Annual epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data.

BACKGROUND: Health services utilization related to hip osteoarthritis imposes a significant burden on society and health care systems. Our aim was to analyse the epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data. METHODS: Data were extracted from the nationwide financial database of the National Health Insurance Fund Administration (NHIFA) of Hungary for the year 2018. The analysed data included annual patient numbers, prevalence, and age-standardized prevalence per 100,000 population in outpatient care, health insurance costs calculated for age groups and sexes for all types of care. Patients with hip osteoarthritis were identified using code M16 of the International Classification of Diseases (ICD), 10th revision. Age-standardised prevalence rates were calculated using the European Standard Population 2013 (ESP2013). RESULTS: Based on patient numbers of outpatient care, the prevalence per 100,000 among males was 1,483.7 patients (1.5%), among females 2,905.5 (2.9%), in total 2,226.2 patients (2.2%). The age-standardised prevalence was 1,734.8 (1.7%) for males and 2,594.8 (2.6%) for females per 100,000 population, for a total of 2,237.6 (2.2%). The prevalence per 100,000 population was higher for women in all age groups. In age group 30-39, 40-49, 50-59, 60-69 and 70 + the overall prevalence was 0.2%, 0.8%, 2.7%, 5.0% and 7.7%, respectively, describing a continuously increasing trend. In 2018, the NHIFA spent 42.31 million EUR on the treatment of hip osteoarthritis. Hip osteoarthritis accounts for 1% of total nationwide health insurance expenditures. 36.8% of costs were attributed to the treatment of male patients, and 63.2% to female patients. Acute inpatient care, outpatient care and chronic and rehabilitation inpatient care were the main cost drivers, accounting for 62.7%, 14.6% and 8.2% of the total health care expenditure for men, and 51.0%, 20.0% and 11.2% for women, respectively. The average annual treatment cost per patient was 3,627 EUR for men and 4,194 EUR for women. CONCLUSIONS: The prevalence of hip osteoarthritis was 1.96 times higher (the age-standardised prevalence was 1.5 times higher) in women compared to men. Acute inpatient care was the major cost driver in the treatment of hip osteoarthritis. The average annual treatment cost per patient was 15.6% higher for women compared to men.

Comparative analysis of the quality of life regarding patients who underwent hip replacement in public versus private hospitals in Hungary.

The study aimed to investigate the impact of hip replacement surgery on the quality of life and to compare the outcomes by sociodemographic and surgical data in Hungarian public and private hospitals. Patients were selected at the Department of Orthopaedics (Clinical Centre, University of Pécs) and at the Da Vinci Private Clinic in Pécs. Patients completed the SF-36 and Oxford Hip Score (OHS) questionnaires before the surgery, 6 weeks and 3 months later. We also evaluated socio-demographic data, disease and surgical conditions. The research involved 128 patients, 60 patients in public, 68 patients in private hospital. Despite the different sociodemographic characteristics and surgical outcomes of public and private healthcare patients, both groups had significantly improved the quality of life 3 months after hip replacement surgery measured by OHS and SF-36 physical health scores (p < 0.001). In the mental health score, only the patients of the private health sector showed a significant improvement (p < 0.001). The extent of improvement did not differ between the two healthcare sectors according to the OHS questionnaire (p = 0.985). While the SF-36 physical health score showed a higher improvement for public patients (p = 0.027), the mental health score showed a higher improvement for private patients (p = 0.015).

Competing Domino Knoevenagel-Cyclization Sequences with N-Arylcinnamylamines.

Domino Knoevenagel-cyclization reactions of N-arylcinnamylamines were carried out with active methylene reagents, which took place with five competing cyclization mechanisms: intramolecular hetero Diels-Alder reaction, stepwise polar [2 + 2] cycloaddition, styryl or aza-Diels-Alder reactions followed by rearomatization, and [1,5]-hydride shift-6-endo cyclization. In the stepwise aza-Diels-Alder reaction, the N-vinylpyridinium moiety acted as an azadiene, producing a condensed heterocycle with tetrahydroquinolizinium and tetrahydroquiniline subunits. Antiproliferative activity with low micromolar IC50 values was identified for some of the novel scaffolds.

