Management of thyroglossal tract disease after failed Sistrunk’s procedure

Sistrunk’s procedure for thyroglossal duct remnants has a very high success rate, there remains the occasional patient, however, that will have recurrent disease despite a competently performed operation. Applied anatomy and embryology proffer a solution to this problem. Extending the Sistrunk operation, with an anterior wide local excision remaining within normal tissue, enables removal of the entire thyroglossal tract remnant. A retrospective case note review was conducted to study our experience using this extended procedure to treat patients with thyroglossal tract disease that had recurred after a previous Sistrunk’s operation. Six patients aged from five to 33 years were included in the study. There was one recurrence and the complication rate was comparable to the standard operation. It was concluded that a wide local excision is a valuable extension of the Sistrunk operation for the management of recurrent disease

Tissue engineering and ENT surgery

Tissue engineering is the development of biological substitutes for the repair and regeneration of damaged tissues. We explain the principles of this emerging field of biotechology. The present and potential applications of tissue engineering technologies in ENT surgery are then reviewed

IL-17A increases TNF-α-induced COX-2 protein stability and augments PGE<inf>2</inf> secretion from airway smooth muscle cells: Impact on β<inf>2</inf>-adrenergic receptor desensitization

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Background IL-17A plays an important role in respiratory disease and is a known regulator of pulmonary inflammation and immunity. Recent studies have linked IL-17A with exacerbation in asthma and COPD. We have shown that the enzyme cyclooxygenase-2 (COX-2) and its prostanoid products, prostaglandin E2 (PGE2) in particular, are key contributors in in vitro models of infectious exacerbation; however, the impact of IL-17A was not known. Methods and Results We address this herein and show that IL-17A induces a robust and sustained upregulation of COX-2 protein and PGE2 secretion from airway smooth muscle (ASM) cells. COX-2 can be regulated at transcriptional, post-transcriptional and/or post-translational levels. We have elucidated the underlying molecular mechanisms responsible for the sustained upregulation of TNF-α-induced COX-2 by IL-17A in ASM cells and show that is not via increased COX-2 gene expression. Instead, TNF-α-induced COX-2 upregulation is subject to regulation by the proteasome, and IL-17A acts to increase TNF-α-induced COX-2 protein stability as confirmed by cycloheximide chase experiments. In this way, IL-17A acts to amplify the COX-2-mediated effects of TNF-α and greatly enhances PGE2 secretion from ASM cells. Conclusion As PGE2 is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL-17A in airway inflammation by showing for the first time that IL-17A impacts on the COX-2/PGE2 pathway, molecules known to contribute to disease exacerbation

TLR2 ligation induces corticosteroid insensitivity in A549 lung epithelial cells: Anti-inflammatory impact of PP2A activators

© 2016 Elsevier Ltd Corticosteroids are effective anti-inflammatory therapies widely utilized in chronic respiratory diseases. But these medicines can lose their efficacy during respiratory infection resulting in disease exacerbation. Further in vitro research is required to understand how infection worsens lung function control in order to advance therapeutic options to treat infectious exacerbation in the future. In this study, we utilize a cellular model of bacterial exacerbation where we pretreat A549 lung epithelial cells with the synthetic bacterial lipoprotein Pam3CSK4 (a TLR2 ligand) to mimic bacterial infection and tumor necrosis factor α (TNFα) to simulate inflammation. Under these conditions, Pam3CSK4 induces corticosteroid insensitivity; demonstrated by substantially reduced ability of the corticosteroid dexamethasone to repress TNFα-induced interleukin 6 secretion. We then explored the molecular mechanism responsible and found that corticosteroid insensitivity induced by bacterial mimics was not due to altered translocation of the glucocorticoid receptor into the nucleus, nor an impact on the NF-κB pathway. Moreover, Pam3CSK4 did not affect corticosteroid-induced upregulation of anti-inflammatory MAPK deactivating phosphatase—MKP-1. However, Pam3CSK4 can induce oxidative stress and we show that a proportion of the MKP-1 produced in response to corticosteroid in the context of TLR2 ligation was rendered inactive by oxidation. Thus to combat inflammation in the context of bacterial exacerbation we sought to discover effective strategies that bypassed this road-block. We show for the first time that known (FTY720) and novel (theophylline) activators of the phosphatase PP2A can serve as non-steroidal anti-inflammatory alternatives and/or corticosteroid-sparing approaches in respiratory inflammation where corticosteroid insensitivity exists

