Living with Alzheimer’s Disease: A Study of Adult Day Health Services in Massachusetts

The role of adult day health care (ADHC) is gaining increased attention as the nation prepares for the large cohort of baby boomers entering their later years. Many boomers are aging with physical and cognitive impairments, including Alzheimer\u27s disease and related dementias. Projections indicate that Massachusetts, along with the nation as a whole, is experiencing an increasing rate of older persons as baby boomers enter late-life. The Commonwealth can expect that persons with Alzheimer\u27s disease and their care partners will need community-based services that are specifically designed for adults with cognitive impairments. However, a report by the Robert Wood Johnson Foundation found that there is a serious lack of adult day care services for the state\u27s elderly population. The 2003 report found that Massachusetts is only meeting 62% of needs for adults with physical and cognitive impairments, and at least 78 more programs are needed in the state. Yet, programs in Massachusetts continue to close. The specific objectives of the study were to: (1) describe existing practices of adult day health care services in Massachusetts for persons living with Alzheimer\u27s disease and related dementias, (2) explore programs that are specifically designed for participants who are in late-stage dementia, (3) address challenges that adult day health care services are now encountering, and (4) envision new paradigms for meeting the needs of persons with early-stage and early-onset dementia

Stepwise multimodality imaging assists in atrial myxoma diagnosis and management

The case of a 67-year-old man who presented for elective gastroenterology procedures and was in atrial fibrillation is discussed. Transthoracic echocardiography revealed a large atrial mass. Preoperative coronary angiography revealed a heavily vascularized mass. Use of cardiac magnetic resonance identified the cardiac mass as likely an atrial myxoma.

The Pseudophosphatase MK-STYX Induces Neurite-Like Outgrowths in PC12 Cells

The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway is required. Here, we investigate the function of MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in neuronal differentiation. MK-STYX is a member of the MAPK phosphatase (MKP) family, which is generally responsible for dephosphorylating the ERKs. However, MK-STYX lacks catalytic activity due to the absence of the nucleophilic cysteine in the active site signature motif HC(X-5)R that is essential for phosphatase activity. Despite being catalytically inactive, MK-STYX has been shown to play a role in important cellular pathways, including stress responses. Here we show that PC12 cells endogenously express MK-STYX. In addition, MK-STYX, but not its catalytically active mutant, induced neurite-like outgrowths in PC12 cells. Furthermore, MK-STYX dramatically increased the number of cells with neurite extensions in response to nerve growth factor (NGF), whereas the catalytically active mutant did not. MK-STYX continued to induce neurites in the presence of a MEK (MAP kinase kinase) inhibitor suggesting that MK-STYX does not act through the Ras-ERK/MAPK pathway but is involved in another pathway whose inactivation leads to neuronal differentiation. RhoA activity assays indicated that MK-STYX induced extensions through the Rho signaling pathway. MK-STYX decreased RhoA activation, whereas RhoA activation increased when MK-STYX was down-regulated. Furthermore, MK-STYX affected downstream players of RhoA such as the actin binding protein cofilin. The presence of MK-STYX decreased the phosphorylation of cofilin in non NGF stimulated cells, but increased its phosphorylation in NGF stimulated cells, whereas knocking down MK-STYX caused an opposite effect. Taken together our data suggest that MK-STYX may be a regulator of RhoA signaling, and implicate this pseudophosphatase as a regulator of neuronal differentiation

Community production modulates coral reef pH and the sensitivity of ecosystem calcification to ocean acidification

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 745–761, doi:10.1002/2016JC012326.Coral reefs are built of calcium carbonate (CaCO3) produced biogenically by a diversity of calcifying plants, animals, and microbes. As the ocean warms and acidifies, there is mounting concern that declining calcification rates could shift coral reef CaCO3 budgets from net accretion to net dissolution. We quantified net ecosystem calcification (NEC) and production (NEP) on Dongsha Atoll, northern South China Sea, over a 2 week period that included a transient bleaching event. Peak daytime pH on the wide, shallow reef flat during the nonbleaching period was ∼8.5, significantly elevated above that of the surrounding open ocean (∼8.0–8.1) as a consequence of daytime NEP (up to 112 mmol C m−2 h−1). Diurnal-averaged NEC was 390 ± 90 mmol CaCO3 m−2 d−1, higher than any other coral reef studied to date despite comparable calcifier cover (25%) and relatively high fleshy algal cover (19%). Coral bleaching linked to elevated temperatures significantly reduced daytime NEP by 29 mmol C m−2 h−1. pH on the reef flat declined by 0.2 units, causing a 40% reduction in NEC in the absence of pH changes in the surrounding open ocean. Our findings highlight the interactive relationship between carbonate chemistry of coral reef ecosystems and ecosystem production and calcification rates, which are in turn impacted by ocean warming. As open-ocean waters bathing coral reefs warm and acidify over the 21st century, the health and composition of reef benthic communities will play a major role in determining on-reef conditions that will in turn dictate the ecosystem response to climate change.NSF Grant Number: 12205292017-07-3

Observational Constraints on the Molecular Gas Content in Nearby Starburst Dwarf Galaxies

