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1.
Health Place ; 88: 103267, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38763049

RESUMO

Unsheltered homelessness is an increasingly prevalent phenomenon in major cities that is associated with adverse health and mortality outcomes. This creates a need for spatial estimates of population denominators for resource allocation and epidemiological studies. Gaps in the timeliness, coverage, and spatial specificity of official Point-in-Time Counts of unsheltered homelessness suggest a role for geospatial data from alternative sources to provide interim, neighborhood-level estimates of counts and trends. We use citizen-generated data from homeless-related 311 requests, provider-based administrative data from homeless street outreach cases, and expert reports of unsheltered count to predict count and emerging hotspots of unsheltered homelessness in census tracts across the City of Los Angeles for 2019 and 2020. Our study shows that alternative data sources can contribute timely insights into the state of unsheltered homelessness throughout the year and inform the delivery of interventions to this vulnerable population.

2.
PLoS One ; 14(2): e0212117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30763400

RESUMO

OBJECTIVE: To examine the association between socioeconomic status (SES) and racial and ethnic disparities in medication adherence for three widely prescribed therapeutic classes. METHODS: We linked longitudinal claims data from a large US-based insurance provider (2011-2013) to detailed SES information to identify patients treated with oral antidiabetic (N = 56,720), antihypertensive (N = 156,468) or antihyperlipidemic (N = 144,673) medications. We measured adherence and discontinuation by therapeutic class, and conducted regression analysis to quantify the contributions of different factors in the association between race/ethnicity and medication adherence. RESULTS: During an average follow-up period of 2.5 years, average adherence rates of Blacks and Hispanics were at least 7.5 percentage points lower than those of Whites. Controlling for demographics, health status, out-of-pocket costs, convenience of refilling prescriptions and SES attenuated the association by 30 to 50 percent, nonetheless substantial racial disparities persisted (4.1-5.8 percentage points), particularly for asymptomatic conditions. Separating adherence among existing users from those that discontinued therapies indicates that racial/ethnic disparities in adherence reflect inconsistent pill-taking rather than differential rates of discontinuation. CONCLUSIONS: Racial/ethnic disparities in adherence are mitigated, but persist after controlling for detailed socioeconomic measures. Interventions should focus more on improving medication adherence of existing users, particularly in treating asymptomatic conditions.


Assuntos
Etnicidade/estatística & dados numéricos , Seguro Saúde , Adesão à Medicação/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Classe Social , Estados Unidos
3.
J Gerontol B Psychol Sci Soc Sci ; 73(suppl_1): S38-S47, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29669100

RESUMO

Objectives: We assessed potential benefits for older Americans of reducing risk factors associated with dementia. Methods: A dynamic simulation model tracked a national cohort of persons 51 and 52 years of age to project dementia onset and mortality in risk reduction scenarios for diabetes, hypertension, and dementia. Results: We found reducing incidence of diabetes by 50% did not reduce number of years a person ages 51 or 52 lived with dementia and increased the population ages 65 and older in 2040 with dementia by about 115,000. Eliminating hypertension at middle and older ages increased life expectancy conditional on survival to age 65 by almost 1 year, however, it increased years living with dementia. Innovation in treatments that delay onset of dementia by 2 years increased longevity, reduced years with dementia, and decreased the population ages 65 and older in 2040 with dementia by 2.2 million. Conclusions: Prevention of chronic disease may generate health and longevity benefits but does not reduce burden of dementia. A focus on treatments that provide even short delays in onset of dementia can have immediate impacts on longevity and quality of life and reduce the number of Americans with dementia over the next decades.


