Identification of the causative mutation using next-generation sequencing in autosomal-dominant hereditary hearing impairment, as mutation analysis in hereditary hearing impairment by classic genetic ...methods, is hindered by the high heterogeneity of the disease.
Two Swiss families with autosomal-dominant hereditary hearing impairment.
Amplified DNA libraries for next-generation sequencing were constructed from extracted genomic DNA, derived from peripheral blood, and enriched by a custom-made sequence capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq instrument, 300 cycles and paired-end sequencing. Technical data analysis was performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The detection of mutations in genes related to hearing loss by next-generation sequencing was subsequently confirmed using specific polymerase-chain-reaction and Sanger sequencing.
Mutation detection in hearing-loss-related genes.
The first family harbored the mutation c.5383+5delGTGA in the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified.
Next-generation sequencing successfully identified the causative mutation in families with autosomal-dominant hereditary hearing impairment. The results helped to clarify the pathogenic role of a known mutation and led to the detection of a novel one. NGS represents a feasible approach with great potential future in the diagnostics of hereditary hearing impairment, even in smaller labs.
Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, ...it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways.
The REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia) follows a cohort of pregnant women from early pregnancy until delivery to examine longitudinally the associations of maternal LCPUFA with clinical outcome in preeclampsia. A multisite centre for advanced research was established and pregnant women coming to Bharati hospital and Gupte hospital, Pune, India for their first antenatal visit are recruited and followed up at 11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery. Their personal, obstetric, clinical, and family history are recorded. Anthropometric measures (height, weight), food frequency questionnaire (FFQ), physical activity, socioeconomic status, fetal ultrasonography, and color Doppler measures are recorded at different time points across gestation. Maternal blood at all time points, cord blood, and placenta at delivery are collected, processed and stored at - 80 °C. The children's anthropometry is assessed serially up to the age of 2 years, when their neurodevelopmental scores will be assessed.
This study will help in early identification of pregnant women who are at risk of developing preeclampsia. The prospective design of the study for the first time will establish the role of LCPUFA in understanding the underlying biochemical and molecular mechanisms involved in preeclampsia and their association with developmental programming in children.
The authors had previously mapped a new locus—DFNA17, for nonsyndromic hereditary hearing impairment—to chromosome 22q12.2-q13.3. DFNA17 spans a 17- to 23-cM region, and
MYH9, a nonmuscle–myosin ...heavy-chain gene, is located within the linked region. Because of the importance of myosins in hearing,
MYH9 was tested as a candidate gene for DFNA17. Expression of
MYH9 in the rat cochlea was confirmed using reverse transcriptase–PCR and immunohistochemistry.
MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of
MYH9 in a family with DFNA17 identified, at nucleotide 2114, a G→A transposition that cosegregated with the inherited autosomal dominant hearing impairment. This missense mutation changes codon 705 from an invariant arginine (R) to histidine (H), R705H, within a highly conserved SH1 linker region. Previous studies have shown that modification of amino acid residues within the SH1 helix causes dysfunction of the ATPase activity of the motor domain in myosin II. Both the precise role of MYH9 in the cochlea and the mechanism by which the R705H mutation leads to the DFNA17 phenotype (progressive hearing impairment and cochleosaccular degeneration) remain to be elucidated.
The "Me" I Claim to Be Lalwani, Ashok K; Shavitt, Sharon
Journal of personality and social psychology,
07/2009, Letnik:
97, Številka:
1
Journal Article
Recenzirano
In 12 studies, respondents with an independent (vs. interdependent) self-construal showed an increased tendency and readiness to present themselves as skillful and capable and a decreased tendency ...and readiness to present themselves as socially sensitive and appropriate. This emerged in the form of differential scores on direct measures of self-presentation-self-deceptive enhancement and impression management (Study 1), differential social sensitivity in a gift-giving scenario (Study 2), differential performance on questions assessing general knowledge (Studies 5-6) and etiquette (Studies 7-8), and different choices between tests purportedly measuring one's self-reliance versus social-appropriateness (Studies 9A and 9D). These relationships were observed when participants focused on their own self-presentational concerns but disappeared when participants focused on others' outcomes (Study 3) or when they had a prior opportunity to satisfy their goals via self-affirmation (Studies 4, 5, 6, 7, 8, 9B, 9D). Finally, self-construal effects were eliminated or reversed when participants were led to doubt their ability to achieve their self-presentational goals (Study 9C).
Objective. Enjoyment of music remains an elusive goal following cochlear implantation. We test the hypothesis that reengineering music to reduce its complexity can enhance the listening experience ...for the cochlear implant (CI) listener. Methods. Normal hearing (NH) adults ( N = 16 ) and CI listeners ( N = 9 ) evaluated a piece of country music on three enjoyment modalities: pleasantness, musicality, and naturalness. Participants listened to the original version along with 20 modified, less complex, versions created by including subsets of the musical instruments from the original song. NH participants listened to the segments both with and without CI simulation processing. Results. Compared to the original song, modified versions containing only 1–3 instruments were less enjoyable to the NH listeners but more enjoyable to the CI listeners and the NH listeners with CI simulation. Excluding vocals and including rhythmic instruments improved enjoyment for NH listeners with CI simulation but made no difference for CI listeners. Conclusions. Reengineering a piece of music to reduce its complexity has the potential to enhance music enjoyment for the cochlear implantee. Thus, in addition to improvements in software and hardware, engineering music specifically for the CI listener may be an alternative means to enhance their listening experience.
Imbalance and gait disturbances are common in patients with vestibular schwannoma (VS) and can result in significant morbidity. Current methods for quantitative gait analysis are cumbersome and ...difficult to implement. Here, we use custom-engineered instrumented insoles to evaluate the gait of patients diagnosed with VS.
Twenty patients with VS were recruited from otology, neurosurgery, and radiation oncology clinics at a tertiary referral center. Functional gait assessment (FGA), 2-minute walk test (2MWT), and uneven surface walk test (USWT) were performed. Custom-engineered instrumented insoles, equipped with an 8-cell force sensitive resistor (FSR) and a 9-degree-of-freedom inertial measurement unit (IMU), were used to collect stride-by-stride spatiotemporal gait parameters, from which mean values and coefficients of variation (CV) were determined for each patient.
FGA scores were significantly correlated with gait metrics obtained from the 2MWT and USWT, including stride length, stride velocity, normalized stride length, normalized stride velocity, stride length CV, and stride velocity CV. Tumor diameter was negatively associated with stride time and swing time on the 2MWT; no such association existed between tumor diameter and FGA or DHI.
Instrumented insoles may unveil associations between VS tumor size and gait dysfunction that cannot be captured by standardized clinical assessments and self-reported questionnaires.
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