Problematic usage of the internet among Hungarian elementary school children: a cross-sectional study.

INTRODUCTION: Problematic usage of the internet (PUI) is perhaps one of the most frequently studied phenomena of the 21st century receiving increasing attention in both scientific literature and the media. Despite intensive research there have been relatively few meaningful studies among elementary school students in Hungary and worldwide, who may be considered as a high-risk population with regard to problematic internet use. The aim of our study was to carry out a complex research focusing on the prevalence and risk factors of PUI among elementary school children aged 10-15 years (Grade 5-8). METHODS: Demographics included were gender, age, place of stay, type of residence, family type, parental education, start of internet use, used devices, daily internet use, purpose of internet use, internet accounts, ways of keeping in touch with friends and sporting activities. PUI was evaluated using the paper-based version of the Potentially Problematic Use of the Internet Questionnaire. RESULTS: Overall, 2000 paper-based questionnaires were successfully delivered and the final analysis included 1168 responses (overall response rate 58.4%). Mean age was 12.55 ± 1.24 years. Female gender (OR = 2.760, p = 0,006, CI 95% 0.065 to 0.384), younger age (11-12 years) (OR = 3.812, p < 0.001, 95% CI: 1.747-4.731), early exposure to the internet (OR = 3.466, p = 0.001, 95% CI 1.535-5.446), living in a small village (OR = 1.081, p = 0.002, 95% CI 1.041-1.186) urgency to answer online (OR = 4.677, p < 0.001, 95% CI: 2.714-6.639), decreased frequency of personal contact with friends (OR = 2.897, p = 0.004, 95% CI: 1.037-1.681), spending more than 6 h online (OR = 12.913, p < 0.001, 95% CI: 10.798-14.892), morning and nighttime internet use (OR = 3.846, p < 0.001, CI 95% 1.886-5.810) and never doing any sports (OR = 2.016, p = 0.044, 95% CI: 1.050-3.354) were independently associated with problematic internet use. CONCLUSIONS: Based on the results of our questionnaire survey more than 10% seemed to be problematic users in our study population, which is a relatively high rate. Early exposure to the internet as well as younger age were strongly related to this phenomenon. Duration of being online as well as daily time interval of internet use are important predisposing factors. Scarcely studied social factors such as being online at the expense of personal relationships and the lack of physical activity should be payed more attention to prevent the development of PUI.

New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, and In Vitro Effect on Glioblastoma.

Pharmacologically active salicylanilides (2-hydroxy-N-phenylbenzamides) have been a promising area of interest in medicinal chemistry-related research for quite some time. This group of compounds has shown a wide spectrum of biological activities, including but not limited to anticancer effects. In this study, substituted salicylanilides were chosen to evaluate the in vitro activity on U87 human glioblastoma (GBM) cells. The parent salicylanilide, salicylanilide 5-chloropyrazinoates, a 4-aminosalicylic acid derivative, and the new salicylanilide 4-formylbenzoates were chemically and in vitro characterized. To enhance the internalization of the compounds, they were conjugated to delivery peptides with the formation of oxime bonds. Oligotuftsins ([TKPKG]n, n = 1-4), the ligands of neuropilin receptors, were used as GBM-targeting carrier peptides. The in vitro cellular uptake, intracellular localization, and penetration ability on tissue-mimicking models of the fluorescent peptide derivatives were determined. The compounds and their peptide conjugates significantly decreased the viability of U87 glioma cells. Salicylanilide compound-induced GBM cell death was associated with activation of autophagy, as characterized by immunodetection of autophagy-related processing of light chain 3 protein.

Potential subtype-specific therapeutic approaches in small cell lung cancer.