Assuntos
Demência/prevenção & controle , Expectativa de Vida , Saúde da População , Comportamento de Redução do Risco , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/prevenção & controle , Diabetes Mellitus/prevenção & controle , Feminino , Previsões , Humanos , Hipertensão/prevenção & controle , Incidência , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Estados Unidos
4.
Med Care ; 55(8): 782-788, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28617703

RESUMO

BACKGROUND: Two common ways of measuring disease prevalence include: (1) using self-reported disease diagnosis from survey responses; and (2) using disease-specific diagnosis codes found in administrative data. Because they do not suffer from self-report biases, claims are often assumed to be more objective. However, it is not clear that claims always produce better prevalence estimates. OBJECTIVE: Conduct an assessment of discrepancies between self-report and claims-based measures for 2 diseases in the US elderly to investigate definition, selection, and measurement error issues which may help explain divergence between claims and self-report estimates of prevalence. DATA: Self-reported data from 3 sources are included: the Health and Retirement Study, the Medicare Current Beneficiary Survey, and the National Health and Nutrition Examination Survey. Claims-based disease measurements are provided from Medicare claims linked to Health and Retirement Study and Medicare Current Beneficiary Survey participants, comprehensive claims data from a 20% random sample of Medicare enrollees, and private health insurance claims from Humana Inc. METHODS: Prevalence of diagnosed disease in the US elderly are computed and compared across sources. Two medical conditions are considered: diabetes and heart attack. RESULTS: Comparisons of diagnosed diabetes and heart attack prevalence show similar trends by source, but claims differ from self-reports with regard to levels. Selection into insurance plans, disease definitions, and the reference period used by algorithms are identified as sources contributing to differences. CONCLUSIONS: Claims and self-reports both have strengths and weaknesses, which researchers need to consider when interpreting estimates of prevalence from these 2 sources.


Assuntos
Diabetes Mellitus/epidemiologia , Revisão da Utilização de Seguros , Infarto do Miocárdio/epidemiologia , Autorrelato , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Vigilância da População/métodos , Prevalência , Reprodutibilidade dos Testes
5.
Proc Natl Acad Sci U S A ; 113(6): E754-61, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26712028

RESUMO

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Ritmo Circadiano , Sono , Actigrafia , Cromossomos Humanos Par 1/genética , Família , Feminino , Humanos , Padrões de Herança/genética , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Característica Quantitativa Herdável
6.
Res Aging ; 37(6): 646-66, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25651590

RESUMO

OBJECTIVE: We analyze correlates of the direction and magnitude of changes in out-of-pocket (OOP) payments for dental care by older Americans over a recent 4-year period. METHODS: We analyzed data from the 2006 and 2008 waves of the Health and Retirement Study. We estimated multinomial logistic models of the direction and linear regression models of the amounts of OOP changes over survey periods. RESULTS: Financial-based factors were more strongly associated with the direction and magnitude of changing self-payments for dental care than were health factors. DISCUSSION: Findings suggested that dental coverage, income, and wealth and changes in these financial factors were more strongly correlated with the persistence of and changes in OOP payments for dental care over time than were health status and changes in health status. The sensitivity to dental coverage changes should be considered as insurance and retirement policy reforms are deliberated.


Assuntos
Assistência Odontológica/economia , Assistência Odontológica/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Seguro Odontológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
7.
Health Serv Res ; 50(1): 117-35, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25040355

RESUMO

OBJECTIVE: To determine if providing dental insurance to older Americans would close the current gaps in dental use and expenditure between insured and uninsured older Americans. DATA SOURCES/STUDY SETTING: We used data from the 2008 Health and Retirement Survey (HRS) supplemented by data from the 2006 Medical Expenditure Panel Survey (MEPS). STUDY DESIGN: We compared the simulated dental use and expenditures rates of newly insured persons against the corresponding rates for those previously insured. DATA COLLECTION/EXTRACTION METHODS: The HRS is a nationally representative survey administered by the Institute for Social Research (ISR). The MEPS is a nationally representative household survey sponsored by the Agency for Healthcare Research and Quality (AHRQ). PRINCIPAL FINDINGS: We found that expanding dental coverage to older uninsured Americans would close previous gaps in dental use and expense between uninsured and insured noninstitutionalized Americans 55 years and older. CONCLUSIONS: Providing dental coverage to previously uninsured older adults would produce estimated monthly costs net of markups for administrative costs that comport closely to current market rates. Estimates also suggest that the total cost of providing dental coverage targeted specifically to nonusers of dental care may be less than similar costs for prior users.


