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/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β 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.

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.

SARS-CoV-2 has driven a pandemic crisis. Serological surveys have been conducted to establish prevalence for covid-19 antibody in various cohorts and communities. However, the prevalence among healthcare workers is still being analyzed. 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 participants were recruited from the entire hospital employee workforce and the independent medical staff. Data were collected for job title, location, 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 3,013 tested individuals, a total 2,932 were included in the analysis due to some missing data. 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). 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, possible greater presence of cross-reactive adaptive T cell mediated immunity in healthcare workers vs. the general population may have contributed. Determining antibody prevalence in front-line workers, and duration of antibody presence may help stratify the workforce for risk, establish better health place policies and procedures, and potentially better mitigate transmission.

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 twoarm 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 coachingThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Background Understanding SARS-CoV-2 antibody prevalence in a spectrum of healthcare workers (HCWs) may provide benchmarks of susceptibility, help understand risk stratification, and support enactment of better health policies and procedures. Method Blood serum was sampled at enrollment and 8-week follow-up from HCWs (n=3,458) and from community first responders (n=226) for IgG analyses. Demographics, job duties, location, and COVID-19 related information were collected. Results Observed IgG antibody prevalence was 0.93% and 2.58% at enrollment (May/June) and 8-week follow-up (July/Aug), respectively, for HCWs, and 5.31% and 4.35% for first responders. For HCWs, significant differences (p &lt; .05) between negative vs. 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 to 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.