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1.
J Psychohist ; 44(3): 178-99, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29443482

RESUMO

In the psychohistory of the antebellum South, the extent of child abuse in slaveholder families is important for understanding how members of the southern elite were reared and the extent to which they were infected with the toxic residue of their elders' passions and rages. It is argued that the Old South was a developing region, rather than an already developed one. Consequently, the rate of child abuse that is characteristic of contemporary postindustrial societies is not the proper paradigm for conceptualizing the abuse rate in slaveholder families. It is proposed instead that the rate of child abuse in contemporary developing societies is a better fit for estimating abuse in the antebellum South. Societal and familial variables impinging on the abuse of slaveholder children­corporal punishment, alcohol consumption, hyper-masculinity, a traumatogenic culture of violence, wife abuse, maternal ambivalence and neglect, miscegenation and incest are discussed, as is the likelihood of maltreatment by slaves. Using a study of child abuse across 28 nations, tentative rates of abuse are proposed.


Assuntos
Maus-Tratos Infantis/história , Escravização/história , Maus-Tratos Conjugais/história , Consumo de Bebidas Alcoólicas/história , Consumo de Bebidas Alcoólicas/psicologia , Criança , Maus-Tratos Infantis/psicologia , Escravização/psicologia , Feminino , História do Século XIX , Humanos , Incesto/história , Incesto/psicologia , Masculino , Masculinidade/história , Comportamento Materno/história , Comportamento Materno/psicologia , Relações Pais-Filho , Poder Familiar , Trauma Psicológico/psicologia , Maus-Tratos Conjugais/psicologia , Estados Unidos , Violência/psicologia
2.
J Psychohist ; 44(1): 2-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27480011

RESUMO

Examining the inner workings of the slaveholder family, including slave caretakers, this article probes the psychodynamics of slaveholder development to assess the extent of child abuse in the Old South. Childcare was haphazard and premised on paternal absence, maternal ambivalence, and the exigencies of slave surrogacy. Corporal punishment, sanctified by southern religion, was the rule. The likelihood of slave negligence and retaliatory attacks against slaveholder children are addressed. Childrearing practices such as swaddling, aunt adoption, and maternal incest are considered, as well as the possible usage of a West African cleansing ritual. The article classifies planter families within the Ambivalent Mode of parent-child relations and suggests the restaging of childhood trauma as the underlying dynamic in the march to civil war.


Assuntos
Maus-Tratos Infantis/história , Pessoas Escravizadas/história , Escravização/história , Poder Familiar/história , Punição/história , Criança , Cristianismo/história , Escravização/psicologia , Feminino , Identidade de Gênero , História do Século XIX , Humanos , Masculino , Relações Pais-Filho , Poder Familiar/psicologia , Sudeste dos Estados Unidos
3.
J Psychohist ; 43(3): 167-86, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26856182

RESUMO

This article examines the macroscopic reasons for maternal rage and its injection into slaveholder children in the antebellum South. It is argued that the misogyny that infected antebellum life metastasized in southern mistresses and affected the way they felt about themselves and their children. As mothers, they were casual parents, concerned with molding the character of their charges, rearing warriors and proper ladies, but uninterested in caring for them and helping them realize their own aspirations. It is argued that the misanthropic rage that they injected into their children constituted the poison that each generation of slaveholders had to ventilate into poison containers, slaves, as a homeostatic means of psycho-emotional survival. This intergenerational process of poison injection--from father to mother, from mother to child, from child to slave, constituted the process that insured the perpetuation of the psychic structure necessary for the continuation of slavery from generation to generation.


