Publications by authors named "David Wynne"

40 Publications

Tumefactive Demyelination Appearing as Multiple Cystic Brain Lesions.

World Neurosurg 2021 Jun 12;153:6-8. Epub 2021 Jun 12.

Department of Neurosurgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

Tumefactive demyelinating lesions (TDLs) are a rare sequelae of idiopathic inflammatory demyelinating diseases of the central nervous system. Their propensity to mimic tumor and abscess poses a diagnostic challenge for the clinician. Our case depicts TDLs causing right-hand focal sensory seizures in an otherwise healthy 35-year-old female. The differential diagnosis of metastatic disease and infection were excluded on histology. Ensuing magnetic resonance imaging of the cord, in addition to cerebral spinal fluid analysis, supported the diagnosis of idiopathic inflammatory demyelinating diseases. This case highlights the need to consider the rare diagnosis of TDL when imaging shows cystic brain lesions in an otherwise healthy young adult.
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http://dx.doi.org/10.1016/j.wneu.2021.05.132DOI Listing
June 2021

Quality of Literature Searches Published in Leading Neurosurgical Journals: A Review of Reviews.

Neurosurgery 2021 04;88(5):891-899

National Trauma Research Institute, Prahran, Australia.

Background: There is mounting evidence that the search strategies upon which systematic reviews (SRs) are based frequently contain errors are incompletely reported or insensitive.

Objective: To appraise the quality of search strategies in the 10 leading specialty neurosurgical journals and identify factors associated with superior searches.

Methods: This research-on-research study systematically surveyed SRs published in the 10 leading neurosurgical journals between 01/10/2017 and 31/10/2019. All SRs were eligible for assessment using a predefined coding manual that was adapted from the preferred reporting items for systematic reviews and meta-analyses (PRISMA), a measurement tool to assess systematic reviews (AMSTAR), and Cochrane Collaboration guidelines. The PubMed interface was used to search the MEDLINE database, which was supplemented by individual journal searches. Descriptive statistics were utilized to identify factors associated with improved search strategies.

Results: A total of 633 articles were included and contained a median of 19.00 (2.00-1654.00) studies. Less than half (45.97%) of included search strategies were considered to be reproducible. Aggregated reporting score was positively associated with in-text reference to reporting guideline adherence (τb = 0.156, P < .01). The number of articles retrieved by a search (τb = 0.11, P < .01) was also associated with the reporting of a reproducible search strategy.

Conclusion: This study demonstrates that the search strategies used in neurosurgical SRs require improvement. In addition to increasing awareness of reporting standards, we propose that this be achieved by the incorporation of PRISMA and other guidelines into article submission and peer-review processes. This may lead to the conduct of more informative SRs, which may result in improved clinician decision-making and patient outcomes.
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http://dx.doi.org/10.1093/neuros/nyaa573DOI Listing
April 2021

Aerosolisation in endonasal endoscopic pituitary surgery.

Pituitary 2021 Aug 19;24(4):499-506. Epub 2021 Jan 19.

Department of Anaesthesia and Acute Pain Medicine, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, VIC, 3065, Australia.

Purpose: To determine the particle size, concentration, airborne duration and spread during endoscopic endonasal pituitary surgery in actual patients in a theatre setting.

Methods: This observational study recruited a convenience sample of three patients. Procedures were performed in a positive pressure operating room. Particle image velocimetry and spectrometry with air sampling were used for aerosol detection.

Results: Intubation and extubation generated small particles (< 5 µm) in mean concentrations 12 times greater than background noise (p < 0.001). The mean particle concentrations during endonasal access were 4.5 times greater than background (p = 0.01). Particles were typically large (> 75 µm), remained airborne for up to 10 s and travelled up to 1.1 m. Use of a microdebrider generated mean aerosol concentrations 18 times above baseline (p = 0.005). High-speed drilling did not produce aerosols greater than baseline. Pituitary tumour resection generated mean aerosol concentrations less than background (p = 0.18). Surgical drape removal generated small and large particles in mean concentrations 6.4 times greater than background (p < 0.001).

Conclusion: Intubation and extubation generate large amounts of small particles that remain suspended in air for long durations and disperse through theatre. Endonasal access and pituitary tumour resection generate smaller concentrations of larger particles which are airborne for shorter periods and travel shorter distances.
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http://dx.doi.org/10.1007/s11102-021-01125-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814858PMC
August 2021

Endoscopic Fenestration of a Symptomatic Porencephalic Cyst in an Adult.

World Neurosurg 2020 09 20;141:245-246. Epub 2020 Jun 20.

