective nerve that leaves the terminal abdominal ganglion was recorded using extracellular electrodes. LqhαIT (5 × 10 −8 M) induced modifications of neuronal activity that were observed in the control cockroach preparations and in the ones exposed to ELF-EMF (0.7 mT). The exposure to ELF-EMF was carried out using coils with a size appropriate to the examined objects.Results The exposure to ELF-EMF (0.7 mT) modified the effects of LqhαIT (5 × 10−8 M) on activity of the cercal nerve and of the connective nerve. We observed a decrease of the toxin effect on the cercal nerve activity, but the toxic effect of LqhαIT on the connective nerve was increased. Biotests showed that toxicity of LqhαIT (10 −8 M) on cockroaches was reduced by the exposure to ELF-EMF (0.7 and 7 mT).Conclusions The exposure to 50 Hz ELF-EMF modified the mode of action of the anti-insect scorpion alpha toxin LqhαIT at cellular level of the cockroach nervous system and in biotests. Toxin appeared as a usefull tool in distinguishing between the primary and the secondary effects of ELF-EMF.

Cerebrovascular diseases (including strokes) are currently the second leading cause of death in the world [1,2]. In Poland, statistical data are quite diverse, depending on their source. Stroke patients are often at risk of chronic disability. A significant number of them are doomed to lose their independence and self-care for the rest of their lives. The aim of the study is to present selected nursing problems and ways to solve them in a patient after ischemic stroke who requires round-the-clock care in the field of nursing and care services as part of inpatient long-term care. The subject of the study is the process of nursing a patient diagnosed with ischemic stroke who requires round-the-clock care in the field of nursing and care services as part of long-term care. The study uses a research method - a case study, supported by individual observation, measurements, interview and analysis of medical records. Two scales were used to assess the patient's condition: Barthel and Norton. Conclusions: • The individual care plan takes into account the most important problems arising from the specificity of the disease entity, needs and individual situation of the patient. • The patient's care problems after a stroke are presented and proposed an effective solution to ensure the best possible care. • Nursing and care difficulties have been properly recognized, which has enabled appropriate nursing interventions. • Due to systematic prophylactic measures, the patient did not suffer from complications. • A detailed interview and careful observation made it possible to plan and implementation of interventions (not only nursing) to provide comprehensive care. • The urgent procedure of admitting the patient to the care and treatment facility contributed to the improvement of the quality and availability of health care services, which translated into an improvement in the patient's general condition.

This paper will discuss the Wiindigo, a cannibalistic character among some Indigenous peoples of North America. Illustrated through the Anishinaabeg and Oji-Cree, two Algonquin-speaking Indigenous groups, the Wiindigo serves as a personification of fear and hunger, and alludes to the cultural heritage elements of the boreal forest food system as well as the differing legal systems in Canada. In examining the Wiindigo from the Indigenous cultural and historical perspectives related to the author by several knowledge-holders, as well as from EuroCanadian popular culture representations, the paper illustrates the importance of the Wiindigo to Anishinaabe and Oji-Cree world views, customary governance, and contemporary lived experience.

Social councils (SCs) are local collegial actors formally created by local authorities as consultative bodies for different policy issues. The main objective of this article is to define the role of SCs in collaborative governance (CG). The paper is based on the quantitative research conducted in 65 Polish cities. The research is focused on the members of youth, senior citizen councils, and councils for residents with disabilities. The research results indicate that SCs meet many of the prerequisites of CG, however their potential to influence decisions and consensus seeking has not been entirely proven.

Abstract Background The differences between adults and children in inflammatory bowel disease (IBD) phenotype, severity, complications, co-morbidities, and response to the therapy resulted in the extraction of paediatric IBD. It has been revealed that the substantial role in the development of IBD in children under 6 years of age plays a single genetic mutation (monogenic IBD). On the other hand, in older children and adolescents IBD is usually associated with number of interactions between susceptibility loci (polygenic IBD). Main body Until now there have been described about 60 monogenic defects which affect the variety of immune mechanisms in IBD pathogenesis including epithelial barrier, function of neutrophil granulocytes and phagocytes, T- and B-cell selection and activation, immune inhibitory mechanisms, or apoptosis. Il-10 is an anti-inflammatory cytokine which modulates innate and adaptive immunity affecting expression of pro-inflammatory molecules and function of the variety of immune cells. Patients with identified defects in Il-10 pathway manifest with life-threating colitis with perianal lesions which occurs within first months of life. Allogenic hematopoietic stem cell transplantation is curative therapy in children with Il-10 signalling defects. Conclusion Clinical awareness of Il-10 signalling defects enables early recognition and prompt management of the disease.

