570 research outputs found
Restricted access to private properties limits management of invasive alien species: A literature review and case studies
OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.
Hearing impairment is the second most prevalent clinical feature after optic atrophy in Dominant Optic Atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception.
We studied two groups of OPA1 subjects, one comprising 11 patients (7 males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (3 males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harboring OPA1 missense mutations and were compared to recordings obtained from 20 normally-hearing controls and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after one year of cochlear implant use.
Nine out of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harboring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five subjects out of six, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant.
These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fiber activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by by-passing the site of lesion
Therapeutic Options in Hereditary Optic Neuropathies
Options for the effective treatment of hereditary optic neuropathies have been a long time coming. The successful launch of the antioxidant idebenone for Leber’s Hereditary Optic Neuropathy (LHON), followed by its introduction into clinical practice across Europe, was an important step forward. Nevertheless, other options, especially for a variety of mitochondrial optic neuropathies such as dominant optic atrophy (DOA), are needed, and a number of pharmaceutical agents, acting on different molecular pathways, are currently under development. These include gene therapy, which has reached Phase III development for LHON, but is expected to be developed also for DOA, whilst most of the other agents (other antioxidants, anti-apoptotic drugs, activators of mitobiogenesis, etc.) are almost all at Phase II or at preclinical stage of research. Here, we review proposed target mechanisms, preclinical evidence, available clinical trials with primary endpoints and results, of a wide range of tested molecules, to give an overview of the field, also providing the landscape of future scenarios, including gene therapy, gene editing, and reproductive options to prevent transmission of mitochondrial DNA mutations
Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions
Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have
been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON),
mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe
the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads
also to a Leigh-like phenotype.
Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated
with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute
visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1
mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous
homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6)
subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H
background, were also present.
Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which
may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous
variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the
primary LHON mutation
Bot and gender detection of twitter accounts using distortion and LSA notebook for PAN at CLEF 2019
In this work, we present our approach for the Author Profiling task of PAN 2019. The task is divided into two sub-problems, bot, and gender detection, for two different languages: English and Spanish. For each instance of the problem and each language, we address the problem differently. We use an ensemble architecture to solve the Bot Detection for accounts that write in English and a single SVM for those who write in Spanish. For the Gender detection we use a single SVM architecture for both the languages, but we pre-process the tweets in a different way. Our final models achieve accuracy over the 90% in the bot detection task, while for the gender detection, of 84.17% and 77.61% respectively for the English and Spanish languages
Cross-domain authorship attribution combining instance-based and profile-based features notebook for PAN at CLEF 2019
Being able to identify the author of an unknown text is crucial. Although it is a well-studied field, it is still an open problem, since a standard approach has yet to be found. In this notebook, we propose our model for the Authorship Attribution task of PAN 2019, that focuses on cross-domain setting covering 4 different languages: French, Italian, English, and Spanish. We use n-grams of characters, words, stemmed words, and distorted text. Our model has an SVM for each feature and an ensemble architecture. Our final results outperform the baseline given by PAN in almost every problem. With this model, we reach the second place in the task with an F1-score of 68%
A second case with the V374A KCND3 pathogenic variant in an Italian patient with early-onset spinocerebellar ataxia
Background and Objectives To date, approximately 20 heterozygous mainly loss-of-function variants in KCND3 have been associated with spinocerebellar ataxia (SCA) type 19 and 22, a clinically heterogeneous group of neurodegenerative disorders. We aimed at reporting the second patients with the V374A KCND3 mutation from an independent family, confirming its pathogenic role. Methods We describe the clinical history of a patient with SCA and conducted genetic investigations including mitochondrial DNA analysis and exome sequencing. Results This male patient was reported to have unstable gait with tremors at the lower limbs and dysarthric speech since childhood. A neurologic examination also showed dysarthria, nystagmus, action tremor, dysmetria, and weak deep tendon reflexes. He had marked cerebellar atrophy at brain MRI, more evident at vermis. Molecular analysis, including exome sequencing and an in silico panel analysis of genes associated with SCA, revealed the c.1121T>C [p.V374A] mutation in KCND3. Discussion This report consolidates the pathogenicity of the V374A KCND3 mutation and suggests that the ataxic paroxysmal exacerbations are not a key phenotypic feature of this mutation
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