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In 2015, ISO published ISO 90012015, a significant revision to the ISO 9001 Quality Management System standard. This 2015 version contained extensive changes and a new structure. This revision to ISO 9001 raises the question of whether ICH Q10 should be reviewed and potentially revised, and whether ICH Q10 continues to meet the ISO 9000 principles. This article assesses whether the changes to the ISO 90012015 standard could make a revision of the ICH Q10 guideline necessary and whether ICH Q10 still represents a current model of a pharmaceutical quality management system.Diagnostic radiologists are experts in discriminating and classifying medical images for clinically significant anomalies. Does their perceptual expertise confer an advantage in unfamiliar visual tasks? Here, this issue was investigated by comparing the performance of 10 radiologists and 2 groups of novices on the ability to detect novel visual signals band-limited textures in noise. Observers performed a yes/no detection task in which texture spatial frequency and external noise levels were varied. The task was performed on two consecutive days. Contrast thresholds and response bias were measured. Contrast thresholds of radiologists were superior to the control groups in all stimulus conditions on both days. Performance improved by an equivalent amount for all groups across days. Response bias differed consistently across stimulus conditions and days but not across groups. The difference in thresholds between the radiologists and control groups suggests that experience in diagnostic medical imaging produces perceptual skills that that transfer beyond the trained domain.Asbestos causes malignant transformation of primary human mesothelial cells (HM), leading to mesothelioma. The mechanisms of asbestos carcinogenesis remain enigmatic, as exposure to asbestos induces HM death. However, some asbestos-exposed HM escape cell death, accumulate DNA damage, and may become transformed. We previously demonstrated that, upon asbestos exposure, HM and reactive macrophages releases the high mobility group box 1 (HMGB1) protein that becomes detectable in the tissues near asbestos deposits where HMGB1 triggers chronic inflammation. HMGB1 is also detectable in the sera of asbestos-exposed individuals and mice. Searching for additional biomarkers, we found higher levels of the autophagy marker ATG5 in sera from asbestos-exposed individuals compared to unexposed controls. As we investigated the mechanisms underlying this finding, we discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM to survive asbestos exposure. HMGB1 silencing inhibited autophagy and increased asbestos-induced HM death, thereby decreasing asbestos-induced HM transformation. We demonstrate that autophagy was induced by the cytoplasmic and extracellular fractions of HMGB1 via the engagement of the RAGE receptor and Beclin 1 pathway, while nuclear HMGB1 did not participate in this process. We validated our findings in a novel unique mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model. Compared to HMGB1 wild-type mice, mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death. Autophagy inhibitors chloroquine and desmethylclomipramine increased cell death and reduced asbestos-driven foci formation. In summary, HMGB1 released upon asbestos exposure induces autophagy, promoting HM survival and malignant transformation.Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model organism Dictyostelium discoideum using a microfluidic chip design. This design allowed us to monitor the behavior of single cells via live imaging when confronted with bifurcating microchannels, presenting different combinations of hydraulic and chemical stimuli. Under the conditions employed we find no evidence in support of a barotactic response; the cells base their directional choices on the chemotactic cues. When the cells are confronted by a microchannel bifurcation, they often split their leading edge and start moving into both channels, before a decision is made to move into one and retract from the other channel. Analysis of this decision-making process has shown that cells in steeper nonhydrolyzable adenosine- 3′, 5′- cyclic monophosphorothioate, Sp- isomer (cAMPS) gradients move faster and split more readily. Furthermore, there exists a highly significant strong correlation between the velocity of the pseudopod moving up the cAMPS gradient to the total velocity of the pseudopods moving up and down the gradient over a large range of velocities. This suggests a role for a critical cortical tension gradient in the directional decision-making process.B cell depletion via anti-CD20 antibodies is a highly effective treatment for multiple sclerosis (MS). However, little is known about the maturation/activation stage of the returning B cell population after treatment cessation and the wider effects on other immune cells. In the present study, 15 relapsing-remitting MS patients receiving 1,000 mg of rituximab were included. B, T, and myeloid cells were analyzed before anti-CD20 administration and in different time intervals thereafter over a period of 24 mo. In comparison to the phenotype before anti-CD20 treatment, the reappearing B cell pool revealed a less mature and more activated phenotype 1) reappearing B cells were significantly enriched in transitional (before 10.1 ± 1.9%, after 58.8 ± 5.2%) and mature naive phenotypes (before 45.5 ± 3.1%, after 25.1 ± 3.5%); 2) the frequency of memory B cells was reduced (before 36.7 ± 3.1%, after 8.9 ± 1.7%); and 3) reappearing B cells showed an enhanced expression of activation markers CD25 (before 2.1 ± 0.4%, after 9.3 ± 2.1%) and CD69 (before 5.9 ± 1.0%, after 21.4 ± 3.0%), and expressed significantly higher levels of costimulatory CD40 and CD86. Selleckchem MEK inhibitor T cells showed 1) a persistent increase in naive (CD4+ before 11.8 ± 1.3%, after 18.4 ± 3.4%; CD8+ before 12.5 ± 1.4%, after 16.5 ± 2.3%) and 2) a decrease in terminally differentiated subsets (CD4+ before 47.3 ± 3.2%, after 34.4 ± 3.7%; CD8+ before 53.7 ± 2.1%, after 49.1 ± 2.7%).