Acute pancreatitis (AP) appears to be rare disease in childhood. In children, it has a different aetiology and course, and requires different management than in adult patients. The diagnosis of AP is based on at least two of the three criteria, which include typical clinical symptoms, abnormalities in laboratory tests and/or imaging studies of the pancreas. There are many known causes leading to AP in children including infections, blunt abdominal trauma, genetic factors, gallstone disease, metabolic disorders, anatomical defects of the pancreas, systemic diseases, as well as drugs, including antiepileptic drugs, and especially preparations of valproic acid. In our study, we present four cases of young patients diagnosed with acute pancreatitis as a complication of valproic acid therapy and we present a review of the literature. We believe that the activity of pancreatic enzymes should be monitored in children treated with valproate preparations in the case of clinical symptoms suggesting AP.

In the recent years we have witnessed the growing criticism of the representative framework and the way it operates in many European countries. At the local level, numerous authorities try to answer the shortcomings of representation by applying new participatory agendas. This, however, not only influences the governing process, but also often leads to the clash between elected politicians and citizens. By examining the attitudes of local councilors from Finland and Poland toward citizens’ involvement, the present article contributes to the discussion on the coexistence of representative and participative schedules. The analysis draws on empirical data gathered in selected municipalities of both countries. The research findings demonstrate that, in spite of different governing models, the Finnish and Polish local representatives have quite similar, positive attitudes towards increasing the citizens’ direct involvement. However, they still consider voting in local elections the key instrument of civic engagement. The results of the research also display the barriers the expanded participative framework encounters and this can be interesting for local practitioners who design participative instruments and monitor their operation.

The aim of this study was to test the effect of hyaluronic acid cross-linked with polyethylene glycol containing micronized portions of calcium hydroxyapatite (Neauvia Stimulate) on both local tissue and systemic consequences, which are crucial from the perspective of long-term safety, in patients suffering from Hashimoto’s disease. This most common autoimmune disease is a frequently mentioned contraindication to the use of fillers based on hyaluronic acid as well as biostimulants based on calcium hydroxyapatite. Broad-spectrum aspects of histopathology were analyzed to identify key features of inflammatory infiltration before the procedure and 5, 21, and 150 days after the procedure. A statistically significant effect on the reduction of the intensity of the inflammatory infiltration in the tissue in relation to the state before the procedure was demonstrated, combined with a reduction in the occurrence of both antigen-recognizing (CD4) and cytotoxic (CD8) T lymphocytes. With complete statistical certainty, it was demonstrated that the treatment with Neauvia Stimulate had no effect on the levels of these antibodies. All this corresponds with the risk analysis that showed no alarming symptoms during the time of observation. The choice of hyaluronic acid fillers cross-linked with polyethylene glycol should be considered justified and safe in the case of patients suffering from Hashimoto’s disease.

Celem artykułu jest przedstawienie roli rządu federalnego jako jednego z aktorów uczestniczących w polityce rozwoju miast amerykańskich w latach 1965–2012. Paradoks implementacji, rozumiany jako ograniczenie możliwości osiągania celów polityk krajowych w związku z poszerzeniem kompetencji ich potencjalnych oponentów oraz zmieniające się poglądy kolejnych prezydentów na federalizm zostały uznane za kluczowe w wyjaśnianiu tytułowego zagadnienia. Posłużono się kategoriami: federalizmu, orientacji i instrumentów rozwoju oraz nakładów finansowych na rozwój. Orientacja i instrumenty rozwoju zostały przedstawione na podstawie wybranych programów federalnych adresowanych do miast, nakłady zaś – na podstawie budżetów federalnych. Ramy teoretyczne pracy stanowią trzy generacje teorii implementacji polityk publicznych. W konkluzji autorka wskazuje na wycofywanie się rządu federalnego i rosnące znaczenie władz stanowych w polityce rozwoju miast.

