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1.
Hepatology ; 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37939079

RESUMO

BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion.

2.
J Viral Hepat ; 30(9): 727-730, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37345810

RESUMO

In a comparison between 50 Alaska Native persons with chronic hepatitis B who cleared HBV surface antigen (HBsAg) and 50 Alaska Native age-, sex-, and HBV genotype-matched controls, we found differences in changes in HBV DNA and HBV RNA levels over time but no difference in hepatitis B core-related antigen. These findings suggest that serial HBV DNA and HBV RNA may be associated with HBV functional cure defined by HBsAg clearance.


Assuntos
Hepatite B Crônica , Humanos , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , DNA Viral , Antígenos do Núcleo do Vírus da Hepatite B , RNA , Antígenos E da Hepatite B
3.
Alcohol Alcohol ; 53(4): 461-469, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29329365

RESUMO

AIMS: To evaluate the feasibility, acceptability and effectiveness of placing FASD prevention messages in the women's restrooms of establishments serving alcohol in Alaska and the Yukon, regions with high rates of FASD. METHODS: Our team placed an FASD educational poster, and posters affixed to a pregnancy test dispenser, in women's restrooms of bars and restaurants. We compared drinking behaviors and knowledge and beliefs about FASD among participants at baseline and at follow-up. RESULTS: Respondents consisted of 2132 women who completed a baseline survey and 1182 women who completed both a baseline and a follow-up survey. Women in both groups showed improvement in knowledge of FASD; the dispenser group scored higher than participants in the poster group on the FASD Health Belief questions at both baseline and follow-up. Forty-three women learned they were pregnant from our pregnancy tests and alcohol consumption among pregnant women was lower at follow-up than at baseline. CONCLUSIONS: FASD prevention messages, particularly paired with pregnancy test dispensers, in the women's restrooms of establishments that serve alcohol can effectively promote informed alcohol consumption decisions among women who are, or may become, pregnant. SHORT SUMMARY: In this FASD prevention feasibility study, we found that FASD prevention messages, particularly paired with pregnancy test dispensers, placed in the women's restrooms of establishments that serve alcohol can effectively promote informed alcohol consumption decisions among women who are, or may become, pregnant.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Gestantes/psicologia , Prevenção Primária/métodos , Adulto , Feminino , Humanos , Testes de Gravidez/psicologia , Adulto Jovem
4.
Ann Fam Med ; 11 Suppl 1: S41-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690385

RESUMO

PURPOSE: This study describes key elements of the transition to a patient-centered medical home (PCMH) model at Southcentral Foundation (SCF), a tribally owned and managed primary care system, and evaluates changes in emergency care use for any reason, for asthma, and for unintentional injuries, during and after the transition. METHODS: We conducted a time series analyses of emergency care use from medical record data. We also conducted 45 individual, in-depth interviews with PCMH patients (customer-owners), primary care clinicians, health system employees, and tribal leaders. RESULTS: Emergency care use for all causes was increasing before the PCMH implementation, dropped during and immediately after the implementation, and subsequently leveled off. Emergency care use for adult asthma dropped before, during, and immediately after implementation, subsequently leveling off approximately 5 years after implementation. Emergency care use for unintentional injuries, a comparison variable, showed an increasing trend before and during implementation and decreasing trends after implementation. Interview participants observed improved access to primary care services after the transition to the PCMH tempered by increased staff fatigue. Additional themes of PCMH transformation included the building of relationships for coordinated, team-based care, and the important role of leadership in PCMH implementation. CONCLUSIONS: All reported measures of emergency care use show a decreasing trend after the PCMH implementation. Before the implementation, overall use and use for unintentional injuries had been increasing. The combined quantitative and qualitative results are consistent with decreased emergency care use resulting from a decreased need for emergency care services due to increased availability of primary care services and same-day appointments.


