Localization of myosin-Va in subpopulations of cells in rat endocrine organs

Myosin-Va is a Ca2+/calmodulin-regulated unconventional myosin involved in the transport of vesicles, membranous organelles, and macromolecular complexes composed of proteins and mRNA. The cellular localization of myosin-Va has been described in great detail in several vertebrate cell types, including neurons, melanocytes, lymphocytes, auditory tissues, and a number of cultured cells. Here, we provide an immunohistochemical view of the tissue distribution of myosin-Va in the major endocrine organs. Myosin-Va is highly expressed in the pineal and pituitary glands and in specific cell populations of other endocrine glands, especially the parafollicular cells of the thyroid, the principal cells of the parathyroid, the islets of Langerhans of the pancreas, the chromaffin cells of the adrenal medulla, and a subpopulation of interstitial testicular cells. Weak to moderate staining has been detected in steroidogenic cells of the adrenal cortex, ovary, and Leydig cells. Myosin-Va has also been localized to non-endocrine cells, such as the germ cells of the seminiferous epithelium and maturing oocytes and in the intercalated ducts of the exocrine pancreas. These data provide the first systematic description of myosin-Va localization in the major endocrine organs of rat.

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with retapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m(2) cyclophosphamide and 10 mu g per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8-11) and patients were discharged from hospital on mean day 11 (range day 8-13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24-48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0.0001), neurological rating scale score (p=0.0001), paced auditory serial addition test (p=0.014), 25-foot walk (p<0.0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0.0001). Interpretation Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na(+) channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na(+) imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na(+) clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na(+) gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K(+) currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a `dual` firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials).

Spontaneous reversibility of damage to outer hair cells after sodium salicylate induced ototoxicity

Background: High sodium salicylate doses can cause reversible hearing loss and tinnitus, possibly due to reduced outer hair cell electromotility. Sodium salicylate is known to alter outer hair cell structure and function. This study determined the reversibility and cochlear recovery time after administration of an ototoxic sodium salicylate dose to guinea pigs with normal cochlear function. Study design: Prospective experimental investigation. Methods: All animals received a single 500 mg sodium salicylate dose, but with different durations of action. Function was evaluated before drug administration and immediately before sacrifice. Cochleae were processed and viewed using scanning electron microscopy. Results: Changes in outer hair cell function were observed to be present 2 hours after drug administration, with recovery of normal anatomy beginning after 24 hours. Subsequently, derangement and distortion of cilia reduced, with effects predominantly in row three. At 168 hours, cilia were near-normal but with mild distortions which interfered with normal cochlear physiology. Conclusions: Ciliary changes persisted for up to 168 hours after ototoxic sodium salicylate administration.

Conductive hearing loss in children with bronchopulmonary dysplasia: A longitudinal follow-up study in children aged between 6 and 24 months

Aims: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD). Study design, subjects and outcome measures: In a longitudinal clinical study. 187 children were evaluated at 6, 9, 12,15 18 and 24 months of age by visual reinforcement audiometry, tympanometry and auditory brain response system. Results: Of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5 min Apgar score. Conclusions: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Comparison of the Use of Tympanic and Extratympanic Electrodes for Electrocochleography

Objectives: To determine the differences between tympanic and extratympanic electrodes regarding recording technique, comfort and ease of execution of the exam, and quality of auditory potential tracings. Study Design: Prospective cross-section investigation. Methods: Determination of the summation potential/action potential (SP/AP) ratio by electrocochleography (EchoG) using tympanic and extratympanic electrodes and separate analysis of SP and AP regarding the amplitude recorded. Results: Twenty-three subjects (15 men and 8 women; mean age: 33.17 years) with normal tonal threshold audiometry were evaluated. EchoG analysis revealed no significant difference between the two tympanic electrodes. Eleven of the 23 subjects reported discomfort with the insertion of the tympanic electrode even with the use of topical xylocaine, whereas no complaints of discomfort were reported with the use of the extratympanic electrode. Conclusions: Both electrodes were effective for EchoG evaluation, but the extratympanic one was easier to insert and did not cause discomfort. However, the tympanic electrode produced tracings of greater amplitude and of better reproducibility. Laryngoscope, 119:563-566, 2009

Predictors of word-level literacy amongst Grade 3 children in five diverse languages

