The total scale and the three domains showed good internal consistency and test-retest reliability. The correlation with SCORAD and other subjective measures was consistent with our hypotheses. Differences in scores between mild, moderate and severe AD patients were significant and the CADIS-SF15 was able to detect changes in 'improving' patients over time. CONCLUSION The CADIS-SF15 with 15 items in three domains is an internally consistent, reliable, valid, responsive, and brief measure of QoL in children affected with AD and their parents. Further evaluation of clinical applicability is required. This article is protected by copyright. All rights reserved.Oligodendrocytes wrap and physically shield axons of the central nervous system with myelin sheaths, resulting in rapid signal transduction and accurate neuronal function. The complex oligodendroglial development from immature oligodendrocyte precursor cells (OPCs) to myelinating oligodendrocytes (OLs) is profoundly dependent on the activity of transcription factors of the Sox protein family. Target genes of the crucial regulator Sox10 have recently been expanded to microRNAs. Here, we report miR-204 as a novel transcriptional target of Sox10. Regulatory regions of miR-204 show responsiveness to and binding of Sox10 in reporter gene assays and electromobility shift assays. Once expressed, miR-204 inhibits OPC proliferation and facilitates differentiation into OLs in the presence of Sox10 as evident from overexpression in primary rat and mouse oligodendroglial cultures. Phenotypes are at least in part caused by miR-204-dependent repression of the pro-proliferative Ccnd2 and the differentiation inhibiting Sox4. These findings argue that the transcriptional activator Sox10 forces oligodendroglial cells to exit the cell cycle and start differentiation by gene inhibition via miR-204 induction. © 2020 The Authors. Glia published by Wiley Periodicals, Inc.BACKGROUND The United Kingdom Working Party's (UKWP) criteria were developed to improve epidemiological research in atopic dermatitis (AD), but have not been validated in an exclusively adult European population. OBJECTIVE To validate the UKWP criteria for AD in adults. METHODS In this cross-sectional study, three independent samples of adult individuals were drawn and interviewed patients with a hospital diagnosis of AD or plaque psoriasis in adulthood, and general population controls. Various versions of the UKWP criteria for AD were utilized. RESULTS A total of 3,490 (general population), 3,834 (AD), and 4,016 (psoriasis) adult individuals were erolled in the study. The best combination of the UKWP criteria lead to a sensitivity of 0.71 and a specificity of 0.96 in the general population. The criteria better captured 'AD ever' compared to 'AD within the past 12 months', and had a higher sensitivity in patients with moderate (87.2-97.7%) or severe (95.8-100%) AD at the time of interview compared to those who where asymptomatic (12.6-36.8%). The UKWP criteria also captured high proportions of psoriasis patients (19.7-47.7%) when applied in a cohort of unique psoriasis patients. CONCLUSIONS It remains a challenge to accurately diagnose a history of AD in adulthood since symptoms are shared with other skin conditions and AD may have resolved or can be waxing and waning, in turn leading to recall bias. The UKWP criteria performed well in the general population for the purpose of determining the prevalence, but should be used cautiously when studying comorbidity. This article is protected by copyright. All rights reserved.Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present LEAP, a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and co-variant information. L2-regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer-related genes, and 5,398 variants from 30 cardiovascular-related genes). Using 10-fold cross-validated predictions, the logistic regression model achieved an AUROC of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability makes LEAP effective in the clinical setting as a high-throughput quality control layer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND After an emergent surgery for type A acute aortic syndrome, medical management is based on optimal blood pressure (BP) control. We assessed the prognostic significance of BP monitoring and its relationship with aortic morphology following type A acute aortic syndrome. METHODS The data of 120 patients who underwent BP monitoring after a type A acute aortic syndrome from January 2005 to June 2016 were retrospectively collected. The first CT angiogram performed after surgery was used for the morphological analysis. RESULTS The population included 79 males, with an overall mean age of 60 ± 12 years. Seven patients (5.8%) died during a median follow-up of 5.5 years. The median delay between BP monitoring and discharge was 3 (1-5) months. https://www.selleckchem.com/products/riluzole-hydrochloride.html The mean 24-hour BP of the cohort was 127/73 mm Hg ± 10/17. During follow-up, different parameters of BP monitoring were not associated with the risk of aortic events. However, the diameter of the false lumen of the descending thoracic aorta was the best predictor associated with the risk of new aortic events during follow-up, particularly for the threshold of 28 mm or more (P less then .001; Hazard ratio 4.7[2.7-8.2]). The diameter of the false lumen was associated with night-time systolic BP (P = .025; r = .2), 24-hour pulse pressure (P = .002; r = .28), and night-time pulse pressure (P = .008; r = .24). CONCLUSION The risk of new aortic events following type A acute aortic syndrome is associated with the size of the residual false lumen, but not directly with BP parameters. Night-time BP parameters are associated with the size of the residual false lumen. © 2020 Wiley Periodicals, Inc.
