RESUMO
OBJECTIVE: American College of Cardiology and American Heart Association (ACC/AHA) published new guidelines which lower the cut-off for hypertension. We sought to evaluate the impact of these guidelines to cost and benefit of various low-dose aspirin prophylaxis approaches. STUDY DESIGN: Decision tree analysis was created using R software to evaluate four approaches to aspirin prophylaxis in the United States: no aspirin, United States Preventive Service Task Force (USPSTF) with Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) hypertension guidelines, USPSTF with ACC/AHA hypertension guidelines, as well as universal aspirin prophylaxis. This model was executed to simulate a hypothetical cohort of 4 million pregnant women in the United States. RESULTS: The new guidelines would expand the aspirin eligibility by 8% (76,953 women) in the USPSTF guidelines. Even with this increased eligibility, the USPSTF guidelines continue to be the approach with the most cost savings ($386.5 million) when compared with universal aspirin and no aspirin prophylaxis. The new hypertension guidelines are projected to increase the cost savings of the USPSTF approach by $9.4 million. CONCLUSION: Despite the small change in aspirin prophylaxis, using ACC/AHA definition of hypertension still results in an annual cost-saving of $9.4 million in the United States when compared with JNC7.
Assuntos
Aspirina/administração & dosagem , Análise Custo-Benefício , Definição da Elegibilidade/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Pré-Eclâmpsia/prevenção & controle , American Heart Association , Aspirina/economia , Pressão Sanguínea , Feminino , Humanos , Hipertensão/diagnóstico , Pré-Eclâmpsia/economia , Gravidez , Fatores de Risco , Estados UnidosRESUMO
Mutation studies previously showed that the lentivirus lytic peptide (LLP2) sequence of the cytoplasmic C-terminal tail of the HIV-1 gp41 envelope protein inhibited viral-initiated T-cell death and T-cell syncytium formation, at which time in the HIV life cycle the gp41 protein is embedded in the T-cell membrane. In striking contrast, the mutants did not affect virion infectivity, during which time the gp41 protein is embedded in the HIV envelope membrane. To examine the role of LLP2/membrane interactions, we applied synchrotron x-radiation to determine structure of hydrated membranes. We focused on WT LLP2 peptide (+3 charge) and MX2 mutant (-1 charge) with membrane mimics for the T-cell and the HIV-1 membranes. To investigate the influence of electrostatics, cholesterol content, and peptide palmitoylation, we also studied three other LLP2 variants and HIV-1 mimics without negatively charged lipids or cholesterol as well as extracted HIV-1 lipids. All LLP2 peptides bound strongly to T-cell membrane mimics, as indicated by changes in membrane structure and bending. In contrast, none of the weakly bound LLP2 variants changed the HIV-1 membrane mimic structure or properties. This correlates well with, and provides a biophysical basis for, previously published results that reported lack of a mutant effect in HIV virion infectivity in contrast to an inhibitory effect in T-cell syncytium formation. It shows that interaction of LLP2 with the T-cell membrane modulates biological function.
Assuntos
Membrana Celular/química , Proteína gp41 do Envelope de HIV/química , Fragmentos de Peptídeos/química , Animais , Membrana Celular/metabolismo , Colesterol/metabolismo , Proteína gp41 do Envelope de HIV/genética , Proteína gp41 do Envelope de HIV/metabolismo , HIV-1/química , Humanos , Lipoilação , Mutação , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Eletricidade Estática , Linfócitos T/metabolismoRESUMO
Background: The goal of this study was to provide up-to-date and comprehensive statistics on incidence, survival, and prevalence rates for selected malignant brain and other CNS tumors in adults. Methods: The current study used data from the Central Brain Tumor Registry of the United States, provided by the Centers for Disease Control and Prevention, to examine incidence and data from the Surveillance, Epidemiology, and End Results program to examine survival and prevalence in 16 distinct malignant brain and other CNS histologies in adults (aged 20 y and older at diagnosis) from 2000-2014 overall and by sex, age group, race, and ethnicity. Results: Glioblastoma had the highest incidence (4.40 per 100000) and prevalence (9.23 per 100000). Ependymal tumors had the highest 5- and 10-year relative survivals (87.8% and 84.5%, respectively), while glioblastoma had the lowest 5- and 10-year relative survivals (5.4% and 2.7%, respectively). Females generally had better survival and lower prevalence than males. Younger adults tended to have better survival than older adults, and prevalence varied greatly by age and histology. While survival did not vary significantly by race, white adults had higher prevalence than the other race groups. Hispanics generally had better survival rates and lower prevalence than non-Hispanics. Conclusions: Survival varied greatly by age and ethnicity. Prevalence differed by sex, age, race, and ethnicity.
Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias do Sistema Nervoso Central/mortalidade , Sistema de Registros/estatística & dados numéricos , Sobrevivência , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Cardiolipins (CLs) are important biologically for their unique role in biomembranes that couple phosphorylation and electron transport like bacterial plasma membranes, chromatophores, chloroplasts and mitochondria. CLs are often tightly coupled to proteins involved in oxidative phosphorylation. The first step in understanding the interaction of CL with proteins is to obtain the pure CL structure, and the structure of mixtures of CL with other lipids. In this work we use a variety of techniques to characterize the fluid phase structure, material properties and thermodynamics of mixtures of dimyristoylphosphatidylcholine (DMPC) with tetramyristoylcardiolipin (TMCL), both with 14-carbon chains, at several mole percentages. X-ray diffuse scattering was used to determine structure, including bilayer thickness and area/lipid, the bending modulus, KC, and SXray, a measure of chain orientational order. Our results reveal that TMCL thickens DMPC bilayers at all mole percentages, with a total increase of â¼6 Å in pure TMCL, and increases AL from 64 Å(2) (DMPC at 35 °C) to 109 Å(2) (TMCL at 50 °C). KC increases by â¼50%, indicating that TMCL stiffens DMPC membranes. TMCL also orders DMPC chains by a factor of â¼2 for pure TMCL. Coarse grain molecular dynamics simulations confirm the experimental thickening of 2 Å for 20mol% TMCL and locate the TMCL headgroups near the glycerol-carbonyl region of DMPC; i.e., they are sequestered below the DMPC phosphocholine headgroup. Our results suggest that TMCL plays a role similar to cholesterol in that it thickens and stiffens DMPC membranes, orders chains, and is positioned under the umbrella of the PC headgroup. CL may be necessary for hydrophobic matching to inner mitochondrial membrane proteins. Differential scanning calorimetry, SXray and CGMD simulations all suggest that TMCL does not form domains within the DMPC bilayers. We also determined the gel phase structure of TMCL, which surprisingly displays diffuse X-ray scattering, like a fluid phase lipid. AL=40.8 Å(2) for the ½TMCL gel phase, smaller than the DMPC gel phase with AL=47.2 Å(2), but similar to AL of DLPE=41 Å(2), consistent with untilted chains in gel phase TMCL.