Using star formation histories derived from optically resolved stellar populations in nineteen nearby starburst dwarf galaxies observed with the Hubble Space Telescope, we measure the stellar mass surface densities of stars newly formed in the bursts. By assuming a star formation efficiency (SFE), we then calculate the inferred gas surface densities present at the onset of the starbursts. Assuming a SFE of 1%, as is often assumed in normal star-forming galaxies, and assuming that the gas was purely atomic, translates to very high HI surface densities (~10^2-10^3 Msun pc^-2), which are much higher than have been observed in dwarf galaxies. This implies either higher values of SFE in these dwarf starburst galaxies or the presence of significant amounts of H_2 in dwarfs (or both). Raising the assumed SFEs to 10% or greater (in line with observations of more massive starbursts associated with merging galaxies), still results in HI surface densities higher than observed in 10 galaxies. Thus, these observations appear to require that a significant fraction of the gas in these dwarf starbursts galaxies was in the molecular form at the onset of the bursts. Our results imply molecular gas column densities in the range 10^19-10^21 cm^-2 for the sample. In those galaxies where CO observations have been made, these densities correspond to values of the CO-H_2 conversion factor (X_CO) in the range >3-80x10^20 cm^-2 (K km s^-1)^-1, or up to 40x greater than Galactic X_CO values.Comment: 8 pages, 4 figures, 2 table

Optimizing Wellness in Academic Emergency Medicine

Introduction Academic Emergency Physicians (EPs) face additional unique challenges in optimizing wellness compared to community EPs. Objective Our objective was to explore specific individual and systems challenges that academic EPs encounter that affect their wellbeing and professional fulfillment in emergency medicine (EM). Methods An expert group of academic EPs convened in 2019 at the annual meeting of the Society of Academic Emergency Medicine to investigate the overall causes of burnout in healthcare providers, the effects of burnout on the healthcare system, specific causes of burnout in EM, and the distinct challenges facing academic emergency physicians. Results We outline specific causes of burnout in EM and the effects of burnout on the healthcare system. Scholarly productivity pressures, variable reimbursement gaps, time allotment, and work-life balance are challenges facing academic EPs. Conclusion Understanding the unique challenges of academic EPs in optimizing wellness is vital to inform future research and effective interventions

Tobacco use and asking prices of used cars: prevalence, costs, and new opportunities for changing smoking behavior

Secondhand smoke (SHS) causes premature death and disease in children and adults, and the scientific evidence indicates that there is no risk-free level of exposure to SHS. Smoking tobacco in a car can pollute the microenvironment of the car with residual SHS, leaving telltale signs to potential buyers (e.g., odor, used ash tray). This study examined (a) the proportion of used cars sold in the private party market that may be polluted with tobacco smoke and (b) whether asking prices of smoker and nonsmoker cars differed for cars of otherwise equivalent value. A random sample of 1,642 private party sellers were interviewed by telephone, and content analyses of print advertisements were conducted. Findings indicate that 22% of used cars were advertised by smokers or had been smoked in during the previous year. Among nonsmokers, 94% did not allow smoking in their car during the past year. Only 33% of smokers had the same restrictions. The smoking status of the seller and tobacco use in the car were significantly (p < .01) associated with the asking price independent of a car's Kelley Blue Book value (KBB). Used nonsmoker cars were offered at a considerable premium above their KBB value (>11%) and above comparable smoker cars (7–9%). These findings suggest that community preferences are affecting the value of smoke-free cars. New directions for research, tobacco control policies, and health education are discussed to further reduce smoking behavior, to help consumers make informed purchasing decisions, and to protect nonsmokers from SHS exposure

Metabolomic analysis of insulin resistance across different mouse strains and diets

Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high-fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle. There was significant metabolic heterogeneity between strains, diets, and individual animals. Distinct metabolites were changed with insulin resistance, diet, and between strains. Computational analysis revealed 113 metabolites that were correlated with metabolic phenotypes. Using these 113 metabolites, combined with machine learning to segregate mice based on insulin sensitivity, we identified C22:1-CoA, C2-carnitine, and C16-ceramide as the best classifiers. Strikingly, when these three metabolites were combined into one signature, they classified mice based on insulin sensitivity more accurately than each metabolite on its own or other published metabolic signatures. Furthermore, C22:1-CoA was 2.3-fold higher in insulin-resistant mice and correlated significantly with insulin resistance. We have identified a metabolomic signature composed of three functionally unrelated metabolites that accurately predicts whole-body insulin sensitivity across three mouse strains. These data indicate the power of simultaneous analysis of individual, genetic, and environmental variance in mice for identifying novel factors that accurately predict metabolic phenotypes like whole-body insulin sensitivity

Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis.

The phosphoinositide 3-kinase (PI3K)-Akt network is tightly controlled by feedback mechanisms that regulate signal flow and ensure signal fidelity. A rapid overshoot in insulin-stimulated recruitment of Akt to the plasma membrane has previously been reported, which is indicative of negative feedback operating on acute timescales. Here, we show that Akt itself engages this negative feedback by phosphorylating insulin receptor substrate (IRS) 1 and 2 on a number of residues. Phosphorylation results in the depletion of plasma membrane-localised IRS1/2, reducing the pool available for interaction with the insulin receptor. Together these events limit plasma membrane-associated PI3K and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) synthesis. We identified two Akt-dependent phosphorylation sites in IRS2 at S306 (S303 in mouse) and S577 (S573 in mouse) that are key drivers of this negative feedback. These findings establish a novel mechanism by which the kinase Akt acutely controls PIP3 abundance, through post-translational modification of the IRS scaffold