Department of Neurosurgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

A porencephalic cyst is an aberrant accumulation of cerebrospinal fluid within the brain parenchyma. Its occurrence is rare, with an incidence of 3.5 per 100,000 live births. Etiology is considered the result of perinatal cerebral ischemia or hemorrhage, leading to parenchymal loss. Porencephalic cysts are diagnosed radiologically, and management depends on the clinical manifestation. Our case depicts a porencephalic cyst presenting with nondominant parietal lobe symptoms in adulthood. We hypothesize that a membrane between the cyst and ventricle allowed formation of a 1-way valve that led to slowly progressive cyst enlargement, eventually causing mass effect and nondominant parietal lobe symptoms. Endoscopic fenestration of the cyst membrane into the lateral ventricle was successful in reducing cyst volume and improving mass effect.
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http://dx.doi.org/10.1016/j.wneu.2020.06.092DOI Listing
September 2020

iron transport mutant has normal pathogenicity in .

MicroPubl Biol 2019 Aug 8;2019. Epub 2019 Aug 8.

University of Portland, Swindells Hall 108, Portland, Oregon USA 97203-5798.

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http://dx.doi.org/10.17912/micropub.biology.000124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252244PMC
August 2019

Prevalence, risk factors and management strategies for otological problems in girls with Turner syndrome.

Acta Paediatr 2020 10 29;109(10):2075-2083. Epub 2019 Dec 29.

Section of Child Health, School of Medicine, University of Glasgow, Glasgow, UK.

Aim: To determine the prevalence and risk factors of ear disease in Turner syndrome (TS), propose an algorithm for future surveillance and recommend preventative strategies.

Methods: Review of TS patients seen in the West of Scotland between 1989 and 2015, with questionnaire follow-up in 2015.

Results: Of 168 girls, median age 27.3 (3.8-47.2) years, ear problems occurred more frequently with 45,X and 45,X/46,XiXq than other karyotypes: 71/103 (69%) versus 23/65 (35%). Recurrent acute otitis media (AOM) first developed at 0-5 years in 23 (40%) girls, persisting in 16 (10%) at 5-10 years; and first developing at 5-10 years in 11 (7%). Persistent otitis media with effusion (OME) first developed at 0-5 and 5-10 years in 23 (40%) and 14 (8%) girls. Recurrent AOM was significantly linked with cholesteatoma in 8 (4.9%) girls (7 aged >10 years). Permanent hearing loss was documented in 28 girls (16.7%), with 16 (9.5%) receiving hearing aids (bone-anchored in 3).

Conclusion: Acute otitis media and OME occur commonly in preschool TS girls and may persist or newly develop in later childhood. Recurrent AOM predisposes to cholesteatoma. Strategies to reduce otological morbidity include: intensive patient education, annual audiology, vaccinations and a randomised trial of antibiotic prophylaxis in high-risk groups.
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http://dx.doi.org/10.1111/apa.15128DOI Listing
October 2020

Validation of Animal Models for Simulation Training in Pediatric Laryngotracheal Reconstruction.

Ann Otol Rhinol Laryngol 2020 Jan 30;129(1):46-54. Epub 2019 Aug 30.

Department of Otolaryngology, Head and Neck Surgery, Royal Hospital for Children, Glasgow, UK.

Objectives: To assess and compare the face (FV) and content validity (CV) of three ex vivo animal models for simulation training in pediatric laryngotracheal reconstruction (LTR).

Methods: Feasibility of performing LTR was assessed on the head and neck of three different animals (lamb/suckling-pig/rabbit) and laryngeal dimensions and qualitative observations were recorded. A 19-item five-point Likert scale questionnaire was completed for each model to assess FV and CV. Data was prospectively collected and analyzed using descriptive and nonparametric statistics.

Results: All three models were suitable for LTR simulation with laryngeal dimensions corresponding to 0-2 years (rabbit), 5-10 (pig) and >10 years (lamb model). Five trainees and five expert pediatric otolaryngologists performed LTR on each model. The overall median FV score was 5 for the lamb model (IQR 4-5), 3 for the rabbit (IQR 2-3), and 4 for the pig (IQR 4-4). The overall median CV score was 5 for the lamb (IQR 5-5), 2 for the rabbit (IQR 2-3), and 4 for the pig model (IQR 4-4). Comparison of the models demonstrated the lamb to be favored as the most realistic and practical model for simulation training in pediatric LTR, with both the lamb and the porcine model attaining validation thresholds.

Conclusion: Our study is the first comparative validation assessment of animal models for use in pediatric LTR simulation and it supports the use of ex vivo lamb and porcine models for use in LTR surgical skills training. The lamb model was the favored simulation model while the rabbit was considered inferior for simulation training in pediatric LTR.

Level Of Evidence: 3b.
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http://dx.doi.org/10.1177/0003489419870820DOI Listing
January 2020

A systematic review of simulated laryngotracheal reconstruction animal models.

Laryngoscope 2019 01 16;129(1):235-243. Epub 2018 Oct 16.

