Psychometric properties and clinical utility of COVID-19-related distress scale among children and adolescents with Disabilities.

BACKGROUND: The aim was to estimate the psychometric properties of the COVID-19-related distress scale in our society, as well as verifying the global structure of the COVID-19-related distress scale through exploratory factor analysis and the confirmatory factor analysis model for the dimensions prepared in the light of previous studies and the general factor model. METHODS: The study follows the design of the exploratory cross-sectional studies by applying a scale electronically using the Google Forms tool. Construct validity was evaluated using confirmatory factor analysis, exploratory factor analysis, and content validity. Pearson product-moment correlation, Cronbach's alpha reliability coefficient, and test-retest methods were used to evaluate reliability. RESULTS: In the analysis made for internal consistency in the reliability study of the scale, the Cronbach's alpha reliability coefficients were determined as α = 0.93 for the physical dimension subscale, 0.90 for the psychological and emotional dimension, 0.92 for cognitive dimension, 0.91 for the social dimension, 0.92 for behavioral dimension, 0.87 for living Dimension and 0.94 for the whole scale. The total number of items on the scale is 62. It is clear that the items of the scale explained 55.49 % of the variance of the correlation matrix between the items, which indicates that the scale has an appropriate degree to extract the variance that explains COVID-19-related distress. The fit indices were found to be Chi square = 862.30 (p < .001), degree of freedom = 210 (χ2 = 862.30; df = 210, χ2/df = 4.10), root mean square error of approximation (RMSEA) = 0.07 (p < .05) standardized root mean- square residual (SRMR) = 0.05, comparative fit index (CFI) = 0.92, non-normed fit index (NNFI) = 0.95, goodness of fit index (GFI) = 0.95, and adjusted goodness of fit index (AGFI) = 0.94. CONCLUSIONS: The COVID-19-related distress scale is an easy to administer, valid, and reliable instrument to assess COVID-19-related distress. This instrument can be a helpful tool informing us about distress related to COVID-19 and hence may prevent adverse long-term consequences arising due to pandemic.

Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response.

Endoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in the ER, elicits a homeostatic mechanism known as the Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation to chronic ER stress. The UPR comprises an acute phase involving inhibition of bulk protein synthesis and a chronic phase of transcriptional induction coupled with the partial recovery of protein synthesis. However, the role of transcriptional regulation in the acute phase of the UPR is not well understood. Here we analyzed the fate of newly synthesized mRNA encoding the protective and homeostatic transcription factor X-box binding protein 1 (XBP1) during this acute phase. We have previously shown that global translational repression induced by the acute UPR was characterized by decreased translation and increased stability of XBP1 mRNA. We demonstrate here that this stabilization is independent of new transcription. In contrast, we show XBP1 mRNA newly synthesized during the acute phase accumulates with long poly(A) tails and escapes translational repression. Inhibition of newly synthesized RNA polyadenylation during the acute phase decreased cell survival with no effect in unstressed cells. Furthermore, during the chronic phase of the UPR, levels of XBP1 mRNA with long poly(A) tails decreased in a manner consistent with co-translational deadenylation. Finally, additional pro-survival, transcriptionally-induced mRNAs show similar regulation, supporting the broad significance of the pre-steady state UPR in translational control during ER stress. We conclude that the biphasic regulation of poly(A) tail length during the UPR represents a previously unrecognized pro-survival mechanism of mammalian gene regulation.

Adaptation to chronic ER stress enforces pancreatic ß-cell plasticity.

Pancreatic ß-cells are prone to endoplasmic reticulum (ER) stress due to their role in insulin secretion. They require sustainable and efficient adaptive stress responses to cope with this stress. Whether episodes of chronic stress directly compromise ß-cell identity is unknown. We show here under reversible, chronic stress conditions ß-cells undergo transcriptional and translational reprogramming associated with impaired expression of regulators of ß-cell function and identity. Upon recovery from stress, ß-cells regain their identity and function, indicating a high degree of adaptive plasticity. Remarkably, while ß-cells show resilience to episodic ER stress, when episodes exceed a threshold, ß-cell identity is gradually lost. Single cell RNA-sequencing analysis of islets from type 1 diabetes patients indicates severe deregulation of the chronic stress-adaptation program and reveals novel biomarkers of diabetes progression. Our results suggest ß-cell adaptive exhaustion contributes to diabetes pathogenesis.