Assuntos
Avaliação de Processos e Resultados em Cuidados de Saúde , Assistência Centrada no Paciente/organização & administração , Atenção Primária à Saúde/organização & administração , Alaska , Assistência Integral à Saúde/organização & administração , Acessibilidade aos Serviços de Saúde , Humanos , Indígenas Norte-Americanos , Inuíte , Equipe de Assistência ao Paciente , Atenção Primária à Saúde/estatística & dados numéricos
5.
Int J Geriatr Psychiatry ; 28(4): 331-40, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22674539

RESUMO

OBJECTIVE: There is a widely recognised need to develop effective Alzheimer's disease (AD) biomarkers to aid the development of disease-modifying treatments, to facilitate early diagnosis and to improve clinical care. This overview aims to summarise the utility of key neuroimaging and cerebrospinal fluid (CSF) biomarkers for AD, before focusing on the latest efforts to identify informative blood biomarkers. DESIGN: A literature search was performed using PubMed up to September 2011 for reviews and primary research studies of neuroimaging (magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and amyloid imaging), CSF and blood-based (plasma, serum and platelet) biomarkers in AD and mild cognitive impairment. Citations within individual articles were examined to identify additional studies relevant to this review. RESULTS: Evidence of AD biomarker potential was available for imaging techniques reflecting amyloid burden and neurodegeneration. Several CSF measures are promising, including 42 amino acid ß-amyloid peptide (Aß42 ); total tau (T-tau) protein, reflecting axonal damage; and phosphorylated tau (P-tau), reflecting neurofibrillary tangle pathology. Studies of plasma Aß have produced inferior diagnostic discrimination. Alternative plasma and platelet measures are described, which represent potential avenues for future research. CONCLUSIONS: Several imaging and CSF markers demonstrate utility in predicting AD progression and determining aetiology. These require standardisation before forming core elements of diagnostic criteria. The enormous potential available for identifying a minimally-invasive, easily-accessible blood measure as an effective AD biomarker currently remains unfulfilled.


Assuntos
Doença de Alzheimer/diagnóstico , Imageamento por Ressonância Magnética/métodos , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Precoce , Humanos
6.
Cells ; 12(18)2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37759460

RESUMO

As the world transitions from the acute phase of the COVID-19 pandemic, a novel concern has arisen-interstitial lung disease (ILD) as a consequence of SARS-CoV-2 infection. This review discusses what we have learned about its epidemiology, radiological, and pulmonary function findings, risk factors, and possible management strategies. Notably, the prevailing radiological pattern observed is organising pneumonia, with ground-glass opacities and reticulation frequently reported. Longitudinal studies reveal a complex trajectory, with some demonstrating improvement in lung function and radiographic abnormalities over time, whereas others show more static fibrotic changes. Age, disease severity, and male sex are emerging as risk factors for residual lung abnormalities. The intricate relationship between post-COVID ILD and idiopathic pulmonary fibrosis (IPF) genetics underscores the need for further research and elucidation of shared pathways. As this new disease entity unfolds, continued research is vital to guide clinical decision making and improve outcomes for patients with post-COVID ILD.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Humanos , Masculino , Pandemias , COVID-19/complicações , SARS-CoV-2 , Doenças Pulmonares Intersticiais/complicações , Progressão da Doença , Pulmão
7.
JGH Open ; 7(8): 545-552, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37649864

RESUMO

Background and Aim: High autoimmune hepatitis (AIH) and overlap syndrome (OS) prevalence have been previously documented among Alaska Native people. The purpose of this project is to report changes in AIH/OS prevalence over time, clinical characteristics, and factors associated with biochemical remission. Methods: We reviewed medical records for Alaska Native/American Indian (AN/AI) patients diagnosed with AIH/OS between 1984 and 2021. Point prevalence was calculated based on AIH/OS patients alive at the end of 2021 and at 5-year intervals from July 1, 2000, to July 1, 2020. Results: We identified 189 AN/AI persons diagnosed with AIH or OS (157 AIH, 32 OS). Of these 189, 137 were alive at the end of 2021 for a point prevalence of 91.2 per 100 000 (95% confidence interval [CI]: 77.2-107.8)-75.9 (95% CI: 63.2-91.2) for AIH and 15.3 (95% CI: 10.2-23.0) for OS. Prevalence for both AIH and OS has risen steadily since 2000. Eighty-nine consented participants (62.7%) achieved biochemical remission with a median time from diagnosis to start of remission of 1.9 years (IQR 0.5-5.0 years). Consented patients with fatty liver were less likely to achieve remission, but their time to remission was shorter than for patients without fatty liver. Conclusion: The AN/AI population in Alaska continues to have the highest reported prevalence of AIH/OS in the world, with prevalence rising steadily since 2000. High reported AIH/OS prevalence is likely due in part to strong referral networks for liver disease. Detection and treatment can lead to biochemical remission and improved health outcomes.

