Illness Self-Schema in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a relatively rare autoimmune disease with no known aetiology or cure. In addition to numerous physical symptoms, those living with SLE have also been shown to experience significant emotional and psychosocial difficulties. There has been little psychological research into SLE despite the rapidly increasing interest in health psychology and quality of life issues over the last two decades. One such issue that has commanded particular attention is that of cognitive bias in individuals with chronic pain and/or chronic illness. Cognitive bias toward illness-related information is theorised to indicate the presence of an illness self-schema, and is a valuable tool of investigation as it permits access to a level of cognitive structure that is inaccessible via self-report instruments. The primary focus of the present study is to investigate recall bias for pain- and illness-related words in SLE patients. This bias is explored relative to the recall of neutral words and depression-related words, and also relative to the responses of rheumatoid arthritis (RA) patients and healthy controls. Two hypotheses are proposed: firstly, that bias is related to disease activity; and secondly, that bias is related to the combination of illness and depression. The findings provide support for the second hypothesis, with the additional caveat that the nature of the pain/illness stimuli used is important in determining the presence of cognitive bias. No recall bias for illness-related words as a whole was found in any of the groups, nor was there evidence of a recall bias in the SLE and RA patients when they were divided according to depression status. However, when the illness words were examined separately according to �sensory pain� and �disability-related� words, a clear bias for disability words was found in the depressed patient group. It is concluded that there is a relationship between depression in chronically ill individuals, and the way in which such individuals process disability-related words. In accordance with the schema-enmeshment model (Pincus & Morley, 2001), it is suggested that both a pain-schema and an illness-schema exist, and it is when these two schemas become enmeshed with the self-schema that depression occurs in chronic pain/chronically ill patients. The cognitive bias assessment paradigm adopted in this study-one that is typically used in similar investigations-is lengthy, requires sophisticated equipment and can be difficult to interpret on an individual level. The present study investigates the relationship between cognitive biases in SLE patients and a recently-developed task, PRISM, which appears to symbolise the enmeshment of illness-, pain- and self-schemas. Analyses confirmed that recall of negative illness words was the only independent predictor of PRISM scores. This suggests that PRISM, a quick and easy task to administer, may have considerable usefulness as a clinical tool to assess information relevant to the enmeshment of illness- and self-schema. A greater understanding of schema and the processing styles of chronically ill patients will allow for more effective psychological treatment such that quality of life can be improved

A Case Study in the Future Challenges in Electricity Grid Infrastructure

The generation by renewables and the loading by electrical vehicle charging imposes severe challenges in the redesign of today’s power supply systems. Indeed, accommodating these emerging power sources and sinks requires traditional power systems to evolve from rigid centralized unidirectional architectures to intelligent decentralized entities allowing a bidirectional power flow. In the case study proposed by ENDINET, we investigate how the penetration of solar panels and of battery charging stations on large scale affects the voltage quality and loss level in a distribution network servicing a residential area in Eindhoven, NL. In our case study we take the average household load during summer and winter into account and consider both a radial and meshed topology of the network. Our study results for both topologies considered in a quantification of the levels of penetration and a strategy for electrical vehicle loading strategy that meet the voltage and loss requirements in the network

Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition

Tools for rapid and efficient transgenesis in "safe harbor" loci in an isogenic context remain important to exploit the possibilities of human pluripotent stem cells (hPSCs). We created hPSC master cell lines suitable for FLPe recombinase-mediated cassette exchange (RMCE) in the AAVS1 locus that allow generation of transgenic lines within 15 days with 100% efficiency and without random integrations. Using RMCE, we successfully incorporated several transgenes useful for lineage identification, cell toxicity studies, and gene overexpression to study the hepatocyte lineage. However, we observed unexpected and variable transgene expression inhibition in vitro, due to DNA methylation and other unknown mechanisms, both in undifferentiated hESC and differentiating hepatocytes. Therefore, the AAVS1 locus cannot be considered a universally safe harbor locus for reliable transgene expression in vitro, and using it for transgenesis in hPSC will require careful assessment of the function of individual transgenes

PRPH2 mutation update: in silico assessment of 245 reported and 7 novel variants in patients with retinal disease