Department of Otolaryngology-Head and Neck Surgery, Royal Hospital for Children, Glasgow, United Kingdom.

Objectives: Review of the literature to identify practical, high-fidelity, commercially available animal models for simulation training and surgical skills maintenance in laryngotracheal reconstruction (LTR).

Methods: A systematic review of PubMed and Embase databases was conducted independently by two authors, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms included "laryngotracheal reconstruction," "laryngotracheoplasty," "pig and larynx," "sheep and larynx," and "rabbit and larynx." Articles were then assessed, identifying model cost and availability, model validation, feasibility as a training tool, and verisimilitude to pediatric LTR.

Results: In total, 79 articles were considered suitable for inclusion in the study, incorporating both in vitro and in vivo models. Models utilized included rabbit (n = 69), pig (n = 7), sheep (n = 1), and goat (n = 2). The rabbit model was similar in size to the neonate, but differences in laryngeal anatomy and cartilage texture made graft insertion difficult. The anatomy of the pig, sheep, and goat larynges more closely resembled the pediatric patient, allowing improved grafting, but corresponded more in size to that of an older child. Commercial availability of the pig and sheep was considered greatest, and was reflected in cost. None of the animal models identified in the literature have been validated as a simulation tool.

Conclusions: The rabbit, sheep and pig models seemed to demonstrate the greatest potential for use as advanced pediatric airway surgery simulation models, with the rabbit model being most utilized in the literature. However, as yet there have been no models formally validated as a simulation training tool. Laryngoscope, 129:235-243, 2019.
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http://dx.doi.org/10.1002/lary.27288DOI Listing
January 2019

Perceptual Evaluation of Voice Disorder in Children Who Have Had Laryngotracheal Reconstruction Surgery and the Relationship Between Clinician Perceptual Ratingof Voice Quality and Parent Proxy/Child Self-Report of Voice-Related Quality of Life.

J Voice 2019 Nov 23;33(6):945.e27-945.e35. Epub 2018 Aug 23.

University Hospital Crosshouse, NHS Ayrshire and Arran, Kilmarnock, United Kingdom.

Reliability of the GRBAS tool for perceptual evaluation of paediatric voice disorder is measured in this study of children with a history of laryngotracheal reconstruction surgery (LTR). Additionally, the relationship between parent proxy/child self-report of voice-related quality of life with clinician perceptual rating of voice quality is analysed. Eleven children with a history of LTR provided voice recordings following the stimuli set by the CAPE-V protocol. Subjective impact of voice quality on life was measured using the paediatric voice-related quality of life questionnaire. Four trained judges rated the sound files according to both the GRBAS and CAPE-V protocol. Intra-class correlation coefficients were high for both intra-rater and inter-rater judgments across all parameters of the GRBAS protocol, and a strong correlation was found between the grade rating of the GRBAS and the overall severity rating of the CAPE-V. Some elements of parent proxy reporting of voice-related quality of life were significantly negatively correlated with clinician perceptual rating of voice quality, while there was no significant relationship between child self-report and clinician perceptual rating.
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http://dx.doi.org/10.1016/j.jvoice.2018.07.009DOI Listing
November 2019

The kallikrein-Kinin system modulates the progression of colorectal liver metastases in a mouse model.

BMC Cancer 2018 04 4;18(1):382. Epub 2018 Apr 4.

Department of Surgery, University of Melbourne, Austin Health, Lance Townsend Building Level 8, Studley Rd, Heidelberg, VIC, 3084, Australia.

Background: The Kallikrein-Kinin System (KKS) has been found to play a role in tumor progression in several cancers. The KKS metabolic cascade depends on signalling through two cross talking receptors; bradykinin receptor 1 (B1R) and bradykinin receptor 2 (B2R). Activation of the Kinin receptor is responsible for multiple pathophysiologic functions including increase of vascular permeability and induction of host inflammatory responses that exert diverse effects on tumor growth.

Methods: B1R and B2R expression on mouse and human CRC cell lines was investigated. Changes in tumor growth and progression was assessed in male CBA mice bearing colorectal liver metastases (CRLM) following treatment with B1R or B2R blockers. In vitro cultures of human SW-480 and mouse colorectal cancer (MoCR) cell lines were examined for changes in their proliferation and migration properties following treatment with B1R or B2R blockers.

Results: Both colorectal cancer cell lines tested strongly positive for B1R and B2R expression. Inhibition of both receptors retarded tumor growth but only B1R blockade significantly reduced tumor load and increased tumor apoptosis. Blockade of either receptor reduced tumor vascularization in vivo and significantly inhibited proliferation and migration of colorectal cancer cells in vitro.

