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

Patients dropping out of treatment in Italy

Valutazione dei drop out in un sevizio pubblic

Primary Care Physicians’ Decisions About Discharging Patients from Their Practices

OBJECTIVE: There are few data available about factors which influence physicians' decisions to discharge patients from their practices. To study general internists' and family medicine physicians' attitudes and experiences in discharging patients from their practices.DESIGN: A cross-sectional mailed survey was used.PARTICIPANTS: One thousand general internists and family medicine physicians participated in this study.MEASUREMENTS AND MAIN RESULTS: We studied the likelihood physicians would discharge 12 hypothetical patients from their practices, and whether they had actually discharged such patients. The effect of demographic data on the number of scenarios in which patients were likely to be discharged, and the number of patients actually discharged were analyzed via ANOVA and multiple logistic regression analysis. Of 977 surveys received by subjects, 526 (54%) were completed and returned. A majority of respondents were willing to discharge patients in 5 of 12 hypothetical scenarios. Eighty-five percent had actually discharged at least one patient from their practices. Most respondents (71%) had discharged 10 or fewer patients, but 14% had discharged 11 to 200 patients. Respondents who were in private practice (p= 48 years old) were more likely to discharge actual patients from their practices (p=0.005) as were physicians practicing in rural settings (p=0.003).CONCLUSIONS: Most physicians in our sample were willing to discharge actual and hypothetical patients from their practices. This tendency may have significant implications for the initiation of pay-for-performance programs. Physicians should be educated about the importance of the patient-physician relationship and their fiduciary obligations to the patient

Physicians' Experiences with Patients Who Transgress Boundaries

BACKGROUND: Boundary violations have been discussed in the literature, but most studies report on physician transgressions of boundaries or sexual transgressions by patients. We studied the incidence of all types of boundary transgressions by patients and physicians' responses to these transgressions. METHODS: We surveyed 1,000 members of the Society of General Internal Medicine (SGIM) for the number of patient transgressions of boundaries which had occurred in the previous year. Categories were created by the investigators based on the literature. Physicians picked the most important transgression, and then were asked about their response to the transgression and its effect on the patient-physician relationship. Attitudinal questions addressed the likelihood of discharging patients who transgressed boundaries. The impact of demographic variables on the incidence of transgressions was analyzed using analysis of variance. RESULTS: Three hundred thirty (37.5%) randomly selected SGIM members responded to the survey. Almost three quarters of the respondents had patients who used their first name, while 43% encountered verbal abuse, 39% had patients who asked personal questions, 31% had patients who were overly affectionate, and 27% encountered patients who attempted to socialize. All other transgressions, including physical abuse and attempts at sexual contact, were uncommon. Only gender affected the incidence of transgressions; female physicians encountered more personal questions (P = .001), inappropriate affection (P < .005), and sexually explicit language (P < .05) than male physicians and responded more negatively to boundary transgressions. Respondents dealt with transgressions by discussion with the patient or colleagues or by ignoring the incident, but such transgressions generally had a negative impact on the relationship. Most physicians would discharge patients who engaged in physical abuse or attempts at sexual contact, but were more tolerant of verbal abuse and overly affectionate patients. CONCLUSIONS: Boundary transgressions by patients is common, but usually involves more minor infractions. Female physicians are more likely to encounter certain types of transgressions. The incidence and outcomes of such transgressions are important in assisting physicians to deal effectively with this issue