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Objective: Because free sample of prescription medications have been shown to influence prescribing habits of physicians, we sought to discern if promotional efforts of a retail pharmacy influenced prescriptions filled in our county after a free antibiotic program was initiated. Methods: Retrospective analysis of prescription antibiotics filled throughout the county was performed. Prescriptions filled during the first 6 months of the year before the program was initiated were compared to prescriptions filled during the first 6 months of the year immediately following initiation of the promotion. Results: A total of 436,372 antibiotic prescriptions were dispensed during that time. The number of antibiotics filled that were included in the promotion increased by 13.4% while the number of antibiotics filled that were excluded from the promotion decreased by 20.4%. Conclusion: These data suggest that the promotional pricing of the antibiotics had a significant impact on the number of prescriptions filled in each category. Because a prescription written does not always equate to a prescription filled, further investigation is needed to confirm the relationship between these promotions and actual prescriber habits.

Abstract Background Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.

Abstract Background Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES - Paediatric Asthma Gene Environment Study). Methods Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. Results To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV1 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. Conclusions It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

The purpose of the study was to assess the radiological risk to users and the environment related to the Glo system used to heat tobacco. The concentration of 210 Po, radioactivity per cartridge, and radiation dose assessment were evaluated. For comparison purposes, to present the exposure scale, the same analyses were also performed for several traditional cigarettes. The tests were carried out on an alpha spectrometer equipped with a PIPS detector. After examining 60 samples, the concentration of 210 Po was found in tobacco that was a filling of Neo cartridges and in traditional cigarettes. 210 Po concentrations [in mBq∙g -1 ] in heated tobacco were higher than in unheated. After heating, a little release of polonium (mBq per cartridge) was observed. The research was also done taking into account the flavor of the Neo cartridges and cartridges from different packages. The 210 Po concentrations in heated Neo cartridges were greater than 30 mBq∙g -1 and in traditional cigarettes up to 50 mBq∙g -1 . The estimated annual effective dose for Neo cartridges was lower than that for traditional smoking. However, it cannot be concluded that the use of Neo cartridges is healthier and does not affect the environment. What is disturbing is the increase in the number of cartridges used daily, resulting in the creation of waste containing 210 Po and, of course, a higher effective dose received by the user., Competing Interests: Declarations. Ethics approval: The study did not require ethical approval since it didn’t involve human subjects and/or animals. Consent to participate: All the authors mentioned in the manuscript have agreed for authorship and read and approved the manuscript. Consent for publication: All the authors mentioned in the manuscript have given consent for submission and subsequent publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The aim of the study was to estimate the degree of anthropogenic risk by evaluating the level of the contamination of sediments collected from the Rybnik reservoir. The results of the determination of radionuclides ( 137 Cs, 40 K, 228 Th, 228 Ra, 226 Ra, 210 Pb, 238 U) and heavy metals (Zn, Cd, Pb, Cu, Cr, Ni) were presented. The Rybnik reservoir is located in a highly urbanised area, the Lower Silesian Voivodeship in Poland. Radionuclides ( 137 Cs, 40 K, 228 Th, 228 Ra, 226 Ra, 210 Pb, 238 U) were measured using gamma spectrometry. The heavy metal (Zn, Cd, Pb, Cu, Ni and Cr) content was determined using an inductively coupled plasma optical emission spectrophotometer (ICP-OES). The classification of sediment pollution was made on the basis of geochemical and ecotoxicological indices. Radioactivity was varied with the highest for 40 K (more than 200 Bq·kg -1 ). The concentrations for the remaining radionuclides were mostly below 20 Bq·kg -1 . At the inlet zone (no. 9) an increase in radioactivity of each radioisotope was observed. The values of heavy metals from the lowest to the highest total amount in the sediments were as follows: Cd < Cr < Pb < Ni < Cu < Zn. The sediments of the reservoir are largely contaminated with Cu, but the sediments generally are contaminated to an average degree. Most pollutants accumulate in the inlet zone and near the dam wall. The content of artificial radionuclides, as well as the geochemical and ecological indicators used, can serve as an indicator of the level of anthropopressure in the vicinity of the Rybnik reservoir., (© 2024. The Author(s).)