Conclusion: Taken together, the present study demonstrated that kinin receptor blockade inhibited tumor growth and reduced its invading properties suggesting that KKS manipulation could be a novel target in colorectal cancer therapy.
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http://dx.doi.org/10.1186/s12885-018-4260-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885419PMC
April 2018

Combined membranous nephropathy and tubulointerstitial nephritis as a rare renal manifestation of IgG4-related disease: a case-based literature review.

CEN Case Rep 2018 May 1;7(1):137-142. Epub 2018 Feb 1.

Internal Medicine Residency Program, Brookwood Baptist Health, 817 Princeton Ave. SW, Birmingham, AL, 35211, USA.

IgG4-related disease (IgG4-RD) is a newly recognized immune-mediated multisystemic disease characterized by a fibro-inflammatory condition with tissue infiltration of IgG4-positive plasma cells and often associated with elevated serum IgG4 levels. Typical renal involvement of IgG4-RD presents as tubulointerstitial nephritis (TIN), membranous or membranoproliferative nephropathy. We are presenting a case with combined IgG4 membranous nephropathy and TIN, as well as a literature review on pathophysiology, diagnosis and treatment of IgG4-RD. A 62-year-old man presented with weight loss and fatigue. Labs showed significant proteinuria and hematuria with elevated serum creatinine (2.5 mg/dL). CT/PET scan found scattered lymphadenopathy without increased FDG uptake. Kidney biopsy showed glomerular lesions as well as severe interstitial fibrosis and tubular atrophy. Immunohistochemistry study was negative for anti-phospholipase A2 receptor antibodies and showed interstitial lymphocytic infiltration with IgG4 positive plasma cells. Patient also had elevated serum IgG4 level and IgG4 to total IgG ratio. Prednisone treatment was initiated soon after the diagnosis was made, patient responded well with proteinuria and hematuria both resolved. IgG4-related disease (IgG4-RD) is a newly increasingly recognized immune-mediated multisystemic disease; IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with proteinuria.
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http://dx.doi.org/10.1007/s13730-018-0311-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886942PMC
May 2018

Protein Immunodepletion and Complementation in Egg Extracts.

Cold Spring Harb Protoc 2018 09 4;2018(9). Epub 2018 Sep 4.

Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, New York 10065;

The egg extract system has been widely used to study cell cycle events, including DNA replication, nuclear envelope formation, spindle assembly, chromosome condensation and kinetochore formation. The functional roles of the proteins involved in these processes can be determined by immunodepleting a protein of interest from the extract. As immunodepletion may result in co-depletion of other proteins, the protein of interest can be added back to the extract to verify its function. Additionally, proteins harboring point mutations or domain deletions may be added to assess their functions. Here we outline the immunodepletion procedure and two separate methods for restoring a protein of interest: addition of either a recombinant protein or an mRNA that supports translation in egg extracts. The tradeoffs between these two methods are discussed.
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http://dx.doi.org/10.1101/pdb.prot097113DOI Listing
September 2018

Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression.

J Cell Biol 2017 04 17;216(4):925-941. Epub 2017 Mar 17.

Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065

The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain. The microtubule-binding capacity of the SAH domain is important for mitotic arrest in conditions of suppressed microtubule dynamics, and the duration of mitotic arrest dictates the probability, but not the timing, of cell death. Although independent targeting of INCENP to microtubules or the kinetochore/centromere promotes the mitotic checkpoint, it is insufficient for a robust mitotic arrest. Altogether, our results demonstrate that dual recognition of chromatin and microtubules by CPC is important for checkpoint maintenance and determination of cell fate in mitosis.
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http://dx.doi.org/10.1083/jcb.201609061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379950PMC
April 2017

Heterogeneous architecture of vertebrate kinetochores revealed by three-dimensional superresolution fluorescence microscopy.

Mol Biol Cell 2016 11 11;27(22):3395-3404. Epub 2016 May 11.

Laboratory of Chromosome and Cell Biology, Rockefeller University, New York, NY 10065

The kinetochore is often depicted as having a disk-like architecture in which the outer layer of proteins, which engage microtubules and control checkpoint signaling, are built on a static inner layer directly linked to CENP-A chromatin. Here, applying three-dimensional (3D) structural illumination microscopy (SIM) and stochastic optical reconstruction microscopy (STORM) to Xenopus egg extracts and tissue culture cells, we report various distribution patterns of inner and outer kinetochore proteins. In egg extracts, a configuration in which outer kinetochore proteins surround the periphery of CENP-A chromatin is common, forming an ∼200-nm ring-like organization that may engage a bundle of microtubule ends. Similar rings are observed in Xenopus tissue culture cells at a lower frequency but are enriched in conditions in which the spindle is disorganized. Although rings are rare in human cells, the distribution of both inner and outer kinetochore proteins elongates in the absence of microtubule attachment in a manner dependent on Aurora B. We propose a model in which the 3D organization of both the outer and inner kinetochore regions respond to the progression from lateral to end-on microtubule attachments by coalescing into a tight disk from less uniform distributions early in prometaphase.
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http://dx.doi.org/10.1091/mbc.E16-02-0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221576PMC
November 2016

Clinical Decision Support at the Point-of-Order Entry: An Education Simulation Pilot with Medical Students.