Mutations in PRPH2, encoding peripherin-2, are associated with the development of a wide variety of inherited retinal diseases (IRDs). To determine the causality of the many PRPH2 variants that have been discovered over the last decades, we surveyed all published PRPH2 variants up to July 2020, describing 720 index patients that in total carried 245 unique variants. In addition, we identified seven novel PRPH2 variants in eight additional index patients. The pathogenicity of all variants was determined using the ACMG guidelines. With this, 107 variants were classified as pathogenic, 92 as likely pathogenic, one as benign, and two as likely benign. The remaining 50 variants were classified as variants of uncertain significance. Interestingly, of the total 252 PRPH2 variants, more than half (n = 137) were missense variants. All variants were uploaded into the Leiden Open source Variation and ClinVar databases. Our study underscores the need for experimental assays for variants of unknown significance to improve pathogenicity classification, which would allow us to better understand genotype-phenotype correlations, and in the long-term, hopefully also support the development of therapeutic strategies for patients with PRPH2-associated IRD.Ophthalmic researc

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

<p>Abstract</p> <p>Background</p> <p>Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries.</p> <p>Methods</p> <p>Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE).</p> <p>Results</p> <p>CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (<it>P </it>< 0.0001 and <it>P </it>= 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement.</p> <p>Conclusions</p> <p>CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.</p

A Host Small GTP-binding Protein ARL8 Plays Crucial Roles in Tobamovirus RNA Replication

Tomato mosaic virus (ToMV), like other eukaryotic positive-strand RNA viruses, replicates its genomic RNA in replication complexes formed on intracellular membranes. Previous studies showed that a host seven-pass transmembrane protein TOM1 is necessary for efficient ToMV multiplication. Here, we show that a small GTP-binding protein ARL8, along with TOM1, is co-purified with a FLAG epitope-tagged ToMV 180K replication protein from solubilized membranes of ToMV-infected tobacco (Nicotiana tabacum) cells. When solubilized membranes of ToMV-infected tobacco cells that expressed FLAG-tagged ARL8 were subjected to immunopurification with anti-FLAG antibody, ToMV 130K and 180K replication proteins and TOM1 were co-purified and the purified fraction showed RNA-dependent RNA polymerase activity that transcribed ToMV RNA. From uninfected cells, TOM1 co-purified with FLAG-tagged ARL8 less efficiently, suggesting that a complex containing ToMV replication proteins, TOM1, and ARL8 are formed on membranes in infected cells. In Arabidopsis thaliana, ARL8 consists of four family members. Simultaneous mutations in two specific ARL8 genes completely inhibited tobamovirus multiplication. In an in vitro ToMV RNA translation-replication system, the lack of either TOM1 or ARL8 proteins inhibited the production of replicative-form RNA, indicating that TOM1 and ARL8 are required for efficient negative-strand RNA synthesis. When ToMV 130K protein was co-expressed with TOM1 and ARL8 in yeast, RNA 5′-capping activity was detected in the membrane fraction. This activity was undetectable or very weak when the 130K protein was expressed alone or with either TOM1 or ARL8. Taken together, these results suggest that TOM1 and ARL8 are components of ToMV RNA replication complexes and play crucial roles in a process toward activation of the replication proteins' RNA synthesizing and capping functions

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells.

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C-C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood. Here we show that small intestinal murine CD11b &lt;sup&gt;+&lt;/sup&gt; CD103 &lt;sup&gt;+&lt;/sup&gt; DCs express Placenta-expressed transcript 1 (Plet1), a glycophoshatidylinositol (GPI)-anchored surface protein involved in migration of keratinocytes during wound healing. In the absence of Plet1, CD11b &lt;sup&gt;+&lt;/sup&gt; CD103 &lt;sup&gt;+&lt;/sup&gt; DCs display aberrant migratory behavior, and accumulate in the small intestine, independent of CCR7 responsiveness. RNA-sequencing indicated involvement of Plet1 in extracellular matrix-interactiveness, and subsequent in-vitro migration assays revealed that Plet1 augments the ability of DCs to migrate through extracellular matrix containing environments. In conclusion, our findings reveal that expression of Plet1 facilitates homeostatic interstitial migration of small intestinal DCs