Do Patients with Craniosynostosis Have an Increased Incidence of Auditory Neuropathy as Newborns?

Neuroscience - Vision & Functional Brain Imaging Poster SessionOBJECTIVE: To investigate the incidence of auditory neuropathy, abnormal auditory brainstem response (ABR) with normal otoacoustic emissions, in newborn patients with craniosynostosis as compared to published standards. DESIGN: A retrospective review of consecutive patients with single or multiple-suture craniosynostosis who were seen between 2002 and 2009. Patients identified by the diagnostic code of craniosynostosis were divided into groups based on suture involvement. The newborn ABR screening and, if patients were referred, diagnosis from audiologic diagnostic testing were obtained from the Missouri Department of Health. Institutional review board approval was obtained. PATIENTS: One hundred and thirty-five patients were identified. Seventy-two were excluded; 3 were listed as “missed” and 69 were not born in-state. The 63 patients included in the study were grouped by involved sutures: 2 left coronal, 7 right coronal, 2 nonsyndromic bicoronal, 3 syndromic bicoronal, 13 sagittal, 17 operative metopic, 15 nonoperative metopic, 1 pansynostosis, and 3 multiple-suture. MAIN OUTCOME MEASURES: The newborn screening results for each patient were recorded as well as the diagnosis from audiologic diagnostics if the patient was referred. RESULTS: Of the 63 patients, 94% (59/63) passed their ABR screening. Four were referred for diagnostic exam in both ears. Of those, one had a normal exam (right coronal) and three did not have diagnostic exams on file (right coronal, bicoronal syndromic and bicoronal non-syndromic). CONCLUSIONS: According to the Centers for Disease Control, 1.8 percent of newborns failed their ABR screening in 2007. Of those, 37% were found to have normal hearing on diagnostic exam. Although our study was inconclusive due to inadequate state records, it does demonstrate an increased incidence in abnormal ABR's in patients with coronal craniosynostosis. This is consistent with a recent publication that demonstrated higher incidence of abnormal ABR's in syndromic coronal craniosynostosis. If auditory abnormalities are present at birth, as our study suggests, the etiology would be unrelated to increased intracranial pressures

Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes

Skeletal muscle insulin resistance (IR) is considered a critical component of type II diabetes, yet to date IR has evaded characterization at the global gene expression level in humans. MicroRNAs (miRNAs) are considered fine-scale rheostats of protein-coding gene product abundance. The relative importance and mode of action of miRNAs in human complex diseases remains to be fully elucidated. We produce a global map of coding and non-coding RNAs in human muscle IR with the aim of identifying novel disease biomarkers. We profiled >47,000 mRNA sequences and >500 human miRNAs using gene-chips and 118 subjects (n = 71 patients versus n = 47 controls). A tissue-specific gene-ranking system was developed to stratify thousands of miRNA target-genes, removing false positives, yielding a weighted inhibitor score, which integrated the net impact of both up- and down-regulated miRNAs. Both informatic and protein detection validation was used to verify the predictions of in vivo changes. The muscle mRNA transcriptome is invariant with respect to insulin or glucose homeostasis. In contrast, a third of miRNAs detected in muscle were altered in disease (n = 62), many changing prior to the onset of clinical diabetes. The novel ranking metric identified six canonical pathways with proven links to metabolic disease while the control data demonstrated no enrichment. The Benjamini-Hochberg adjusted Gene Ontology profile of the highest ranked targets was metabolic (P < 7.4 × 10-8), post-translational modification (P < 9.7 × 10-5) and developmental (P < 1.3 × 10-6) processes. Protein profiling of six development-related genes validated the predictions. Brain-derived neurotrophic factor protein was detectable only in muscle satellite cells and was increased in diabetes patients compared with controls, consistent with the observation that global miRNA changes were opposite from those found during myogenic differentiation. We provide evidence that IR in humans may be related to coordinated changes in multiple microRNAs, which act to target relevant signaling pathways. It would appear that miRNAs can produce marked changes in target protein abundance in vivo by working in a combinatorial manner. Thus, miRNA detection represents a new molecular biomarker strategy for insulin resistance, where micrograms of patient material is needed to monitor efficacy during drug or life-style interventions

Amphibians in agricultural landscapes: the habitat value of crop areas, linear plantings and remnant woodland patches