Assuntos
Serviços de Saúde Bucal/economia , Serviços de Saúde Bucal/estatística & dados numéricos , Gastos em Saúde , Seguro Odontológico , Pessoas sem Cobertura de Seguro de Saúde , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos
8.
Forum Health Econ Policy ; 18(1): 25-39, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27134606

RESUMO

Alzheimer's disease (AD) extracts a heavy societal toll. The value of medical advances that delay onset of AD could be significant. Using data from nationally representative samples from the Health and Retirement Study (1998-2008) and Aging Demographics and Memory Study (2001-2009), we estimate the prevalence and incidence of AD and the formal and informal health care costs associated with it. We use microsimulation to project future prevalence and costs of AD under different treatment scenarios. We find from 2010 to 2050, the number of individuals ages 70+ with AD increases 153%, from 3.6 to 9.1 million, and annual costs increase from $307 billion ($181B formal, $126B informal costs) to $1.5 trillion. 2010 annual per person costs were $71,303 and double by 2050. Medicare and Medicaid are paying 75% of formal costs. Medical advances that delay onset of AD for 5 years result in 41% lower prevalence and 40% lower cost of AD in 2050. For one cohort of older individuals, who would go on to acquire AD, a 5-year delay leads to 2.7 additional life years (about 5 AD-free), slightly higher formal care costs due to longer life but lower informal care costs for a total value of $511,208 per person. We find Medical advances delaying onset of AD generate significant economic and longevity benefits. The findings inform clinicians, policymakers, businesses and the public about the value of prevention, diagnosis, and treatment of AD.

9.
J Public Health Dent ; 74(1): 1-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-22994647

RESUMO

OBJECTIVE: The purpose of this article is to examine the relationship between changes in household finances (wealth and income) and changes in dental utilization at the onset of the recent recession in a population of older Americans. METHODS: Data from the Health and Retirement Study (HRS) were analyzed for U.S. individuals aged 51 years and older during the 2006 and 2008 waves of the HRS. We estimated logistic models of (a) starting and (b) stopping dental use between 2006 and 2008 survey periods as a function of changes in household wealth and income, controlling for other potentially confounding covariates. RESULTS: We found that only when household wealth falls by 50 percent or more were older adults less likely to seek dental care. Changes in household income and other changes in household wealth were not associated with changes in dental utilization among this population. CONCLUSIONS: Older Americans' dental care utilization appeared to be fairly resilient to changes in household finances; only when wealth fell by 50 percent or more did individuals decrease dental use. This finding might extend to other health-care services that are preventive, routine, and relatively inexpensive.


Assuntos
Serviços de Saúde Bucal/estatística & dados numéricos , Financiamento Pessoal , Serviços de Saúde Bucal/economia , Humanos , Pessoa de Meia-Idade , Estados Unidos
10.
Am J Public Health ; 103(7): 1314-24, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23678922

RESUMO

OBJECTIVES: We analyzed correlates of older Americans' continuous and transitional health care utilization over 4 years. METHODS: We analyzed data for civilian, noninstitutionalized US individuals older than 50 years from the 2006 and 2008 waves of the Health and Retirement Study. We estimated multinomial logistic models of persistent and intermittent use of physician, inpatient hospital, home health, and outpatient surgery over the 2004-2008 survey periods. RESULTS: Individuals with worse or worsening health were more likely to persistently use medical care and transition into care and not transition out of care over time. Financial variables were less often significant and, when significant, were often in an unexpected direction. CONCLUSIONS: Older individuals' health and changes in health are more strongly correlated with persistence of and changes in care-seeking behavior over time than are financial status and changes in financial status. The more pronounced sensitivity to health status and changes in health are important considerations in insurance and retirement policy reforms.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Atenção à Saúde/tendências , Serviços de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Atenção à Saúde/economia , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Renda , Cobertura do Seguro , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico/estatística & dados numéricos , Fatores de Tempo , Estados Unidos
11.
J Public Health Dent ; 72(3): 179-89, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22515635

RESUMO

OBJECTIVE: The purpose of this article is to examine the relationship of wealth and income and the relative impact of each on dental utilization in a population of older Americans, using data from the Health and Retirement Study (HRS). METHODS: Data from the HRS were analyzed for US individuals aged 51 years and older during the 2008 wave of the HRS. The primary focus of the analysis is the relationship between wealth, income, and dental utilization. We estimate a multivariable model of dental use controlling for wealth, income, and other potentially confounding covariates. RESULTS: We find that both wealth and income each have a strong and independent positive effect on dental care use of older Americans (P < 0.05). A test of the interaction between income and wealth in our model failed to show that the impact on dental care utilization as wealth increases depends on a person's income level or, alternatively, that the impact on dental use as income increases depends on a person's household wealth status (P > 0.05). CONCLUSIONS: Relative to those living in the wealthiest US households, the likelihood of utilizing dental care appears to decrease with a decline in wealth. The likelihood of utilizing dental care also appears to decrease with a decline in income as well.


Assuntos
Serviços de Saúde Bucal/estatística & dados numéricos , Classe Social , Acessibilidade aos Serviços de Saúde , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estados Unidos
12.
Am J Public Health ; 101(10): 1882-91, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21852656

RESUMO

OBJECTIVES: We examined dental care utilization transition dynamics between 2004 and 2006 in the context of changing dental coverage status. METHODS: We used data from the Health and Retirement Study for persons aged 51 years and older to estimate a multivariable model of dental care use transitions with controls for dental coverage and retirement transitions and other potentially confounding covariates. RESULTS: We found that Americans aged 51 years and older who lost dental coverage between the 2004 and 2006 survey periods were more likely to stop dental care use between periods, and those who gained coverage were more likely to start dental care use between periods, than those without coverage in both periods. CONCLUSIONS: Dental coverage transitions and status have a strong effect on transitions in dental care use. Given that retirement is a time when many experience a loss of dental coverage, older adults may be at risk for sporadic dental care and even stopping use, leading to worse dental and potentially overall health.


Assuntos
Assistência Odontológica/estatística & dados numéricos , Seguro Odontológico/estatística & dados numéricos , Aposentadoria/estatística & dados numéricos , Fatores Etários , Idoso , Emprego/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores Socioeconômicos , Estados Unidos
13.
J Public Health Dent ; 70(1): 67-75, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19765203

RESUMO

OBJECTIVE: The authors examine the relationship of dental care coverage, retirement, and utilization in an aging population using data from the Health and Retirement Study (HRS). METHODS: The authors estimate dental care use as a function of dental care coverage status, retirement, and individual and household characteristics. They also estimate a multivariate model controlling for potentially confounding variables. RESULTS: The authors show that that the loss of income and dental coverage associated with retirement may lead to lower use rates but this effect may be offset by other unobserved aspects of retirement including more available free time leading to an overall higher use rate. CONCLUSIONS: The authors conclude from this study that full retirement accompanied by reduced income and dental insurance coverage produces lower utilization of dental services. However, they also show that retirement acts as an independent variable, whereas income, coverage, and free time (unobserved) act as intervening variables.


Assuntos
Assistência Odontológica/estatística & dados numéricos , Seguro Odontológico/estatística & dados numéricos , Aposentadoria/estatística & dados numéricos , Idoso , Fatores de Confusão Epidemiológicos , Emprego/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Política de Saúde , Humanos , Renda , Atividades de Lazer , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Aposentadoria/economia , Fatores Socioeconômicos , Estados Unidos
14.
J Public Health Dent ; 70(1): 1-12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19694939

RESUMO

OBJECTIVES: To examine the convergence of an aging population and a decreased availability of dental care coverage using data from the Health and Retirement Study (HRS). METHODS: We calculate national estimates of the number and characteristics of those persons age 51 years and above covered by dental insurance by labor force, retirement status, and source of coverage. We also estimate a multivariate model controlling for potentially confounding variables. RESULTS: We show that being in the labor force is a strong predictor of having dental coverage. For older retired adults not in the labor force, the only source for dental coverage is either a postretirement health benefit or spousal coverage. CONCLUSIONS: Dental care, generally not covered in Medicare, is an important factor in the decision to seek dental care. It is important to understand the relationship between retirement and dental coverage in order to identify the best ways of improving oral health and access to care among older Americans.