This paper presents an innovative approach to the integration of thermoelectric microgenerators (μTEGs) based on thick-film thermopiles of planar constantan-silver (CuNi-Ag) and calcium cobaltite oxide-silver (Ca 3 Co 4 O 9 -Ag) thick-film thermopiles with radio frequency identification (RFID) technology. The goal was to consider using the TEG for an active or semi-passive RFID tag. The proposed implementation would allow the communication distance to be increased or even operated without changing batteries. This article discusses the principles of planar thermoelectric microgenerators (μTEGs), focusing on their ability to convert the temperature difference into electrical energy. The concept of integration with active or semi-passive tags is presented, as well as the results of energy efficiency tests, considering various environmental conditions. On the basis of the measurements, the parameters of thermopiles consisting of more thermocouples were simulated to provide the required voltage and power for cooperation with RFID tags. The conclusions of the research indicate promising prospects for the integration of planar thermoelectric microgenerators with RFID technology, opening the way to more sustainable and efficient monitoring and identification systems. Our work provides the theoretical basis and practical experimental data for the further development and implementation of this innovative technology.

Background: We are currently experiencing a third digital revolution driven by artificial intelligence (AI), and the emergence of new chat generative pre-trained transformer (ChatGPT) represents a significant technological advancement with profound implications for global society, especially in the field of education., Methods: The aim of this study was to see how well ChatGPT performed on medical school exams and to highlight how it might change medical education and practice. Recently, OpenAI's ChatGPT (OpenAI, San Francisco; GPT-4 May 24 Version) was put to the test against a significant Polish medical specialization licensing exam (PES), and the results are in. The version of ChatGPT-4 used in this study was the most up-to-date model at the time of publication (GPT-4). ChatGPT answered questions from June 28, 2023, to June 30, 2023., Results: ChatGPT demonstrates notable advancements in natural language processing models on the tasks of medical question answering. In June 2023, the performance of ChatGPT was assessed based on its ability to answer a set of 120 questions, where it achieved a correct response rate of 67.1%, accurately responding to 80 questions., Conclusions: ChatGPT may be used as an assistance tool in medical education. While ChatGPT can serve as a valuable tool in medical education, it cannot fully replace human expertise and knowledge due to its inherent limitations.

Hypercholesterolemia affects the neurovascular unit, including the cerebral blood vessel endothelium. Operation of this system, especially in the context of energy metabolism, is controlled by extracellular concentration of purines, regulated by ecto-enzymes, such as e-NTPDase-1/CD39, ecto-5'-NT/CD73, and eADA. We hypothesize that hypercholesterolemia, via modulation of the activity of nucleotide metabolism-regulating ecto-enzymes, deteriorates glycolytic efficiency and energy metabolism of endothelial cells, which may potentially contribute to development of neurodegenerative processes. We aimed to determine the effect of hypercholesterolemia on the concentration of purine nucleotides, glycolytic activity, and activity of ecto-enzymes in the murine brain microvascular endothelial cells (mBMECs). We used 3-month-old male LDLR -/- /Apo E -/- double knockout mice to model hypercholesterolemia and atherosclerosis. The age-matched wild-type C57/BL6 mice were a control group. The intracellular concentration of ATP and NAD and extracellular activity of the ecto-enzymes were measured by HPLC. The glycolytic function of mBMECs was assessed by means of the extracellular acidification rate (ECAR) using the glycolysis stress test. The results showed an increased activity of ecto-5'-NT and eADA in mBMECs of the hypercholesterolemic mice, but no differences in intracellular concentration of ATP, NAD, and ECAR between the hypercholesterolemic and control groups. The changed activity of ecto-5'-NT and eADA leads to increased purine nucleotides turnover and a shift in their concentration balance towards adenosine and inosine in the extracellular space. However, no changes in the energetic metabolism of the mBMECs are reported. Our results confirm the influence of hypercholesterolemia on regulation of purine nucleotides metabolism, which may impair the function of the cerebral vascular endothelium. The effect of hypercholesterolemia on the murine brain microvascular endothelial cells (mBMECs). An increased activity of ecto-5'-NT and eADA in mBMECs of the LDLR -/- /Apo E -/- mice leads to a shift in the concentration balance towards adenosine and inosine in the extracellular space with no differences in intracellular concentration of ATP. Figure was created with Biorender.com., (© 2023. The Author(s).)

