RESUMEN
Dystrophinopathies cover a spectrum of X-linked muscle disorders including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and cardiomyopathy due to pathogenic variants in the DMD gene. Neuropsychiatric manifestations occur approximately in one-third of patients with dystrophinopathy. Epilepsy has been described. Here we report seizure and electroencephalographic features of boys with dystrophinopathy and epilepsy. This is a retrospective chart review of eight patients with dystrophinopathy and epilepsy seen at Arkansas Children's Hospital and University of Rochester Medical center. Six patients had DMD and two had BMD. Five patients had generalized epilepsy. Three patients had focal epilepsy and the seizures were intractable in two of them. Brain imaging was available for five patients and were within normal limits. EEG abnormalities were noted in six patients. Seizures were well controlled on the current antiepileptic medication regimen in all patients. Further research is needed to better elucidate the underlying mechanisms and genotype-phenotype correlations.
RESUMEN
BACKGROUND: Distinct molecular, inflammatory, and metabolic signatures are present in oocytes and follicular fluid derived from women with obesity when compared to those derived from normal weight women, which suggest existing signals that may program future offspring for metabolic diseases. This study aims to assess the feasibility and efficacy of a peri-conception nutrition and exercise intervention on mitigating obesity-associated changes in oocyte gene expression profiles and follicular fluid metabolites. METHODS: This single blinded randomized control trial will include 120 women with a BMI of 25-45 kg/m2, ≥21 years of age, and undergoing in vitro fertilization (IVF) treatments. Participants will be randomized to standard of care (N = 60) or an intervention group (N = 60) in a block design by polycystic ovary syndrome status. The intervention will combine a dietary component (Mediterranean meal plan) with exercise prescription following the Physical Activity Guidelines for Americans. Participants will be assessed pre- and post-intervention. The standard of care group will be offered to join the intervention group if the IVF treatments are unsuccessful as a cross over design. Recruitment is anticipated to start in July of 2021. Primary outcomes will include single oocyte gene expression profiles and follicular fluid metabolites. Mann-Whitney U nonparametric tests will be used to assess potential differences for each stratum. Follicular fluid and serum metabolites will be analyzed using a one-factor Analysis of Covariance (ANCOVA) at four levels, pair-wise comparisons using Tukey-Kramer post-hoc tests will be used to identify groups whose means differ significantly while retaining the family-wise error rate at 5%. When the design is balanced, two-way Analysis of Variance (ANOVA), or non-parametric Friedman test will be used in data analysis. Additionally, general linear models and ANCOVA may be used to control for covariates. Significance will be set at p < 0.05. Findings will be disseminated via peer-reviewed manuscripts and presentations at scientific conferences. DISCUSSION: This study will provide novel data and key information on the impact of a dietary and exercise intervention on oocyte gene expression and follicular fluid content. Results will demonstrate the potential of such intervention in mitigating obesity-induced changes in oocyte gene expression and follicular fluid metabolites. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04273048 ): submitted November 13, 2019; posted February 17, 2020.