Acad Radiol 2016 10 29;23(10):1309-18. Epub 2016 Apr 29.

Baylor College of Medicine, 1 Baylor Plaza, MS: BCM 360, Houston, TX 77030.

Rationale And Objectives: We have been called to reform radiology undergraduate medical education (UME) curricula. Clinically available clinical decision support provides an opportunity to improve education regarding appropriate imaging utilization, patient safety, and cost-effective care.

Material And Methods: We created an education simulation portal utilizing integrated clinical decision support. The portal was then piloted with 34 volunteer medical students at our institution in a blended learning environment. A program assessment was performed utilizing the results from a qualitative survey, pre-test, and post-test.

Results: The large majority of medical students felt this supplemental education resource should be included in our UME curriculum (85.29%). All students perceived value in the education simulation portal. The students performed significantly better on the post-test in multiple categories (overall P <.0001), including Choosing Wisely topics (P = .0207).

Conclusions: Based on our program assessment from this pilot program, we believe this innovative educational resource has significant potential to fill curricular gaps in radiology UME curricula. This platform is scalable and can be further customized to fill needs across the continuum of medical education.
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http://dx.doi.org/10.1016/j.acra.2016.01.020DOI Listing
October 2016

Improving the practice of the World Health Organisation's surgical pause checklist at a tertiary paediatric surgical unit.

Scott Med J 2016 May 9;61(2):88-91. Epub 2016 Jun 9.

Consultant in Paediatric Otolaryngology, Hospital for Children, UK.

Background And Aims: The World Health Organisation (WHO) surgical checklist acts as a safety check before surgery. The three components are: sign in, surgical pause and sign out. This study aims to assess and improve the surgical pause at a tertiary paediatric surgical unit.

Methods And Results: Theatre nurses used as a standardised tool to record how the pause was carried out. All other theatre staff were blinded. Presentation of these data at departmental meetings allowed creation of a checklist poster which was placed in every theatre. Data collection was repeated five months later. Data on 114 operations were initially collected. Fifty-one per cent of operations completed all four steps to guideline. Introduction step met guideline in 61% of operations, identity and procedure in 90%, checklist in 98% and concerns in 71%. Following intervention, data were collected from 39 operations; 77% of operations completed all four steps to guideline. Introduction step met guideline in 87% of operations, identity and procedure in 100%, checklist in 100% and concerns in 90%.

Conclusions: This study shows that by engaging with theatre staff to create an acceptable checklist poster, better standard of patient safety in the operating theatre can be achieved.
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http://dx.doi.org/10.1177/0036933016649873DOI Listing
May 2016

Kinetochore function is controlled by a phospho-dependent coexpansion of inner and outer components.

J Cell Biol 2015 Sep;210(6):899-916

It is widely accepted that the kinetochore is built on CENP-A-marked centromeric chromatin in a hierarchical order from inner to outer kinetochore. Recruitment of many kinetochore proteins depends on microtubule attachment status, but it remains unclear how their assembly/disassembly is orchestrated. Applying 3D structured illumination microscopy to Xenopus laevis egg extracts, here we reveal that in the absence of microtubule attachment, proteins responsible for lateral attachment and spindle checkpoint signaling expand to form micrometer-scale fibrous structures over CENP-A-free chromatin, whereas a core module responsible for end-on attachment (CENP-A, CENP-T, and Ndc80) does not. Both outer kinetochore proteins (Bub1, BubR1, Mad1, and CENP-E) and the inner kinetochore component CENP-C are integral components of the expandable module, whose assembly depends on multiple mitotic kinases (Aurora B, Mps1, and Plx1) and is suppressed by protein phosphatase 1. We propose that phospho-dependent coexpansion of CENP-C and outer kinetochore proteins promotes checkpoint signal amplification and lateral attachment, whereas their selective disassembly enables the transition to end-on attachment.
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http://dx.doi.org/10.1083/jcb.201506020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576862PMC
September 2015

Early identification of pituitary dysfunction in congenital nasal pyriform aperture stenosis: recommendations based on experience in a single centre.

Horm Res Paediatr 2015 14;83(5):302-10. Epub 2015 Mar 14.

Department of Paediatric Endocrinology, Royal Hospital for Sick Children, Glasgow, UK.

Background: Congenital nasal pyriform aperture stenosis (CNPAS) is an increasingly recognised cause of upper airway obstruction associated with midline abnormalities. Studies have described pituitary dysfunction in 40% of patients. We aimed to develop guidelines for: (a) the early identification of pituitary insufficiency to minimise surgical risk and (b) to stratify patients for follow-up.

