Molecular regulatory mechanism of human myosin-7a.

Myosin-7a is an actin-based motor protein essential for vision and hearing. Mutations of myosin-7a cause type 1 Usher syndrome, the most common and severe form of deafblindness in humans. The molecular mechanisms that govern its mechanochemistry remain poorly understood, primarily because of the difficulty of purifying stable intact protein. Here, we recombinantly produce the complete human myosin-7a holoenzyme in insect cells and characterize its biochemical and motile properties. Unlike the Drosophila ortholog that primarily associates with calmodulin (CaM), we found that human myosin-7a utilizes a unique combination of light chains including regulatory light chain, CaM, and CaM-like protein 4. Our results further reveal that CaM-like protein 4 does not function as a Ca2+ sensor but plays a crucial role in maintaining the lever arm's structural-functional integrity. Using our recombinant protein system, we purified two myosin-7a splicing isoforms that have been shown to be differentially expressed along the cochlear tonotopic axis. We show that they possess distinct mechanoenzymatic properties despite differing by only 11 amino acids at their N termini. Using single-molecule in vitro motility assays, we demonstrate that human myosin-7a exists as an autoinhibited monomer and can move processively along actin when artificially dimerized or bound to cargo adaptor proteins. These results suggest that myosin-7a can serve multiple roles in sensory systems such as acting as a transporter or an anchor/force sensor. Furthermore, our research highlights that human myosin-7a has evolved unique regulatory elements that enable precise tuning of its mechanical properties suitable for mammalian auditory functions.

Caracterización fenotípica de la retinitis pigmentaria asociada a sordera / Phenotypic characterization of retinitis pigmentosa associated with deafness

Introducción. El síndrome de Usher es una alteración genética caracterizada por la asociación de retinitis pigmentaria y sordera. Sin embargo, hay casos con familias en las cuales, a pesar de presentarse dicha asociación, no se puede diagnosticar un síndrome de Usher ni ninguno otro. Objetivo. Reevaluar fenotípicamente a 103 familias con diagnóstico previo de posible síndrome de Usher o retinitis pigmentaria asociada con sordera. Materiales y métodos. Se revisaron las historias clínicas de 103 familias con un posible diagnóstico clínico de síndrome de Usher o retinitis pigmentaria asociada con sordera. Se seleccionaron las familias cuyo diagnóstico clínico no correspondía a un síndrome de Usher típico. Los afectados fueron valorados oftalmológica y audiológicamente. Se analizaron variables demográficas y clínicas. Resultados. Se reevaluaron 14 familias cuyo diagnóstico clínico no correspondía al de síndrome de Usher. De las familias con diagnóstico inicial de síndrome de Usher típico, el 13,6 % recibieron uno posterior de "retinitis pigmentaria asociada con sordera" de "otro síntoma ocular asociado con hipoacusia',' o en forma aislada en una misma familia, de "retinitis pigmentaria" o "hipoacusia'.' Conclusiones. Es fundamental el estudio familiar en los casos en que la clínica no concuerda con el diagnóstico de síndrome de Usher típico. En los pacientes con retinitis pigmentaria asociada con sordera, el diagnóstico clínico acertado permite enfocar los análisis moleculares y, así, establecer un diagnóstico diferencial. Es necesario elaborar guías de nomenclatura en los casos con estos hallazgos atípicos para orientar a médicos e investigadores en cuanto a su correcto manejo.

Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings. Objective: To reassess the phenotypes of 103 families previously diagnosed as possible Usher syndrome and/or retinitis pigmentosa associated with deafness. Materials and methods: We conducted a descriptive and retrospective study by reviewing the medical records of 103 families with a probable clinical diagnosis of Usher syndrome and/or retinitis pigmentosa associated with deafness. Families whose clinical diagnosis did not correspond to the typical Usher syndrome were selected and evaluated ophthalmologically and audiologically. Demographic and clinical variables were analyzed. Results: We selected and then reevaluated 14 families and 55 individuals as they did not correspond to a clinical diagnosis of Usher syndrome; 13.6% of the families initially considered to have typical Usher syndrome were later diagnosed with retinitis pigmentosa associated with deafness, another ocular symptom associated with hearing loss, retinitis pigmentosa, or isolated hearing loss in the same family. Conclusions: Family studies are essential in cases where the symptoms do not match the typical Usher' syndrome. In the cases of retinitis pigmentosa associated with deafness, a correct clinical diagnosis allows for focusing on the molecular analyses to establish a differential diagnosis. The need for nomenclature guidelines on these atypical findings is relevant to aid physicians and researchers in the best approach to these cases.