Long-Acting β<inf>2</inf>-Agonists Increase Fluticasone Propionate-Induced Mitogen-Activated Protein Kinase Phosphatase 1 (MKP-1) in Airway Smooth Muscle Cells

Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type. © 2013 Manetsch et al

Trends in thyroid hormone prescribing and consumption in the UK

<p>Abstract</p> <p>Background</p> <p>Thyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine.</p> <p>Methods</p> <p>Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out.</p> <p>Results</p> <p>The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing.</p> <p>Conclusion</p> <p>Amongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy.</p

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

Spatiotemporal patterns of population in mainland China, 1990 to 2010

According to UN forecasts, global population will increase to over 8 billion by 2025, with much of this anticipated population growth expected in urban areas. In China, the scale of urbanization has, and continues to be, unprecedented in terms of magnitude and rate of change. Since the late 1970s, the percentage of Chinese living in urban areas increased from ~18% to over 50%. To quantify these patterns spatially we use time-invariant or temporally-explicit data, including census data for 1990, 2000, and 2010 in an ensemble prediction model. Resulting multi-temporal, gridded population datasets are unique in terms of granularity and extent, providing fine-scale (~100 m) patterns of population distribution for mainland China. For consistency purposes, the Tibet Autonomous Region, Taiwan, and the islands in the South China Sea were excluded. The statistical model and considerations for temporally comparable maps are described, along with the resulting datasets. Final, mainland China population maps for 1990, 2000, and 2010 are freely available as products from the WorldPop Project website and the WorldPop Dataverse Repository

Interference Screw vs. Suture Anchor Fixation for Open Subpectoral Biceps Tenodesis: Does it Matter?

<p>Abstract</p> <p>Background</p> <p>Bioabsorbable interference screw fixation has superior biomechanical properties compared to suture anchor fixation for biceps tenodesis. However, it is unknown whether fixation technique influences clinical results.</p> <p>Hypothesis</p> <p>We hypothesize that subpectoral interference screw fixation offers relevant clinical advantages over suture anchor fixation for biceps tenodesis.</p> <p>Study Design</p> <p>Case Series.</p> <p>Methods</p> <p>We performed a retrospective review of a consecutive series of 88 patients receiving open subpectoral biceps tenodesis with either interference screw fixation (34 patients) or suture anchor fixation (54 patients). Average follow up was 13 months. Outcomes included Visual Analogue Pain Scale (0–10), ASES score, modified Constant score, pain at the tenodesis site, failure of fixation, cosmesis, deformity (popeye) and complications.</p> <p>Results</p> <p>There were no failures of fixation in this study. All patients showed significant improvement between their preoperative and postoperative status with regard to pain, ASES score, and abbreviated modified Constant scores. When comparing IF screw versus anchor outcomes, there was no statistical significance difference for VAS (p = 0.4), ASES score (p = 0.2), and modified Constant score (P = 0.09). One patient (3%) treated with IF screw complained of persistent bicipital groove tenderness, versus four patients (7%) in the SA group (nonsignificant).</p> <p>Conclusion</p> <p>Subpectoral biceps tenodesis reliably relieves pain and improves function. There was no statistically significant difference in the outcomes studied between the two fixation techniques. Residual pain at the site of tenodesis may be an issue when suture anchors are used in the subpectoral location.</p