Over recent years, the global healthcare system has experienced a notable increase in the prevalence of obesity and its associated health complications such as hypertension, type 2 diabetes, lipid disorders, etc. What is more, one of the significant phenomena is the increasing demand for bariatric procedures among individuals of working age due to the high prevalence of type III obesity and type II obesity with co-morbidities. This trend is pronounced in Poland, due to the increasing number of patients meeting the qualifying criteria for surgery among professionally active and inactive patients. The aim of this study is to characterize the alarmingly high number of candidates for bariatric procedures among professionally active Poles. In total, the results of 2,056,861 initial, control, and periodic visits as part of the occupational medicine certificate were analyzed-collected from 1,342,749 unique patients (51.7% men; mean age of whole group: 36.81, SD = 10.91). Statistical calculations were performed, qualitative data were assessed using percentage and occurrence counts, while qualitative data were described using mean (M), standard deviation (SD), median, skewness, kurtosis, and range values. Results with p < 0.05 were deemed significant. Chi-square analysis and one-way ANOVA (with Scheffe's post hoc test) were employed. Charts were created in the R program. It was noticed that there was a consistent rise in the proportion of individuals classified as candidates for bariatric procedures (an increase of 0.3%) alongside a notable decrease in the percentage of individuals maintaining a healthy body weight. Moreover, it is imperative to conduct yearly evaluations of the prevalence of obesity and its associated health conditions. It should be noted that hypertension occurred in 42.2% of patients, type 2 diabetes in 6.2% of patients, and lipid disorders in 8.4% of patients with third-degree obesity. This proactive approach is essential in order to adequately equip the healthcare system to address the increasing population of obese individuals, especially candidates for bariatric procedures.

One of the effects of hypercholesterolemia (Hch) exerted on the central nervous system (CNS) is damage to the blood-brain barrier (BBB). Increased permeability of BBB results from structural changes in the vascular wall, loss of the tight junctions and barrier function, as well as alterations in the concentration of proteins located in the layers of the vascular wall. These changes occur in the course of metabolic and neurodegenerative diseases. The important role in the course of these processes is attributed to agrin, matrix metalloproteinase-9, and aquaporin-4. In this study, we aimed to determine: 1) the extent of Hch-induced damage to the BBB during maturation, and 2) the distribution of the above-mentioned markers in the vascular wall. Immunohistochemical staining and confocal microscopy were used for vascular wall protein assessment. The size of BBB damage was studied based on perivascular leakage of fluorescently labeled dextran. Three- and twelve-month-old male LDLR -/- /Apo E -/- double knockout mice (EX) developing Hch were used in the study. Age-matched male wild-type (WT) C57BL/6 mice were used as a control group. Differences in the concentration of studied markers coexisted with BBB disintegration, especially in younger mice. A relationship between the maturation of the vascular system and reduction of the BBB damage was also observed. We conclude that the extent of BBB permeability depends on animal age, duration of Hch, and brain region. These may explain different susceptibility of various brain areas to Hch, and different presentation of this pathology depending on age and its duration., Competing Interests: Declaration of competing interest No conflict of interest is claimed by all Authors of this publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to assess the association of long-term exposure to particulate matter with aerodynamic diameter, PM2.5, PM10, NO 2 and SO 2 as well as CO, with lung adenocarcinoma (AD) in south-east Poland for the years from 2004 to 2014. The study group consisted of 4296 patients with lung adenocarcinoma and the level of selected pollutants. To analyse the data, a standard statistics for cohort data, that is a risk ratio (RR), was used. The dependencies occurring in the distribution of pollutants and cancer incidence were examined using Moran's I correlation coefficient. The current study suggests that PM10, NO 2 and SO 2 exposure as an air pollutant may increase female lung adenocarcinoma incidence. In men, the increased risk of adenocarcinoma lung cancer is affected by SO 2 and PM10. A high morbidity rate in urban areas and suburbs may be connected with commuting from moderately polluted living areas to highly polluted working areas.