Assuntos
Seguro Odontológico/estatística & dados numéricos , Aposentadoria/estatística & dados numéricos , Idoso , Emprego/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Estados Unidos
15.
J Public Health Dent ; 70(2): 148-55, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20002876

RESUMO

OBJECTIVES: To examine the relationship of dental care coverage, retirement, and out-of-pocket (OOP) dental expenditures in an aging population, using data from the Health and Retirement Study (HRS). METHODS: We estimate OOP dental expenditures among individuals who have dental utilization as a function of dental care coverage status, retirement, and individual and household characteristics. We also estimate a multivariate model controlling for potentially confounding variables. RESULTS: Overall, mean OOP dental expenditures among those with any spending were substantially larger for those without coverage than for those with coverage. However, controlling for coverage shows that there is little difference in spending by retirement status. CONCLUSIONS: Although having dental coverage is a key determinant of the level of OOP expenditures on dental care; spending is higher among those without coverage than those who have dental insurance. We also found that while retirement has no independent effect on OOP dental expenditures once controlling for coverage, dental coverage rates are much lower among retirees.


Assuntos
Assistência Odontológica/economia , Financiamento Pessoal , Aposentadoria , Fatores Etários , Idoso , Assistência Odontológica/estatística & dados numéricos , Escolaridade , Etnicidade , Feminino , Financiamento Pessoal/economia , Humanos , Renda , Cobertura do Seguro/economia , Seguro Odontológico/economia , Masculino , Estado Civil , Pessoa de Meia-Idade , Boca Edêntula/economia , Aposentadoria/economia , Estados Unidos
16.
Am J Manag Care ; 15(10): 729-35, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19845424

RESUMO

OBJECTIVE: To examine dental insurance transition dynamics in the context of changing employment and retirement status. STUDY DESIGN: Data from the Health and Retirement Study (HRS) were analyzed for individuals 51 years and older between the 2004 and 2006 waves of the HRS. METHODS: The primary focus of the analysis is the relationship between retirement and transitions in dental care coverage. We calculate and present bivariate relationships between dental coverage and retirement status transitions over time and estimate a multivariable model of dental coverage controlling for retirement and other potentially confounding covariates. RESULTS: Older adults are likely to lose their dental coverage on entering retirement compared with those who remain in the labor force between waves of the HRS. While more than half of those persons in the youngest group (51-64 years) were covered over this entire period, two-thirds of those in the oldest group (>or=75 years) were without coverage over the same period. We observe a high percentage of older persons flowing into and out of dental coverage over the period of our study, similar to flows into and out of poverty. CONCLUSIONS: Dental insurance is an important factor in the decision to seek dental care. Yet, no dental coverage is provided by Medicare, which provides medical insurance for almost all Americans 65 years and older. This loss of coverage could lead to distortions in the timing of when to seek care, ultimately leading to worse oral and overall health.


Assuntos
Mobilidade Ocupacional , Cobertura do Seguro/organização & administração , Seguro Odontológico , Idoso , Feminino , Planos de Assistência de Saúde para Empregados , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Estados Unidos
17.
Breast Cancer Res Treat ; 118(1): 213-28, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18953692

RESUMO

The molecular mechanism for the beneficial effect of fish oil on breast tumor growth is largely undefined. Using the xenograft model in nude mice, we for the first time report that the fish oil diet significantly increased the level of PTEN protein in the breast tumors. In addition, the fish oil diet attenuated the PI 3 kinase and Akt kinase activity in the tumors leading to significant inhibition of NFkappaB activation. Fish oil diet also prevented the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in the breast tumors with concomitant increase in caspase 3 activity. To extend these findings we tested the functional effects of DHA and EPA, the two active omega-3 fatty acids of fish oil, on cultured MDA MB-231 cells. In agreement with our in vivo data, DHA and EPA treatment increased PTEN mRNA and protein expression and inhibited the phosphorylation of p65 subunit of NFkappaB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFkappaB DNA binding activity and NFkappaB-dependent transcription of Bcl-2 and Bcl-XL genes were also prevented by DHA and EPA treatment. Finally, we showed that PTEN expression significantly inhibited NFkappaB-dependent transcription of Bcl-2 and Bcl-XL genes. Taken together, our data reveals a novel signaling pathway linking the fish oil diet to increased PTEN expression that attenuates the growth promoting signals and augments the apoptotic signals, resulting in breast tumor regression.


