The Tele-STELLA protocol: Telehealth-based support for families living with later-stage Alzheimer's disease.

AIMS: We aim to establish the feasibility and acceptability of the Tele-STELLA (Support via Telehealth: Living and Learning with Advancing Alzheimer's Disease and Related Dementias) intervention. We will also assess the efficacy of the intervention in reducing the frequency of behavioural symptoms of dementia as well as family Care Partner reactivity to the symptoms. DESIGN: This is a multi-component, quasi-experimental study that focuses on facilitating effective management of behavioural symptoms that occur in the later stages of dementia. METHODS: Family Care Partners (n = 124) for persons with Alzheimer's disease will participate in two 8-week videoconferencing components that address behavioural symptoms-in both the persons with Alzheimer's disease and their Care Partners. In the first component ('Nova'), Care Partners work with one nurse for an hour/week for 4 weeks, then they join a small group for another 4 weeks. In the second component ('Constellation'), Care Partners work in a larger group to hone skills and knit supportive relationships. Behavioural symptom frequency and Care Partner reactivity to the behaviours will be measured prior to, during and after the intervention. The study is funded by the United States National Institute on Aging (R01AG067546); funding was initiated as on February, 2021. DISCUSSION: Tele-STELLA fills a gap in current videoconference-based psychoeducational interventions in that it offers real-time interaction with nurses and peers. The intervention was designed with feedback by pilot participants. This study will assess Tele-STELLA in its current, novel format; thus, preparing it for a larger, future randomized controlled trial. IMPACT: Tele-STELLA addresses symptoms that occur in the later stages of dementia, providing families with tools to facilitate effective behavioural management. Because Tele-STELLA is implemented via videoconferencing, it targets Care Partners who face barriers to support, such as cost and transportation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (#NCT04627662).

Portland Water Fluoridation: A Newspaper Analysis.

Portland, Oregon is the largest city in the United States without community water fluoridation (CWF). A newspaper analysis was conducted of the failed 2013 CWF campaign to evaluate anti-fluoridation and pro-fluoridation messaging provided by newspapers during the campaign. News content was categorized by type and slant (pro-fluoridation, anti-fluoridation, or neutral) and 34 variables were tabulated (23 anti-fluoridation, 11 pro-fluoridation). Results showed overall messaging was slightly pro-fluoridation, as compared to anti-fluoridation or neutral content (35%, 32%, and 33% respectively). Editorial content was 85% pro-fluoridation and 15% anti-fluoridation. The most frequent anti-fluoridation variables were alternatives to water fluoridation, mass/forced medication and concerns about the political process. Conversely, tooth decay and social justice were the most commonly cited pro-fluoridation variables. Newspapers can be influential in shaping public policy opinions in the fight for community water fluoridation.

Conatumumab, a fully human agonist antibody to death receptor 5, induces apoptosis via caspase activation in multiple tumor types.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death receptors 4 and 5 (DR4, DR5) to transduce apoptotic signals. Conatumumab (AMG 655) is an investigational, fully human monoclonal agonist antibody (IgG(1)) to human DR5, which induces apoptosis via caspase activation. In this study, we demonstrate that conatumumab binds to DR5, activating intracellular caspases in vitro in the presence of a cross-linker. We also show that conatumumab has activity in vivo and inhibits tumor growth in colon (Colo205 and HCT-15), lung (H2122) and pancreatic (MiaPaCa2/T2) xenograft models. Conatumumab also enhances the antitumor activity of chemotherapeutics in vivo. Caspase activation in Colo205 tumors is dose-dependent and correlated with serum concentrations of conatumumab. We demonstrate for the first time that increases in serum caspase-3/7 activity and levels of M30 (neoepitope of caspase-cleaved cytokeratin-18) are linked to activation of the extrinsic apoptotic pathway using conatumumab in a preclinical model. These data suggest that conatumumab has potential as a therapeutic agent for treating patients with multiple tumor types, and that serum caspase-3/7 and M30 levels may serve as biomarkers of conatumumab activity.

High-level expression of full-length antibodies using trans-complementing expression vectors.

Recombinant antibodies are increasingly used as therapeutics for a wide variety of diseases. Generation of cell lines expressing high levels of recombinant antibody typically requires labor-intensive cloning and screening steps. We describe a mammalian expression system for the high-level production of full-length antibody molecules. It has been shown that the dihydrofolate reductase (DHFR) selectable marker can be divided into two fragments that, with the aid of a leucine zipper, can re-associate to form an active molecule. Using bicistronic vectors, we linked the expression of each antibody chain to the expression of a DHFR fragment. Survival in selective media requires expression of both DHFR fragments that, by virtue of these vectors, also selects for the expression of both antibody chains. Initial pools produced 5 microg of Ab/10(6) cells/d (qP = microg/10(6) cells/d). Expression of each antibody chain in conjunction with a portion of DHFR also leads to concurrent amplification of both antibody chains in the presence of methotrexate, a DHFR inhibitor, and results in a two- to fivefold increase in antibody production with basal qPs ranging from 10-25 ug/10(6) cells/d. Shake-flask cultures of amplified pools produced up to 600 mg/L of antibody in 7 days. This system allows for rapid generation of antibodies without cloning and greatly simplifies selection of cell lines for the production of potential antibody therapeutics.