A Novel Drosophila Model of Alzheimer's Disease to Study Aß Proteotoxicity in the Digestive Tract.

Amyloid-ß (Aß) proteotoxicity is associated with Alzheimer's disease (AD) and is caused by protein aggregation, resulting in neuronal damage in the brain. In the search for novel treatments, Drosophila melanogaster has been extensively used to screen for anti-Aß proteotoxic agents in studies where toxic Aß peptides are expressed in the fly brain. Since drug molecules often are administered orally there is a risk that they fail to reach the brain, due to their inability to cross the brain barrier. To circumvent this problem, we have designed a novel Drosophila model that expresses the Aß peptides in the digestive tract. In addition, a built-in apoptotic sensor provides a fluorescent signal from the green fluorescent protein as a response to caspase activity. We found that expressing different variants of Aß1-42 resulted in proteotoxic phenotypes such as reduced longevity, aggregate deposition, and the presence of apoptotic cells. Taken together, this gut-based Aß-expressing fly model can be used to study the mechanisms behind Aß proteotoxicity and to identify different substances that can modify Aß proteotoxicity.

Understanding the Workflow of Home Health Care for Patients with Heart Failure: Challenges and Opportunities.

BACKGROUND: Readmission rates are high among heart failure (HF) patients who require home health care (HHC) after hospitalization. Although HF patients who require HHC are often sicker than those who do not, HHC delivery itself may also be suboptimal. OBJECTIVE: We aimed to describe the workflow of HHC among adults discharged home after a HF hospitalization, including the roles of various stakeholders, and to determine where along these workflow challenges and opportunities for improvement exist. DESIGN AND PARTICIPANTS: In this qualitative study, we used purposeful sampling to approach and recruit a variety of key stakeholders including home health aides, nurses, HF patients, family caregivers, physicians, social workers, home care agency leaders, and policy experts. The study took place in New York, NY, from March to October 2018. APPROACH: Using a semi-structured topic guide, we elicited participants' experiences with HHC in HF through a combination of one-on-one interviews and focus groups. Data were recorded, transcribed, and analyzed thematically. We also asked selected participants to depict in a drawing their understanding of HHC workflow after hospitalization for HF patients. We synthesized the drawings into a final image. KEY RESULTS: Study participants (N = 80) described HHC for HF patients occurring in 6 steps, with home health aides playing a main role: (1) transitioning from hospital to home; (2) recognizing clinical changes; (3) making decisions; (4) managing symptoms; (5) asking for help; and (6) calling 911. Participants identified challenges and opportunities for improvement for each step. CONCLUSIONS: Our findings suggest that HHC for HF patients occurs in discrete steps, each with different challenges. Rather than a one-size-fits-all approach, various interventions may be required to optimize HHC delivery for HF patients in the post-discharge period.