Groups of Grade 3 children were tested on measures of word-level literacy and undertook tasks that required the ability to associate sounds with letter sequences and that involved visual, auditory and phonological-processing skills. These groups came from different language backgrounds in which the language of instruction was Arabic, Chinese, English, Hungarian or Portuguese. Similar measures were used across the groups, with tests being adapted to be appropriate for the language of the children. Findings indicated that measures of decoding and phonological-processing skills were good predictors of word reading and spelling among Arabic- and English-speaking children, but were less able to predict variability in these same early literacy skills among Chinese- and Hungarian-speaking children, and were better at predicting variability in Portuguese word reading than spelling. Results were discussed with reference to the relative transparency of the script and issues of dyslexia assessment across languages. Overall, the findings argue for the need to take account of features of the orthography used to represent a language when developing assessment procedures for a particular language and that assessment of word-level literacy skills and a phonological perspective of dyslexia may not be universally applicable across all language contexts. Copyright (C) 2008 John Wiley & Sons, Ltd.

Influence of gender on the vestibular evoked myogenic potential

There is no consensus on the relevance of factors that influence gender differences in the behavior of muscles. Some studies have reported a relationship between muscle tension and amplitude of the vestibular evoked myogenic potential; others, that results depend on which muscles are studied or on how much load is applied. Aims: This study aims to compare vestibular evoked myogenic potential parameters between genders in young individuals. Methods: Eighty young adults were selected - 40 men and 40 women. Stimuli were averaged tone-bursts at 500 Hz, 90 dBHL intensity, and a 10-1000 Hz bandpass filter with amplification of 10-25 microvolts per division. The recordings were made in 80 ms windows. Study type: An experimental and prospective study. Results: No significant gender differences were found in wave latency - p = 0.19 and p = 0.50 for waves P13 and N23, respectively. No differences were found in amplitude values - p = 0.28 p = 0.40 for waves P13 and N23, respectively. Conclusion: There were no gender differences in latency and amplitude factors; the sternocleidomastoid muscle strain was monitored during the examination.

Audiological findings in pacients treated with radiotherapy for head and neck tumors

Radiotherapy has been widely used given its increase in the successful outcomes and cure of some cancers. Aim: To evaluate the functionality of the auditory system in patients who underwent radiotherapy treatment for head and neck tumors. Materials and Methods: From May 2007 to May 2008, otorhinolaryngological and audiological evaluation (Pure Tone Audiometry (air and bone conduction), Speech Audiometry, Tympanometry, Acoustic Reflex testing and Distortion Product Otoacoustic Emissions) were performed in 19 patients diagnosed with head and neck neoplasia and treated with radiotherapy. Prospective case series study. Results: 10.5% left ears and 26.3% right ears had bilateral hearing loss soon after radiotherapy according to ASHA criteria. Conclusions: Radiotherapy treatment for head and neck cancer has ototoxic effects. Early programs of auditory rehabilitation should be offered to these patients.

Relational learning in children with deafness and cochlear implants

This four-experiment series sought to evaluate the potential of children with neurosensory deafness and cochlear implants to exhibit auditory-visual and visual-visual stimulus equivalence relations within a matching-to-sample format. Twelve children who became deaf prior to acquiring language (prelingual) and four who became deaf afterwards (postlingual) were studied. All children learned auditory-visual conditional discriminations and nearly all showed emergent equivalence relations. Naming tests, conducted with a subset of the: children, showed no consistent relationship to the equivalence-test outcomes.. This study makes several contributions: to the literature on stimulus equivalence. First; it demonstrates that both pre- and postlingually deaf children-can: acquire auditory-visual equivalence-relations after cochlear implantation, thus demonstrating symbolic functioning. Second, it directs attention to a population that may be especially interesting for researchers seeking to analyze the relationship. between speaker and listener repertoires. Third, it demonstrates the feasibility of conducting experimental studies of stimulus control processes within the limitations of a hospital, which these children must visit routinely for the maintenance of their cochlear implants.

Audiology in Brazil

The profession of audiology took root in Brazil nearly a half a century ago and has since blossomed into a flourishing, well-developed field. Currently, audiologists in Brazil work at private institutions, including private medical practices and dedicated speech and hearing clinics. They are also employed in a wide array of public institutions, including community clinics, elementary schools, colleges, and universities. In both the private sector and health clinics, audiologists perform diagnostic evaluations of auditory and vestibular disorders, select and fit hearing aids, and provide aural rehabilitation. At the public level, they assist with workers` health programs, dispense hearing aids, and aural rehabilitation. There is always room to grow, however, and the future of audiology in Brazil holds both challenges and opportunity. The following article will sketch the development of audiology training and practice in Brazil, provide a picture of how the field stands today, and summarize the unique challenges which the profession faces in this large and diverse nation.

