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1.
J Headache Pain ; 23(1): 85, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864440

RESUMO

BACKGROUND AND AIM: Headache attributed to intracranial endovascular procedures is described in the ICHD-3. Our aim was to study the frequency and characteristics of headache specifically related to thrombectomy in patients with ischemic stroke. METHODS: Prospective evaluation of clinical features of headache after thrombectomy using an ad hoc questionnaire. RESULTS: One hundred seventeen patients were included (52.1% females). Most had an anterior circulation artery occlusion (91.5%). 93 (79.5%) received general anaesthesia. 111 (94.9%) required stent retriever, 21 (24.4%) angioplasty and 19 (16.2%) aspiration thrombectomy. 31 (26.5%; 95% CI 18.8-35.5%) had headache related to thrombectomy, and it was associated with a history of primary headache (p = 0.004). No differences about sex, initial NIHSS score, or the type or complexity of the procedure were observed. Headache was usually moderate and oppressive, ipsilateral to the artery occlusion and usually lasted less than 48 hours. CONCLUSIONS: Almost one-third of patients with ischemic stroke who undergo endovascular thrombectomy experience headache in the first 24 hours, occurring more frequently in patients who had a previous history of headaches regardless of the procedure complexity.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/cirurgia , Procedimentos Endovasculares/métodos , Feminino , Cefaleia/etiologia , Cefaleia/cirurgia , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/cirurgia , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Resultado do Tratamento
2.
Cerebrovasc Dis ; 50(3): 303-309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730721

RESUMO

INTRODUCTION: Mediterranean diet (MeDiet) has been associated with lower risk of stroke. Additionally, animal models suggested that some components of MeDiet are associated with better outcomes after ischemic stroke (IS). We aimed to evaluate the association between global adherence to the MeDiet and the consumption of particular components of the MeDiet with stroke outcomes. MATERIAL AND METHODS: Multicenter observational study of consecutive IS patients treated with endovascular therapy. Inclusion criteria were large anterior circulation vessel occlusion and pre-stroke modified Rankin scale (mRS) <2. Adherence to MeDiet prior to stroke was evaluated using MEDAS 14-item scale. We evaluated the total score and also individual components of the scale. Clinical, radiological, and prognostic variables were collected. Good functional prognosis was considered as mRS ≤2 and complete recanalization as thrombolysis in cerebral infarction 3. RESULTS: From January 1 to October 30, 2018, 239 patients were included (mean age 71 years, 48% women, median baseline NIHSS 16). Median MEDAS scale was 8 points (7-10). Patients with a higher adherence to MeDiet had significantly lower total and LDL-cholesterol levels. Total adherence score was not associated with stroke outcomes. In multivariate analyses, consumption of olive oil as the principal source of fat was independently associated with good functional outcome at 3 months, OR 3.2 (1.1-10.1) and daily consumption of wine was independently associated with complete recanalization, OR 2.0 (1.1-3.8). CONCLUSIONS: Our study suggests that some components of MeDiet, such as olive oil and wine consumption, are related to better prognosis after stroke. More studies are needed to confirm these findings.


Assuntos
Dieta Mediterrânea , Procedimentos Endovasculares , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Azeite de Oliva , Cooperação do Paciente , Estudos Prospectivos , Espanha , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vinho
3.
Cephalalgia ; 36(6): 552-60, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26395894

RESUMO

BACKGROUND AND OBJECTIVE: Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. METHODS: Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. RESULTS: A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p = 0.031), and increased cIMT (p = 0.028). Fibrinogen (r = 0.277; p = 0.006), C-reactive protein (r = 0.288; p = 0.003), and erythrocyte rate sedimentation (r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. CONCLUSIONS: Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.


Assuntos
Endotélio Vascular/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Doenças Vasculares/fisiopatologia , Adolescente , Adulto , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Doenças Vasculares/complicações , Rigidez Vascular , Vasodilatação , Adulto Jovem
4.
Cephalalgia ; 33(4): 236-44, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23223547

