Effect of radiotherapy on the DNA cargo and cellular uptake mechanisms of extracellular vesicles.

In the past decades, plenty of evidence has gathered pointing to the role of extracellular vesicles (EVs) secreted by irradiated cells in the development of radiation-induced non-targeted effects. EVs are complex natural structures composed of a phospholipid bilayer which are secreted by virtually all cells and carry bioactive molecules. They can travel certain distances in the body before being taken up by recipient cells. In this review we discuss the role and fate of EVs in tumor cells and highlight the importance of DNA specimens in EVs cargo in the context of radiotherapy. The effect of EVs depends on their cargo, which reflects physiological and pathological conditions of donor cell types, but also depends on the mode of EV uptake and mechanisms involved in the route of EV internalization. While the secretion and cargo of EVs from irradiated cells has been extensively studied in recent years, their uptake is much less understood. In this review, we will focus on recent knowledge regarding the EV uptake of cancer cells and the effect of radiation in this process.

RENEB Inter-Laboratory Comparison 2021: The Gamma-H2AX Foci Assay.

The Running the European Network of biological and retrospective dosimetry (RENEB) network of laboratories has a range of biological and physical dosimetry assays that can be deployed in the event of a radiation incident to provide exposure assessment. To maintain operational capability and provide training, RENEB runs regular inter-laboratory comparison (ILC) exercises. The RENEB ILC2021 was carried out with all the biological and physical dosimetry assays employed in the network. The focus of this paper is to evaluate the results from 6 laboratories that took part using the gamma-H2AX radiation-induced foci assay. For two laboratories this was their first RENEB ILC. Blood samples were homogenously exposed to 240 kVp X rays (1 Gy/min) to provide calibration data, (0-4 Gy), and a few weeks later three blind coded test samples, (0, 1.2 and 3.5 Gy) were prepared. All samples were allowed a 2 h repair time at 37°C before being transported, on ice packs, to the participating laboratories. On arrival, the samples were processed, scored either manually or automatically for gamma-H2AX foci and dose estimates for the 3 blind coded samples sent to the organizing laboratory. The temperature of samples during transit and the time taken to report the dose estimates were recorded. Subsequent examination of the data from each laboratory used the doses estimates to assign triage categories to the samples. After receipt of the samples, the quickest report of dose estimates was 4.6 h. Analysis of variance revealed that the laboratory carrying out the assay had a significant effect on the foci yield (P < 0.001) for the calibration data, but not on the dose estimates of the blind coded samples (P = 0.101). All laboratories correctly identified the unirradiated and irradiated samples, although the dose estimates for the latter tended to under-estimate the dose. Two participants seriously under-estimated the dose for the highly exposed sample, which resulted in the sample being placed in the lowest triage category not the highest. However, this under-estimation resulted from the samples not remaining cold during shipment, due to a delay in transit and was not related to the experience of the participating laboratory. Overall, the RENEB network laboratories have demonstrated it is possible to quickly identify a recent whole-body acute exposure using the gamma-H2AX assay within the conditions of the ILC. In addition, an ILC provides a useful training and harmonization exercise for laboratories.

Pathological personality traits of maladaptive daydreamers measured by the Personality Inventory for DSM-5 in a psychiatric sample.

This study aimed to estimate the frequency of maladaptive daydreaming and to explore the pathological personality traits of probable maladaptive daydreamers. Our sample consisted of 239 psychiatric patients. After screening, 42 persons were probable maladaptive, while 197 participants prove to be normal daydreamers. Two pathological domains and three facets measured by the Personality Inventory for DSM-5 showed a moderate significant correlation with the Maladaptive Daydreaming Scale. The score of nearly every domain and facet was slightly higher among probable maladaptive daydreamers. To quantify the difference between the groups, effect sizes were calculated: Significant difference was found on the domain level in Antagonism, while on the facet level in Hostility, Grandiosity, Attention Seeking, Unusual Beliefs and Experiences, Cognitive and Perceptual Dysregulation. The group of probable maladaptive daydreamers was further examined to identify potential subgroups. Cluster analysis revealed heterogeneity in the severeness and patterns of pathological personality domains. Cluster 1 showed higher mean scores on the PID domains and on the MDS compared to Cluster 2. Clusters 1 and 2 broke further down into two subclusters: Cluster 1a and Cluster 1b differed in their mean scores on the domains of Antagonism and Detachment; the mean scores of Cluster 2a were uniformly low on each domain, while the mean values of Cluster 2b were scattered in a mixed way on the domains. Our results suggest that maladaptive daydreaming might manifest with differently pathological personality profiles in the background. This aspect might worth considering in planning treatment.

Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations.

BACKGROUND: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. METHODS: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. RESULTS: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. CONCLUSIONS: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system.

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow.

Ionizing radiation (IR)-induced bystander effects contribute to biological responses to radiation, and extracellular vesicles (EVs) play important roles in mediating these effects. In this study we investigated the role of bone marrow (BM)-derived EVs in the bystander transfer of radiation damage. Mice were irradiated with 0.1Gy, 0.25Gy and 2Gy, EVs were extracted from the BM supernatant 24 h or 3 months after irradiation and injected into bystander mice. Acute effects on directly irradiated or EV-treated mice were investigated after 4 and 24 h, while late effects were investigated 3 months after treatment. The acute effects of EVs on the hematopoietic stem and progenitor cell pools were similar to direct irradiation effects and persisted for up to 3 months, with the hematopoietic stem cells showing the strongest bystander responses. EVs isolated 3 months after irradiation elicited no bystander responses. The level of seven microRNAs (miR-33a-3p, miR-140-3p, miR-152-3p, miR-199a-5p, miR-200c-5p, miR-375-3p and miR-669o-5p) was altered in the EVs isolated 24 hour but not 3 months after irradiation. They regulated pathways highly relevant for the cellular response to IR, indicating their role in EV-mediated bystander responses. In conclusion, we showed that only EVs from an early stage of radiation damage could transmit IR-induced bystander effects.

[Assessment of pathological personality traits and gender characteristics by Personality Inventory for DSM-5 in a psychiatric and a normal sample].

INTRODUCTION: The DSM-5 describes two types of classification of personality disorders: a categorical and a dimensional classification. The alternative model of personality disorders in the DSM-5 determines new diagnostic criteria for personality disorders with a criterion B describing the presence of pathological personality facets. For the assessment of these domains and facets, the Personality Inventory for DSM-5 (PID-5) was created. METHODS: A sample of patients receiving psychiatric care (n=239) and a normal sample (n=226) were involved in the study. The two samples did not differ significantly regarding gender, age, and the levels of education. The PID-5 was applied to assess the pathological domains and facets. RESULTS: Psychiatric patients scored significantly higher on four out of five PID domains compared to the members of the general population. Regarding the PID facets, the two study groups differed significantly in 18 out of 25 facets. Regarding the PID domains and facets, gender differences were found in the clinical sample: Negative Affectivity was more typical for women, while Antagonism was more dominant for men. Women receiving psychiatric care were cha - rac terized by Emotional Lability and Anxiousness, while Manipulativeness, Deceitfulness, Callousness and Risk Taking were more dominant for men of the clinical sample. CONCLUSION: Our results confirmed the applicability of the dimensional personality model. The PID-5 can discriminate between psychiatric and normal samples. Our findings suggested that in the case of the general population, traditional gender characteristics disappeared, while psychiatric patients seemed to preserve the traditional gender roles.

Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients.

Prostate cancer is among the most frequent cancers in men worldwide. Despite the fact that multiple therapeutic alternatives are available for its treatment, it is often discovered in an advanced stage as a metastatic disease. Prostate cancer screening is based on physical examination of prostate size and prostate-specific antigen (PSA) level in the blood as well as biopsy in suspect cases. However, these markers often fail to correctly identify the presence of cancer, or their positivity might lead to overdiagnosis and consequent overtreatment of an otherwise silent non-progressing disease. Moreover, these markers have very limited if any predictive value regarding therapy response or individual risk for therapy-related toxicities. Therefore, novel, optimally liquid biopsy-based (blood-derived) markers or marker panels are needed, which have better prognostic and predictive value than the ones currently used in the everyday routine. In this review the role of circulating tumour cells, extracellular vesicles and their microRNA content, as well as cellular and soluble immunological and inflammation- related blood markers for prostate cancer diagnosis, prognosis and prediction of therapy response is discussed. A special emphasis is placed on markers predicting response to radiotherapy and radiotherapy-related late side effects.

