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Use of Pericranial Flap Coverage in Cochlear Implantation of the Radical Cavity: Rationale, Technique, and Experience. - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
Cochlear implant (CI) surgery in the setting of an open mastoid cavity is evolving. Two strategies are commonly pursued: a staged approach, clearing the disease, closing the meatus or the external auditory canal (EAC), and reevaluating in 3 to 6 months prior to implantation, or a single-stage procedure with mastoid obliteration without EAC closure. Meatal closure is often employed in the setting of an open mastoid cavity to reduce the risk of electrode extrusion and infection. An open cavity offers the advantages of being a single-stage procedure, permitting direct surveillance for recurrent cholesteatoma, and reducing the need for repeat computed tomography scans. We describe an approach to the coverage of a CI within a dry, open mastoid cavity using an anteriorly-based postauricular pericranial flap.Â© American Academy of Otolaryngologyâ€”Head and Neck Surgery Foundation 2016.
Genetic Analysis of the Rhodopsin Gene Identifies a Mosaic Dominant Retinitis Pigmentosa Mutation in a Healthy Individual. - Investigative ophthalmology & visual science
Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous hereditary retinal diseases that result in blindness due to photoreceptor degeneration. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP) and are responsible for 16% to 35% of adRP cases in the Western population. Our purpose was to investigate the contribution of RHO to adRP in the Israeli and Palestinian populations.Thirty-two adRP families participated in the study. Mutation detection was performed by whole exome sequencing (WES) and Sanger sequencing of RHO exons. Fluorescence PCR reactions of serially diluted samples were used to predict the percentage of mosaic cells in blood samples.Eight RHO disease-causing mutations were identified in nine families, with only one novel mutation, c.548-638dup91bp, identified in a family where WES failed to detect any causal variant. Segregation analysis revealed that the origin of the mutation is in a mosaic healthy individual carrying the mutation in approximately 13% of blood cells.This is the first report of the mutation spectrum of a known adRP gene in the Israeli and Palestinian populations, leading to the identification of seven previously reported mutations and one novel mutation. Our study shows that RHO mutations are a major cause of adRP in this cohort and are responsible for 28% of adRP families. The novel mutation exhibits a unique phenomenon in which an unaffected individual is mosaic for an adRP-causing mutation.
Imaging the Neocortex Functional Architecture Using Multiple Intrinsic Signals: Implications for Hemodynamic-Based Functional Imaging. - Cold Spring Harbor protocols
Optical imaging based on intrinsic signals has provided a new level of understanding of the principles underlying cortical development, organization, and function, providing a spatial resolution of up to 20 Âµm for mapping cortical columns in vivo. This introduction briefly reviews the development of this technique, the types of applications that have been pursued, and the general implications of some findings for other neuroimaging techniques based on hemodynamic responses (e.g., functional magnetic resonance imaging).Â© 2016 Cold Spring Harbor Laboratory Press.
Skeletal ligament healing using the recombinant human amelogenin protein. - Journal of cellular and molecular medicine
Injuries to ligaments are common, painful and debilitating, causing joint instability and impaired protective proprioception sensation around the joint. Healing of torn ligaments usually fails to take place, and surgical replacement or reconstruction is required. Previously, we showed that in vivo application of the recombinant human amelogenin protein (rHAM(+) ) resulted in enhanced healing of the tooth-supporting tissues. The aim of this study was to evaluate whether amelogenin might also enhance repair of skeletal ligaments. The rat knee medial collateral ligament (MCL) was chosen to prove the concept. Full thickness tear was created and various concentrations of rHAM(+) , dissolved in propylene glycol alginate (PGA) carrier, were applied to the transected MCL. 12 weeks after transection, the mechanical properties, structure and composition of transected ligaments treated with 0.5 Î¼g/Î¼l rHAM(+) were similar to the normal un-transected ligaments, and were much stronger, stiffer and organized than control ligaments, treated with PGA only. Furthermore, the proprioceptive free nerve endings, in the 0.5 Î¼g/Î¼l rHAM(+) treated group, were parallel to the collagen fibres similar to their arrangement in normal ligament, while in the control ligaments the free nerve endings were entrapped in the scar tissue at different directions, not parallel to the axis of the force. Four days after transection, treatment with 0.5 Î¼g/Î¼l rHAM(+) increased the amount of cells expressing mesenchymal stem cell markers at the injured site. In conclusion application of rHAM(+) dose dependently induced mechanical, structural and sensory healing of torn skeletal ligament. Initially the process involved recruitment and proliferation of cells expressing mesenchymal stem cell markers.Â© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. - Human molecular genetics
A growing number of human diseases have been linked to defects in protein glycosylation that affects a wide range of organs. Among them, O-mannosylation is an unusual type of protein glycosylation that is largely restricted to the muscular and nerve system. Consistently, mutations in genes involved in the O-mannosylation pathway result in infantile-onset, severe developmental defects involving skeleton muscle, brain and eye, such as the muscle-eye-brain disease (MIM no. 253280). However, the functional importance of O-mannosylation in these tissues at later stages remains largely unknown. In our study, we have identified recessive mutations in POMGNT1, which encodes an essential component in O-mannosylation pathway, in three unrelated families with autosomal recessive retinitis pigmentosa (RP), but without extraocular involvement. Enzymatic assay of these mutant alleles demonstrate that they greatly reduce the POMGNT1 enzymatic activity and are likely to be hypomorphic. Immunohistochemistry shows that POMGNT1 is specifically expressed in photoreceptor basal body. Taken together, our work identifies a novel disease-causing gene for RP and indicates that proper protein O-mannosylation is not only essential for early organ development, but also important for maintaining survival and function of the highly specialized retinal cells at later stages.Â© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Toward Practice Advancement in Emergency Care for Children With Autism Spectrum Disorder. - Pediatrics
There is increasing recognition that children with autism spectrum disorder (ASD) experience challenges in busy clinical environments such as the emergency department (ED). ASD may heighten adverse responses to sensory input or transitions, which can impose greater difficulty for a child to cope with situational demands. These problems can be amplified in the ED because of its busy and unpredictable nature, wait times, and bodily care. There is little literature documenting ED-based needs of children with ASD to inform clinical guidelines. The objective was to identify stakeholder perspectives in determining clinical priorities and recommendations to guide ED service delivery for children with ASD.After qualitative interviews with children, parents, and health care providers conducted in a previous phase of this study, focus groups were convened with parents of children with ASD, ED clinicians, and ED administrators (total n = 60). Qualitative data were analyzed based on an interpretive description approach.Participants identified the ED and its delivery of care as insufficient to meet the unique needs of children with ASD. The following clinical priorities were identified: ASD-focused preparedness for ED procedures and processes, wait time management, proactive strategies for sedation and restraint, child-focused support, health care provider capacity building, post-ED follow-up resources, and transition planning to adult care. Heightened child- and family-centered care were strongly recommended.Copyright Â© 2016 by the American Academy of Pediatrics.
Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma. - The Journal of steroid biochemistry and molecular biology
Genes regulated cell-cell and cell-matrix adhesion and degradation of the extracellular matrix (ECM) have been screened as potential markers of malignant thyroid nodules. The mRNA expression levels of two of them, the ECM protein-1 (ECM1) and the type II transmembrane serine protease-4 (TMPRSS4), were shown to be an independent predictor of an existing thyroid carcinoma. The vitamin D receptor (VDR) is expressed in epithelial cells of the normal thyroid gland, as well as in malignant dividing cells, which respond to the active metabolite of vitamin D by decreased proliferative activity in vitro. We evaluated the relationship between mRNA gene expressions of TMPRSS4, ECM1 and VDR in 21 papillary thyroid carcinoma samples and compared it to 21 normal thyroid tissues from the same patients. Gene expression was considered as up- or down-regulated if it varied by more or less than 2-fold in the cancer tissue relative to the normal thyroid tissue (Ca/N) from the same patient. We found an overall significant adjusted correlation between the mRNA expression ratio (ExR) of VDR and that of ECM1 in Ca/N thyroid tissue (R=0.648, P<0.001). There was a high ExR of VDR between Ca/N thyroid tissue from the same patient (3.06Â±2.9), which also exhibited a high Ca/N ExR of ECM1 and/or of TMPRSS4 (>2, P=0.05).The finding that increased VDR expression in human thyroid cancer cells is often linked to increased ECM1 and/or TPMRSS4 expression warrants further investigation into the potential role of vitamin D analogs in thyroid carcinoma.Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging. - Scientific reports
A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.
OR2W3 sequence variants are unlikely to cause inherited retinal diseases. - Ophthalmic genetics
Because of its formidable throughput, whole exome sequencing (WES) is significantly increasing the power of investigations in ophthalmic genetics. However, when applied to Mendelian conditions, WES results often contain many false positives, e.g. candidate mutations that are unrelated to the disease. For instance, highly polymorphic genes such as olfactory receptor genes carry a plethora of both common and rare alleles that are part of the normal set of variations of the human genome. Following a WES-based study, the heterozygous missense variant p.R142W in the olfactory receptor gene OR2W3 was recently reported as a pathogenic mutation causing autosomal dominant retinitis pigmentosa (RP). This variant, however, was not scored against data contained in public WES repositories, indicating that p.R142W is present in ~1 in 6500 control individuals. Therefore, if it really was pathogenic, it would be responsible for a percentage of dominant RP cases corresponding to the double of those recorded so far worldwide, or 2/3 of all RP cases (dominant, recessive, and X-linked). We therefore conclude that this sequence variant, and hence the OR2W3 gene, do not cause RP. Prompted by these findings and based on simple principles of population genetics, we suggest that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population. In addition, we propose that DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases.
An Analysis of UCNS Certified Headache Center Patient Intake Forms. - Headache
Compare the similarities and differences among headache intake forms from headache centers with United Council of Neurologic Subspecialties (UCNS) accredited headache medicine fellowships in the United States. Patient intake forms establish a first communication with patients. There have been no studies evaluating them at headache centers. Analysis of these forms can provide insight into their content and potential for improvement.This observational study involved collection and analysis of intake forms from 25 UCNS fellowship accredited headache centers from July 2014 to October 2014. Forms were compared and contrasted in terms of data fields included, response format, and use of validated assessment tools.Forms shared many common elements, yet were highly variable in content, style, scales, and methods of analysis. Twenty percent (5/20) of centers did not have a formal intake form. Forms ranged from 1 to 28 pages. Seventy percent (12/17) utilized a check box format, 23% (4/17) utilized an open ended/fill in the blank format, and 6% (1/17) utilized a circle the response(s) format. Family history was inquired about in 82% (14/17) of forms and past medical history (PMH) in 58% (10/17) of forms. Gender questions were asked 82% (14/17) of the time for women, 29% (5/17) for men. Eighty-eight percent (15/17) of forms had questions concerning any type of previous medication tried.Patient intake forms are useful for clinical purposes, but vary markedly between UCNS headache centers. Ultimately, a universal intake form could be generated, providing a research-based alternative to the form currently used at each center. Use of a standardized intake form by UCNS centers would streamline data collection, a good first step in the eventual generation of a headache registry.Â© 2016 American Headache Society.
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