3,121 research outputs found
Potentially Inappropriate Prescribing of Proton Pump Inhibitors Among Older Patients in the US
The American Geriatrics Society list of Potentially Inappropriate Medication (Beers Criteria) use in older adults (\u3e64-years) includes Proton Pump Inhibitors (PPIs), and specifically cautions against their use for \u3e8 weeks. PPIs are prescribed to reduce the production of stomach acid, however there is strong evidence older adults are at risk of infection and bone loss from prolonged exposure to PPIs. This study used data from the 2017 Medical Expenditure Panel Survey (MEPS) and the FDA Adverse Event Report System (FAERS, as of June 30, 2019) to characterize the current prescribing practices of PPIs to older adults and the risks those patients may face. 4,288 patients \u3e64-years were included in this study, weighted to represent over 46 million Americans. Of these, 19.6% had been prescribed a PPI in 2017, and 10.05% had a long-term (\u3e8 week) prescription. Results from a generalized linear model using a quasibinomial link function demonstrated that patients with arthritis (adjusted-OR: 1.52, 95% CI: 1.17-1.98) and asthma (adjusted-OR: 1.73, 95% CI: 1.24-2.41) were more likely to have long-term PPI use, as were patients with 5+ other prescriptions (adjusted-OR: 4.31, 95% CI: 2.71-6.85). The adjusted odds ratios (OR) did not differ by age, gender, income, or education-level. For all PPIs, 28,031 (age\u3e64) adverse event (AE) cases were found in FAERS. The most commonly reported AEs were gastrointestinal disorders, and renal or urinary disorders, which appeared in 50% of included cases. Overall, our study reported current risks from and potential predictors of long-term PPI use among older adults
Geographic Disparities in COVID-19 Testing: An Urgent Call to Action
This research brief shows that testing rates are lower in states with the unhealthiest populations and worst health care access. Disparities in testing rates are troubling because delays in testing increase the risk of a surge in silent spread and severe COVID-19 cases in these states
COVID-19 Testing Rates are Lower in States with More Black and Poor Residents
This data slice shows that testing rates to date have been lower in states with higher percent black populations and higher poverty rates. Without proper testing and physical distancing protocols, these states risk a surge in severe COVID-19 cases, overwhelming their already resource strapped healthcare systems
Decoding Information from noisy, redundant, and intentionally-distorted sources
Advances in information technology reduce barriers to information
propagation, but at the same time they also induce the information overload
problem. For the making of various decisions, mere digestion of the relevant
information has become a daunting task due to the massive amount of information
available. This information, such as that generated by evaluation systems
developed by various web sites, is in general useful but may be noisy and may
also contain biased entries. In this study, we establish a framework to
systematically tackle the challenging problem of information decoding in the
presence of massive and redundant data. When applied to a voting system, our
method simultaneously ranks the raters and the ratees using only the evaluation
data, consisting of an array of scores each of which represents the rating of a
ratee by a rater. Not only is our appraoch effective in decoding information,
it is also shown to be robust against various hypothetical types of noise as
well as intentional abuses.Comment: 19 pages, 5 figures, accepted for publication in Physica
Rural-Urban and Within-Rural Differences in COVID-19 Mortality Rates
Since late-2020, COVID-19 mortality rates have been higher in rural than in urban America, but there has also been substantial within-rural heterogeneity. Using CDC data, we compare COVID-19 mortality rates across the rural-urban continuum as well as within rural counties across different types of labor markets and by metropolitan adjacency. As of October 1, 2021, the cumulative COVID-19 mortality rate was 247.0 per 100,000 population in rural counties compared to 200.7 in urban counties. Higher COVID-19 mortality rates in rural counties are explained by lower average educational attainment and lower median household income. Within rural counties, mortality rates have been highest in farming-dependent counties and lowest in recreation-dependent counties. Those differences are similarly explained by differences in educational attainment and median household income. Our findings have implications for ongoing COVID-19 prevention and vaccination efforts as well as for informing preparation efforts for future infectious disease outbreaks
Chalcogenide and Pnictide Nanocrystals from the Silylative Deoxygenationof Metal Oxides
Transition metal chalcogenide and pnictide nanocrystals are of interest for optoelectronic and catalytic applications. Here, we present a generalized route to the synthesis of these materials from the silylative deoxygenation of metal oxides with trimethylsilyl reagents. Specific nanophases produced in this way include Ni3S2, Ni5Se5, Ni2P, Co9S8, Co3Se4, CoP, Co2P, and heterobimetallic (Ni/Co)9S8. The resulting chalcogenide nanocrystals are hollow, likely due to differential rates of ion diffusion during the interfacial phase transformation reaction (Kirkendall-type effect). In contrast, the phosphide nanocrystals are solid, likely because they form at higher reaction temperatures. In all cases, simultaneous partial decomposition of the deoxygenating silyl reagent produces a coating of amorphous silica around the newly formed nanocrystals, which could impact their stability and recyclability
Biochemical characterization of Cdk2-Speedy/Ringo A2