Over the past few years, artificial intelligence (AI) has significantly improved healthcare. Once the stuff of science fiction, AI is now widely used, even in our daily lives - often without us thinking about it. All healthcare professionals - especially executives and medical doctors - need to understand the capabilities of advanced AI tools and other breakthrough innovations. This understanding will allow them to recognize opportunities and threats emerging technologies can bring to their organizations. We hope to contribute to a meaningful public discussion about the role of this new type of AI and how our approach to healthcare and medicine can best evolve with the rapid development of this technology. Since medicine learns by example, only a few possible uses of AI in medicine are provided, which merely outline the system's capabilities. Among the examples, it is worth highlighting the roles of AI in medical notes, education, preventive programs, consultation, triage and intervention. It is believed by the authors that large language models such as chat generative pre-trained transformer (ChatGPT) are reaching a level of maturity that will soon impact clinical medicine as a whole and improve the delivery of individualized, compassionate, and scalable healthcare. It is unlikely that AI will replace physicians in the near future. The human aspects of care, including empathy, compassion, critical thinking, and complex decision-making, are invaluable in providing holistic patient care beyond diagnosis and treatment decisions. The GPT-4 has many limitations and cannot replace direct contact between an experienced physician and a patient for even the most seemingly simple consultations, not to mention the ethical and legal aspects of responsibility for diagnosis.

Brain injury triggers a complex response involving morphological changes, cellular proliferation, and differentiation of newly formed neuroglial subpopulations. These processes have been extensively studied in animal stroke models with permanent large vessel occlusion. However, less is known about neuroglial response after transient cerebral ischemia. Herein, we aimed to determine an astrocytic and NG2 glial proliferative response, potential changes in expression of developmental neuroglial markers: vimentin, nestin, oligodendrocyte transcription marker (Olig2), and a role of neuroglial subpopulations as a source of cells replenishing structural deficiencies in the ischemic brain. Results showed an induction of a proliferative neuroglial response in the peri-infarct area reflected in an increased percentage of GFAP/Ki67 + and NG2/Ki67 + cells within 4 weeks after transient MCAO. The peak of GFAP+ astrocytes proliferation of 30.3 ± 10.3% was observed in the first week, and a peak of NG2 + cells proliferation of 23.1 ± 11.8% in the second week after stroke. The presence of GFAP/Vimentin+ and GFAP/Nestin+ cells, as well as GFAP/Olig2 + and NG2/Olig2 + cells indicated an induction of developmental phenotypes with a differentiation potential. Finally, observed between day 1 and week 3 transient GFAP/NG2 + colocalization suggests the heterogeneous source of the reactive neuroglia after transient MCAO. Altogether, one-hour MCAO is a sufficient pathological stimulus to trigger a strong proliferative response of GFAP+ and NG2 + neuroglial cells and induce their early developmental phenotype. Our results suggest that transient ischemia may initiate a change in the direction of differentiation within the neuroglia cell population., Competing Interests: Declarations of interest none., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The development of medicine is based not only on the introduction of new methods of treatment, but also on the use of increasingly effective drugs, including antithrombotic drugs. Drugs that inhibit the activity of platelets (antiplatelet and anti-aggregating drugs) and pharmaceuticals that inhibit the activity of plasma coagulation factors (anticoagulants) are used in antithrombotic therapy. In our daily practice we encounter patients who take chronic antiplatelet or anticoagulant drugs. However, more and more often we are dealing with patients who are treated with two antiplatelet drugs, an antiplatelet and an anticoagulant or even undergoing triple antithrombotic therapy. When preparing the patient for invasive craniofacial procedures, it should be assessed whether the temporary discontinuation of antithrombotic treatment due to the fear of excessive perioperative bleeding is justified and will not result in life-threatening thromboembolic complications. The authors discuss in detail the medications used in modern antithrombotic treatment and present a perioperative management procedure with a patient who takes l4 z of these medications chronically.