Methods: Retrospective case note review of patients with CNPAS between 2000 and 2014 in a tertiary paediatric unit.

Results: 20 patients (12 female:8 male) were analysed; 16 were diagnosed during the neonatal period while 4 were diagnosed later. There was no consistent approach in the evaluation of the pituitary axis at diagnosis. Pituitary dysfunction was identified in 3 (15%) patients, 2 of whom were found during evaluation of short stature in mid-late childhood. Hypoglycaemia and conjugated hyperbilirubinaemia, but not the degree of stenosis, were highly predictive of pituitary dysfunction (p < 0.05). Available height standard deviation score (SDS) data at 1 year of 70% of our patients identified both of the late-diagnosed growth hormone-deficient patients, with SDS of -2.6 and -3.6, respectively.

Conclusion: All CNPAS patients should have MRI of the brain and baseline endocrine investigations at diagnosis. Growth monitoring for at least 1 year is recommended as low, or falling, height SDS at 1 year is a good predictor of pituitary dysfunction.
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http://dx.doi.org/10.1159/000369805DOI Listing
March 2016

Using Hyaluronic Acid for Improving Vocal Function in a Prepubescent Boy With an Atrophied Right Vocal Fold.

J Voice 2015 Jul 19;29(4):494-7. Epub 2015 Feb 19.

Ear, Nose and Throat Department, Royal Hospital for Sick Children, Yorkhill Hospitals, Glasgow, Scotland.

Objectives: A single case study is reported of a child who underwent several surgical procedures as result of congenital grade III subglottic stenosis. The anterior aspect of the right vocal cord was damaged and underwent atrophy during one of these procedures. Now, an active 10-year-old, the patient has become increasingly aware of his vocal limitations on functional activities. Injection of hyaluronic acid into the vocal folds has been known to provide improved voice quality in adults although there are no known cases reported of this procedure in children.

Methods: This article reports voice outcomes after injection of hyaluronic acid into the Reinke's space in a single case study. Voice recordings were made before, after, and 1 month after injection. The voice recordings were subject to acoustic and perceptual analysis.

Results: Post and follow-up voice recordings demonstrate decreased jitter, shimmer, and harmonics-to-noise ratio. Perceptual evaluation indicates improved voice quality.

Conclusion: Injection of hyaluronic acid in children who require voice augmentation is possible and may contribute to increased vocal function and improved voice outcomes.
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http://dx.doi.org/10.1016/j.jvoice.2014.09.020DOI Listing
July 2015

A critical appraisal of ventilation tube insertion in children with cleft palate--reply.

JAMA Otolaryngol Head Neck Surg 2015 Feb;141(2):190

Department of Plastic Surgery, Royal Hospital for Sick Children, Glasgow, Scotland.

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http://dx.doi.org/10.1001/jamaoto.2015.38DOI Listing
February 2015

Parent and Child Responses to the Pediatric Voice-Related Quality-of-Life Questionnaire.

J Voice 2015 May 22;29(3):299-303. Epub 2015 Jan 22.

Ear, Nose and Throat Department, Royal Hospital for Sick Children, Yorkhill Hospitals, Glasgow, Scotland.

Objectives: When assessing pediatric dysphonia, there are different approaches that can be taken in gathering a subjective view of the impact voice difficulties have on a child. Most valid questionnaires require parent-proxy reporting, although it has become increasingly important to gather the views of children themselves. This study reports a pilot study of an adaptation to the Pediatric Voice-Related Quality-of-Life Questionnaire (PVRQoL).

Methods: A total of 24 parent and child dyads were recruited from a tertiary pediatric voice clinic. Children were aged between 3 years and 8 months and 15 years and 3 months. Parents completed the existing PVRQoL questionnaire, whereas their children were given a child-adapted version. Follow-up completion of the child questionnaire was conducted after a 2-week period.

Results: There was a good correlation between the two time periods when children completed the adapted PVRQoL and also between parent and child responses. Of particular interest, however, was the different ratings on individual items by parents and their children with parents tending to overestimate the extent to which their children may be emotionally affected by their voice disorder.

Conclusions: This study shows that children have much to tell about their own voice-related quality of life, so our conclusion is that they should also be self-assessed. The PVRQoL when adapted for use with children offers an additional insight that can be gathered in a relatively short timeframe and be considered with other assessments of vocal function.
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http://dx.doi.org/10.1016/j.jvoice.2014.08.004DOI Listing
May 2015

Complications of ventilation tube insertion in children with and without cleft palate: a nested case-control comparison.

JAMA Otolaryngol Head Neck Surg 2014 Oct;140(10):940-3

Department of Plastic Surgery, Royal Hospital for Sick Children, Glasgow, Scotland.