Assuntos
Escravização/história , Racismo/história , Sexismo/história , Adolescente , Adulto , Idoso , Criança , Educação Infantil/psicologia , Pré-Escolar , Escravização/psicologia , Família/psicologia , Feminino , História do Século XVII , História do Século XVIII , História do Século XIX , Humanos , Masculino , Pessoa de Meia-Idade , Poder Familiar/psicologia , Racismo/psicologia , Sexismo/psicologia , Estados Unidos , Adulto Jovem
4.
J Psychohist ; 44(2): 114-36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29442486

RESUMO

The inability of contemporary society to transition from fossil fuels to green energy was engineered by the oil industry, which has worked for decades to stifle the emergence of ecological awareness. Climate change presents a clear and present danger to our society. The present dilemma is the result of the psychopathic corporate system, that pillages the earth for profit (extractivism), evades the real costs of production (externalizing costs), and pursues only self-interest (the best interests of the corporation). The well-being of the environment is thereby sacrificed for profit and our collective future is jeopardized. The corporate practice of creative destruction has gained such Thanatos-like momentum that it threatens the earth in its obsession with profit. Conservatives, under the sway of the unreality principle, dismiss climate change and block efforts to solve climate issues. For them, science is wish fulfillment based on denial. Their willingness to endanger the world results from their authoritarian upbringing. The corporal punishment they endured as children left a residue of rage­the impulse to destroy life­that underlies corporate rationality's assault on the environment. Fearing death, they inflict death in a perverse ritual to feel alive. Compensating for the narcissistic wounds of childhood through the formation of a grandiose self, they are identified with the omnipotent parent, and alternate between suicidal impulse and escape via godlike technology. Conservative attacks on women highlight the residual wounds of relatedness to their dragon mothers, just as their relatedness to the environment involves a restaging of their encounters with their breast and toilet mothers. Solving environmental problems, however, will require more than overcoming conservative intransigence. The concept of ecological debt accentuates the importance of consumer choice for the environment. The United Nations Human Development Report 2015 regarding CO2 emissions demonstrates the massive environmental debt of Northern Hemisphere societies and suggests the magnitude of the transformation necessary to resolve the problem of climate change.


Assuntos
Mudança Climática/história , Planeta Terra , Autoritarismo , História do Século XX , História do Século XXI , Humanos , Narcisismo
5.
Prev Med ; 72: 126-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25565483

RESUMO

OBJECTIVE: Describe the prevalence of colonoscopy before age 50, when guidelines recommend initiation of colorectal cancer screening for average risk individuals. METHOD: We assembled administrative health records that captured receipt of colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old members of four US health plans and used backward recurrence time models to estimate trends in receipt of colonoscopy before age 50 and variation in early colonoscopy by age and sex. We also used self-reported receipt of colonoscopy from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview Survey (NHIS) to estimate the association between early colonoscopy and sex, race/ethnicity, and geographic location based on logistic regression models that accounted for the complex NHIS sampling design. RESULTS: About 5% of the health plan cohort had a record of colonoscopy before age 50. Receipt of early colonoscopy increased significantly from 1999 to 2010 (test for linear trend, p<0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in the east coast health plan compared to west coast and Hawaii plans. The NHIS analysis found that early colonoscopy was more likely in Northeastern residents compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39). CONCLUSION: Colonoscopy before age 50 is increasingly common.


Assuntos
Neoplasias do Colo/prevenção & controle , Colonoscopia/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Adulto , Fatores Etários , Estudos de Coortes , Neoplasias do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Estados Unidos
6.
J Psychohist ; 43(2): 110-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26462403

RESUMO

"Psychohistory and Slavery: Preliminary Issues," begins an examination of slavery in the antebellum South. The paper suggests that how slavery and the group-fantasy of white male supremacy were perpetuated among slaveholders is a question of fundamental importance for psychohistorians. The family and childrearing are the focus of attention. Given the ferocity of slavery, it is argued that the psychological and emotional consequences of this barbarism were not limited to the slaves themselves, but had significant impact on the slaveholders as well-their parenting, their children, and their children's parenting of the next generation. In each generation the trauma of slavery was injected into slaveholder children and became a fundamental component of elite Southern personality.