8.
Hepatol Commun ; 7(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37347221

RESUMO

HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estados Unidos/epidemiologia , Etnicidade , Grupos Minoritários , Carcinoma Hepatocelular/terapia , Acessibilidade aos Serviços de Saúde , Neoplasias Hepáticas/terapia
9.
Eur J Immunol ; 41(4): 902-15, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21416464

RESUMO

Members of the CD28 family play important roles in regulating T-cell functions and share a common gene structure profile. We have identified VSTM3 as a protein whose gene structure matches that of the other CD28 family members. This protein (also known as TIGIT and WUCAM) has been previously shown to affect immune responses and is expressed on NK cells, activated and memory T cells, and Tregs. The nectin-family proteins CD155 and CD112 serve as counter-structures for VSTM3, and CD155 and CD112 also bind to the activating receptor CD226 on T cells and NK cells. Hence, this group of interacting proteins forms a network of molecules similar to the well-characterized CD28-CTLA-4-CD80-CD86 network. In the same way that soluble CTLA-4 can be used to block T-cell responses, we show that soluble Vstm3 attenuates T-cell responses in vitro and in vivo. Moreover, animals deficient in Vstm3 are more sensitive to autoimmune challenges indicating that this new member of the CD28 family is an important regulator of T-cell responses.


Assuntos
Antígenos CD28/imunologia , Receptores Imunológicos/imunologia , Linfócitos T/imunologia , Animais , Doenças Autoimunes/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Humanos , Camundongos , Ratos , Receptores Imunológicos/deficiência , Linfócitos T/química
10.
Public Health Rep ; 126(1): 73-83, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21337932

RESUMO

OBJECTIVES: Historically, Alaska Native (AN) people have exhibited low overall rates of heart disease mortality compared with the U.S. white (USW) population. We compared AN and USW heart disease mortality rates during the 27-year period from 1981 through 2007. METHODS: We compared AN and USW heart disease mortality rates overall and by gender, age, and disease subtype. We calculated age-adjusted rates for AN people for three nine-year periods from 1981 through 2007 and compared them with the rates for USW people. RESULTS: AN people > or = 35 years of age had a significantly lower rate of heart disease mortality compared with their USW counterparts (rate ratio [RR] = 0.80). The lower overall RR was due primarily to a lower ischemic heart disease mortality RR (RR = 0.63). Overall heart disease mortality decreased during the 27-year study period for both the AN (33.1%) and USW (35.0%) populations. However, hypertensive heart disease mortality increased 155.2% for AN people and 13.7% for USW people. Age-specific heart disease mortality was about 30.0% lower for AN people > or = 75 years of age compared with their USW counterparts, while it was virtually identical for the two racial/ethnic groups among people 35-74 years of age. CONCLUSIONS: The age-adjusted AN heart disease mortality rate was consistently about 20.0% lower than the USW rate from 1981 through 2007, with similar RRs for men and women. However, combining all ages and all heart disease subgroups into a single, age-adjusted statistic obscures many important differences across ages and disease subtypes.


Assuntos
Cardiopatias/etnologia , Cardiopatias/mortalidade , Indígenas Norte-Americanos , Adulto , Distribuição por Idade , Idoso , Alaska/epidemiologia , Distribuição de Qui-Quadrado , Comparação Transcultural , Feminino , Cardiopatias/classificação , Cardiopatias/etiologia , Humanos , Hipertensão/complicações , Hipertensão/etnologia , Indígenas Norte-Americanos/etnologia , Indígenas Norte-Americanos/estatística & dados numéricos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Vigilância da População , Febre Reumática/complicações , Febre Reumática/etnologia , Fatores de Risco , Distribuição por Sexo , Estados Unidos/epidemiologia , População Branca/etnologia , População Branca/estatística & dados numéricos
11.
Am J Med Genet B Neuropsychiatr Genet ; 156B(7): 764-71, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21812096

RESUMO

We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Homozigoto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cromossomos Humanos Par 8/genética , Feminino , Genes/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino
12.
PLoS One ; 16(12): e0260970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855920

RESUMO

BACKGROUND: Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. METHODS: AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. RESULTS: We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. CONCLUSIONS: In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.


