Subject(s)
Accountable Care Organizations , Medicare , Aged , Humans , United States , Public Health , Health Expenditures , Fee-for-Service PlansABSTRACT
OBJECTIVES: To evaluate the impact of transitioning from Medicaid to Medicare Part D drug coverage on the use of noncancer treatments among dual enrollees with cancer. METHODS: We leveraged a representative 5% national sample of all fee-for-service dual enrollees in the United States (2004-2007) to evaluate the impact of the removal of caps on the number of reimbursable prescriptions per month (drug caps) under Part D on 1) prevalence and 2) average days' supply dispensed for antidepressants, antihypertensives, and lipid-lowering agents overall and by race (white and black). RESULTS: The removal of drug caps was associated with increased use of lipid-lowering medications (days' supply 3.63; 95% confidence interval [CI] 1.57-5.70). Among blacks in capped states, we observed increased use of lipid-lowering therapy (any use 0.08 percentage points; 95% CI 0.05-0.10; and days' supply 4.01; 95% CI 2.92-5.09) and antidepressants (days' supply 2.20; 95% CI 0.61-3.78) and increasing trends in antihypertensive use (any use 0.01 percentage points; 95% CI 0.004-0.01; and days' supply 1.83; 95% CI 1.25-2.41). The white-black gap in the use of lipid-lowering medications was immediately reduced (-0.09 percentage points; 95% CI -0.15 to -0.04). We also observed a reversal in trends toward widening white-black differences in antihypertensive use (level -0.08 percentage points; 95% CI -0.12 to -0.05; and trend -0.01 percentage points; 95% CI -0.02 to -0.01) and antidepressant use (-0.004 percentage points; 95% CI -0.01 to -0.0004). CONCLUSIONS: Our findings suggest that the removal of drug caps under Part D had a modest impact on the treatment of hypercholesterolemia overall and may have reduced white-black gaps in the use of lipid-lowering and antidepressant therapies.
Subject(s)
Antidepressive Agents/administration & dosage , Antihypertensive Agents/administration & dosage , Hypolipidemic Agents/administration & dosage , Medicare Part D/economics , Neoplasms/drug therapy , Black or African American/statistics & numerical data , Aged , Antidepressive Agents/economics , Antihypertensive Agents/economics , Fee-for-Service Plans , Female , Health Services Accessibility , Humans , Hypercholesterolemia/drug therapy , Hypercholesterolemia/economics , Hypolipidemic Agents/economics , Male , Medicaid/economics , Middle Aged , United States , White People/statistics & numerical dataABSTRACT
Amino acid taste is expected to be a universal property among animals. Although sweet, bitter, salt, and water tastes have been well characterized in insects, the mechanisms underlying amino acid taste remain elusive. From a Drosophila RNAi screen, we identify an ionotropic receptor, Ir76b, as necessary for yeast preference. Using calcium imaging, we identify Ir76b+ amino acid taste neurons in legs, overlapping partially with sweet neurons but not those that sense other tastants. Ir76b mutants have reduced responses to amino acids, which are rescued by transgenic expression of Ir76b and a mosquito ortholog AgIr76b. Co-expression of Ir20a with Ir76b is sufficient for conferring amino acid responses in sweet-taste neurons. Notably, Ir20a also serves to block salt response of Ir76b. Our study establishes the role of a highly conserved receptor in amino acid taste and suggests a mechanism for mutually exclusive roles of Ir76b in salt- and amino-acid-sensing neurons.
Subject(s)
Amino Acids/pharmacology , Drosophila Proteins/metabolism , Drosophila melanogaster/physiology , Receptors, Ionotropic Glutamate/metabolism , Sodium Channels/metabolism , Taste/drug effects , Animals , Animals, Genetically Modified/physiology , Base Sequence , Behavior, Animal/drug effects , CRISPR-Cas Systems/genetics , Calcium/metabolism , Drosophila Proteins/antagonists & inhibitors , Drosophila Proteins/deficiency , Drosophila Proteins/genetics , Drosophila melanogaster/drug effects , Female , Male , Microscopy, Confocal , Neurons/metabolism , Neurons/pathology , Phenotype , RNA Interference , Receptors, Ionotropic Glutamate/antagonists & inhibitors , Receptors, Ionotropic Glutamate/genetics , Sodium Channels/genetics , Sodium Chloride/pharmacology , Sugars/pharmacology , Taste/physiologyABSTRACT
HL9 is a nonapeptide fragment of human lysozyme which has been shown to have anti-HIV-1 activity in nanomolar concentration. This study aims to explain this inhibitory activity by using molecular dynamics (MD) simulation, focusing on the ectodomain of gp41, the envelope glycoprotein of HIV-1 crucial to membrane fusion. It was found that in HL9, two Trp residues separated by two others occupy the conserved hydrophobic pocket on gp41 and thus inhibit fusion in dominant-negative manner. Detailed HL9-gp41 binding interactions and free energies of binding were obtained through MD simulation and solvated interaction energies (SIE) calculation, giving a binding free energy of -8.25 kcal/mol which is in close agreement with the experimental value of -9.96 kcal/mol. Since C-helical region (C34) of gp41 also has two Trp residues separated by two others, this arrangement may be generalised and used to scan peptide library and to find those having similar manner of inhibition.
Subject(s)
HIV Envelope Protein gp41/metabolism , Muramidase/metabolism , Peptide Fragments/metabolism , Amino Acid Sequence , Humans , Models, Molecular , Molecular Sequence Data , Muramidase/chemistry , Protein BindingABSTRACT
Molecular dynamics (MD) simulations were carried out to study the behavior of human receptor molecule in the hemagglutinin (HA) of 1918 and 2009 H1N1 influenza viruses respectively. The 2009 HA model was obtained by virtually mutating the 1918 HA crystal structure based on A/Mexico City/MCIG01/2009(H1N1) segment 4 sequence. We found that human receptor molecule has no binding preference between the 2009 HA and the 1918 HA. In addition, among the four sugar moieties in the human receptor molecule, sialic acid contributes the most to the electrostatic and non-polar interaction energy during binding. Furthermore, the hydrogen bonds between sialic acid and the surrounding residues in 1918 HA are preserved in 2009 HA. We also found that the mutated residues contribute to a more favorable binding of hemagglutinin to the human receptor molecule.
Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Influenza A Virus, H1N1 Subtype/chemistry , Molecular Dynamics Simulation , Receptors, Virus/chemistry , Amino Acid Sequence , Binding Sites , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Hydrogen Bonding , Influenza A Virus, H1N1 Subtype/genetics , Molecular Sequence Data , Protein Binding/physiology , Sequence AlignmentABSTRACT
Claims for injury care provided to aged fee-for-service (FFS) beneficiaries cost Medicare more than $8 billion in 1999, almost 6 percent of Medicare claims spending for elders. More than one-fifth of aged FFS beneficiaries had an injury that resulted in a claim. Fractures, which were experienced by one in seventeen aged beneficiaries, were responsible far 67 percent of total injury claims expenses. Medicare could realize substantial savings if these injuries could be prevented; the program should consider underwriting effective prevention activities.