The differential role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in the adherence, migration and podosome formation of human macrophages and dendritic cells under inflammatory conditions.

CR3 and CR4, the leukocyte specific ß2-integrins, involved in cellular adherence, migration and phagocytosis, are often assumed to have similar functions. Previously however, we proved that under physiological conditions CR4 is dominant in the adhesion to fibrinogen of human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Here, using inflammatory conditions, we provide further evidence that the expression and function of CR3 and CR4 are not identical in these cell types. We found that LPS treatment changes their expression differently on MDMs and MDDCs, suggesting a cell type specific regulation. Using mAb24, specific for the high affinity conformation of CD18, we proved that the activation and recycling of ß2-integrins is significantly enhanced upon LPS treatment. Adherence to fibrinogen was assessed by two fundamentally different approaches: a classical adhesion assay and a computer-controlled micropipette, capable of measuring adhesion strength. While both receptors participated in adhesion, we demonstrated that CR4 exerts a dominant role in the strong attachment of MDDCs. Studying the formation of podosomes we found that MDMs retain podosome formation after LPS activation, whereas MDDCs lose this ability, resulting in a significantly reduced adhesion force and an altered cellular distribution of CR3 and CR4. Our results suggest that inflammatory conditions reshape differentially the expression and role of CR3 and CR4 in macrophages and dendritic cells.

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients.

Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.

Facial emotion recognition deficits and alexithymia in borderline, narcissistic, and histrionic personality disorders.

Previous studies that aimed to support emotion recognition deficits and alexithymia in B cluster personality disorders have mainly focused on borderline personality disorder (BPD), and resulted in mixed findings. In our study we examine emotion recognition and alexithymia in patients with histrionic (HPD), narcissistic (NPD) and borderline (BPD) personality disorders compared to each other and healthy controls. Furthermore, the possibility is investigated that it is not the type of PD but the severity of psychopathology which predicts the severity of emotion recognition deficits and alexithymia. Patients with HPD, NPD, BPD and healthy controls (N = 20 for each group) were examined by using the Ekman 60 Faces Test (FEEST) and the Toronto Alexithymia Scale (TAS-20). To measure the extent and severity of psychopathology, the Symptom-Checklist-90 Revised (SCL-90-R) was used. Patient groups performed significantly worse compared to healthy controls on the Ekman test and TAS-20, while we found no significant differences among patient groups in emotion recognition and alexithymia. Furthermore, higher scores on the SCL-90-R predicted poorer emotion recognition performance and higher alexithymic features. The empirical data supports the conclusion that the severity of psychopathology plays an important role in predicting emotion recognition deficits and alexithymia in borderline, narcissistic, and histrionic personality disorders.

[Fear appealing health communication and coping style].

INTRODUCTION: The purpose of the reported study was to investigate how people respond to social advertisements which differ in topic and in the extent of fear appeal given their typical coping strategy. This is a topical issue as it has practical relevance to the design of persuasive communication in the service of health behavior, based on the relation between persuasion and personality. For a theoretical frame we used two cognitive evaluating models: Kim Witte's Extended Parallel Process Model and Endler and Parker's conception about different coping styles. METHOD: Online questionnaire was applied in the study. The sample consisted of 140 young adults. Every respondent perceived two fear appealing social advertisements and filled out Witte, McKeon, Cameron and Berkowitz' Risk Behavior Diagnosis Scale to assess health communications. Finally, they answered the items of Coping Inventory for Stressful Situations by Endler and Parker. RESULTS: Based on the results of the applied repeated measures ANOVA, we found that the link between coping mechanism and responses of adverts is neither linear, nor is general. CONCLUSIONS: A general consequence cannot be drawn regarding the relationship of constructs, but it seems that the relationship between the typical coping strategy and the reaction to the advertisements moderated or mediated by the presented topic of fear appealing messages.

["Better late than never". Studying procrastination among students].