Telehealth in audiology: The need and potential to reach underserved communities

Permanent hearing loss is a leading global health care burden, with 1 in 10 people affected to a mild or greater degree. A shortage of trained healthcare professionals and associated infrastructure and resource limitations mean that hearing health services are unavailable to the majority of the world population. Utilizing information and communication technology in hearing health care, or tele-audiology, combined with automation offer unique opportunities for improved clinical care, widespread access to services, and more cost-effective and sustainable hearing health care. Tele-audiology demonstrates significant potential in areas such as education and training of hearing health care professionals, paraprofessionals, parents, and adults with hearing disorders; screening for auditory disorders; diagnosis of hearing loss; and intervention services. Global connectivity is rapidly growing with increasingly widespread distribution into underserved communities where audiological services may be facilitated through telehealth models. Although many questions related to aspects such as quality control, licensure, jurisdictional responsibility, certification and reimbursement still need to be addressed; no alternative strategy can currently offer the same potential reach for impacting the global burden of hearing loss in the near and foreseeable future.

Genetic influence on the variance in P3 amplitude and latency

The P3(00) event-related potential (ERP) component is widely used as a measure of cognitive functioning and provides a sensitive electrophysiological index of the attentional and working memory demands of a task. This study investigated what proportion of the variance in the amplitude and latency of the P3, elicited in a delayed response working memory task, could be attributed to genetic factors. In 335 adolescent twin pairs and 48 siblings, the amplitude and latency of the P3 were examined at frontal, central, and parietal sites. Additive genetic factors accounted for 48% to 61% of the variance in P3 amplitude. Approximately one-third of the genetic variation at frontal sites was mediated by a common genetic factor that also influenced the genetic variation at parietal and central sites. Familial resemblance in P3 latency was due to genetic influence that accounted for 44% to 50% of the variance. Genetic covariance in P3 latency across sites was substantial, with a large part of the variance found at parietal, central, and frontal sites attributed to a common genetic factor. The findings provide further evidence that the P3 is a promising phenotype of neural activity of the brain and has the potential to be used in linkage and association analysis in the search for quantitative trait loci (QTLs) influencing cognition.

Effect of probe stimulus intensity on the dissociation between autonomic orienting and secondary probe reaction time

Information processing accounts propose that autonomic orienting reflects the amount of resources allocated to process a stimulus. However, secondary task reaction time (RT), a supposed measure of processing resources, has shown a dissociation from autonomic orienting. The present study tested the hypothesis that secondary task RT reflects a serial processing mechanism. Participants (N = 24) were presented with circle and ellipse shapes and asked to count the number of longer-than-usual presentations of one shape (task-relevant) and to ignore presentations of a second shape (task-irrelevant). Concurrent with the counting task, participants performed a secondary RT task to an auditory probe presented at either a high or low intensity and at two different probe positions following shape onset (50 and 300 ms). Electrodermal orienting was larger during task-relevant shapes than during task-irrelevant shapes, but secondary task RT to the high-intensity probe was slower during the latter. In addition, an underadditive interaction between probe stimulus intensity and probe position was found in secondary RT. The findings are consistent with a serial processing model of secondary RT and suggest that the notion of processing stages should be incorporated into current information-processing models of autonomic orienting.

Haptic information stabilizes and destabilizes coordination dynamics

Goal-directed, coordinated movements in humans emerge from a variety of constraints that range from 'high-level' cognitive strategies based oil perception of the task to 'low-level' neuromuscular-skeletal factors such as differential contributions to coordination from flexor and extensor muscles. There has been a tendency in the literature to dichotomize these sources of constraint, favouring one or the other rather than recognizing and understanding their mutual interplay. In this experiment, subjects were required to coordinate rhythmic flexion and extension movements with an auditory metronome, the rate of which was systematically increased. When subjects started in extension on the beat of the metronome, there was a small tendency to switch to flexion at higher rates, but not vice versa. When subjects: were asked to contact a physical stop, the location of which was either coincident with or counterphase to the auditor) stimulus, two effects occurred. When haptic contact was coincident with sound, coordination was stabilized for both flexion and extension. When haptic contact was counterphase to the metronome, coordination was actually destabilized, with transitions occurring from both extension to flexion on the beat and from flexion to extension on the beat. These results reveal the complementary nature of strategic and neuromuscular factors in sensorimotor coordination. They also suggest the presence of a multimodal neural integration process-which is parametrizable by rate and context - in which intentional movement, touch and sound are bound into a single, coherent unit.