Assuntos
Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Idoso , Alaska/epidemiologia , Combinação de Medicamentos , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resposta Viral Sustentada
13.
Am J Epidemiol ; 171(11): 1203-13, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20427327

RESUMO

The effect of change in reproductive hormones and menopause on incident obesity (body mass index > or =30 kg/m(2)) and severe obesity (body mass index > or =35 kg/m(2)) was evaluated over 9 years in 3,260 US women recruited in the multiethnic Study of Women's Health Across the Nation in 1996-1997. After 9 years, cumulative incidences of obesity and severe obesity reached 21.8% and 12.3%, respectively. In multivariate analysis, hormone changes, chronic health conditions, lower physical activity, race/ethnicity, and age were significantly associated with incident obesity and/or severe obesity. The odds of incident severe obesity increased with surgical menopause (odds ratio (OR) = 5.07, 95% confidence interval (CI): 2.29, 11.20; P < 0.001) and initiation of hormone therapy prior to 12 months of amenorrhea (OR = 2.94, 95% CI: 1.14, 7.58; P = 0.03). Predictors of obesity included an increase in free androgen index (OR = 1.37, 95% CI: 1.12, 1.68; P = 0.002) and a decrease in sex hormone-binding globulin (OR = 0.60, 95% CI: 0.45, 0.80; P = 0.0005). Similar results were found for severe obesity. Obesity rates varied by race, but no hormone-by-race interactions were observed. These longitudinal data demonstrate that higher androgens, lower sex hormone-binding globulin, surgical menopause, and early hormone therapy use predict incident obesity and/or severe obesity in a multiracial cohort of women transitioning into menopause.


Assuntos
Hormônios Esteroides Gonadais/sangue , Obesidade/sangue , Fatores Etários , Amenorreia/complicações , Índice de Massa Corporal , Intervalos de Confiança , Estudos Transversais , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/fisiologia , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Menopausa/fisiologia , Análise Multivariada , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade/fisiopatologia , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/etiologia , Obesidade Mórbida/fisiopatologia , Razão de Chances , Prevalência , Grupos Raciais , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Estados Unidos/epidemiologia
14.
Prev Chronic Dis ; 7(4): A85, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20550843

RESUMO

INTRODUCTION: The Alaska Education and Research Towards Health (EARTH) Study is being conducted to determine the prevalence of clinically measured chronic disease risk factors in a large population of American Indian/Alaska Native people (AI/AN). We report these estimates and compare them with those for the overall US population, as assessed by the National Health and Nutrition Examination Survey (NHANES). METHODS: We measured blood pressure, height, weight, and fasting serum lipids and glucose in a prospective cohort of 3,822 AI/AN participants who resided in Alaska during 2004 through 2006. We categorized participants as having chronic disease risk factors if their measurements exceeded cutoffs that were determined on the basis of national recommendations. We analyzed the prevalence of risk factors by sex and age and compared the age-adjusted prevalence with 1999-2004 NHANES measurements. RESULTS: EARTH participants were significantly more likely than NHANES participants to be overweight or obese and to have impaired fasting glucose, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, and hypertension. The prevalence of high total cholesterol and triglycerides was not significantly different between the 2 study populations. CONCLUSION: We provide baseline clinical measurements for chronic disease risk factors for a larger study sample than any previous study of AI/AN living in Alaska. The prevalence of most risk factors measured exceeded national rates. These data can be used to tailor health interventions and reduce health disparities.