Assuntos
Escravização/história , Racismo/história , Sexismo/história , Adolescente , Adulto , Idoso , Criança , Educação Infantil/psicologia , Pré-Escolar , Escravização/psicologia , Família/psicologia , História do Século XVIII , História do Século XIX , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Poder Familiar/psicologia , Racismo/psicologia , Sexismo/psicologia , Estados Unidos , Adulto Jovem
7.
Am J Epidemiol ; 179(2): 135-44, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24173550

RESUMO

Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and Health Study is an observational cohort study of US men and women who were aged 50-71 years at entry in 1995-1996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years' follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 50-69 years.


Assuntos
Índice de Massa Corporal , Mortalidade , Aumento de Peso , Adiposidade , Adolescente , Adulto , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Risco , Fumar/epidemiologia , Fumar/mortalidade , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem
8.
BMC Cancer ; 14: 95, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24529031

RESUMO

BACKGROUND: Accurate indication classification is critical for obtaining unbiased estimates of colonoscopy effectiveness and quality improvement efforts, but there is a dearth of published systematic classification approaches. The objective of this study was to evaluate the effects of data-source and adjudication on indication classification and on estimates of the effectiveness of screening colonoscopy on late-stage colorectal cancer diagnosis risk. METHODS: This was an observational study in members of four U.S. health plans. Eligible persons (n = 1039) were age 55-85 and had been enrolled for 5 years or longer in their health plans during 2006-2008. Patients were selected based on late-stage colorectal cancer diagnosis in a case-control design; each case patient was matched to 1-2 controls by study site, age, sex, and health plan enrollment duration. Reasons for colonoscopies received in the 10-year period before the reference date were collected from three medical records sources (progress notes; referral notes; procedure reports) and categorized using an algorithm, with committee adjudication of some tests. We evaluated indication classification concordance before and after adjudication and used logistic regressions with the Wald Chi-square test to compare estimates of the effects of screening colonoscopy on late-stage colorectal cancer diagnosis risk for each of our data sources to the adjudicated indication. RESULTS: Classification agreement between each data-source and adjudication was 78.8-94.0% (weighted kappa = 0.53-0.72); the highest agreement (weighted kappa = 0.86-0.88) was when information from all data sources was considered together. The choice of data-source influenced the association between screening colonoscopy and late-stage colorectal cancer diagnosis; estimates based on progress notes were closest to those based on the adjudicated indication (% difference in regression coefficients = 2.4%, p-value = 0.98), as compared to estimates from only referral notes (% difference in coefficients = 34.9%, p-value = 0.12) or procedure reports (% difference in coefficients = 27.4%, p-value = 0.23). CONCLUSION: There was no single gold-standard source of information in medical records. The estimates of colonoscopy effectiveness from progress notes alone were the closest to estimates using adjudicated indications. Thus, the details in the medical records are necessary for accurate indication classification.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/classificação , Neoplasias Colorretais/diagnóstico , Bases de Dados Factuais , Detecção Precoce de Câncer/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Casos e Controles , Colonoscopia/normas , Bases de Dados Factuais/normas , Detecção Precoce de Câncer/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Ann Intern Med ; 158(5 Pt 1): 312-20, 2013 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-23460054

RESUMO

BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: Four U.S. health plans. PATIENTS: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. MEASUREMENTS: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. RESULTS: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. LIMITATION: The small number of screening colonoscopies affected the precision of the estimates. CONCLUSION: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Programas de Rastreamento , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colonoscopia/economia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/economia , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco , Sensibilidade e Especificidade , Sigmoidoscopia
10.
J Neurosci ; 32(43): 15181-92, 2012 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-23100439