PURPOSE OF REVIEW: Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients. RECENT FINDINGS: Substantial research on the biological and molecular heterogeneity of SCLC has been conducted in the last years. Recent results from comprehensive profiling studies have shown that unique major SCLC subtypes can be distinguished based on the relative expression of key transcription regulators (ASCL1, NEUROD1, POU2F3) or distinct inflammatory features. Understanding the differing molecular characteristics of these distinct subtypes has resulted in the identification of specific therapeutic vulnerabilities. SUMMARY: The recently introduced molecular SCLC subtype classification represents a substantial progress towards a personalized and more efficacious approach in SCLC. The consequences of this paradigm shift provide hope for improved patient care and clinical outcomes in this exceptionally lethal thoracic malignancy.

Unfolding the secrets of small cell lung cancer progression: Novel approaches and insights through rapid autopsies.

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.

[Small cell lung cancer heterogeneity and molecular subtypes: biological and clinical relevance]. / A molekuláris altípusok szerinti heterogenitás biológiai és klinikai jelentosége kissejtes tüdorákban.

Small-cell lung cancer (SCLC) is a highly aggressive malignancy characterised by genomic instability and early metastatic spread. Patients are typically diagnosed at advanced disease stage, when platinum-based chemotherapy with immunotherapy represents the standard therapeutic approach. The role of radiotherapy with concomitant systemic therapy is also well established in the management of SCLC patients. Although these therapeutic approaches are initially effective, most patients rapidly develop resistance. This clearly highlights the need to improve therapeutic efficacy and broaden the scope of current therapeutic strategies. Recent advances in the study of this disease, once considered homogeneous, have led to a new model of the SCLC classification scheme based on the relative expression of certain transcriptional regulators and inflammatory characteristics. New biological insights into the molecular subtypes of SCLC could lead to the implementation of subtype-specific therapeutic approaches. Here, we summarise our key findings concerning the biological and clinical relevance of SCLC molecular subtypes.

The association of problematic usage of the internet with burnout, depression, insomnia, and quality of life among Hungarian high school students.

Introduction: The extensive availability of the internet has led to the recognition of problematic usage of the internet (PUI) or so called internet addiction (IA), probably mostly involving adolescents. Aim: Here we present a study focusing on the incidence and consequences (including burnout, which is relatively rarely studied) of internet addiction among high school students using a questionnaire-based non-random sampling cross-sectional survey. Included questionnaires were the Problematic Internet Use Questionnaire, the Maslach Burnout Inventory General Survey for Students MBI-GS (S), the 9-item short version of Beck Depression Inventory (BDI-SF), the Athens Insomnia Questionnaire and the EQ-5D (quality of life) questionnaire. Data were evaluated the exertion of Student's t-test, chi square test and Pearson's rank-order correlation. Logistic regression analysis was used to determine the significance of the different parameters as independently associated with PUI. Results: Overall 3,000 paper-based questionnaires were successfully delivered and 2,540 responses received (response rate of 84.6%). 1,309 males (mean age 17.6 ± 1.43 years) (51.5%) and 1,231 females (mean age 17.5 ± 1.4 years) (48.5%) took part in our study. Problematic usage of the internet was detected in 486 (19.1%) students (232 males, mean age 17.6 ± 1.35 years and 254 females, mean age 17.34 ± 1.37 years). In a logistic regression analysis sleep disturbance (OR: 1.84, 95% CI: 1.83-2.03), depression (OR: 1.97, 95% CI: 1.77-2.02) and burnout (OR: 1.8, 95% CI: 1.16-1.94) were significantly associated with PUI. Conclusion: Nearly one fifth of our study population suffered from PUI, which was strongly associated with school burnout, insomnia and depression, which underlines the importance of this phenomenon.

Inequalities in premature mortality from ischaemic heart disease in the WHO European region.