Assuntos
Doença Crônica/epidemiologia , Disparidades nos Níveis de Saúde , Indígenas Norte-Americanos/estatística & dados numéricos , Inuíte/estatística & dados numéricos , Adulto , Idoso , Alaska/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença Crônica/etnologia , Feminino , Humanos , Hipertensão/epidemiologia , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Adulto Jovem
15.
J Neurochem ; 108(2): 341-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19094065

RESUMO

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the Abeta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Plaquetas/ultraestrutura , Membrana Celular/metabolismo , Colesterol/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/metabolismo , Plaquetas/citologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Colesterol/farmacologia , Transtornos Cognitivos/sangue , Meios de Cultura Livres de Soro/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Modelos Lineares , Masculino , Neuroblastoma/patologia , Neuroblastoma/ultraestrutura , Estatísticas não Paramétricas , Frações Subcelulares , Fatores de Tempo , beta-Ciclodextrinas/farmacologia
16.
Int J Geriatr Psychiatry ; 24(9): 927-32, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19194887

RESUMO

OBJECTIVES: Renal disease is increasingly regarded as an independent risk factor for vascular disease which in itself is believed to influence risk of AD. Alterations in amyloid homeostasis via reduced renal clearance of peripheral beta-amyloid (A|*beta*|) may represent another potential role for variation in renal function leading to increased risk of AD. We sought to examine estimates of glomerular filtration rate in AD and control groups. METHODS: AD patients were randomly recruited from the Memory Clinic of the Belfast City Hospital (n = 83). Genomic DNA was extracted from peripheral leucocytes and was genotyped for Apolipoprotein E using standard methods. Using creatinine values, age and gender, estimated Glomerular Filtration Rates (eGFR) were calculated using the isotope dilution mass spectrometry (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) Study equation (using the United Kingdom National External Quality Assessment Scheme (UKNEQAS) correction factor). IDMS eGFR values were then compared between AD and control groups. RESULTS: Significant baseline differences in age, diastolic blood pressure, education level attained and APOE |*epsilon*|4 carriage were noted between cases and controls. The AD group had a significantly lower eGFR versus controls (69 vs 77 ml/min) which persisted after adjustment for possible confounders (p = 0.045). CONCLUSIONS: This case-control analysis suggests that using a relatively accurate estimate of renal function, patients with AD have greater renal impairment than cognitively normal controls. This may reflect impaired renal clearance of peripheral A|*beta*| or be a marker of shared vascular processes altering cerebral and renal functioning.


Assuntos
Doença de Alzheimer/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Nefropatias/fisiopatologia , Doenças Vasculares/fisiopatologia , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Apolipoproteínas E/sangue , Apolipoproteínas E/genética , Estudos de Casos e Controles , Intervalos de Confiança , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Nefropatias/sangue , Nefropatias/complicações , Masculino , Fatores de Risco , Doenças Vasculares/sangue , Doenças Vasculares/complicações
17.
Womens Health Issues ; 19(3): 202-10, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19447324

RESUMO

OBJECTIVE: To evaluate if there are racial differences between African-American and Caucasian women who have hysterectomy for benign conditions in terms of (1) presenting symptoms (prolapse, vaginal bleeding, pain, and known history of leiomyomas), (2) serum estradiol and testosterone levels at the visit before hysterectomy, and (3) uterine weight. METHODS: A multi-ethnic, multisite, community-based longitudinal cohort study of 3,302 women ages 42-52 at enrollment was conducted. During 9 years of follow-up, 203 African-American and Caucasian women reported a hysterectomy, 90 with evidence of uterine leiomyomas. Women were surveyed regarding their overall perceived health before and after hysterectomy, presenting symptoms, and their motivations for surgery. Serum estradiol and testosterone levels were measured. Uterine weight at time of hysterectomy and clinical pathology were determined via medical record abstraction. RESULTS: Previously diagnosed leiomyomas were presenting symptoms more frequently in African-American women than Caucasian women (85% vs. 63%; p = .02). African-American women had less prolapse than Caucasian women (0% vs. 10%; p = 0.04). Chronic pain was a more frequent reason for hysterectomy in African-American women than in Caucasian women (49% vs. 29%; p = .05). There were no differences between the groups in levels of estradiol or testosterone. African-American women had almost twice the uterine weight as that of Caucasian women (448 vs. 240 g; p = .0005). CONCLUSION: Racial differences in frequency of hysterectomy for benign conditions are consistent with differences in presenting symptoms, where African-American women seemingly have larger, more symptomatic fibroids.


