RESUMO
Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will expand the range of potential treatment options and enable better control of disease progression. Epigenetic dysregulation has been implicated in the pathogenesis of microvascular complications in patients with T2DM. We sought to explore the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for DR, taking advantage of a highly sensitive technique, the 5hmC-Seal. The genome-wide 5hmC profiles in cfDNA samples from 35 patients diagnosed with DR and 35 age-, gender-, diabetic duration-matched T2DM controls were obtained using the 5hmC-Seal, followed by a case-control analysis and external validation. The genomic distribution of 5hmC in cfDNA from patients with DR reflected potential gene regulatory relevance, showing co-localization with histone modification marks for active expression (e.g., H3K4me1). A three-gene signature (MESP1, LY6G6D, LINC01556) associated with DR was detected using the elastic net regularization on the multivariable logistic regression model, showing high accuracy to distinguish patients with DR from T2DM controls (AUC [area under curve] = 91.4%; 95% CI [confidence interval], 84.3- 98.5%), achieving a sensitivity of 88.6% and a specificity of 91.4%. In an external testing set, the 5hmC model detected 5 out of 6 DR patients and predicted 7 out of 8 non-DR patients with other microvascular complications. Circulating cfDNA from patients with DR contained 5hmC information that could be exploited for DR detection. As a novel non-invasive approach, the 5hmC-Seal holds the promise to be an integrated part of patient care and surveillance tool for T2DM patients.
Assuntos
5-Metilcitosina/análogos & derivados , Ácidos Nucleicos Livres/genética , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/genética , 5-Metilcitosina/metabolismo , Adulto , Idoso , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/sangue , Ácidos Nucleicos Livres/química , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Feminino , Humanos , Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genéticaRESUMO
Home and community-based services (HCBS) assist people with disabilities and older adults to remain in their homes. Direct support professionals and care managers who facilitate the development of support plans need to employ person-centered approaches to ensure services are tailored to peoples' needs and preferences. The aims were to identify the key competencies needed for delivery of person-centered supports and examine the relationship between HCBS and its' outcomes in the United States. We used the competencies developed by the National Center on advancing Person-Centered Practices and Systems as a framework. We conducted a systematic review to identify the skills necessary to deliver person-centered HCBS. We coded 43 articles and identified seven competencies. Most frequently mentioned competencies related to culturally informed practice, cultivating connections, and promoting rights, choice, and control. Policy makers should create training standards for person-centered practices to ensure that people receiving HCBS live the lives they want.
Assuntos
Pessoas com Deficiência , Serviços de Assistência Domiciliar , Humanos , Estados Unidos , Idoso , Serviços de Saúde ComunitáriaRESUMO
The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.