OBJECTIVES: Ischaemic heart disease (IHD) is one of the leading causes of premature mortality. Our aim was to analyse standardised premature mortality rates from IHD by geographical groups in the age group 45-59 years. METHODS: We performed a retrospective, quantitative analysis of age-standardized mortality rates from IHD between 1990-2014 per 100,000 population in Western European (WE: N = 17), Eastern European countries (EE: N = 10), and countries of the former Soviet Union (fSU: N = 15) within the European Region of the World Health Organisation (WHO) based on data retrieved from the WHO European Mortality Database. Descriptive statistics, time series analysis and statistical tests were used for the analyses (ANOVA, Kruskal-Wallis test, Mann-Whitney test, paired t-test). RESULTS: On average, age-standardized death rates (ASDR) from IHD per 100,000 population were the lowest in WE (men 1990: 143.67, 2014: 50.29; women 1990: 29.06, 2014: 9.89), and the highest in fSU (men 1990: 358.69, 2014: 253.25; women 1990: 99.78, 2014: 57.85). Between 1990 and 2014, all three groups experienced significant decrease in ASDR both in men and women (fSU: -29.39%, -42.02%; EE: -49.41%, -50.57%; WE: -64.99%, -65.97%, respectively) (p < 0.05). Between 1990 and 2004, ASDR decreased in WE in both sexes (p < 0.001), in EE among males (p = 0.032). Between 2004 and 2014, ASDR from IHD decreased significantly in both sexes in fSU and WE, in EE only among women (p < 0.05). CONCLUSIONS: During the whole period analysed, ischaemic heart disease mortality significantly decreased in both sexes in all the groups.

Disease-Specific Quality of Life among Patients with Peripheral Artery Disease in Hungary.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease significantly impacting functional status and health-related quality of life (HRQoL). This study aimed to investigate HRQoL among PAD patients in Hungary using the validated Hungarian version of the PADQoL questionnaire. Patients with symptomatic PAD were consecutively recruited from the Department of Angiology, Clinical Center, University of Pécs, Hungary. Demographics, risk factors, and comorbidities were registered. Disease severity was measured by Fontaine and WIFI stages. Descriptive statistical analysis, Chi-square test, and non-parametric tests were performed (p < 0.05). Overall, 129 patients (mean age 67.6 ± 11.9 years, men 51.9%) participated in our study. The Hungarian PADQoL demonstrated good internal consistency (α range: 0.745-0.910). Factors on intimate and social relationships gave the best (89.15 ± 20.91; 63.17 ± 26.05) and sexual function (28.64 ± 27.42), and limitations in physical functioning (24.68 ± 11.40) the worst scores. PAD had a significant negative impact on the social relationships of patients aged 21-54 years (51.6 ± 25.4). Fontaine stage IV patients experienced significantly lower HRQoL due to fear and uncertainty (46.3 ± 20.9) and limited physical functioning (33.2 ± 24.8). The Hungarian PADQoL identified central aspects of HRQoL. Advanced PAD was found to impact several areas of HRQoL, primarily physical functioning and psycho-social well-being, drawing attention to the importance of early diagnosis and management.

The prevalence and risk factors of burnout and its association with mental issues and quality of life among hungarian postal workers: a cross-sectional study.

BACKGROUND: Burnout is one of the most extensively studied phenomena of the twenty-first century; which has been extensively studied among helping professions, although it can be broadened to several other types of occupation. Based on our knowledge and literature search, no similar studies have been carried out among postal workes to date. METHODS: This cross-sectional questionnaire-based epidemiological study was carried out between May 2021 and January 2022 in five counties in Hungary with the recruitment of postal delivery workers focusing on (1) the prevalence of burnout among postal delivery workers; (2) including the role of demographic parameters, duration of employment as well as the presence of secondary employment; (3) and also analyzed the role of several risk factors and medical conditions; (4) and we also examined the possible association between depression, insomnia and quality of life and burnout. RESULTS: Overall 1300 questionnaires were successfully delivered and 1034 responses received (response rate of 79.5%). Three hundred sixty-eight males (35.6%) and six hundred sixty-six females (64.4%) participated in our study. The prevalence of burnout was 50.8% (525/1034) in this study population (mean score 2.74 ± 0.33). Logistic regression analysis showed that female gender [OR = 2.380, 95% CI: 1.731 to 2.554], first workplace [OR = 1.891, 95% CI: 1.582 to 2.162] and working more than 30 years [OR = 1.901, 95% CI: 1.608 to 2.326] have significantly increased the likelyhood of burnout as well as the history of muscoskeletal pain [OR = 1.156, 95% CI: 1.009 to1.342], current quality of life [OR = 1.602, 95% CI: 1.473 to 1.669] and the presence of sleep disturbance [OR = 1.289, 95% CI: 1.066 to 1.716]. CONCLUSION: This is the first study in Hungary to investigate the prevalence of burnout among postal workers and to explore the relationship between burnout and mental health problems. Our study underlines the clinical importance of burnout and draws attention to the need for appropriate prevention and treatment strategies.