Assuntos
Negro ou Afro-Americano , Histerectomia/estatística & dados numéricos , Leiomioma/etnologia , Neoplasias Uterinas/etnologia , Útero/patologia , População Branca , Estudos de Coortes , Estradiol/sangue , Feminino , Humanos , Leiomioma/cirurgia , Modelos Logísticos , Estudos Longitudinais , Pessoa de Meia-Idade , Tamanho do Órgão , Dor/etnologia , Testosterona/sangue , Neoplasias Uterinas/cirurgia , Prolapso Uterino/etnologia
18.
J Clin Endocrinol Metab ; 93(3): 861-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18160467

RESUMO

CONTEXT: Rates of bone loss across the menopause transition and factors associated with variation in menopausal bone loss are poorly understood. OBJECTIVE: Our objective was to assess rates of bone loss at each stage of the transition and examine major factors that modify those rates. DESIGN, SETTING, AND PARTICIPANTS: We conducted a longitudinal cohort study of 1902 African-American, Caucasian, Chinese, or Japanese women participating in The Study of Women's Health Across the Nation. Women were pre- or early perimenopausal at baseline. OUTCOME MEASURE: We assessed bone mineral density (BMD) of the lumbar spine and total hip across a maximum of six annual visits. RESULTS: There was little change in BMD during the pre- or early perimenopause. BMD declined substantially in the late perimenopause, with an average loss of 0.018 and 0.010 g/cm2.yr from the spine and hip, respectively (P<0.001 for both). In the postmenopause, rates of loss from the spine and hip were 0.022 and 0.013 g/cm2.yr, respectively (P<0.001 for both). During the late peri- and postmenopause, bone loss was approximately 35-55% slower in women in the top vs. the bottom tertile of body weight. Apparent ethnic differences in rates of spine bone loss were largely explained by differences in body weight. CONCLUSIONS: Bone loss accelerates substantially in the late perimenopause and continues at a similar pace in the first postmenopausal years. Body weight is a major determinant of the rate of menopausal BMD loss, whereas ethnicity, per se, is not. Healthcare providers should consider this information when deciding when to screen women for osteoporosis.


Assuntos
Densidade Óssea , Menopausa/etnologia , Negro ou Afro-Americano , Povo Asiático , Peso Corporal , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , População Branca
19.
BMC Mol Biol ; 9: 46, 2008 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-18460208

RESUMO

BACKGROUND: Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Quantitative real-time PCR (RT qPCR) is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. RESULTS: The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], beta-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA]) in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan(R) Gene Expression Assays). Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. CONCLUSION: This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.


Assuntos
Encéfalo/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Humanos , RNA/metabolismo , Padrões de Referência , Reprodutibilidade dos Testes , Software
20.
Am J Epidemiol ; 167(8): 935-43, 2008 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-18250080

RESUMO

Physical functioning measures are considered integrated markers of the aging process. This prospective investigation examined relations between dietary intake of women at midlife in 1996-1997 and prevalence of physical functioning limitations 4 years later, defined by the Medical Outcomes Study Short-Form 36. The sample included 2,160 multiethnic women, aged 42-52 years, from six geographic areas participating in the Study of Women's Health Across the Nation (SWAN). Associations between measures of diet quality and number of fruit and vegetable servings and prevalent physical functional limitations (no, moderate, or substantial limitations) were tested by logistic regression. The prevalence of moderate and substantial functional limitations was 31% and 10%, respectively. Women in the highest quartile of cholesterol intake had 40% greater odds (odds ratio = 1.4, 95% confidence interval: 1.1, 1.8) of being more limited versus those in the lowest quartile. Women in the highest quartile of fat and saturated fat intakes were 50% and 60% more likely to be more limited, with respective odds ratios of 1.5 and 1.6 (95% confidence intervals: 1.2, 2.0 and 1.2, 2.1) versus those in the lowest quartiles. Lower fruit, vegetable, and fiber intakes were related to reporting greater functional limitations. Modifying dietary practices could be important in minimizing physical limitations.


Assuntos
Envelhecimento/fisiologia , Dieta , Nível de Saúde , Estado Nutricional , Adulto , Fatores Etários , Algoritmos , Gorduras na Dieta/administração & dosagem , Feminino , Frutas , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos Nutricionais , Razão de Chances , Prevalência , Inquéritos e Questionários , Verduras
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