La surdité brusque résultats thérapeutique et facteurs pronostiques / Sudden sensorineural hearing loss: therapeutic outcome and prognostic factors

Objectifs: évaluer les résultats thérapeutiques et étudier les facteurs pronostiques de la surdité brusque.Patients et méthodes: Il s'agit d'une étude rétrospective à propos de 61 patients (39 hommes et 22 femmes) pris en charge pour surdité brusque dans le service d'Otorhinolaryngologie et de Chirurgie Cervico-Faciale de l'hôpital Bourguiba de Monastir durant une période de 16 ans (2001-2016). Une analyse statistique a été réalisée afin d'identifier les facteurs influençant le pronostic de la surdité brusque. Le seuil de significativité retenu était de 5%. Résultats:L'âge moyen était de 43 ans [16-80 ans]. Le taux global de récupération auditive était de 45%. Les facteurs pronostiques selon l'analyse uni variée étaient: un antécédent d'hypoacousie controlatérale, la présence d'un vertige associé, la sévérité de la perte auditive initiale, une courbe audiométrique de type E, l'absence du réflexe stapédien et le recours à l'oxygénothérapie hyperbare (OHB). En analyse multivariée, les seuls facteurs retenus étaient une perte auditive initiale supérieure ou égale à 70 dB, la présence d'un vertige et l'absence d'un épisode infectieux précédant la survenue de la surdité. Conclusion: Notre étude a permis de retenir comme facteurs de mauvais pronostic indépendants la perte auditive initiale supérieure ou égale à 70 dB, la présence d'un vertige et l'absence d'un épisode infectieux précédant la survenue de la surdité. Ceci nous incite à une réflexion quant au protocole thérapeutique adopté dans notre service et à indiquer l'OHB, qui est normalement prescrite en cas de non réponse, en première intention, afin d'optimiser la récupération auditive.

La corrección-compensación en niños sordociegos con alteraciones motrices a través de actividades físicas adaptadas / Correction-compensation in the deafblind children with motor alterations through adapted physical activities

Introducción: La sordoceguera es una discapacidad doble que implica problemas en el campo auditivo y visual, provoca problemas comunicativos y motrices únicos. Por lo que es necesario trazar estrategias docente-educativas especiales y personalizadas. Objetivo: Proponer actividades físicas adaptadas como parte de la terapia ocupacional para la corrección-compensación de las alteraciones motrices presentadas en niños sordociegos que estudian en el Instituto Especial Mariana de Jesús. Métodos: La muestra estuvo conformada por 20 niños, entre los 6-10 años de edad con problemas visuales y auditivos parciales provocados por diferentes padecimientos. La investigación se inició con el diagnóstico realizado a 11 especialistas, que estaban implicados directamente en el proceso docente-educativo. Se delimitaron las variables de investigación antes de la implementación de la estrategia. Se diseñaron 10 juegos adaptados a las individualidades y necesidades de la muestra estudiada, y aplicados durante el curso docente 2016-2017. Resultados: Con la aplicación de las 7 pruebas motrices antes y después de implementada la mejora, se obtuvieron progresos significativos en las habilidades motrices de los sujetos, aumentando el porcentaje de evaluados de bien, según se demostró estadísticamente al calcular las proporciones para muestras relacionadas. Conclusiones: Las actividades físicas adaptadas, dentro de estrategias lúdicas como terapia ocupacional, permiten mejorar el trabajo correctivo-compensativo y las capacidades motrices de niños sordociegos. Estas estrategias deben desarrollarse bajo los principios de una ética humanista e inclusiva y sobre la base de una atención personalizada(AU)

Visual field, and causes unique communicative and motor problems. So, it is necessary to draw special and customised educational-teaching strategies. Objective: To propose adapted physical activities as part of the occupational therapy for the correction-compensation of motor alterations presented in deafblind children studying in Mariana de Jesus Special Institute. Methods: The sample consisted of 20 children in the ages from 6 to10 years old with visual and auditory problems caused by different diseases. The investigation began with a diagnosis to 11 specialists whom were directly involved in the educational process. The research variables were defined prior to the implementation of the strategy. There were designed ten games adapted to the individualities and needs of the sample studied, and those were used during the school year 2016-2017. Results: With the implementation of the 7 motor tests before and after the implementation of the improvement, significant breakthroughs in the motor skills of the subjects were achieved, and with it an increase in the percentage of subjects evaluated as well, as demonstrated statistically when calculating the proportions for related samples. Conclusions: The adapted physical activities, within playful strategies as occupational therapy, improve the corrective-compensative work and the motor abilities of deafblind children. These strategies should be developed under the principles of a humanist and inclusive ethics and on the basis of a personalized attention(AU)

Horseback riding therapy for a deafblind individual enabled by a haptic interface.

