51 research outputs found

    Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men

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    BACKGROUND: The Deleted-in-AZoospermia-Like (DAZL) gene has homologs required for germ cell development in many organisms. Recently, we showed that there are several common polymorphisms within the DAZL gene that are associated with age at ovarian failure/menopause and sperm count. METHODS: Here we sought to identify rare mutations in DAZL and examine their phenotypes in men and women. We sequenced the DAZL gene in 519 individuals; sequences spanned the entire coding region of the gene. RESULTS: We report the identification of four putative missense mutations in DAZL. Three individuals that were heterozygous for a DAZL mutation reported having children, while two individuals that were homozygous reported no children. These mutations were found only in infertile men and women. CONCLUSION: Given the strong data associating DAZL polymorphisms and deletions with fertility in humans and model organisms, we suggest that these mutations may be associated with age at menopause and/or sperm count and warrant further biochemical and genetic investigation

    A Home-Based Telerehabilitation Program for Patients with Stroke

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    Background. Although rehabilitation therapy is commonly provided after stroke, many patients do not derive maximal benefit because of access, cost, and compliance. A telerehabilitation-based program may overcome these barriers. We designed, then evaluated a home-based telerehabilitation system in patients with chronic hemiparetic stroke. Methods. Patients were 3 to 24 months poststroke with stable arm motor deficits. Each received 28 days of telerehabilitation using a system delivered to their home. Each day consisted of 1 structured hour focused on individualized exercises and games, stroke education, and an hour of free play. Results. Enrollees (n = 12) had baseline Fugl-Meyer (FM) scores of 39 ± 12 (mean ± SD). Compliance was excellent: participants engaged in therapy on 329/336 (97.9%) assigned days. Arm repetitions across the 28 days averaged 24,607 ± 9934 per participant. Arm motor status showed significant gains (FM change 4.8 ± 3.8 points, P = .0015), with half of the participants exceeding the minimal clinically important difference. Although scores on tests of computer literacy declined with age (r = −0.92; P \u3c .0001), neither the motor gains nor the amount of system use varied with computer literacy. Daily stroke education via the telerehabilitation system was associated with a 39% increase in stroke prevention knowledge (P = .0007). Depression scores obtained in person correlated with scores obtained via the telerehabilitation system 16 days later (r = 0.88; P = .0001). In-person blood pressure values closely matched those obtained via this system (r = 0.99; P \u3c .0001). Conclusions. This home-based system was effective in providing telerehabilitation, education, and secondary stroke prevention to participants. Use of a computer-based interface offers many opportunities to monitor and improve the health of patients after stroke

    Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

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    DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P <7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.Peer reviewe

    COMPROMISE AMONG SOVEREIGNS

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    Feasibility of home hand rehabilitation using musicglove after chronic spinal cord injury

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    Study designRandomized, controlled single-blind cross over study. This study was registered on ClinicalTrials.gov (NCT02473614).ObjectivesExamine usership patterns and feasibility of MusicGlove for at home hand rehabilitation therapy following chronic spinal cord injury.SettingHomes of participants.MethodsTen participants with chronic spinal cord injury completed two baseline assessments of hand function. After a stable baseline was determined all participants were randomized into two groups: Experimental and Control. Each group was given a recommended therapy dosage. Following this participants switched interventions.ResultsOn average participants had higher levels of compliance (6.1 ± 3.5 h.), and completed more grips (15,760 ± 9,590 grips) compared to participants in previous stroke studies using the same device. Participants modulated game parameters in a manner consistent with optimal challenge principles from motor learning theory. Participants in the experimental group increased their prehension ability (1 ± 1.4 MusicGlove, 0.2 ± 0.5 Control) and performance (1.4 ± 2.2 MusicGlove, 0.4 ± 0.55 Control) on the Graded and Redefined Assessment of Strength, Sensibility, and Prehension subtests. Increases in performance on the Box and Blocks Test also favored the experimental group compared to the conventional group at the end of therapy (4.2 ± 5.9, -1.0 ± 3.4 respectively).ConclusionsMusicGlove is a feasible option for hand therapy in the home-setting for individuals with chronic SCI. Participants completed nearly twice as many gripping movements compared to individuals from the sub-acute and chronic stroke populations, and a number far greater than the number of movements typically achieved during traditional rehabilitation

    Feasibility of Wearable Sensing for In-Home Finger Rehabilitation Early After Stroke

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    Wearable grip sensing shows potential for hand rehabilitation, but few studies have studied feasibility early after stroke. Here, we studied a wearable grip sensor integrated with a musical computer game (MusicGlove). Among the stroke patients admitted to a hospital without limiting complications, 13% had adequate hand function for system use. Eleven subjects used MusicGlove at home over three weeks with a goal of nine hours of use. On average they achieved 4.1 ± 3.2 (SD) hours of use and completed 8627 ± 7500 grips, an amount comparable to users in the chronic phase of stroke measured in a previous study. The rank-order usage data were well fit by distributions that arise in machine failure theory. Users operated the game at high success levels, achieving note-hitting success &gt;75% for 84% of the 1061 songs played. They changed game parameters infrequently (31% of songs), but in a way that logically modulated challenge, consistent with the Challenge Point Hypothesis from motor learning. Thus, a therapy based on wearable grip sensing was feasible for home rehabilitation, but only for a fraction of subacute stroke subjects. Subjects made usage decisions consistent with theoretical models of machine failure and motor learning
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