Importance: Optimizing hearing in patients with cleft lip and/or palate (CLP) by early recognition and management of otitis media with effusion is essential for speech development. Some evidence has suggested higher complication rates from ventilation tube (VT) insertion in patients with CLP and has led to a trend not to treat these patients surgically. However, studies have failed to match comparison groups for age and sex.

Objective: To compare complication rates from VT insertion in pediatric patients with and without CLP.

Design, Setting, And Participants: The study used a nested case-control design to evaluate 60 pediatric patients with CLP who underwent VT insertion at a children's hospital. The control group of age- and sex-matched patients was selected from a database of 2943 VT insertions.

Interventions: All patients were administered general anesthesia and underwent VT insertion by a pediatric otorhinolaryngology (ENT) team.

Main Outcomes And Measures: The primary outcomes were numbers of otorrhea complications. Secondarily, rates of attendance at an ENT clinic specifically for complications were evaluated. Finally, numbers of complications other than otorrhea were assessed but not statistically analyzed owing to the varied types and low numbers in each group.

Results: The control cohort had 151 documented cases of otorrhea compared with 121 in the CLP group (ratio 1.25:1); the difference between groups was not statistically significant (P = .52). There was no significant difference in mean ENT clinic visits per patient for complications between groups (0.80 in the CLP group, 0.78 for controls) (P = .66). Regarding complications other than otorrhea, the control group reported more than the CLP group (43 vs 25; ratio, 1.7:1).

Conclusions And Relevance: Complication rates of VT placement among patients with CLP were not higher than those among patients without CLP. Therefore, treatment with VT insertion should be administered to patients with CLP under the same guidelines as for those without CLP. Indeed, there could be an argument for a shift in practice toward more aggressive treatment of patients with CLP, who are already vulnerable to speech and social developmental delay.
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http://dx.doi.org/10.1001/jamaoto.2014.1657DOI Listing
October 2014

The paediatric voice clinic.

Arch Dis Child 2014 Oct 28;99(10):912-5. Epub 2014 May 28.

Department of Paediatric Otolaryngology, Royal Hospital for Sick Children, Glasgow, UK.

Background: Prevalence of paediatric voice disorders has been reported as 6-9% in children of school age. The appropriate diagnosis and management of paediatric voice disorders is essential for progress in education and psychosocial development. This paper presents a review of a UK tertiary paediatric voice clinic experience of referral patterns, diagnosis, management and socioeconomic variations.

Methods: An audit of 195 consecutive appointments (154 were new patients) between October 2009 and September 2013 at a monthly paediatric voice clinic based at the Royal Hospital for Sick Children in Glasgow.

Results: Of the 154 new patients, 86 were male and 68 were female. The age at first clinic appointment shows a trimodal peak at ages 5, 8 and 11 years. General practitioners were the main referral source (46%). Vocal cord nodules accounted for 52% of diagnoses with a male predominance. Clinic attendance was most common from Scottish Index of Multiple Deprivation groups 1 (most deprived) and 5 (least deprived). Analysis of the muscle tension dysphonia group indicates that they are more likely to come from social groups 4 or 5 (69%) and an older age group (mean age 10.4 years).

Discussion: A dedicated paediatric voice clinic is the optimal method for assessment, diagnosis and management of these patients. Diagnosis is possible on the majority of the patients in clinic, with the predominant pathology being vocal cord nodules that receive speech and language therapy. Socioeconomic group appears to have an influence on paediatric voice particularly vocal cord nodules and muscle tension dysphonia.
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http://dx.doi.org/10.1136/archdischild-2013-305683DOI Listing
October 2014

The thyroid: review of imaging features and biopsy techniques with radiologic-pathologic correlation.

Radiographics 2014 Mar-Apr;34(2):276-93

From the Department of Radiology (A.C.N., Z.A.M., B.S.H., D.M.W.) and Department of Pathology and Immunology (R.A.P., M.L.O.), Baylor College of Medicine, One Baylor Plaza, MS: BCM 360, Houston, TX 77030.

Knowledge of the normal and abnormal imaging appearances of the thyroid gland is essential for appropriate identification and diagnosis of thyroid lesions. Thyroid nodules are often detected incidentally at computed tomography, magnetic resonance imaging, and positron emission tomography; however, ultrasonography (US) is the most commonly used imaging modality for characterization of these nodules. US characteristics that increase the likelihood of malignancy in a thyroid nodule include microcalcifications, solid composition, and central vascularity. Nuclear scintigraphy is commonly used for evaluation of physiologic thyroid function and for identification of metabolically active and inactive nodules. When fine-needle aspiration biopsy (FNAB) of a lesion is indicated based on clinical and radiologic features, appropriate US-guided biopsy technique and careful cytologic analysis are crucial for making the diagnosis. FNAB and core biopsy are the two percutaneous techniques used to obtain a specimen, with the latter technique being indicated following nondiagnostic or indeterminate FNAB. Specimen adequacy and diagnostic accuracy vary due to several factors, including location of aspiration and biopsy technique used. The radiologist must have a basic knowledge of thyroid disease, be familiar with specimen processing, and recognize the cytologic and radiologic appearances of thyroid lesions, all of which will facilitate the management of these lesions. Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/rg.342135067DOI Listing
January 2015

Making an effective switch at the kinetochore by phosphorylation and dephosphorylation.

