Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes.

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer's disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer's disease and the impairment of cholesterol homeostasis

Active video game playing in children and adolescents with cystic fibrosis : exercise or just fun?

BACKGROUND: Xbox Kinect has been proposed as an exercise intervention in cystic fibrosis (CF), but its potential has not been compared with standard training modalities. METHODS: Using a crossover design, subjects were randomized to 2 intervention groups: Xbox Kinect and a traditional stationary cycle. Heart rate, SpO2, dyspnea, and fatigue were measured. Subject satisfaction was tested. RESULTS: Thirty subjects with CF (11 males, mean \ub1 SD age of 12 \ub1 2.5 y, mean \ub1 SD FEV1 of 73 \ub1 16% of predicted) were enrolled. Xbox Kinect provided a cardiovascular demand similar to a stationary cycle, although the modality was different (interval vs. continuous). Maximum heart rates were similar (P = .2). Heart rate target was achieved more frequently with a stationary cycle (P = .02). Xbox Kinect caused less dyspnea (P = .001) and fatigue (P < .001) and was more enjoyable than a stationary cycle (P < .001). CONCLUSIONS: Subjects preferred Xbox Kinect for its interactivity. Xbox Kinect has the potential to be employed as an exercise intervention in young subjects with CF, but investigation over longer periods is needed

262 How to measure dyspnea and cough in CF subjects?

Spirometric and anthropometric data are historically used as outcome measures in CF studies and clinical settings. Few tools are available to determine patient perceived symptoms and there is increasing interest in patient-reported outcomes. Dyspnea and cough are the most frequently reported symptoms and their changes are identified by patients as primary indicators of a respiratory exacerbation or its resolution. Given their prevalence and severity, there may be value in utilising tools that specifically measure the degree of cough and dyspnea in clinical practice. Aim: To describe the change of dyspnea and cough in CF patients during hospitalization. Methods: Dyspnea and cough of 33 CF adult in-patients (23 F, 32 \ub1 12 yrs, mean BMI 20.3 \ub1 2.7 and mean FEV1%pred 49.5 \ub1 19.9) were evaluated with Modified Medical Research Council (MRC) and Cough Visual Analogic Scale (VAS) respectively. Data were collected in patients admitted on November and December 2016. Descriptive and statistical analyses were conducted to detect possible changes at hospital discharge. Results: Patients described cough impact with a mean VAS score of 4.6/10 at admission, with a statistical significant improvement at the end of hospitalization (mean VAS score at discharge 1/10, p < 0.001). Almost the 50% of patients referred breathlessness MRC score 652/4 at hospital admission with a significant decrease at discharge (p = 0.001). A difference of one point is stated as the minimal clinical important difference and the 54.5% of subjects declared a reduction of dyspnea of at least 1. Conclusions: Our results suggest that the use of symptomatic standard scales such as MRC and Cough VAS could integrate instrumental evaluation and highlight the impact of CF disease in the quality of life. Both symptoms were severe at hospital admission and showed a statistical significant recover. Further studies are needed to identify tools that could be outcome markers of efficacy of a health treatment