Piptoporus betulinus is a fungus known for its medicinal properties. It possesses antimicrobial, anti-inflammatory, and anti-cancer activity. In this study, several tests were performed to evaluate the cytotoxic effect of the ethanolic extract of Piptoporus betulinus on two melanoma human cell lines, WM115 primary and A375 metastatic cell lines, as well as Hs27 human skin fibroblasts. The extract proved to affect cancer cells in a dose-dependent manner, and at the same time showed a low cytotoxicity towards the normal cells. The total phenolic content (TPC) was determined spectrophotometrically by the Folin-Ciocalteu method (F-C), and the potential antioxidant activity was measured by ferric-reducing antioxidant power (FRAP) assay. One of the active compounds in the extract is betulin. It was isolated and then its cytotoxic activity was compared to the results obtained from the Piptoporus betulinus extract. To further understand the mechanism of action of the extract's anticancer activity, tests on model cell membranes were conducted. A model membrane of a melanoma cell was designed and consisted of 1,2-dimyristoyl-sn-glycero-3-phosphocholine, disialoganglioside-GD 1a and cholesterol: DMPC:GD 1a :chol (5:2:3 mole ratio). Changes in a Langmuir monolayer were observed and described based on Π - A mol isotherm and compressibility modulus changes. LB lipid bilayers were deposited on a hydrophilic gold substrate and analyzed by IR and X-ray photoelectron spectroscopy. Our study provides new data on the effect of Piptoporus betulinus extract on melanoma cells and its impact on the model of melanoma plasma membranes.

The work presents innovative quadruple disk iridium, platinum, and iridium-platinum voltammetric electrodes with a special design, dedicated to the testing of samples with a complex organic composition. Noble metal wires are tightened in one silver rod, and therefore each of them acts as a single sensor. It was demonstrated that the signals of the iridium-platinum sensor combine the electrode responses constructed from one metal, which increases the possibilities and range of applications of this sensor, and it can be used as an electronic tongue. These single and combined noble metal electrodes were successfully verified to profile the seasonal variability of honey collected from an apiary in Małopolska (voivodeship in Poland). Data obtained by the differential pulse voltammetry, according to the principles of green chemistry, without using any reagents, were interpreted by principal component analysis, preceded by the optimized variable selection procedure. The best results in distinguishing 12 honeys were obtained using a multimetallic electrode. The classification model calculated using deep convolutional neural networks indicated the proper belonging of honeys to the groups with 100% accuracy for the training and validation set. The proposed solution proved that noble metals quadruple disk electrodes are a promising tool supporting voltammetric profiling of samples and this strategy, considering deep learning, can be developed to a large extent., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The pandemic declared in many countries in 2020 due to COVID-19 led to the freezing of economies and the introduction of distance learning in both schools and universities. This unusual situation has affected the mental state of citizens, which has the potential to lead to the development of post-traumatic stress and depression. This study aimed to assess the level of stress in dental students in the context of the outbreak of the SARS-CoV-2 virus pandemic. A survey on the PSS-10 scale was prepared to measure the level of perceived stress. The study included 164 dental students at the Faculty of Medical Sciences of the Medical University of Silesia in Katowice, Poland. The results showed the impact of COVID-19 on the stress of students, with 67.7% reporting high levels of stress. The study also revealed that stress was higher among older female students. This paper recommends that the university provide more intensive psychological care as psychological first aid strategies in epidemics or natural disasters and to consider telemedicine in order to deliver services due to the limitations of the pandemic.