BACKGROUND: Normal cell cycle progression requires the precise activation and inactivation of cyclin-dependent protein kinases (CDKs), which consist of a CDK and a cyclin subunit. A novel cell cycle regulator called Speedy/Ringo shows no sequence similarity to cyclins, yet can directly bind to and activate CDKs. Speedy/Ringo proteins, which bind to and activate Cdc2 and Cdk2 in vitro, are required for the G2 to M transition during Xenopus oocyte maturation and for normal S-phase entry in cultured human cells. RESULTS: We have characterized the substrate specificity and enzymatic activity of human Cdk2-Speedy/Ringo A2 in order to gain insights into the possible functions of this complex. In contrast to Cdk2-cyclin A, which has a well-defined consensus target site ((S/T)PX(K/R)) that strongly favors substrates containing a lysine at the +3 position of substrates, Cdk2-Speedy/Ringo A2 displayed a broad substrate specificity at this position. Consequently, Cdk2-Ringo/Speedy A2 phosphorylated optimal Cdk2 substrates such as histone H1 and a KSPRK peptide poorly, only ~0.08% as well as Cdk2-cyclin A, but non-canonical Cdk2 substrates such as a KSPRY peptide relatively well, with an efficiency of ~80% compared to Cdk2-cyclin A. Cdk2-Speedy/Ringo A2 also phosphorylated authentic Cdk2 substrates, such as Cdc25 proteins, which contain non-canonical CDK phosphorylation sites, nearly as well as Cdk2-cyclin A. Phosphopeptide mapping indicated that Cdk2-Speedy/Ringo A2 and Cdk2-cyclin A phosphorylate distinct subsets of sites on Cdc25 proteins. Thus, the low activity that Cdk2-Speedy/Ringo A2 displays when assayed on conventional Cdk2 substrates may significantly underestimate the potential physiological importance of Cdk2-Speedy/Ringo A2 in phosphorylating key subsets of Cdk2 substrates. Unlike Cdk2-cyclin A, whose activity depends strongly on activating phosphorylation of Cdk2 on Thr-160, neither the overall catalytic activity nor the substrate recognition by Cdk2-Speedy/Ringo A2 was significantly affected by this phosphorylation. Furthermore, Cdk2-Speedy/Ringo A2 was not a suitable substrate for metazoan CAK (which phosphorylates Cdk2 at Thr-160), supporting the notion that Speedy/Ringo A2 activates Cdk2 in a CAK-independent manner. CONCLUSION: There are major differences in substrate preferences between CDK-Speedy/Ringo A2 and Cdk2-cyclin complexes. These differences may accommodate the CAK-independent activation of Cdk2 by Speedy/Ringo A2 and they raise the possibility that CDK-Speedy/Ringo A2 complexes could phosphorylate and regulate a subset of non-canonical CDK substrates, such as Cdc25 protein phosphatases, to control cell cycle progression
Rural COVID-19 Mortality Rates are Highest in Counties with the Largest Percentages of Blacks and Hispanics
COVID-19 mortality risk is not distributed equally across the U.S. Among rural counties, the average daily increase in COVID-19 mortality rates has been significantly higher in counties with the largest percentages of Black and Hispanic residents
Biochemical characterization of mammalian Cdk2-Speedy/Ringo
Background: Normal cell cycle progression requires the precise activation and inactivation of cyclin-dependent protein kinases (CDKs), which consist of a CDK and a cyclin subunit. A novel cell cycle regulator called Speedy/Ringo shows no sequence similarity to cyclins, yet can directly bind to and activate CDKs. Speedy/Ringo proteins, which bind to and activate Cdc2 and Cdk2 in vitro, are required for the G2 to M transition during Xenopus oocyte maturation and for normal S-phase entry in cultured human cells.
Results: We have characterized the substrate specificity and enzymatic activity of human Cdk2-Speedy/Ringo A2 in order to gain insights into the possible functions of this complex. In contrast to Cdk2-cyclin A, which has a well-defined consensus target site ((S/T)PX(K/R)) that strongly favors substrates containing a lysine at the +3 position of substrates, Cdk2-Speedy/Ringo A2 displayed a broad substrate specificity at this position. Consequently, Cdk2-Ringo/Speedy A2 phosphorylated optimal Cdk2 substrates such as histone H1 and a KSPRK peptide poorly, only ~0.08% as well as Cdk2-cyclin A, but non-canonical Cdk2 substrates such as a KSPRY peptide relatively well, with an efficiency of ~80% compared to Cdk2-cyclin A. Cdk2-Speedy/Ringo A2 also phosphorylated authentic Cdk2 substrates, such as Cdc25 proteins, which contain non-canonical CDK phosphorylation sites, nearly as well as Cdk2-cyclin A. Phosphopeptide mapping indicated that Cdk2-Speedy/Ringo A2 and Cdk2-cyclin A phosphorylate distinct subsets of sites on Cdc25 proteins. Thus, the low activity that Cdk2-Speedy/Ringo A2 displays when assayed on conventional Cdk2 substrates may significantly underestimate the potential physiological importance of Cdk2-Speedy/Ringo A2 in phosphorylating key subsets of Cdk2 substrates. Unlike Cdk2-cyclin A, whose activity depends strongly on activating phosphorylation of Cdk2 on Thr-160, neither the overall catalytic activity nor the substrate recognition by Cdk2-Speedy/Ringo A2 was significantly affected by this phosphorylation. Furthermore, Cdk2-Speedy/Ringo A2 was not a suitable substrate for metazoan CAK (which phosphorylates Cdk2 at Thr-160), supporting the notion that Speedy/Ringo A2 activates Cdk2 in a CAK-independent manner.
Conclusion: There are major differences in substrate preferences between CDK-Speedy/Ringo A2 and Cdk2-cyclin complexes. These differences may accommodate the CAK-independent activation of Cdk2 by Speedy/Ringo A2 and they raise the possibility that CDK-Speedy/Ringo A2 complexes could phosphorylate and regulate a subset of non-canonical CDK substrates, such as Cdc25 protein phosphatases, to control cell cycle progression
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