Association of diabetes mellitus with depression, anxiety and quality of life / A diabetes mellitus kapcsolata a depresszióval, a szorongással és az életminoséggel

"Introduction: Many studies demonstrated that psychological factors play an important role in the development and course of diabetes mellitus. Objective: The focus of our research, among the first in a Hungarian sample, was to examine depression and anxiety levels and diabetes-specific quality of life in people with type 2 diabetes, to explore gender differences, and to analyze the relationship of depression and anxiety with diabetes-specific quality of life. Method: 157 people diagnosed with type 2 diabetes (women: 58.6%, men: 40.1%) were assessed for levels of depression Center for Epidemiologic Studies Depression Scale ­ Hungarian version), anxiety (Spielberger's Trait Anxiety Questionnaire) and diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life ­ Hungarian version). Results: 65% of subjects did not show depressive symptoms, but 56.1% showed moderate trait anxiety. More severe depressive symptoms (U = 1625, p<0.001) and higher trait anxiety (U = 1556, p<0.001) were significantly more frequent in women compared to men. Depressive symptom severity and trait anxiety were inversely and weakly correlated with diabetes-specific quality of life. Discussion: In summary, the results suggest that the psychological state (depressive symptoms and anxiety) in patients with type 2 diabetes is associated with their diabetes-specific quality of life. Women with diabetes also have higher levels of depression and anxiety compared to men with diabetes. Conclusion: Psychological assessment of patients' depressive and anxiety symptoms and quality of life is recommended in the care of diabetic patients, and appropriate treatment is recommended as needed. This may improve patients' quality of life, therapeutic cooperation and disease prognosis."

Changes in the Number of Physicians and Hospital Bed Capacity in Europe.

OBJECTIVES: Our aim was to examine the numbers of practicing physicians and total numbers of hospital beds in European Organisation for Economic Co-operation and Development countries. METHODS: Data analyzed were derived from the "Organisation for Economic Co-operation and Development Health Statistics 2020" database between 1980 and 2018. The selected countries were compared according to the type of healthcare system and geographical location by parametric and nonparametric tests. RESULTS: In 1980, Bismarck-type systems showed an average number of physicians of 2.3 persons/1000 population; in Beveridge-type systems, it was 1.7 persons. By 2018, it leveled out reaching 3.9 persons in both healthcare system types. In 1980, average physician number/1000 was 2.5 persons in Eastern Europe; in Western Europe, it was 1.9 persons. By 2018 this proportion changed with Western Europe having the higher number (3.7 persons; 3.9 persons). In 1980, average number of hospital beds/1000 population was 9.6 in Bismarck-type systems whereas in Beveridge-type systems it was 8.8. By 2018, it decreased to 5.6 in Bismarck-type systems (-42%) and to 3.1 in Beveridge-type systems (-65%). In 1980, the average number of hospital beds/1000 population in Eastern Europe was 10.3; in Western Europe, it was 8.5. By 2018, the difference between the 2 regions did not change. CONCLUSIONS: Although the number of physicians was 33% higher in 1980 in Eastern Europe than in Western Europe, by 2018 the number of physicians was 5% higher in Western Europe. In general, regardless of the healthcare system and geographical location, the proportion of physicians per 1000 population has improved due to a larger decrease in the number of hospital beds.

Epidemiology of Peripheral Artery Disease: Narrative Review.

