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Andrea Piccin Ciaran Murphy Elva Eakins Maria Beatrice Rondinelli Massimo Daves Cinzia Vecchiato Dominik Wolf Corrina Mc Mahon Owen P. Smith 《European journal of haematology》2019,102(4):319-330
Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA. 相似文献
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Esther I. de Bruin Dominik S. Sieh Bonne J. H. Zijlstra Anne-Marie Meijer 《Child indicators research》2018,11(4):1389-1406
Stress in children and adolescents is common and related to many developmental problems. However, most studies have made no distinction between temporary or chronic stress due to the lack of a suitable questionnaire. This study tested the factor structure, reliability and validity of the 17-item self-report Chronic Stress Questionnaire for Children and Adolescents (CSQ-CA) in three samples, that is, 717 adolescents from the general population, 161 adolescents of parents with a severe chronic medical condition (CMC) like multiple sclerosis, and 113 adolescents with healthy parents. Results showed that a one-factor solution provided a reasonable fit overall. Reliability was good (α = .80 to .88). Convergent validity was supported by positive relations between total stress scores and internalizing and externalizing problem behaviors, experience of daily hassles, and maladaptive emotion regulation strategies and negative relations with quality of life, happiness, mindfulness, self-esteem, and coping skills. Adolescents from all samples, who themselves had a light CMC like asthma, showed higher chronic stress levels than those without a CMC. In line, adolescents of parents with a severe CMC reported more chronic stress than those of healthy parents, and adolescents with a chronic illness themselves and a parent with a chronic illness, showed the highest scores across the two family types. Overall, this study presents good psychometric properties of the first available measure of chronic stress in children and adolescents. 相似文献
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