RESUMO

BACKGROUND: Migraine has been considered a vascular risk factor especially in young women. Factors predisposing to endothelial damage in migraine are still being debated. The insufficiency of circulating endothelial precursor circulating cells (EPCs) suggested a link between migraine and cardiovascular risk. This research aimed to study a subtype of EPCs, those expressing e-selectin, to assess endothelial activation and, therefore, endothelial dysfunction in migraine. METHODS: Consecutive headache patients (n = 99) and 35 adjusted controls were recruited. Total EPCs, defined as CD34+/KDR+ cells, and EPC colony-forming units (CFUs) were assayed. We identified as "early" EPCs those CD62E- EPCs, and "late" EPCs, CD62E+, a surrogate marker for endothelial damage. Plasmatic calcitonin-gene related protein (CGRP) and vascular-endothelial growth factor (VEGF) were analyzed. RESULTS: We did not find differences in the total number of CFUs among clinical groups. Means of total CD34+/KDR+ and "early" EPCs were not significant among clinical groups. Nevertheless, the mean of "late" EPCs was lower (log(10)-transformed mean = 1.715; SD = 0.393) in the control group than in the migraine patients (log(10)-transformed mean = 2.167; SD = 0.685), even after adjustment by VEGF plasma level and other confounding factors. Linear regression analyses disclosed significant predictors for "late" EPCs for controls vs migraine (ß = 0.452 SE ± 0.13; p = 0.001). We did not observe differences between migraine with or without aura. CONCLUSION: We observed higher number of activated EPCs in migraine patients than in controls. CD62E+ EPCs might be considered a marker for vascular damage in migraine patients.


Assuntos
Endotélio Vascular/citologia , Transtornos de Enxaqueca/patologia , Células-Tronco/citologia , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Rev Neurol ; 62(5): 203-10, 2016 Mar 01.
Artigo em Espanhol | MEDLINE | ID: mdl-26916323

RESUMO

INTRODUCTION: After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. AIM: To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). PATIENTS AND METHODS: We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc <= 70 mg/dL and/or reduction in LDLc >= 50%. Furthermore, safety parameters were assessed. RESULTS: Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. CONCLUSIONS: Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated.


TITLE: Utilidad del tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg frente a atorvastatina 80 mg en la reduccion de los niveles de colesterol LDL en pacientes con ictus isquemico o ataque isquemico transitorio.Introduccion. Tras un ictus isquemico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones mas intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg mas ezetimiba 10 mg tras un ictus isquemico o ataque isquemico transitorio (AIT). Pacientes y metodos. Evaluacion de la eficacia del tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificacion de parametros lipidicos tras un ictus isquemico o AIT. Se establecio como objetivo primario la obtencion de niveles de LDLc <= 70 mg/dL o la reduccion de las cifras de LDLc >= 50%. Adicionalmente se evaluo la presencia de efectos secundarios en ambos grupos. Resultados. Se observo un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg mas ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p < 0,001), colesterol total (p = 0,001) y no HDLc (p < 0,001). Ambos tratamientos fueron seguros, con escaso numero de efectos secundarios. Conclusiones. En comparacion con atorvastatina 80 mg, el tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg incrementa la probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados.


Assuntos
Atorvastatina/administração & dosagem , Isquemia Encefálica/sangue , Isquemia Encefálica/prevenção & controle , LDL-Colesterol/sangue , Ezetimiba/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/prevenção & controle , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/prevenção & controle , Anticolesterolemiantes , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Neurosci Lett ; 332(3): 213-5, 2002 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-12399017

RESUMO

Alzheimer's disease (AD) and prion diseases are associated with the occurrence of protein aggregates called amyloid fibrils, containing the amyloid-beta peptide in AD, and a modified form (PrP(Sc)) of the normal cellular prion protein (PrP(c)) in prion diseases. PrP(c) is encoded by the prion protein gene, and a common polymorphism at codon 129 of this gene is a determinant of susceptibility to acquired and sporadic prion diseases but not for sporadic AD. A recently identified novel protein, named Doppel, shares biochemical and structural homology with PrP(c). Preliminary evidence in a German population indicates that a polymorphism at codon 174 of the prion-like protein (PRND) gene encoding for Doppel protein is a predisposing factor for both prion diseases and sporadic AD. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 288 control subjects was performed to test this association. The current study does not demonstrate any significant difference in T174M PRND genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that the PRND gene is causally related to AD.


Assuntos
Doença de Alzheimer/genética , Códon/genética , Polimorfismo Genético/genética , Proteínas PrPSc/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Apolipoproteínas E/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia
8.
Neurology ; 80(7): 621-6, 2013 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-23325906

RESUMO

OBJECTIVE: To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2 G2019S mutation (AsG2019S+). METHODS: These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2 G2019S mutation (AsG2019S-), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls. RESULTS: Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S- also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S- (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%. CONCLUSIONS: Independently of age at examination, the most frequently altered premotor biomarker in LRRK2 G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.


Assuntos
Predisposição Genética para Doença , Mutação/genética , Transtornos do Olfato/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Distribuição de Qui-Quadrado , Estudos de Coortes , Estudos Transversais , Análise Mutacional de DNA , Feminino , Glicina/genética , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Nortropanos/farmacocinética , Transtornos do Olfato/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Serina/genética , Índice de Gravidade de Doença , Olfato/genética , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Ultrassonografia Doppler Transcraniana
11.
Rev. neurol. (Ed. impr.) ; 62(5): 203-210, 1 mar., 2016. tab, graf, ilus
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-148785

RESUMO

Introducción. Tras un ictus isquémico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones más intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg más ezetimiba 10 mg tras un ictus isquémico o ataque isquémico transitorio (AIT). Pacientes y métodos. Evaluación de la eficacia del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificación de parámetros lipídicos tras un ictus isquémico o AIT. Se estableció como objetivo primario la obtención de niveles de LDLc ≤ 70 mg/dL o la reducción de las cifras de LDLc ≥ 50%. Adicionalmente se evaluó la presencia de efectos secundarios en ambos grupos. Resultados. Se observó un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg más ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg más ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p < 0,001), colesterol total (p = 0,001) y no HDLc (p < 0,001). Ambos tratamientos fueron seguros, con escaso número de efectos secundarios. Conclusiones. En comparación con atorvastatina 80 mg, el tratamiento con atorvastatina 40 mg más ezetimiba 10 mg incrementa la probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados (AU)


Introduction. After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. Aim. To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). Patients and methods. We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc ≤ 70 mg/dL and/or reduction in LDLc ≥ 50%. Furthermore, safety parameters were assessed. Results. Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. Conclusions. Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lipoproteínas LDL , LDL-Colesterol/administração & dosagem , LDL-Colesterol , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento , Avaliação de Eficácia-Efetividade de Intervenções , Estudos Retrospectivos , Modelos Logísticos
12.
Headache ; 44(5): 436-7, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15147251

RESUMO

A 14-year-old adolescent was seen with an 8-month history of almost daily incapacitating headaches due to idiopathic intracranial hypertension in Behçet syndrome. All his clinical signs and symptoms, including headache, resolved 2 to 4 weeks after topiramate was initiated. An effect on carbonic anhydrase isoenzymes II and IV, reducing cerebrospinal fluid production, could potentially explain the beneficial effect of topiramate in intracranial hypertension. Further studies are necessary, however, to confirm the significance of topiramate in this indication.


Assuntos
Anticonvulsivantes/uso terapêutico , Síndrome de Behçet/complicações , Frutose/análogos & derivados , Frutose/uso terapêutico , Cefaleia/tratamento farmacológico , Pseudotumor Cerebral/complicações , Adolescente , Cefaleia/etiologia , Humanos , Masculino , Topiramato
13.
Am J Med Genet B Neuropsychiatr Genet ; 126B(1): 66-8, 2004 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15048650

RESUMO

Activation of microglia is a central part of the chronic inflammatory response in Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is a cell surface receptor that may act in AD to adhere microglia to beta amyloid fibrils within senile plaques. Preliminary evidence in an Italian population indicates that a polymorphism at codon 469 of the ICAM-1 gene is a predisposing factor for sporadic AD. Another group has been unable to replicate this association in a Finnish population. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 283 control subjects was performed to test this association in an ethnically homogeneous population from Spain. The current study does not demonstrate any significant difference in E469K genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that polymorphism at codon 469 of the ICAM-1 gene is causally related to AD.


Assuntos
Doença de Alzheimer/genética , Códon/genética , Molécula 1 de Adesão Intercelular/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia
14.
Dement Geriatr Cogn Disord ; 16(3): 132-5, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12826738

RESUMO

A vigorous controversy exists over whether tau tangles or amyloid-beta plaques are the primary cause of neurodegeneration in Alzheimer's disease (AD), and it is not well established whether genetic variation in tau is associated with AD. A recently identified novel protein, named Saitohin (STH), shares tissue expression pattern with tau, and preliminary evidence in a North American population indicates that a polymorphism at codon 7 (Q7R) of the STH gene is a predisposing factor for sporadic AD. A case-control study utilizing a clinically well-defined group of 315 sporadic AD patients and 307 control subjects was performed to test this association. The current study reveals that increased risk of AD associated with the STH RR genotype (OR 2.17, p = 0.04) is limited to late-onset (after the age of 72 years) AD cases.


Assuntos
Envelhecimento/genética , Doença de Alzheimer/genética , Proteínas tau/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Apolipoproteína E4 , Apolipoproteínas E/genética , Estudos de Casos e Controles , Códon , Feminino , Dosagem de Genes , Frequência do Gene , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético
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