Background: Dental schools are considered to be a very stressful environment; the stress levels of dental students are higher than those of the general population. The aim of this study was to assess the level of stress among dental students while performing specific dental procedures., Methods: A survey was conducted among 257 participants. We used an original questionnaire, which consisted of 14 questions assigned to three categories: I-Diagnosis, II-Caries Treatment, and III-Endodontic Treatment. Each participant marked their perceived level of stress during the performed dental treatment procedures. The scale included values of 0-6, where 0 indicates no stress, while 6 indicates high stress., Results: Third- (p=0.006) and fourth-year (p=0.009) women were characterized by a higher level of perceived stress during dental procedures related to caries treatment. Caries treatment procedures were the most stressful for 18.3% of third-year students, 4.3% of fourth-year students, and 3.2% of fifth-year students. Furthermore, 63.4% of third-year students, 47.3% of fourth-year students, and 17.2% of fifth-year students indicated that they felt a high level of stress when performing endodontic procedures., Conclusion: Third- and fourth-year female students are characterized by a higher level of stress during caries and endodontic treatment procedures. The most stressful treatments for participants were endodontic treatment procedures.

Adequate ehealth literacy is one of the key instruments safeguarding people against unreliable health-related information obtained from the Internet. This paper presents an assessment of the reliability and the validity of a Polish version of the ehealth literacy scale (Pl-eHEALS). The assessment was carried out on the basis of two nationally representative samples of the Polish population. In the first survey of adults at least 50 years old, the technique of computer-assisted telephone interviewing (CATI) was applied. In the second survey of young adult women (18-35 years old), the technique of computer-assisted web interviewing (CAWI) was used. The reliability and the validity of the Pl-eHEALS was analyzed. There were no floor or ceiling effects revealed in either sample. The Cronbach's alpha coefficients were 0.90 and 0.88, and Guttman split-half coefficients were 0.89 and 0.81, respectively. Exploratory factors analysis revealed single factor models in both cases. The sum of squared loadings in the first survey was 6.090 and accounted for 58.72% of the variance. In the second survey, the sum was 5.927 and was responsible for 55.06% of the variance. Hypothesis testing showed that, for older adults, higher ehealth literacy was prevalent in the respondents who used the Internet more frequently. Among young adult women, higher readiness to use the Internet as a primary source of health-related information and to undertake specific internet health-related activities was associated with higher ehealth literacy. The analysis reported in this paper confirmed the reliability and the validity of the instrument. It should be stressed that, prior to this study, there was no validated Polish version of the eHEALS that could be used with Polish-speaking respondents.

Aim of the Study: The objective of the study was to analyse the survival rate of women with malignant ovarian tumours in the years 1990-2015 in the Podkarpacie province., Material and Methods: The database used for calculations covered 2399 cancer incidences verified at the end of 2014. The estimated relative survival rates were calculated by means of the Hakulinen method., Results: The number of recorded cases amounted to 196 in 2015 and was higher by 86.7% than in 1990. The rates of one-year, three-year, and five-year survival was 72.5%, 51.2%, and 42.4%, respectively., Conclusions: Survival rates of women with ovarian cancer in the Podkarpacie province are comparable to survivals calculated for the entire Poland region. Despite the low risk factor, women suffering from ovarian adenocarcinoma have lower survival rates than others, and as many as 42.5% of patients with adenocarcinoma were diagnosed in stage IV. Steps aimed at improvement of detectability of ovarian cancers in the earliest possible stage should be taken. This should increase survival rates in each age group., Competing Interests: The authors declare no conflict of interest.

Intrinsically disordered proteins (IDPs) and regions (IDRs) make up a significant part of the proteome and facilitate a wide range of physiological and pathological functions that are only beginning to be understood. As such, they are highly attractive targets for drug development and bioengineering. However, their inability to adopt well-defined structures provides significant obstacles for developing ligands that regulate their behaviors. In this chapter, we review how the conformational flexibility of IDPs and their propensity to phase separate make them tractable targets for small-molecule manipulation. We also describe both theoretical and experimental approaches to characterize disordered proteins, including novel thermodynamic and single-molecule techniques that help identify complimentary partners of IDPs and their ability to shift protein ensembles toward preferred conformations., (© 2018 Elsevier Inc. All rights reserved.)