INTRODUCTION. Pain in the lower spine is an issue that should be considered on many levels - not only from the medical but also social and professional. Disease They limit the physical and consequently contribute to the deterioration of the quality of life. AIM OF THE TESTS. The aim of the study was to evaluate and compare the quality of life of patients with pain syndrome lumbar-sacral spine outpatient rehabilitation treatments before and after. MATERIALS AND METHODS. The study involved 70 patients (34 women and 36 men) who were subjected for 10 days a series of outpatient physiotherapy. The average age of the study group was 58.26 years and a mean BMI was equal to 27.78 kg / m2. Studies performed by a survey tool, based on an original questionnaire containing socio-demographic data. In order to determine the intensity of pain was used analog - visual scale VAS pain, and to evaluate the quality of life questionnaire ODI (Oswestry Disability Index). The statistical analysis was made using Statistica. RESULTS. Examined the quality of life before treatment was 21.13 on a scale ODI, and after a series of treatments - 14.73. The average value expressed in pain VAS before treatment was 6.73 and 4.27 after surgery. In both cases there was a statistically significant difference before and after the level of p

Referendum as an Indicator of the Model of Local Democracy (with Particular Emphasis on the Local Referendum in the United States of America) A model approach to local democracy is proposed through this paper. It also refers to four models of local democracy – representative, hybrid, semi-direct, and direct. Each model is illustrated by an example anchored in one of the European nation states, with special attention payed to the referendum and its role in local decision making. The author formulates the hypothesis that the role of a referendum in American municipal corporations situates them in a model of semi-direct democracy and discusses the constitutional and statutory conditions of the local referendum in American states. The article also analyses the scope of referendum, in reference to the initiating players, issues put to the vote and procedures through several examples. It stresses upon the importance of judicial review. In conclusion, the author refers to the hybrid democracy model that emerges in state politics and juxtaposes it with semi-direct democracy in localities.

The MRKH syndrome has a negative impact on the psychosocial status of a patient and her family. The treatment of aplasia/hypoplasia of the vagina requires an interdisciplinary approach. The choice of treatment and its acceptance by a patient is crucial for the successful therapy. Therefore, it requires careful selection of treatments suited for anatomical conditions and patient’s emotional state and also good cooperation between a patient and the therapeutic team at every stage of treatment. Young women should be mentally and substantively prepared for phantomisation of vagina and undertaking sexual activity. To ensure a proper functionality of the newly formed vagina, the sexual care is indispensable for many women with the MKHR syndrome and their partners.

Introduction Intentional poisonings among children and adolescents are a problem not only for paediatricians, but also constitute a big issue for public health. In many countries worldwide, including Poland, an increase has been observed in suicidal behaviours at developmental age. Objective The aim of the study was a retrospective evaluation of patients hospitalized due to intentional poisoning in the Department of Paediatrics, Children’s University Hospital in Lublin, Poland, in 2007–2012. Material and Methods In the study period, 149 patients were hospitalized in the Paediatric Department of the Children’s University Hospital in Lublin, due to intentional poisoning with medicines or other chemical substances. The study group comprised 135 girls and 14 boys; The majority of patients (n=105) were urban inhabitants, and only 44 lived in the rural areas. Medical records were analyzed, with consideration of medical, psychological and psychiatric examinations. Results Girls constituted as much as 90.6% of the study group. The majority of patients lived in urban areas – 70.46%. A total of 16.77 % of patients came from incomplete families. Alcohol problem occurred in 19 families. The most frequent cause of a suicide attempt was conflict in the family, followed by school problems. During the 6-year-study period, an upward tendency in the incidence of intentional poisoning was observed, particularly in the first 4 years. Discussion and conclusion Suicide attempts in adolescents were mostly undertaken by girls from the urban environment. The majority of those attempts were caused by family problems, including alcoholism.