Past decades have witnessed a major epidemiologic transition with a considerable increase in the disease burden associated with atherosclerotic cardiovascular diseases (CVDs), with low-income and middle-income countries (LMICs) experiencing substantial increase in CVDs. As the global population is aging and peripheral artery disease (PAD) is strongly age-related, it is estimated to become increasingly prevalent in the future. PAD shares risk factors with coronary and cerebrovascular risk factors, particularly diabetes mellitus and smoking, and is associated with significant CVD morbidity and mortality. Despite advances in therapeutic modalities, 236 million people were estimated to be suffering from PAD worldwide in 2015, and numbers have been rising since. The prevalence of asymptomatic PAD has remained high; PAD prevalence seems higher among women and is related to ethnicity. Although several epidemiological studies have been published on PAD during the past decades, data from LMICs are scarce. Besides providing up-to-date epidemiological data retrieved from the literature and the Global Burden of Disease (GBD) study database, this narrative review also intends to draw attention to the substantial disease burden of PAD manifesting in more Years of Life Lost (YLL), age-adjusted mortality and amputation rates, with a special focus on some European countries and especially Hungary, i.e., the country with the highest amputation rate in Europe.

Host cell targeting of novel antimycobacterial 4-aminosalicylic acid derivatives with tuftsin carrier peptides.

Mycobacterium tuberculosis is an intracellular pathogen and the uptake of the antimycobacterial compounds by host cells is limited. Novel antimycobacterials effective against intracellular bacteria are needed. New N-substituted derivatives of 4-aminosalicylic acid have been designed and evaluated. To achieve intracellular efficacy and selectivity, these compounds were conjugated to tuftsin peptides via oxime or amide bonds. These delivery peptides can target tuftsin- and neuropilin receptor-bearing cells, such as macrophages and various other cells of lung origin. We have demonstrated that the in vitro antimycobacterial activity of the 4-aminosalicylic derivatives against M. tuberculosis H37Rv was preserved in the peptide conjugates. The free drugs were ineffective on infected cells, but the conjugates were active against the intracellular bacteria and have the selectivity on various types of host cells. The intracellular distribution of the carrier peptides was assessed, and the peptides internalize and display mainly in the cytosol in a concentration-dependent manner. The penetration ability of the most promising carrier peptide OT5 was evaluated using Transwell-inserts and spheroids. The pentapeptide exhibited time- and concentration-dependent penetration across the non-contact monolayers. Also, the pentapeptide has a fair penetration rate towards the center of spheroids formed of EBC-1 cells.

Prevalence and Risk Factors of Problematic Internet Use among Hungarian Adult Recreational Esports Players.

Background: Esports are highly prevalent in modern culture, particularly among young people, and are a healthy hobby for the majority of users. However, there is a possible link between video gaming (including esports) and problematic internet use (so-called internet addiction, IA), mostly involving adolescents. Methods: Here we present an online survey focusing on the prevalence and risk factors of internet addiction among adult esports players. Demographics included age, gender, family type, type of work, working years and daily internet use. Medical conditions associated with IA such as smoking, alcohol and drug intake, hypertension, diabetes, ischemic heart disease, musculoskeletal pain and history of depression were also recorded. Results: Overall, 2313 players including 176 females (7.6%) and 2137 males (92.4%) participated in our online survey. Age distribution was the following: 18−25 years 90.3% (2088/2313), 26−35 years 7.95% (184/2313), 36−45 years 0.86% (20/2313), 46−55 years 0.82% (19/2313), 56−62 years 0.04% (1/2313) and 62 years or older 0.04% (1/2313). Internet addiction was detected in 19.9% of players (461/2313) based on the Problematic Internet Use Questionnaire. In a multivariate analysis internet addiction was significantly associated with age between 18 and 25 (OR: 1.675, p = 0.002), being single (OR = 1.505, p = 0.014), internet use > 6 h daily (OR = 4.338, p < 0.001), having < 3 children (OR: 2.037, p = 0.023) and having secondary employment (OR = 1.789, p = 0.037). Regular alcohol intake (OR = 18.357, p < 0.001) and history of depression (OR= 5.361, p = 0.032) were also strongly correlated with IA. Conclusion: This is the first study from Hungary investigating the prevalence and risk factors of internet addiction among adult esports players. One out of five adult gamers suffered from IA. Our study also draws attention to increased risk within this group and risk factors such as younger age, family status and type of employment.

