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Background Poor adherence to medical regimens is a serious problem that interferes with heart failure (HF) patients’ disease management and contributes to poor clinical outcomes. Few prospective studies have examined the psychosocial predictors of adherence over time in HF patients. Purpose This study examined the influences of depression, self-efficacy, social support, and their changes on self-reported medical adherence over 6 months in HF patients. Methods Participants were 252 HF outpatients, among whom 168 completed follow-up assessments. Hierarchical multiple regression analyses were conducted to examine whether psychosocial variables and their changes prospectively predicted adherence at 6 months, after adjusting for baseline adherence, age, gender, ethnicity, marital status, education, HF severity, medical comorbidity, and mental health treatment. Results Baseline self-efficacy (β = .22, p < .05), increase in self-efficacy (β = .34, p < .001), and decrease in depression (β = –.15, p = .05) predicted improved adherence over 6 months, but social support did not. In the combined model that included all significant psychosocial predictors from previous analyses, baseline self-efficacy (β = .37, p = .001) and its increase (β = .35, p < .001) emerged as independent predictors of improved adherence at 6 months. Conclusions Promoting self-efficacy and reducing depressive symptoms may be promising targets of behavioral interventions to facilitate long-term disease management in HF patients.

Nonadherence to treatment recommendations is a leading preventable cause of rehospitalization and premature mortality in chronic heart failure (HF) patients. This study examined whether self-efficacy mediates the contributions of social support and depression to treatment adherence. A sample of 252 HF outpatients with a mean age of 54 years completed self-report questionnaires assessing depression, perceived social support, self-efficacy, and treatment adherence. Self-efficacy mediated the associations of social support and depression with treatment adherence after adjusting for demographic (age, gender, marital status, education, and ethnicity) and medical (New York Heart Association Classification and comorbidity) covariates. Self-efficacy explains the influence of social support and depression on treatment adherence and may be a key target for interventions to improve disease management and self-care behaviors in HF patients.

The amyloid precursor protein (APP) and its pathogenic by-product amyloid-beta protein (Abeta) play central roles in Alzheimer disease (AD) neuropathogenesis. APP can be cleaved by beta-secretase (BACE) and alpha-secretase to produce APP-C99 and APP-C83. These C-terminal fragments can then be cleaved by gamma-secretase to produce Abeta and p3, respectively. p3 has been reported to promote apoptosis, and Abeta is the key component of senile plaques in AD brain. APP adaptor proteins with phosphotyrosine-binding domains, including ShcA (SHC1), ShcC (SHC3), and Fe65 (APBB1), can bind to and interact with the conserved YENPTY motif in the APP-C terminus. Here we have described for the first time the effects of RNA interference (RNAi) silencing of ShcA, ShcC, and Fe65 expression on APP processing and Abeta production. RNAi silencing of ShcC led to reductions in the levels of APP-C-terminal fragments (APP-CTFs) and Abeta in H4 human neuroglioma cells stably overexpressing full-length APP (H4-FL-APP cells) but not in those expressing APP-C99 (H4-APP-C99 cells). RNAi silencing of ShcC also led to reductions in BACE levels in H4-FL-APP cells. In contrast, RNAi silencing of the homologue ShcA had no effect on APP processing or Abeta levels. RNAi silencing of Fe65 increased APP-CTF levels, although also decreasing Abeta levels in H4-FL-APP cells. These findings suggest that pharmacologically blocking interaction of APP with ShcC and Fe65 may provide novel therapeutic strategies against AD.

Few studies have examined the prospective influences of depression and anxiety on physical health functioning in heart failure (HF) patients. Prior studies were also limited by employing psychological measures containing somatic items confounded with HF symptoms. This study examined whether depression, anxiety, social support, and their changes predicted the decline of physical functioning in HF patients over 6 months. Participants were 238 HF patients among whom 164 provided follow-up data. The depression and anxiety measures did not contain somatic items. After controlling for baseline physical functioning and demographic and medical covariates, baseline depression and its increase, as well as baseline anxiety and its increase, independently predicted greater decline in physical functioning at 6 months. Social support and its change were not associated with either concurrent or follow-up physical functioning. Depression, anxiety, and their changes independently predicted the decline of physical health functioning over 6 months.

Background. Dementia and delirium have been postulated to share common pathophysiologic mechanisms; however, identification of these unifying mechanisms has remained elusive. The inhalation anesthetic isoflurane has been shown to enhance b-amyloid protein (Ab) oligomerization and generation, to potentiate the cytotoxicity of Ab, and to induce apoptosis. To address the molecular mechanisms of dementia and delirium associated with anesthesia and surgery, we assessed whether the Ab fibrillar aggregation inhibitor Congo red can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells overexpressing human b-amyloid precursor protein (APP). Methods. H4 human neuroglioma cells stably transfected to express human full-length wild-type APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the end of the treatment. Caspase-3 activation was measured with quantitative Western blotting. Results. We found that isoflurane induces cellular apoptosis in a dose-dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4 human neuroglioma cells overexpressing APP. Interestingly, Congo red also inhibits staurosporine-induced apoptosis. Conclusion. The demonstration that isoflurane contributes to well-described mechanisms of Alzheimer’s neuropathogenesis provides a plausible link between the acute effects of anesthesia, a well-described risk factor for delirium, and the more long-term sequelae of dementia. These findings suggest that isoflurane-induced Ab oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia.