RESUMO
The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.
Assuntos
Doença de Alzheimer/genética , Cromossomos Humanos Par 9/genética , Ligação Genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Proteína C9orf72/genética , Hispânico ou Latino/genética , Humanos , Proteínas do Tecido Nervoso/genética , Sequenciamento Completo do GenomaRESUMO
OBJECTIVE: To determine what ocular symptoms and signs are most common and if there are any associations with comorbid conditions in patients with Chikungunya fever. METHODS: A retrospective data review and analysis of the ocular symptomatology of 139 patients with Chikungunya fever who visited a local emergency room from August through September 2014. Frequencies were calculated, and Pearson's chisquare test employed. All the patients were confirmed as having Chikungunya with IgM (ELISA) before admittance into the study. RESULTS: Of the 139 patients, 42 (30.2%) had red eyes, 27 (19.4%) had conjunctivitis, and 13 (9.4%) had symptoms related to anterior uveitis, such as unilateral red eye, ciliary flush, or irregular pupil(s). Patients with a history of diabetes, hypertension, or cancer were more likely to have both red eyes (p = 0.033) and the symptomatology of anterior uveitis (p = 0.006), while patients with nausea or vomiting were more likely to have red eyes only (p = 0.001). CONCLUSIONS AND RELEVANCE: Red eyes, conjunctivitis, and anterior uveitis occur frequently in patients with Chikungunya fever. Systemic diseases, such as diabetes, hypertension, and cancer, may increase the risk of such ocular manifestations. Routine ophthalmic evaluation is warranted in patients with these medical conditions. The relevance of this study lies in the fact that this disease remains an important public health issue, since such ocular sequelae as may be present can range from mild to severe, either as an acute or a delayed manifestation.
Assuntos
Febre de Chikungunya/complicações , Conjuntivite Viral/epidemiologia , Infecções Oculares Virais/epidemiologia , Uveíte Anterior/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Conjuntivite Viral/virologia , Serviço Hospitalar de Emergência , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Virais/virologia , Feminino , Humanos , Imunoglobulina M/imunologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Porto Rico , Estudos Retrospectivos , Fatores de Risco , Uveíte Anterior/virologia , Adulto JovemRESUMO
The effect of vitamin C in cancer has been a subject of great controversy; mainly because of the inconsistent results obtained by oral intakes of ascorbate when used as an anticancer agent. We believe the intravenous application of ascorbate will provide more consistent results in cancer patients since Vitamin C blood levels attained are substantially higher in a range proven cytotoxic to malignant cells. In this article we will present and discuss our proposed mechanism on the chemotherapeutic activity exhibited by ascorbate.
Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Neoplasias/tratamento farmacológico , Terapia Ortomolecular , Humanos , Injeções IntravenosasRESUMO
The effect of vitamin C in cancer has been a subject of great controversy; mainly because of the inconsistent results obtained by oral intakes of ascorbate when used as an anticancer agent. We believe the intravenous application of ascorbate will provide more consistent results in cancer patients since Vitamin C blood levels attained are substantially higher in a range proven cytotoxic to malignant cells. In this article we will present and discuss our proposed mechanism on the chemotherapeutic activity exhibited by ascorbate.