Novel Lysine-Rich Delivery Peptides of Plant Origin ERD and Human S100: The Effect of Carboxyfluorescein Conjugation, Influence of Aromatic and Proline Residues, Cellular Internalization, and Penetration Ability.

The need for novel drug delivery peptides is an important issue of the modern pharmaceutical research. Here, we test K-rich peptides from plant dehydrin ERD14 (ERD-A, ERD-B, and ERD-C) and the C-terminal CPP-resembling region of S100A4 (S100) using the 5(6)-carboxyfluorescein (Cf) tag at the N-terminus. Via a combined pH-dependent NMR and fluorescence study, we analyze the effect of the Cf conjugation/modification on the structural behavior, separately investigating the (5)-Cf and (6)-Cf forms. Flow cytometry results show that all peptides internalize; however, there is a slight difference between the cellular internalization of (5)- and (6)-Cf-peptides. We indicate the possible importance of residues with an aromatic sidechain and proline. We prove that ERD-A localizes mostly in the cytosol, ERD-B and S100 have partial colocalization with lysosomal staining, and ERD-C mainly localizes within vesicle-like compartments, while the uptake mechanism mainly occurs through energy-dependent paths.

Human Belief State-Based Exploration and Exploitation in an Information-Selective Symmetric Reversal Bandit Task.

Humans often face sequential decision-making problems, in which information about the environmental reward structure is detached from rewards for a subset of actions. In the current exploratory study, we introduce an information-selective symmetric reversal bandit task to model such situations and obtained choice data on this task from 24 participants. To arbitrate between different decision-making strategies that participants may use on this task, we developed a set of probabilistic agent-based behavioral models, including exploitative and explorative Bayesian agents, as well as heuristic control agents. Upon validating the model and parameter recovery properties of our model set and summarizing the participants' choice data in a descriptive way, we used a maximum likelihood approach to evaluate the participants' choice data from the perspective of our model set. In brief, we provide quantitative evidence that participants employ a belief state-based hybrid explorative-exploitative strategy on the information-selective symmetric reversal bandit task, lending further support to the finding that humans are guided by their subjective uncertainty when solving exploration-exploitation dilemmas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42113-021-00112-3.

The grass root endophytic fungus Flavomyces fulophazii: An abundant source of tetramic acid and chlorinated azaphilone derivatives.

Fungal endophytes are remarkable sources of biologically active metabolites of ecological and pharmacological significance. In this study, fungal isolates producing yellow pigments and originating from grass roots, were identified as the recently described grass root colonizing dark septate endophyte (DSE), Flavomyces fulophazii (Periconiaceae, Pleosporales). While analyzing the metabolite composition of 17 isolates of this fungus, 11 previously undescribed compounds, including four tetramic acids (dihydroxyvermelhotin, hydroxyvermelhotin, methoxyvermelhotin, oxovermelhotin), and seven chlorinated azaphilones (flavochlorines A-G), together with the known tetramic acid vermelhotin, were tentatively identified by high performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS). Among them, flavochlorine A, flavochlorine G, hydroxyvermelhotin and vermelhotin could be isolated by preparative HPLC, thus their structures were also confirmed by nuclear magnetic resonance (NMR) spectroscopy. Vermelhotin was found to be the main compound, reaching its maximum level of 5.5 mg/g in the in vitro cultures of a selected F. fulophazii isolate. A significant amount of vermelhotin was isolated by preparative HPLC from these cultures (4.8 mg from 1.0 g lyophilized culture), confirming the practical utility of F. fulophazii in high-yield vermelhotin production. The main compounds of this endophyte expressed no activity in standardized plant bioassays (i.e., in the Lactuca sativa seed germination and Lemna minor growth tests). An antiproliferative study of the isolated compounds confirmed moderate activity of vermelhotin against a panel of twelve cancer cell lines, with IC50 ranges of 10.1-37.0 µM, without inhibiting the non-cancer Vero cells, suggesting its selectivity towards cancers.