Assuntos
Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas de Neoplasias/fisiologia , PTEN Fosfo-Hidrolase/fisiologia , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma/dietoterapia , Adenocarcinoma/genética , Animais , Apoptose/fisiologia , Neoplasias da Mama/dietoterapia , Neoplasias da Mama/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Linhagem Celular Tumoral/patologia , DNA de Neoplasias/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Óleos de Peixe/uso terapêutico , Genes bcl-2 , Humanos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Fator de Transcrição RelA/biossíntese , Fator de Transcrição RelA/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X/biossíntese , Proteína bcl-X/genética
18.
Health Educ Behav ; 34(4): 651-68, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17567823

RESUMO

In a recent randomized field trial, Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth-grade adolescents. This article reports effects among ninth-grade at-risk adolescents. Comparisons between at-risk girls in ALERT Plus schools (basic curriculum extended to ninth grade with five booster lessons) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use, at-risk drinking, alcohol use resulting in negative consequences, and attitudinal and perceptual factors conducive to drug use. Program-induced changes in perceived social influences, one's ability to resist those influences, and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use. No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum (covering seventh and eighth grades only) was delivered. Possible reasons for gender differences and implications for prevention programming are discussed.


Assuntos
Comportamento do Adolescente , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Adolescente , Feminino , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Assunção de Riscos , Fumar/epidemiologia , Prevenção do Hábito de Fumar , South Dakota/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
19.
J Biol Chem ; 281(29): 20160-70, 2006 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-16707491

RESUMO

Bone remodeling depends upon proper osteoblast and osteoclast function. Bone morphogenetic protein-2 (BMP-2) stimulates differentiation of osteoblasts from pluripotent precursors. Osteoclast formation depends on the concerted action of osteoblast-derived receptor activator of NF-kappaB ligand and colony-stimulating factor-1 (CSF-1). BMP-2 stimulates receptor activator of NF-kappaB ligand expression. However, the effect of BMP-2 on CSF-1 expression has not been studied. We investigated the role of BMP-2 in CSF-1 expression in osteogenic C2C12 cells. Incubation of C2C12 cells with BMP-2 supported osteoclastogenesis of spleen cells with a concomitant increase in expression of CSF-1 mRNA and protein. To determine the mechanism, we identified a BMP-responsive element between -627 bp and -509 bp in the CSF-1 promoter. DNase I footprint analysis revealed the presence of consensus Smad binding motif in this region. Electrophoretic mobility shift assay showed BMP-2-stimulated binding of proteins to this motif. Mutation of core sequence as well as its 5'- and 3'-flanking sequences abolished the DNA-protein interaction resulting in inhibition of CSF-1 transcription. Supershift analysis detects the presence of Smads 1, 5, and 4 and the transcriptional coactivator CREB-binding protein in the BMP-responsive element-protein complex. In addition, Smads 1 and 5 alone or in combination with Smad 4 increased CSF-1 transcription. Furthermore, CREB-binding protein markedly increased transcription of CSF-1. These data represent the first evidence that BMP-2 increases the osteoclastogenic CSF-1 expression by a transcriptional mechanism using the canonical Smad pathway and provide a mechanism for BMP-2-induced osteoclast differentiation.


Assuntos
Proteínas Morfogenéticas Ósseas/farmacologia , Proteína de Ligação a CREB/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Osteoclastos/citologia , Osteoclastos/fisiologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Células Musculares/efeitos dos fármacos , Células Musculares/fisiologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/efeitos dos fármacos , Regiões Promotoras Genéticas , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Transcrição Gênica/efeitos dos fármacos
20.
J Biol Chem ; 280(29): 27383-92, 2005 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-15888451

RESUMO

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.


Assuntos
Neoplasias do Colo/patologia , Receptor ErbB-2/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular , Neoplasias do Colo/etiologia , Dimerização , Retículo Endoplasmático/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Humanos , Região Variável de Imunoglobulina/farmacologia , Proteínas Oncogênicas v-erbB/fisiologia , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Receptor ErbB-2/imunologia , Transdução de Sinais , Transfecção
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