Chromosoma 2013 Jun 20;122(3):135-58. Epub 2013 Mar 20.

Laboratory of Chromosome and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.

The kinetochore, the proteinaceous structure on the mitotic centromere, functions as a mechanical latch that hooks onto microtubules to support directional movement of chromosomes. The structure also brings in a number of signaling molecules, such as kinases and phosphatases, which regulate microtubule dynamics and cell cycle progression. Erroneous microtubule attachment is destabilized by Aurora B-mediated phosphorylation of multiple microtubule-binding protein complexes at the kinetochore, such as the KMN network proteins and the Ska/Dam1 complex, while Plk-dependent phosphorylation of BubR1 stabilizes kinetochore-microtubule attachment by recruiting PP2A-B56. Spindle assembly checkpoint (SAC) signaling, which is activated by unattached kinetochores and inhibits the metaphase-to-anaphase transition, depends on kinetochore recruitment of the kinase Bub1 through Mps1-mediated phosphorylation of the kinetochore protein KNL1 (also known as Blinkin in mammals, Spc105 in budding yeast, and Spc7 in fission yeast). Recruitment of protein phosphatase 1 to KNL1 is necessary to silence the SAC upon bioriented microtubule attachment. One of the key unsolved questions in the mitosis field is how a mechanical change at the kinetochore upon microtubule attachment is converted to these and other chemical signals that control microtubule attachment and the SAC. Rapid progress in the field is revealing the existence of an intricate signaling network created right on the kinetochore. Here we review the current understanding of phosphorylation-mediated regulation of kinetochore functions and discuss how this signaling network generates an accurate switch that turns on and off the signaling output in response to kinetochore-microtubule attachment.
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http://dx.doi.org/10.1007/s00412-013-0401-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665160PMC
June 2013

Dynein-dependent processive chromosome motions promote homologous pairing in C. elegans meiosis.

J Cell Biol 2012 Jan;196(1):47-64

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Meiotic chromosome segregation requires homologue pairing, synapsis, and crossover recombination, which occur during meiotic prophase. Telomere-led chromosome motion has been observed or inferred to occur during this stage in diverse species, but its mechanism and function remain enigmatic. In Caenorhabditis elegans, special chromosome regions known as pairing centers (PCs), rather than telomeres, associate with the nuclear envelope (NE) and the microtubule cytoskeleton. In this paper, we investigate chromosome dynamics in living animals through high-resolution four-dimensional fluorescence imaging and quantitative motion analysis. We find that chromosome movement is constrained before meiosis. Upon prophase onset, constraints are relaxed, and PCs initiate saltatory, processive, dynein-dependent motions along the NE. These dramatic motions are dispensable for homologous pairing and continue until synapsis is completed. These observations are consistent with the idea that motions facilitate pairing by enhancing the search rate but that their primary function is to trigger synapsis. This quantitative analysis of chromosome dynamics in a living animal extends our understanding of the mechanisms governing faithful genome inheritance.
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http://dx.doi.org/10.1083/jcb.201106022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255982PMC
January 2012

Development of a minimum protocol for assessment in the paediatric voice clinic. Part 2: subjective measurement of symptoms of voice disorder.

Logoped Phoniatr Vocol 2012 Apr 13;37(1):39-44. Epub 2011 Dec 13.

University of Strathclyde, School of Psychological Sciences and Health, Speech and Language Therapy, 76 Southbrae Drive, Glasgow, G13 1PP, UK.

The European Laryngological Society (ELS) recommend that functional assessment of voice disorder in adults requires evaluation of a number of different parameters. These include perceptual evaluation of voice, videostroboscopic imaging of vocal fold movement, acoustic analysis of specific voicing aspects, aerodynamic support for voicing, and a subjective rating of voice impact. No specific guidelines are available for children, but a similar range of parameters is needed to guide intervention and measure outcomes. The development of subjective voice measures for adults and their adaptations for the paediatric population are reviewed and compared to the research comparing these to evaluation of vocal function. The need for further refinement of child assessment measures, and a proposal of how these might be developed, is discussed.
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http://dx.doi.org/10.3109/14015439.2011.638671DOI Listing
April 2012
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