The incidence of malignant melanoma, the most aggressive skin cancer, is increasing constantly. Despite new targeted therapies, the prognosis for patients with metastatic disease remains poor. Thus, there is a need for new combinational treatments, and antineoplastic agents potentially valuable in this approach are inhibitors of the ubiquitin-proteasome system (UPS). In this work, we analyze the cytotoxicity mechanisms of proteasome inhibitors (MG-132, epoxomicin, and lactacystin) in a specific form of melanoma which does not synthesize melanin-the amelanotic melanoma (Ab cells). We found that the most cytotoxic of the compounds tested was epoxomicin. Caspase-9 activation as well as cytochrome C and AIF release from mitochondria indicated that exposure to epoxomicin induced the mitochondrial pathway of apoptosis. Epoxomicin treatment also resulted in accumulation of Bcl-2 family members-proapoptotic Noxa and antiapoptotic Mcl-1, which were postulated as the targets for bortezomib in melanoma. Inhibition of caspases by BAF revealed that cell death was partially caspase-independent. We observed no cell cycle arrest preceding the apoptosis of Ab cells, even though cdk inhibitors p21 Cip1/Waf1 and p27 Kip1 were up-regulated. The cell cycle was blocked only after inactivation of caspases by the pan-caspase inhibitor BAF. In summary, this is the first study exploring molecular mechanisms of cell death induced by epoxomicin in melanoma. We found that Ab cells died on the mitochondrial pathway of apoptosis and also partially by the caspase-independent way of death. Apoptosis induction was fast and efficient and was not preceded by cell cycle arrest.

Background: Complex mechanisms of responsible for originating and maintaining of atrial fibrillation (AF) are involved in pathophysiology of this arrhythmia. Inflammation substantially contribute to arrhythmic remodelling of atrial tissue.The aim of the present study is to assess an applicability of ferritin and high sensitive C-reactive protein (hs-CRP) as biomarkers of atrial fibrillation and their usefulness in evaluation of efficacy of cryoablation., Materials and Methods: The study population consisted of 40 patients who underwent first AF cryoablation procedure. The whole follow-up time was for 6 months. The efficacy of cryoablation was defined as lack of episodes of AF longer than 30 s reported either in patient's medical documentation or present in standard or Holter ECG records. Concentrations of hs-CRP (latex method ) and ferritin (immunochemical method) were determined in standard way in hospital laboratory., Results: The recurrence of atrial fibrillation during follow-up was detected in 7 of 40 patients (efficacy 82.5%). Basal concentrations of hs-CRP and ferritin were significantly higher in patients who underwent ablation during AF. Ablation resulted in an increase of either hs-CRP or ferritin concentrations. After seven days, both hs-CRP and ferritin concentrations returned to basal level. The trend toward the higher concentration of hs-CRP was observed in AF recurrence subgroup in 30th and the 90th day after the procedure. Ferritin concentrations were significantly higher in recurrence subgroup after 30 and 90 days., Conclusion: Our results suggest that the evaluation of ferritin serum level can be a potential tool for assessment of AF treatment efficacy.

Sunflower trypsin inhibitor (SFTI-1) is recognized as an attractive scaffold to designed potent inhibitors of various proteases. We have recently found that its analogues inhibit noncovalently both human and yeast 20S proteasomes. Here, a set of novel and more potent in vitro inhibitors is presented. The inhibitory potency of the peptides was assessed with human 20S proteasome in the presence or absence of sodium dodecyl sulfate and with human 26 proteasome. Their antiproliferative action against tumor (human melanoma cells A375) and normal cells (46 BR.1N human fibroblasts and HaCaT keratinocytes) was determined. The selected fluoresceine-labeled inhibitors were able to internalize into A375 cells and were sometimes present as foci in the cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 685-696, 2016., (© 2016 Wiley Periodicals, Inc.)