INTRODUCTION: The purpose of the study is to investigate dispositional procrastination, procrastination types, and an operative measurement of this behavior in academic environment. Procrastination is a common and problematic phenomenon that explains the need for a comprehensive and complex approach of this behavior. The main focus of the study was to investigate the incidence and incidence of the different types of procrastination. Furthermore, we aimed to test the correspondence between dispositional procrastination and the operative measurement. METHODS: The sample consisted of 131 participants. Lay's Procrastination Scale was used to measure dispositional procrastination and the Types of procrastination questionnaire was applied to assess the frequency of its different types. Furthermore an operative measurement was gained by assigning a deadline for returning the paper and pensil form of the questionnaire. Participants received a message informing them that the deadline had been extended by three more days on the last night before the deadline. RESULTS: Based on the empirical results 63% of the participants can be classified as procrastinator. In regards of the different types of procrastination, "perfectionist" and "crisis-maker" types were the most frequent. A positive correlation was found between dispositional procrastination and the operative measurement of procrastination. CONCLUSIONS: The results proved the common presence of procrastination, as well as the close connection between its dispositional and operative measure. Besides, they raise attention to the perfectionist and crisis-maker types of procrastination.

Characterization factors for land use impacts on biodiversity in life cycle assessment based on direct measures of plant species richness in European farmland in the 'Temperate Broadleaf and Mixed Forest' biome.

Life Cycle Assessment (LCA) is a widely used tool to assess environmental sustainability of products. The LCA should optimally cover the most important environmental impact categories such as climate change, eutrophication and biodiversity. However, impacts on biodiversity are seldom included in LCAs due to methodological limitations and lack of appropriate characterization factors. When assessing organic agricultural products the omission of biodiversity in LCA is problematic, because organic systems are characterized by higher species richness at field level compared to the conventional systems. Thus, there is a need for characterization factors to estimate land use impacts on biodiversity in life cycle assessment that are able to distinguish between organic and conventional agricultural land use that can be used to supplement and validate the few currently suggested characterization factors. Based on a unique dataset derived from field recording of plant species diversity in farmland across six European countries, the present study provides new midpoint occupation Characterization Factors (CF) expressing the Potentially Disappeared Fraction (PDF) to estimate land use impacts on biodiversity in the 'Temperate Broadleaf and Mixed Forest' biome in Europe. The method is based on calculation of plant species on randomly selected test sites in the biome and enables the calculation of characterization factors that are sensitive to particular types of management. While species richness differs between countries, the calculated CFs are able to distinguish between different land use types (pastures (monocotyledons or mixed), arable land and hedges) and management practices (organic or conventional production systems) across countries. The new occupation CFs can be used to supplement or validate the few current CF's and can be applied in LCAs of agricultural products to assess land use impacts on species richness in the 'Temperate Broadleaf and Mixed Forest' biome.

Farmland biodiversity and agricultural management on 237 farms in 13 European and two African regions.

Farmland is a major land cover type in Europe and Africa and provides habitat for numerous species. The severe decline in farmland biodiversity of the last decades has been attributed to changes in farming practices, and organic and low-input farming are assumed to mitigate detrimental effects of agricultural intensification on biodiversity. Since the farm enterprise is the primary unit of agricultural decision making, management-related effects at the field scale need to be assessed at the farm level. Therefore, in this study, data were collected on habitat characteristics, vascular plant, earthworm, spider, and bee communities and on the corresponding agricultural management in 237 farms in 13 European and two African regions. In 15 environmental and agricultural homogeneous regions, 6-20 farms with the same farm type (e.g., arable crops, grassland, or specific permanent crops) were selected. If available, an equal number of organic and non-organic farms were randomly selected. Alternatively, farms were sampled along a gradient of management intensity. For all selected farms, the entire farmed area was mapped, which resulted in total in the mapping of 11 338 units attributed to 194 standardized habitat types, provided together with additional descriptors. On each farm, one site per available habitat type was randomly selected for species diversity investigations. Species were sampled on 2115 sites and identified to the species level by expert taxonomists. Species lists and abundance estimates are provided for each site and sampling date (one date for plants and earthworms, three dates for spiders and bees). In addition, farmers provided information about their management practices in face-to-face interviews following a standardized questionnaire. Farm management indicators for each farm are available (e.g., nitrogen input, pesticide applications, or energy input). Analyses revealed a positive effect of unproductive areas and a negative effect of intensive management on biodiversity. Communities of the four taxonomic groups strongly differed in their response to habitat characteristics, agricultural management, and regional circumstances. The data has potential for further insights into interactions of farmland biodiversity and agricultural management at site, farm, and regional scale.