Mitigating the negative impacts of agriculture on amphibians requires knowledge of how different land uses affect species distribution and community composition. In the case of frogs, there is currently insufficient information on their use of terrestrial habitats in cropping landscapes to inform conservation planning. We examined how four different farmland types (linear plantings, cereal crops, grazing paddocks and woody mulch) and crop harvesting influenced amphibian abundance, richness, body condition and movement. We found the abundance of frogs was significantly higher in linear plantings compared to grazing paddocks and adjacent patches of remnant woodland vegetation. However, species richness and abundance of three individual species did not vary significantly between farmland types. For the most common frog Uperoleia laevigata, body condition was higher at the edges of the woody debris treatment (coupled with higher abundance) and lower in farmland with debris and linear plantings. The body condition of Limnodynastes tasmaniensis and L. interioris was not influenced by farmland type. Frog abundance and condition was largely unaffected by crop harvesting. However, frogs were less common after harvesting at the edges of farmland and within remnant patches. Movement patterns did not suggest mass movement out of crops after harvest, where almost half of all individuals recaptured remained within the farmland. These results suggest that some generalist frog species may have an affinity for habitats within agricultural paddocks, particularly when key habitat features like plantings are present. However, we found overall frog richness was low and did not differ between remnant patches, edges and farmland which may be an indication of habitat degradation within terrestrial habitats across the landscape. Although protection of remnant native vegetation is important, conservation strategies for the protection of amphibians will be ineffective if they do not consider the variety of land uses and the relationships of different species and their microhabitats within and outside of patches.Funding was provided by the Australian Government Research Training Program, Central Tablelands Local Land Services, NSW Environmental Trust and the Lake Cowal Foundation

A Hydroxyquinoline-Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes

We have examined the potential of the noncanonical amino acid (8-hydroxyquinolin-3-yl)alanine (HQAla) for the design of artificial metalloenzymes. HQAla, a versatile chelator of late transition metals, was introduced into the lactococcal multidrug-resistance regulator (LmrR) by stop codon suppression methodology. LmrR_HQAla was shown to complex efficiently with three different metal ions, Cu-II, Zn(II)and Rh(III)to form unique artificial metalloenzymes. The catalytic potential of the Cu-II-bound LmrR_HQAla enzyme was shown through its ability to catalyse asymmetric Friedel-Craft alkylation and water addition, whereas the Zn-II-coupled enzyme was shown to mimic natural Zn hydrolase activity

The influence of land cover roughness on the results of high resolution tsunami inundation modeling

In this paper a local case study is presented in which detailed inundation simulations have been performed to support damage analysis and risk assessment related to the 2004 tsunami in Phang Nga and Phuket, Thailand. Besides tsunami sources, bathymetry and topography, bottom roughness induced by vegetation and built environment is considered to influence inundation characteristics, such as water depths or flow velocities and therefore attracts major attention in this work. Plenty of information available on the 2004 tsunami event, high-resolution satellite imagery and extensive field measurements to derive land cover information and forest stand parameters facilitated the generation of topographic datasets, land cover maps and site-specific Manning values for the most prominent land cover classes in the study areas. The numerical models ComMIT and Mike 21 FM were used to hindcast the observed tsunami inundation and to draw conclusions on the influence of land cover on inundation patterns. Results show a strong influence of dense vegetation on flow velocities, which were reduced by up to 50% by mangroves, while the inundation extent is influenced only to a lesser extent. In urban areas, the disregard of buildings in the model led to a significant overestimation of the inundation extent. Hence different approaches to consider buildings were used and analyzed in the model. The case study highlights the importance and quantifies the effects of considering land cover roughness in inundation simulations used for local risk assessment

How To Get Your Clinical Teaching Team Ready For Curriculum Change: A Practical Guide

Our health care system is constantly adapting to change at an increasingly rapid pace. Unavoidably, this also applies to the field of medical education. As a result, clinical teaching teams face the challenging task of successfully implementing the proposed changes in daily practice. It goes without saying that implementing change takes time and that you need to be patient. However, a successful change process needs more than that. Change models or strategies could offer a helping hand. The questionnaire Specialty training’s Organizational Readiness for curriculum Change (STORC) is a tool aiming to do just that. With a focus on readiness for change, this questionnaire tries to support implementation efforts in PGME. Additionally, since change is a team effort, it focusses on clinical teaching teams particularly. In this paper, we offer a practical guide for clinical teaching teams on how to deal with any concerns or hurdles detected in any of the core elements of readiness for change, in order to smoothen and support the educational change processes these teams are confronted with