RESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons causing muscle atrophy and weakness. Nusinersen, the first effective SMA therapy was approved by Health Canada in June 2017 and has been added to the provincial formulary of all but one Canadian province. Access to this effective therapy has triggered the inclusion of SMA in an increasing number of Newborn Screening (NBS) programs. However, the range of disease-modifying SMN2 gene copy numbers encountered in survival motor neuron 1 (SMN1)-null individuals means that neither screen-positive definition nor resulting treatment decisions can be determined by SMN1 genotype alone. We outline an approach to this challenge, one that specifically addresses the case of SMA newborns with four copies of SMN2. OBJECTIVES: To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result. METHODS: An SMA NBS pilot trial in Ontario using first-tier MassARRAY and second-tier multi-ligand probe amplification (MLPA) was launched in January 2020. Prior to this, Ontario pediatric neuromuscular disease and NBS experts met to review the evidence regarding the diagnosis and treatment of children with SMA as it pertained to NBS. A post-referral evaluation algorithm was developed, outlining timelines for patient retrieval and management. CONCLUSIONS: Ontario's pilot NBS program has created a standardized path to facilitate early diagnosis of SMA and initiation of treatment. The goal is to provide timely access to those SMA infants in need of therapy to optimize motor function and prolong survival.
Assuntos
Atrofia Muscular Espinal , Triagem Neonatal , Diagnóstico Precoce , Seguimentos , Humanos , Recém-Nascido , OntárioAssuntos
Complexo I de Transporte de Elétrons , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Mitocondriais , Humanos , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/deficiência , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Doenças Mitocondriais/diagnóstico , Deleção de Sequência/genética , Masculino , Feminino , CriançaRESUMO
Newborn screening programs have expanded to include molecular-based assays as first-tier tests and the success of these assays depends on the quality and yield of DNA extracted from neonatal dried blood spots (DBS). To meet high throughput and rapid turnaround time requirements, newborn screening laboratories adopted rapid DNA extraction methods that produce crude extracts. Quantification of DNA in neonatal DBS is not routinely performed due to technical challenges; however, this may enhance the performance of assays that are sensitive to amounts of input DNA. In this study, we developed a novel high throughput method to quantify total DNA in DBS. It is based on specific acid-catalyzed depurination of DNA followed by mass spectrometric quantification of adenine. The amount of adenine was used to calculate DNA quantity per 3.2 mm DBS. Reference intervals were established using archived, neonatal DBS (n = 501) and a median of 130.6 ng of DNA per DBS was obtained, which is in agreement with literature values. The intra- and interday variations were <15%. The limits of detection and quantification were 12.5 and 37.8 nmol/L adenine, respectively. We demonstrated that DNA from neonatal DBS can be successfully quantified in high throughput settings using instruments currently deployed in NBS laboratories.
Assuntos
DNA/sangue , Teste em Amostras de Sangue Seco/métodos , DNA/química , Humanos , Recém-Nascido , Limite de Detecção , Triagem Neonatal/métodos , Espectrometria de Massas em TandemRESUMO
To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction.
Assuntos
Transplante de Medula Óssea/métodos , Leucócitos Mononucleares/transplante , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Transplante de Medula Óssea/tendências , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Baseada em Transplante de Células e Tecidos/tendências , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/tendências , Bases de Dados Factuais/tendências , Humanos , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/fisiologia , Estudos Retrospectivos , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
OBJECTIVES: The genetics of binge-eating disorder (BED) is an emerging topic and one candidate pathway, namely the fat mass and obesity-associated (FTO) gene, may be implicated because of its role in food reward sensitivity and self-regulation of eating. The aims of this study were to examine the independent effects of variants of FTO on binge frequency in women with and without BED and to examine the moderating role of interpersonal attachment in this association. METHODS: Secondary data analysis was conducted on a cross-sectional comparison of three groups of women in a trial of group treatment for BED: BED with obesity (nâ¯=â¯73), BED without obesity (nâ¯=â¯55), and normal weight without BED (nâ¯=â¯50). Women were genotyped for five of the most common FTO single-nucleotide polymorphisms, rs9939609, rs8050136, rs3751812, rs1421085, and rs1121980, which have been related to body mass index and energy intake. Binge frequency (Eating Disorder Examination), body composition (bioelectric impedance), and attachment (Attachment Style Questionnaire) were assessed. RESULTS: There were no significant between-group differences for frequencies of FTO alleles, nor were there any significant anthropometric associations. The FTOâ¯×â¯attachment interaction was significant whereby, relative to a low-risk FTO genotype, individuals with a high-risk genotype for the SNP rs1421085 and high-avoidant attachment had higher mean binge frequency than those with high genetic risk but low-avoidant attachment (ßâ¯=â¯-7.96; tâ¯=â¯-2.07; Pâ¯=â¯0.042). CONCLUSIONS: FTO genotypes associated with risk for obesity and loss of control of eating, specifically rs1421085, may interact with insecure attachment in a way that may exacerbate binge eating among women with BED.