RESUMO

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid ß peptide (Aß) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aß have been implicated as the synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD. However, it is still unknown how apoE impacts the process of Aß oligomerization. Here, we found that the level of Aß oligomers in APOE ε4/ε4 AD patient brains is 2.7 times higher than those in APOE ε3/ε3 AD patient brains, matched for total plaque burden, suggesting that apoE4 impacts the metabolism of Aß oligomers. To test this hypothesis, we examined the effect of apoE on Aß oligomer formation. Using both synthetic Aß and a split-luciferase method for monitoring Aß oligomers, we observed that apoE increased the level of Aß oligomers in an isoform-dependent manner (E2 < E3 < E4). This effect appears to be dependent on the ApoE C-terminal domain. Moreover, these results were confirmed using endogenous apoE isolated from the TBS-soluble fraction of human brain, which increased the formation of Aß oligomers. Together, these data show that lipidated apoE, especially apoE4, increases Aß oligomers in the brain. Higher levels of Aß oligomers in the brains of APOE ε4/ε4 carriers compared with APOE ε3/ε3 carriers may increase the loss of dendritic spines and accelerate memory impairments, leading to earlier cognitive decline in AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Encéfalo/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/farmacologia , Análise de Variância , Apolipoproteína E2/genética , Apolipoproteína E2/metabolismo , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Astrócitos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Fluorescência Verde/genética , Células HEK293/efeitos dos fármacos , Células HEK293/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Morfolinos/farmacologia , Fragmentos de Peptídeos/farmacologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transfecção
11.
Oecologia ; 173(2): 507-19, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23532583

RESUMO

Reciprocal subsidies between rivers and terrestrial habitats are common where terrestrial leaf litter provides energy to aquatic invertebrates while emerging aquatic insects provide energy to terrestrial predators (e.g., birds, lizards, spiders). We examined how aquatic insect emergence changed seasonally with litter from two foundation riparian trees, whose litter often dominates riparian streams of the southwestern United States: Fremont (Populus fremontii) and narrowleaf (Populus angustifolia) cottonwood. P. fremontii litter is fast-decomposing and lower in defensive phytochemicals (i.e., condensed tannins, lignin) relative to P. angustifolia. We experimentally manipulated leaf litter from these two species by placing them in leaf enclosures with emergence traps attached in order to determine how leaf type influenced insect emergence. Contrary to our initial predictions, we found that packs with slow-decomposing leaves tended to support more emergent insects relative to packs with fast-decomposing leaves. Three findings emerged. Firstly, abundance (number of emerging insects m(-2) day(-1)) was 25% higher on narrowleaf compared to Fremont leaves for the spring but did not differ in the fall, demonstrating that leaf quality from two dominant trees of the same genus yielded different emergence patterns and that these patterns changed seasonally. Secondly, functional feeding groups of emerging insects differed between treatments and seasons. Specifically, in the spring collector-gatherer abundance and biomass were higher on narrowleaf leaves, whereas collector-filterer abundance and biomass were higher on Fremont leaves. Shredder abundance and biomass were higher on narrowleaf leaves in the fall. Thirdly, diversity (Shannon's H') was higher on Fremont leaves in the spring, but no differences were found in the fall, showing that fast-decomposing leaves can support a more diverse, complex emergent insect assemblage during certain times of the year. Collectively, these results challenge the notion that leaf quality is a simple function of decomposition, suggesting instead that aquatic insects benefit differentially from different leaf types, such that some use slow-decomposing litter for habitat and its temporal longevity and others utilize fast-decomposing litter with more immediate nutrient release.


Assuntos
Biota , Cadeia Alimentar , Insetos/fisiologia , Populus/química , Animais , Arizona , Insetos/efeitos dos fármacos , Folhas de Planta/química , Rios , Especificidade da Espécie
12.
JAMA ; 310(2): 155-62, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23839749

RESUMO

IMPORTANCE: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES: Rates of coronary angiography, PCI, and CABG surgery. RESULTS: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.


