Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

Background: Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC) as compared to wild-type (WT) cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM) and g-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts) after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls. Results: Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion: These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.Toxicogenomics and risk assessmen

Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing

© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. Background: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. Methods: We recruited children between 3 and 6years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. Results: Seventy-four children, mean (standard deviation (SD)) age of 4.32years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P=.003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from −1.66 to −1.17 (P=.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with “well-controlled” asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. Conclusions: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children

Treatment goals and preferences of pediatric psoriasis patients, young adults, and parents

Background Treatment needs of young psoriasis patients and parents are not widely studied and could advance patient-centered care. Objective To explore treatment goals and preferences of pediatric psoriasis patients, young adults, and parents. Methods A web-based survey among Dutch psoriasis patients aged ≥6 to ≤30 years and parents included multiple-choice, open-ended, and 4-point Likert scale questions. Treatment goals and characteristic preferences of pediatric patients (≤17 years) were compared to young adults (≥18 years) and parents. Results 195 young patients (20.2 ± 6.3 years) and 45 parents were included. The most important treatment goals were ‘preventing lesions’, ‘reducing lesions’, ‘no itch’, and ‘no lesions’. Regarding treatment characteristics, ‘long-term safety’, ‘high effectiveness’, and ‘short-term safety’ were most important. We found differences by age, gender, and current treatment. Pediatric patients rated ‘not sticky’, ‘quick results’, and ‘no/few blood samples needed’ higher than parents and/or young adults. Young adults rated ‘feeling more confident’ and ‘better quality of sleep’ higher than pediatric patients. Parents considered safety most important. Psychosocial goals were more important for women and patients on biologics. Conclusion Young psoriasis patients and parents mainly strive to clear lesions and itch with effective and safe treatment. However, revealed differences underline the relevance of addressing individual needs

Dual-Use Quickscan: A Web-Based Tool to Assess the Dual-Use Potential of Life Science Research.

Research on pathogenic organisms is crucial for medical, biological and agricultural developments. However, biological agents as well as associated knowledge and techniques, can also be misused, for example for the development of biological weapons. Potential malicious use of well-intended research, referred to as “dual-use research”, poses a threat to public health and the environment. There are various international resources providing frameworks to assess dual-use potential of the research concerned. However, concrete instructions for researchers on how to perform a dual-use risk assessment is largely lacking. The international need for practical dual-use monitoring and risk assessment instructions, in addition to the need to raise awareness among scientists about potential dual-use aspects of their research has been identified over the last years by the Netherlands Biosecurity Office, through consulting national and international biorisk stakeholders. We identified that Biorisk Management Advisors and researchers need a practical tool to facilitate a dual-use assessment on their specific research. Therefore, the Netherlands Biosecurity Office developed a web-based Dual-Use Quickscan (www.dualusequickscan.com), that can be used periodically by researchers working with microorganisms to assess potential dual-use risks of their research by answering a set of fifteen yes/no questions. The questions for the tool were extracted from existing international open resources, and categorized into three themes: characteristics of the biological agent, knowledge and technology about the biological agent, and consequences of misuse. The results of the Quickscan provide the researcher with an indication of the dual-use potential of the research and can be used as a basis for further discussions with a Biorisk Management Advisor. The Dual-Use Quickscan can be embedded in a broader system of biosafety and biosecurity that includes dual-use monitoring and awareness within organizations. Increased international attention to examine pathogens with pandemic potential has been enhanced by the current COVID-19 pandemic, hence monitoring of dual-use potential urgently needs to be encouraged

Patient-therapist interaction in the behavioral treatment of panic disorder with agoraphobia

Contains fulltext : 29705.pdf (publisher's version ) (Closed access)Although effective behavioral techniques have been developed, what aspects of the patient-therapist interaction affect treatment outcome remain largely unknown. This study hypothesized that the interaction between patient and therapist develops over several phases. Further, the association between behavior modes and treatment outcome was expected to alter as that interaction developed. Thirty patients diagnosed with panic disorder with agoraphobia were treated with a standardized behavioral treatment program of 12 sessions. The interpersonal verbal therapist and patient behavior modes were studied at Sessions 1, 3, and 10, using an observational instrument. It was found that behavior modes change over the course of treatment, in line with predictions derived from social-psychological models. The hypothesis that establishing a therapeutic relationship requires an empathic and nondirective stance by the therapist in Session 1 was partly confirmed

The Vulnerability Scan, a Web Tool to Increase Institutional Biosecurity Resilience.

The importance of vigilance within organizations working with high-risk biological material receives increasing attention. However, an in-depth and comprehensive tool, dedicated to increase awareness of potential risks and to assess an organization's current biosecurity vulnerabilities, has not been available yet. We developed the "Biosecurity Vulnerability Scan," a web tool that identifies biosecurity gaps in an organization based on eight biosecurity pillars of good practice. Although the tool aims primarily to assist biosafety and biosecurity officers, it can also be useful to researchers working with dangerous pathogens, their principal investigators, management, or those responsible for security issues in the life sciences. Results are only stored locally and are provided in an "overview report," which includes information on relevant risks and control measures. This can support well-substantiated decision-making on strengthening biosecurity measures within a specific organization. With this article, we aim to support institutes to increase their overall security resilience and to improve institutional biosecurity in particular by providing practical recommendations. The Biosecurity Vulnerability Scan is available at www.biosecurityvulnerabilityscan.nl