The broad variety of substances that inhibit the action of the ubiquitin-proteasome system (UPS)-known as proteasome inhibitors-have been used extensively in previous studies, and they are currently frequently proposed as a novel form of cancer treatment and as a protective factor in intracerebral hemorrhage treatment. The experimental data on the safest route of proteasome inhibitor administration, their associated side effects, and the possible ways of minimizing these effects have recently become a very important topic. The aim of our present study was to determine the effects of administering of MG-132, lactacystin and epoxomicin, compounds belonging to three different classes of proteasome inhibitors, on the ependymal walls of the lateral ventricle. Observations were made 2 and 8 weeks after the intraventricular administration of the studied substances dissolved in dimethyl sulfoxide (DMSO) into the lateral ventricle of adult Wistar rats. Qualitative and quantitative analysis of brain sections stained with histochemical and inmmunofluorescence techniques showed that the administration of proteasome inhibitors caused a partial occlusion of the injected ventricle in all of the studied animals. The occlusion was due to ependymal cells damage and subsequent ependymal discontinuity, which caused direct contact between the striatum and the lateral nuclei of the septum, mononuclear cell infiltration and the formation of a glial scar between these structures (with the activation of astroglia, microglia and oligodendroglia). Morphologically, the ubiquitin-positive aggregates corresponded to aggresomes, indicating impaired activity of the UPS and the accumulation and aggregation of ubiquitinated proteins that coincided with the occurrence of glial scars. The most significant changes were observed in the wall covering the striatum in animals that were administered epoxomicin, and milder changes were observed in animals administered lactacystin and MG-132. Interestingly, DMSO administration also caused damage to some of the ependymal cells, but the aggresome-like structures were not formed. Our results indicate that all of the studied classes of proteasome inhibitors are detrimental to ependymal cells to some extent, and may cause severe changes in the ventricular system. The safety implications of their usage in therapeutic strategies to attenuate intracerebral hemorrhagic injury and in brain cancer treatment will require further studies.

Today adolescents are highly engaged online. Contrary to common concern, not all highly engaged adolescents develop maladaptive patterns of internet use. The present qualitative study explored the experiences, patterns and impact of use of 124 adolescents (M(age) = 16.0) reporting signs of internet addictive behaviors. The focus was to discern adaptive and maladaptive use patterns, which promote or interfere with adolescents' development, respectively. Semi-structured individual interviews were conducted in seven European countries (Greece, Spain, Poland, Germany, Romania, Netherlands and Iceland) and qualitatively analyzed using grounded theory. Considerable variability emerged in the way adolescents satisfied their personal needs online and offline, in the experienced impact from high online engagement and functional value ascribed to the internet, and in the self-regulatory processes underlying use. Variability in these discriminating processes was linked to adaptive or maladaptive adolescent internet use patterns. The emerged processes can provide direction for designing prevention and intervention programs promoting adaptive use., (Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

A cross-sectional school-based survey study (N=13,284; 53% females; mean age 15.8±0.7) of 14-17-year-old adolescents was conducted in seven European countries (Greece, Spain, Poland, Germany, Romania, the Netherlands, and Iceland). The aim of the study was to investigate the prevalence of Internet addictive behavior (IAB) and related psychosocial characteristics among adolescents in the participating countries. In the study, we distinguish two problematic groups: adolescents with IAB, characterized by a loss of control over their Internet use, and adolescents "at risk for IAB," showing fewer or weaker symptoms of IAB. The two groups combined form a group of adolescents with dysfunctional Internet behavior (DIB). About 1% of adolescents exhibited IAB and an additional 12.7% were at risk for IAB; thus, in total, 13.9% displayed DIB. The prevalence of DIB was significantly higher among boys than among girls (15.2% vs. 12.7%, p<0.001) and varied widely between countries, from 7.9% in Iceland to 22.8% in Spain. Frequent use of specific online activities (e.g., gambling, social networking, gaming) at least 6 days/week was associated with greater probability of displaying DIB. Multiple logistic regression analysis indicated that DIB was more frequent among adolescents with a lower educational level of the parents, earlier age at first use of the Internet, and greater use of social networking sites and gaming sites. Multiple linear regression analysis showed that externalizing (i.e., behavioral) and internalizing (i.e., emotional) problems were associated with the presence of DIB.