The total scale and the three domains showed good internal consistency and test-retest reliability. The correlation with SCORAD and other subjective measures was consistent with our hypotheses. Differences in scores between mild, moderate and severe AD patients were significant and the CADIS-SF15 was able to detect changes in 'improving' patients over time. CONCLUSION The CADIS-SF15 with 15 items in three domains is an internally consistent, reliable, valid, responsive, and brief measure of QoL in children affected with AD and their parents. Further evaluation of clinical applicability is required. This article is protected by copyright. All rights reserved.Oligodendrocytes wrap and physically shield axons of the central nervous system with myelin sheaths, resulting in rapid signal transduction and accurate neuronal function. The complex oligodendroglial development from immature oligodendrocyte precursor cells (OPCs) to myelinating oligodendrocytes (OLs) is profoundly dependent on the activity of transcription factors of the Sox protein family. Target genes of the crucial regulator Sox10 have recently been expanded to microRNAs. Here, we report miR-204 as a novel transcriptional target of Sox10. Regulatory regions of miR-204 show responsiveness to and binding of Sox10 in reporter gene assays and electromobility shift assays. Once expressed, miR-204 inhibits OPC proliferation and facilitates differentiation into OLs in the presence of Sox10 as evident from overexpression in primary rat and mouse oligodendroglial cultures. Phenotypes are at least in part caused by miR-204-dependent repression of the pro-proliferative Ccnd2 and the differentiation inhibiting Sox4. These findings argue that the transcriptional activator Sox10 forces oligodendroglial cells to exit the cell cycle and start differentiation by gene inhibition via miR-204 induction. © 2020 The Authors. Glia published by Wiley Periodicals, Inc.BACKGROUND The United Kingdom Working Party's (UKWP) criteria were developed to improve epidemiological research in atopic dermatitis (AD), but have not been validated in an exclusively adult European population. OBJECTIVE To validate the UKWP criteria for AD in adults. METHODS In this cross-sectional study, three independent samples of adult individuals were drawn and interviewed patients with a hospital diagnosis of AD or plaque psoriasis in adulthood, and general population controls. Various versions of the UKWP criteria for AD were utilized. RESULTS A total of 3,490 (general population), 3,834 (AD), and 4,016 (psoriasis) adult individuals were erolled in the study. The best combination of the UKWP criteria lead to a sensitivity of 0.71 and a specificity of 0.96 in the general population. The criteria better captured 'AD ever' compared to 'AD within the past 12 months', and had a higher sensitivity in patients with moderate (87.2-97.7%) or severe (95.8-100%) AD at the time of interview compared to those who where asymptomatic (12.6-36.8%). The UKWP criteria also captured high proportions of psoriasis patients (19.7-47.7%) when applied in a cohort of unique psoriasis patients. CONCLUSIONS It remains a challenge to accurately diagnose a history of AD in adulthood since symptoms are shared with other skin conditions and AD may have resolved or can be waxing and waning, in turn leading to recall bias. The UKWP criteria performed well in the general population for the purpose of determining the prevalence, but should be used cautiously when studying comorbidity. This article is protected by copyright. All rights reserved.Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present LEAP, a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and co-variant information. L2-regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer-related genes, and 5,398 variants from 30 cardiovascular-related genes). Using 10-fold cross-validated predictions, the logistic regression model achieved an AUROC of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability makes LEAP effective in the clinical setting as a high-throughput quality control layer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND After an emergent surgery for type A acute aortic syndrome, medical management is based on optimal blood pressure (BP) control. We assessed the prognostic significance of BP monitoring and its relationship with aortic morphology following type A acute aortic syndrome. METHODS The data of 120 patients who underwent BP monitoring after a type A acute aortic syndrome from January 2005 to June 2016 were retrospectively collected. The first CT angiogram performed after surgery was used for the morphological analysis. RESULTS The population included 79 males, with an overall mean age of 60 ± 12 years. Seven patients (5.8%) died during a median follow-up of 5.5 years. The median delay between BP monitoring and discharge was 3 (1-5) months. https://www.selleckchem.com/products/riluzole-hydrochloride.html The mean 24-hour BP of the cohort was 127/73 mm Hg ± 10/17. During follow-up, different parameters of BP monitoring were not associated with the risk of aortic events. However, the diameter of the false lumen of the descending thoracic aorta was the best predictor associated with the risk of new aortic events during follow-up, particularly for the threshold of 28 mm or more (P less then .001; Hazard ratio 4.7[2.7-8.2]). The diameter of the false lumen was associated with night-time systolic BP (P = .025; r = .2), 24-hour pulse pressure (P = .002; r = .28), and night-time pulse pressure (P = .008; r = .24). CONCLUSION The risk of new aortic events following type A acute aortic syndrome is associated with the size of the residual false lumen, but not directly with BP parameters. Night-time BP parameters are associated with the size of the residual false lumen. © 2020 Wiley Periodicals, Inc.
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