We present a haptic interface to help deafblind people to practice horseback riding as a recreational and therapeutic activity. Horseback riding is a form of therapy which can improve self-esteem and sensation of independence. It has been shown to benefit people with various medical conditions-including autism. However, in the case of deafblind riders, an interpreter must stand by at all times to communicate with the rider by touch. We developed a simple interface that enables deafblind people to enjoy horseback riding while the instructor is remotely providing cues, which improves their independence. Experiments demonstrated that an autistic deafblind individual exhibits similar responses to navigational cues as an unimpaired rider. Motivation is an important factor in therapy, and is frequently determinant of its outcome; therefore, the user attitude toward the therapy methods is key. The answers to questionnaires filled by the rider, family, and the instructor show that our technique gives the rider a greater sense of independence and more joy compared to standard riding where the instructor is walking along with the horse.

Successful engagement: CBM's holistic approach to the work in the area of ear care, deafness, hard of hearing and deafblindness.

PURPOSE: CBM is an international Christian development organisation, committed to improving the quality of life of persons with disabilities in disadvantaged societies. CBM aims at achieving this in partnership with local organisations and in cooperation with stakeholders at regional and international levels. This article aims at sharing CBM's holistic approach for successful engagement in the work area of ear care, deafness, hard of hearing and deafblindness. METHODS: Review of CBM supporting documents, including strategies, position papers, technical guidelines, criteria of success and information related to partners, centres of excellence and model projects. RESULTS: Description of how partner programmes use participatory methods of planning and implementation, involving persons with disabilities and the community. Recommendations on how to develop national or sub-national strategies to impact the lives, and advocate with governments for the rights and inclusion, of persons with disabilities. CONCLUSIONS: CBM's holistic approach to work in the area of ear care; deafness; hard of hearing and deafblindness includes intervention at all levels of health care provision, Education, CBR and Audiological, Speech Therapy and other interdisciplinary services. This article presents CBM's core principles and shares specific strategic planning and results, together with lessons learnt while searching a sustainable engagement for field work. IMPLICATIONS FOR REHABILITATION: Rehabilitation, in its widest conception, should be approached as a multidisciplinary strategy, and developed in close cooperation with other local, national and international agencies. CBM is positioned in a strategic point from where it can play a key role in the facilitation of an international forum for agencies and stakeholders to reach a consensus to decrease the burden of ear disease and hearing loss, through early intervention and re/habilitation.

Neural plasticity in blind cochlear implant users.

This study, using positron emission tomography, investigates the cortical activation generated by auditory stimulation in two congenitally blind cochlear implant users. In the patient with a relatively short history of deafness, activity increased in both auditory cortices and fell in the visual cortices. The patient with a longer period of deafness had greater activation of the visual cortices than the auditory cortices. A similar pattern of activity was seen when this patient subsequently had a second cochlear implant inserted into the opposite ear. The neural pathways formed after the restoration of auditory input in the congenitally blind can activate either the auditory or visual cortices. We suggest that the visual cortical activation demonstrated is of functional significance.

Psychosocial adaptations to dual sensory loss in middle and late adulthood.

Concurrent losses of hearing and vision function, or dual sensory loss, affect a large number of individuals of all ages and particularly older adults. Dual sensory loss may present at any age as a result of genetic defect, accident, injury, disease, or environmental insult; however, most persons develop this condition as a result of age-related disease processes that rarely result in total deafness or blindness. This condition has wide-ranging implications for physical and psychological functioning and quality of life. In this article, we review the prevalence and causes of dual impairment and its effects on functioning for both individuals affected and their families. We examine psychosocial coping and adaptation to this condition using biopsychosocial-spiritual and ecological models and discuss various strategies for coping and adaptation. The impact of larger societal forces on psychosocial adaptation is presented, followed by recommendations for how rehabilitation and other professionals can meet the challenge of dual sensory loss that awaits us with the aging of the population.