Background: Symptoms of dyspepsia significantly disrupt patients' lives and reliable methods of assessing symptom status are important for patient management. The aim of the current study was to document the psychometric characteristics of the Gastrointestinal Symptom Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD) in Afrikaans, German, Hungarian, Italian, Polish and Spanish patients with dyspepsia.
Background: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. Aims: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. Methods: Patients with symptomatic HF (NYHA Class II-IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (N 40%) and low LVEF (≤40%). Results: In 2709 of the eligible 2744 (98.6%) patients, the summary scores ranged from 0 to 105 (mean 40.9). There were no differences in overall responses of HF patients with preserved vs. low LVEF (41.1 vs. 40.8). Independent factors associated with worse HRQL in both populations included female gender, younger age, higher body mass index, lower systolic blood pressure, greater symptom burden, and worse functional status. Conclusions: In symptomatic HF patients, HRQL is equally impaired in both preserved and low LVEF populations. Targeting improvement in symptoms and HRQL is an important treatment objective in all HF patients.
The crucial role of Myc as an oncoprotein and as a key regulator of cell growth makes it essential to understand the molecular basis of Myc function. The N-terminal region of c-Myc coordinates a wealth of protein interactions involved in transformation, differentiation and apoptosis. We have characterized in detail the intrinsically disordered properties of Myc-1–88, where hierarchical phosphorylation of S62 and T58 regulates activation and destruction of the Myc protein. By nuclear magnetic resonance (NMR) chemical shift analysis, relaxation measurements and NOE analysis, we show that although Myc occupies a very heterogeneous conformational space, we find transiently structured regions in residues 22–33 and in the Myc homology box I (MBI; residues 45–65); both these regions are conserved in other members of the Myc family. Binding of Bin1 to Myc-1–88 as assayed by NMR and surface plasmon resonance (SPR) revealed primary binding to the S62 region in a dynamically disordered and multivalent complex, accompanied by population shifts leading to altered intramolecular conformational dynamics. These findings expand the increasingly recognized concept of intrinsically disordered regions mediating transient interactions to Myc, a key transcriptional regulator of major medical importance, and have important implications for further understanding its multifaceted role in gene regulation.
Reflux symptoms are associated with impaired well-being in the general population. Individuals with symptoms that are mild or more severe report a meaningful reduction in well-being similar to that seen in other diseases. This may represent an appropriate threshold for patient selection in trials of GERD therapy and for more detailed evaluation of patients consulting with reflux symptoms in clinical practice.
The results indicate a high convergent and discriminant validity of the WPAI-GERD questionnaire and also show that patients consulting a physician because of symptoms attributed to GERD report substantial impairment in both productivity and health-related quality of life.
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