Assuntos
Angiografia Coronária/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Planos de Pagamento por Serviço Prestado/estatística & dados numéricos , Medicare Part C/estatística & dados numéricos , Medicare/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Capitação , Estudos Transversais , Feminino , Geografia , Humanos , Masculino , Reembolso de Incentivo , Fatores Sexuais , Estados Unidos
13.
J Biol Chem ; 286(31): 27081-91, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21652708

RESUMO

Amyloid-ß peptide (Aß) is the amyloid component of senile plaques in Alzheimer disease (AD) brains. Recently a soluble oliomeric form of Aß in Aß precursor protein transgenic mouse brains and AD brains was identified as a potential causative molecule for memory impairment, suggesting that soluble Aß oligomers cause neurodegeneration in AD. Further characterization of this species has been hampered, however, because the concentrations are quite small and it is difficult to monitor Aß oligomers specifically. Here we developed a novel method for monitoring Aß oligomers using a split-luciferase complementation assay. In this assay, the N- and C-terminal fragments of Gaussia luciferase (Gluc) are fused separately to Aß. We found that conditioned media from both N- and C-terminal fragments of Gluc-tagged Aß1-42 doubly transfected HEK293 cells showed strong luminescence. We used gel filtration analyses to analyze the size of oligomers formed by the luciferase complementation assay, and found that it matched closely with oligomers formed by endogenous Aß in Tg2576 neurons. Large oligomers (24-36-mers), 8-mers, trimers, and dimers predominate. In both systems, Aß formed oligomers intracellularly, which then appear to be secreted as oligomers. We then evaluated several factors that might impact oligomer formation. The level of oligomerization of Aß1-40 was similar to that of Aß1-42. Homodimers formed more readily than heterodimers. The level of oligomerization of murine Aß1-42 was similar to that of human Aß1-42. As expected, the familial AD-linked Arctic mutation (E22G) significantly enhanced oligomer formation. These data suggest that Gluc-tagged Aß enables the analysis of Aß oligomers.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Biopolímeros/metabolismo , Teste de Complementação Genética , Luciferases/genética , Peptídeos beta-Amiloides/genética , Sequência de Bases , Biopolímeros/genética , Western Blotting , Linhagem Celular , Cromatografia em Gel , Primers do DNA , DNA Complementar , Ensaio de Imunoadsorção Enzimática , Humanos
14.
Am J Epidemiol ; 176(12): 1130-40, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23186750

RESUMO

The authors investigated the relations of body mass index at different ages and adult weight change to incident colorectal cancer risk in the prospective National Institutes of Health-AARP Diet and Health Study (1995-1996), using a subcohort with repeated recall weights (273,679 participants; mean baseline age = 62.8 years). During 2,509,662 person-years follow-up, 4076 incident colorectal cancers were ascertained. For men, an increased risk of colon cancer but not rectal cancer was associated with body mass index at baseline age (per 5-kg/m(2) increase, hazard ratio (HR) = 1.18, 95% confidence interval (CI): 1.11, 1.25), at age 50 years (HR = 1.18, 95% CI: 1.10, 1.26), and at age 35 years (HR = 1.16, 95% CI: 1.07, 1.25) but less so at age 18 years. Weight gained between the ages of 18 and 35 years and between 18 years of age and the baseline age was associated with an increased risk of colon cancer in men (per 0.5-kg/year increase, HR = 1.18, 95% CI: 1.11, 1.25 and HR = 1.29, 95% CI: 1.16, 1.56, respectively). For women, relations throughout were weaker than those observed for men. These findings suggest that weight gains during early to middle adulthood have important influences on colon cancer risk, especially in men.


Assuntos
Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Aumento de Peso , Adolescente , Adulto , Distribuição por Idade , Idoso , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Distribuição por Sexo , Estados Unidos/epidemiologia
15.
Proc Natl Acad Sci U S A ; 106(10): 4012-7, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19228947

