Cochlear delays measured with amplitude-modulated tone-burst-evoked OAEs

Delay times in the mammalian cochlea, whether from measurement of basilar membrane (BM) vibration or otoacoustic emissions (OAEs) have, to date, been largely based on phase-gradient estimates from steady-state responses. Here we report cochlear delays measured directly in the time domain from OAEs evoked by amplitude-modulated tone-burst (AMTB) stimuli. Measurement using OAEs provides a non-invasive estimate of cochlear delay but is confounded by the complexity of generation of such OAEs. At low to moderate stimulus levels, and provided that the stimulus frequency range does not include a region of the cochlea where there is a large change in effective reflectance, AMTB stimuli evoke an OAE with an envelope shape that is similar to the stimulus and allow a direct calculation of cochlear group delay. Such delays are commensurate with BM estimates of delay, estimates of cochlear delay inferred from neural recordings, and previous OAE measures of delay in the guinea pig. However, a nonlinear distortion mechanism, variation in effective reflectance, and intermodulation distortion products generated by the nonlinear interaction in the cochlea of the carrier and sidebands of the AMTB stimulus, may all contribute to OAEs arising with envelope shapes that are not a scaled representation of the stimulus, confounding the estimation of cochlear group delay.     

Preoperative breast MRI in the surgical treatment of ductal carcinoma in situ

Accurate determination of the size or extent of ductal carcinoma in situ (DCIS) by imaging is uncertain, and incomplete resection of tumor results in involved margins in up to 81% of cases. This study examined the accuracy of magnetic resonance imaging (MRI) for assessment of DCIS size, and evaluated the effect of preoperative breast MRI on achievement of tumor-free surgical margins after breast-conserving surgery (BCS). One-hundred and fifty-eight female patients with DCIS were identified from a prospective database: 60 patients (62 cases) had preoperative breast MRI, and 98 patients did not have MRI. The accuracy of tumor size assessed by MRI was determined by comparison with histopathologic size. All patients underwent BCS initially. The rate of involved margins after resection was compared in MRI and no-MRI groups. The overall correlation between MRI size and histopathologic size was high (p < 0.0001). MRI assessment of size was significantly more accurate when DCIS was high grade (p < 0.0001) or intermediate grade (p = 0.005) versus low grade (p = 0.187). The rate of tumor-involved margins was not significantly different in MRI and no-MRI groups (30.7% and 24.7%, respectively; p = 0.414). The rate of mastectomy was significantly higher in the MRI group than the no-MRI group (17.7% versus 4.1%; p = 0.004). These findings indicate that MRI can detect DCIS, especially when lesions are high or intermediate grade, but that MRI does not accurately predict the size of DCIS. In this study, MRI did not improve the surgeon's ability to achieve clear margins following BCS.     

Introduction to the MAUDE database

The Manufacturer and User Facility Device Experience (MAUDE) database represents a reporting system mandated by the Food and Drug Administration for postmarket surveillance. MAUDE has been made into a searchable online database that includes all reported events in which medical devices may have malfunctioned or caused a death or serious injury. For the clinician considering the use of a new medical device, searching the MAUDE database is useful to search for complications not yet reported in the medical literature.     

Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system

During embryonic development, complex events, such as cellular proliferation, differentiation, survival, and guidance of axons, are orchestrated and regulated by a variety of extracellular signals. Receptor tyrosine kinases mediate many of these events, with several playing critical roles in neuronal survival and axonal guidance. It is evident that not all the receptor tyrosine kinases that play key roles in regulating neuronal development have been identified. In this study, we have characterized the spatial-temporal expression profile of a recently identified receptor tyrosine kinase, anaplastic lymphoma kinase (ALK), in embryonic chick by means of whole-mount in situ hybridization in conjunction with immunohistochemistry. Our findings reveal that Alk is expressed in sympathetic and dorsal root ganglia as early as stage 19. In addition, mRNA is expressed from stage 23/24 (E4) to stage 39 (E13) in discrete motor neuron subsets of chick spinal cord along with a select group of muscles that are innervated by one of these particular motor neuron clusters. Expression within the spinal cord is coincident with the onset and duration of motor neuron programmed cell death and during the period of musculature innervation and synapse formation. Hence, the data presented here identify ALK as a novel candidate receptor for regulating critical events in the development of neurons in both the central and the peripheral nervous systems.     

Sources of group differences in functional connectivity: An investigation applied to autism spectrum disorder

An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer “functional connectivity”. In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms — differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased “connectivity”) in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations.     

Itching at night: A review on reducing nocturnal pruritus in children

The most common causes of chronic nocturnal itching in children are atopic dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis contributing to lesser degrees. Despite the prevalence of nocturnal itching, its pathophysiology remains poorly understood. The most troubling consequence of itching at night is poor quality of sleep. Poor sleep quality in children with nocturnal itching has been linked to adverse neurocognitive, behavioral, and physiologic outcomes, including poor performance in school, attention deficit hyperactivity disorder, short stature, hypertension, obesity, and impaired immune function. There is no consensus on the best management of nocturnal itching in children. We conducted a review of the literature evaluating the efficacy of various treatment options for children with chronic nocturnal pruritus. Our review found three recently conducted randomized controlled trials and one case report demonstrating the efficacy of topical corticosteroids, oral melatonin, and clonidine in reducing nocturnal itching or improving sleep quality in children with nocturnal pruritus. Future research is needed to elucidate the pathophysiology of nocturnal itching to best develop targeted, effective treatment strategies.