The Coaching for Cognition in Alzheimer's (COCOA) trial: Study design.

Comprehensive treatment of Alzheimer's disease (AD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. We present the design and methodology for the Coaching for Cognition in Alzheimer's (COCOA) trial. AD and other dementias result from the interplay of multiple interacting dysfunctional biological systems. Monotherapies have had limited success. More interventional studies are needed to test the effectiveness of multimodal multi-domain therapies for dementia prevention and treatment. Multimodal therapies use multiple interventions to address multiple systemic causes and potentiators of cognitive decline and functional loss; they can be personalized, as different sets of etiologies and systems responsive to therapy may be present in different individuals. COCOA is designed to test the hypothesis that coached multimodal interventions beneficially alter the trajectory of cognitive decline for individuals on the spectrum of AD and related dementias (ADRD). COCOA is a two-arm prospective randomized controlled trial (RCT). COCOA collects psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints across 2 years for each participant. These data enable systems biology analyses. One arm receives standard of care and generic healthy aging recommendations. The other arm receives standard of care and personalized data-driven remote coaching. The primary outcome measure is the Memory Performance Index (MPI), a measure of cognition. The MPI is a summary statistic of the MCI Screen (MCIS). Secondary outcome measures include the Functional Assessment Staging Test (FAST), a measure of function. COCOA began enrollment in January 2018. We hypothesize that multimodal interventions will ameliorate cognitive decline and that data-driven health coaching will increase compliance, assist in personalizing multimodal interventions, and improve outcomes for patients, particularly for those in the early stages of the AD spectrum. Highlights: The Coaching for Cognition in Alzheimer's (COCOA) trial tests personalized multimodal lifestyle interventions for Alzheimer's disease and related dementias.Dense longitudinal molecular data will be useful for future studies.Increased use of Hill's criteria in analyses may advance knowledge generation.Remote coaching may be an effective intervention.Because lifestyle interventions are inexpensive, they may be particularly valuable in reducing global socioeconomic disparities in dementia care.

Prevalence and Longevity of SARS-CoV-2 Antibodies Among Health Care Workers.

BACKGROUND: Understanding severe acute respiratory syndrome coronavirus 2 antibody prevalence in a spectrum of health care workers (HCWs) may provide benchmarks of susceptibility, help us understand risk stratification, and support enactment of better health policies and procedures. METHODS: Blood serum was sampled at enrollment and 8-week follow-up from HCWs (n = 3458) and from community first responders (n = 226) for immunoglobulin G (IgG) analyses. Demographics, job duties, location, and coronavirus disease 2019-related information were collected. RESULTS: The observed IgG antibody prevalence was 0.93% and 2.58% at enrollment (May/June) and 8-week follow-up (July/August), respectively, for HCWs, and 5.31% and 4.35% for first responders. For HCWs, significant differences (P < .05) between negative and positive at initial assessment were found for age, race, fever, and loss of smell, and at 8-week follow-up for age, race, and all symptoms. Antibody positivity persisted at least 8 weeks in all positive HCWs. CONCLUSIONS: We found considerably lower antibody prevalence among HCWs compared with other published studies. While rigorous safety process measures instituted in our workplace and heightened awareness at and outside of the workplace among our HCWs may have contributed to our findings, the significant discrepancy from our community prevalence warrants further studies on other contributing factors.

SARS-CoV-2 antibody prevalence in health care workers: Preliminary report of a single center study.

Serological surveys have been conducted to establish prevalence for COVID-19 antibodies in various cohorts and communities, reporting a wide range of outcomes. The prevalence of such antibodies among healthcare workers, presumed at higher risk for infection, has been increasingly investigated, more studies are needed to better understand the risks and infection transmission in different healthcare settings. The present study reports on initial sero-surveillance conducted on healthcare workers at a regional hospital system in Orange County, California, during May and June, 2020. Study subjects were recruited from the entire hospital employee workforce and the independent medical staff. Data were collected for job duties and locations, COVID-19 symptoms, a PCR test history, travel record since January 2020, and existence of household contacts with COVID-19. A blood sample was collected from each subject for serum analysis for IgG antibodies to SARS-CoV-2. Of 2,992 tested individuals, a total 2,924 with complete data were included in the analysis. Observed prevalence of 1.06% (31 antibody positive cases), adjusted prevalence of 1.13% for test sensitivity and specificity were identified. Significant group differences between positive vs. negative were observed for age (z = 2.65, p = .008), race (p = .037), presence of fever (p < .001), and loss of smell (p < .001), but not for occupations (p = .710). Possible explanation for this low prevalence includes a relatively low local geographic community prevalence (~4.4%) at the time of testing, the hospital's timely procurement of personal protective equipment, rigorous employee education, patient triage, and treatment protocol development and implementation. In addition, cross-reactive adaptive T cell mediated immunity, as recently described, may possibly play a greater role in healthcare workers than in the general population.

The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/ß signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/ß protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.