RESUMO

Synapse loss correlates with a cognitive decline in Alzheimer's disease (AD), but whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid beta (Abeta) is controversial. By using array tomography, a technique that combines ultrathin sectioning of tissue with immunofluorescence, allowing precise quantification of small structures, such as synapses, we have tested the hypothesis that oligomeric Abeta surrounding plaques contributes to synapse loss in a mouse model of AD. We find that senile plaques are surrounded by a halo of oligomeric Abeta. Analysis of >14,000 synapses (represented by PSD95-stained excitatory synapses) shows that there is a 60% loss of excitatory synapses in the halo of oligomeric Abeta surrounding plaques and that the density increases to reach almost control levels in volumes further than 50 microm from a plaque in an approximately linear fashion (linear regression, r(2) = 0.9; P < 0.0001). Further, in transgenic cortex, microdeposits of oligomeric Abeta associate with a subset of excitatory synapses, which are significantly smaller than those not in contact with oligomeric Abeta. The proportion of excitatory synapses associated with Abeta correlates with decreasing density (correlation, -0.588; P < 0.0001). These data show that senile plaques are a potential reservoir of oligomeric Abeta, which colocalizes with the postsynaptic density and is associated with spine collapse, reconciling the apparently competing schools of thought of "plaque" vs. "oligomeric Abeta" as the synaptotoxic species in the brain of AD patients.


Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Potenciais Pós-Sinápticos Excitadores , Placa Amiloide/metabolismo , Sinapses/metabolismo , Animais , Camundongos , Estrutura Quaternária de Proteína , Tomografia
16.
Clin Exp Ophthalmol ; 39(1): 37-46, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20662845

RESUMO

BACKGROUND: The study of the clinical and electrophysiological effects of eye muscle surgery on patients with infantile nystagmus has broadened our knowledge of the disease and its interventions. DESIGN: Prospective, comparative, interventional case series. PARTICIPANTS: Twenty-four patients with a vertical head posture because of electrophysiologically diagnosed infantile nystagmus syndrome. The ages ranged from 2.5 to 38 years and follow up averaged 14.0 months. METHODS: Thirteen patients with a chin-down posture had a bilateral superior rectus recession, inferior oblique myectomy and a horizontal rectus recession or tenotomy. Those 11 with a chin-up posture had a bilateral superior oblique tenectomy, inferior rectus recession and a horizontal rectus recession or tenotomy. MAIN OUTCOME MEASURES: Outcome measures included: demography, eye/systemic conditions and preoperative and postoperative; binocular, best optically corrected, null zone acuity, head posture, null zone foveation time and nystagmus waveform changes. RESULTS: Associated conditions were strabismus in 66%, ametropia in 96%, amblyopia in 46% and optic nerve, foveal dysplasia or albinism in 54%. Null zone acuity increased at least 0.1 logMAR in 20 patients (P < 0.05 group mean change). Patients had significant (P < 0.05) improvements in degrees of head posture, average foveation time in milliseconds and infantile nystagmus syndrome waveform improvements. CONCLUSIONS: This study illustrates a successful surgical approach to treatment and provides expectations of ocular motor and visual results after vertical head posture surgery because of an eccentric gaze null in patients with infantile nystagmus syndrome.


Assuntos
Nistagmo Congênito/cirurgia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Postura , Adolescente , Adulto , Criança , Pré-Escolar , Movimentos Oculares , Cabeça , Humanos , Nistagmo Congênito/fisiopatologia , Músculos Oculomotores/fisiopatologia , Estudos Prospectivos , Tenotomia , Resultado do Tratamento , Visão Binocular/fisiologia , Acuidade Visual/fisiologia , Adulto Jovem
17.
J Psychohist ; 44(2): 170-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29443481
19.
Am J Epidemiol ; 179(11): 1403-4, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24786798
20.
N Engl J Med ; 355(8): 763-78, 2006 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-16926275

RESUMO

BACKGROUND: Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. METHODS: We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health-AARP cohort who were 50 to 71 years old at enrollment in 1995-1996. BMI was calculated from self-reported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status. RESULTS: During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated. CONCLUSIONS: Excess body weight during midlife, including overweight, is associated with an increased risk of death.


Assuntos
Obesidade/mortalidade , Sobrepeso , Idoso , Índice de Massa Corporal , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco , Magreza/mortalidade , Estados Unidos/epidemiologia
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