Gains to species diversity in organically farmed fields are not propagated at the farm level.

Organic farming is promoted to reduce environmental impacts of agriculture, but surprisingly little is known about its effects at the farm level, the primary unit of decision making. Here we report the effects of organic farming on species diversity at the field, farm and regional levels by sampling plants, earthworms, spiders and bees in 1470 fields of 205 randomly selected organic and nonorganic farms in twelve European and African regions. Species richness is, on average, 10.5% higher in organic than nonorganic production fields, with highest gains in intensive arable fields (around +45%). Gains to species richness are partly caused by higher organism abundance and are common in plants and bees but intermittent in earthworms and spiders. Average gains are marginal +4.6% at the farm and +3.1% at the regional level, even in intensive arable regions. Additional, targeted measures are therefore needed to fulfil the commitment of organic farming to benefit farmland biodiversity.

[Psychometric properties of the Hungarian version of the Codependence Questionnaire]. / A magyar nyelvu Kodependencia Kérdoív psgichometriai vizsgálata.

UNLABELLED: The purpose of this study is to assess the internal consistency of the subscales of the Hungarian Version of the Codependent Questionnaire (CdQ, Roehling & Gaumond, 1996). Thus, a reliable measurement of codependency for professionals become available in Hungary. The Hungarian Version of the Codependent Questionnaire enables professionals to identify codependent individuals. METHODS: Our sample (N=137) was recruited from the general population and from self-help groups (82 individuals); and patients with borderline personality disorder (55 individuals) were recruited as clinical control group. The reliability of the questionnaire was assessed by Cronbach's alfa and principal component analysis. In addition, in order to investigate the latent structure, factors analyses and hierarchical cluster analysis were used. RESULTS: Based on our results, the Cronbach's alfa values of the subscales of 'control', 'reliability' and 'intimacy' indicate appropriate reliability, however, the subscale of 'enmeshment' indicates poor reliability. The originally assumed factor structure is not supported by the results of the statistical analyses. The subscales are not separate from each other, which is also indicated by the correlations of the total scores of the subscales. CONCLUSION: The reliability of the Hungarian Version of the Codependent Questionnaire is nearly identical to the original data, except for one subscale ('enmeshment subscale'). Based on these results the Hungarian Version of the Codependent Questionnaire is considered to be reliable. Besides the Hungarian adaptation, the strength of this study is the investigation of a clinical sample. The use of the questionnaire is recommended without the subscale of 'enmeshment' and further 5 items, and it is suggested to use as one scale.

Economic inequality is linked to biased self-perception.

People's self-perception biases often lead them to see themselves as better than the average person (a phenomenon known as self-enhancement). This bias varies across cultures, and variations are typically explained using cultural variables, such as individualism versus collectivism. We propose that socioeconomic differences among societies--specifically, relative levels of economic inequality--play an important but unrecognized role in how people evaluate themselves. Evidence for self-enhancement was found in 15 diverse nations, but the magnitude of the bias varied. Greater self-enhancement was found in societies with more income inequality, and income inequality predicted cross-cultural differences in self-enhancement better than did individualism/collectivism. These results indicate that macrosocial differences in the distribution of economic goods are linked to microsocial processes of perceiving the self.

Mixed model estimation methods for the Rasch model.

Mixed models take the dependency between observations based on the same person into account by introducing one or more random effects. After introducing the mixed model framework, it is explained, by taking the Rasch model as a generic example, how item response models can be conceptualized as generalized linear and nonlinear mixed models. Common estimation methods for generalized linear and nonlinear models are discussed. In a simulation study, the performance of four estimation methods is assessed for the Rasch model under different conditions regarding the number of items and persons, and the degree of interindividual differences. The estimation methods included in the study are: an approximation of the integral over the random effect by means of Gaussian quadrature; direct maximization with a sixth-order Laplace approximation to the integrand; a linearized approximation of the nonlinear model employing PQL2; and finally a Bayesian MCMC method. It is concluded that the estimation methods perform almost equally well, except for a slightly worse recovery of the variance parameter for PQL2 and MCMC.