Carcinoma showing thymus like elements: report of a case with EGFR T790M mutation

Abstract

Carcinoma showing thymus-like differentiation of the thyroid (CASTLE) is a rare tumor involving the thyroid and perithyroidal soft tissues. It shares morphological, immunohistochemical and molecular similarities with thymic carcinomas. Due to its relatively better prognosis, it needs differentiation from other primary and metastatic tumors of this region. A 40-year-old lady presented with a gradually progressive anterior neck swelling for one year. Imaging showed bulky right and left lobes of thyroid along with a solid soft tissue mass in the pretracheal region. Fine needle aspiration smears showed features of poorly differentiated carcinoma. Total thyroidectomy with excision of the mass revealed histopathological features characteristic of CASTLE, with evidence of thyroiditis in adjoining thyroid. Epidermal growth factor receptor (EGFR) assay revealed presence of EGFR T790M somatic mutation in exon 20. The same was not detectable on direct sequencing. We present a rare case of CASTLE, occurring in association with Hashimoto thyroiditis, with emphasis on cytological features and report for the first time the presence of a low level somatic mutation in EGFR (EGFR T790M mutation).

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Telecytology: Is it possible with smartphone images?

Introduction

This study aimed to discuss smartphone usage in telecytology and determine intraobserver concordance between microscopic cytopathological diagnoses and diagnoses derived via static smartphone images.

Methods

The study was conducted with 172 cytologic material. A pathologist captured static images of the cytology slides from the ocular lens of a microscope using a smartphone. The images were transferred via WhatsApp® to a cytopathologist working in another center who made all the microscopic cytopathological diagnoses 5-27 months ago. The cytopathologist diagnosed images on a smartphone without knowledge of their previous microscopic diagnoses. The Kappa agreement between microscopic cytopathological diagnoses and smartphone image diagnoses was determined.

Results

The average image capturing, transfer, and remote cytopathological diagnostic time for one case was 6.20 minutes. The percentage of cases whose microscopic and smartphone image diagnoses were concordant was 84.30%, and the percentage of those whose diagnoses were discordant was 15.69%. The highest Kappa agreement was observed in endoscopic ultrasound-guided fine needle aspiration (1.000), and the lowest agreement was observed in urine cytology (0.665). Patient management changed with smart phone image diagnoses at 11.04%.

Conclusions

This study showed that easy, fast, and high-quality image capturing and transfer is possible from cytology slides using smartphones. The intraobserver Kappa agreement between the microscopic cytopathological diagnoses and remote smartphone image diagnoses was high. It was found that remote diagnosis due to difficulties in telecytology might change patient management. The developments in the smartphone camera technology and transfer software make them efficient telepathology and telecytology tools.

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Impact of variant microscopic interpretation of the uCyt+ immunocytological urine test for the detection of bladder cancer

Background

Urinary marker tests for bladder cancer (BC) detection and surveillance represent a desirable approach to diagnosis and follow-up. The SCIMEDX uCyt+ assay detects antigens expressed by BC cells (mucin glycoprotein and carcinoembryonic antigen) using green and red fluorescence and is interpreted according to specific manufacturer's recommendations. In the present study, we evaluated divergent approaches of numeric and morphological analysis of uCyt+ to generate a rationale for alternative test interpretation strategies.

Methods

A total of 444 patients with hematuria and without history of BC underwent uCyt+ analysis, cystoscopy and histological examination of tissue biopsies. Beside positive cells according to the manufacturer's definition (definitely positive cells, DPC), (i) cells showing borderline character (borderline cells, BLC), and (ii) cells with staining present below defined border (subliminal cells, SLC) were included into the analytical algorithm. Different cut-off levels for cell counts (>0, ≥3, ≥5) were evaluated separately with regard to their diagnostic accuracy. Moreover, the influence of clinical factors on test results were evaluated.

Results

Adding BLC at a cut-off of ≥3 cells resulted in Area Under the Curve (AUC) of 0.70 for green and 0.77 for red fluorescence, respectively. Adding SLC led to reduced AUC (0.62 and 0.73, respectively). Male gender was significantly associated with false positive results in the "best AUC" groups (P = .0101). No further correlations to clinical influencing factors were observed.

Conclusions

Adding microscopic BLC as test-positive and adjusting cut-off level for the interpretation of uCyt+ may improve assay performance independent of clinical factors.

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The evolution of the manus of early theropod dinosaurs is characterized by high inter- and intraspecific variation

Abstract

The origin of the avian hand, with its reduced and fused carpals and digits, from the five-fingered hands and complex wrists of early dinosaurs represents one of the major transformations of manus morphology among tetrapods. Much attention has been directed to the later part of this transition, from four- to three-fingered taxa. However, earlier anatomical changes may have influenced these later modifications, possibly paving the way for a later frameshift in digit identities. We investigate the five- to four-fingered transition among early dinosaurs, along with changes in carpus morphology. New three-dimensional reconstructions from computed tomography data of the manus of the Triassic and Early Jurassic theropod dinosaurs Coelophysis bauri and Megapnosaurus rhodesiensis are described and compared intra- and interspecifically. Several novel findings emerge from these reconstructions and comparisons, including the first evidence of an ossified centrale and a free intermedium in some C. bauri specimens, as well as confirmation of the presence of a vestigial fifth metacarpal in this taxon. Additionally, a specimen of C. bauri and an unnamed coelophysoid from the Upper Triassic Hayden Quarry, New Mexico, are to our knowledge the only theropods (other than alvarezsaurs and birds) in which all of the distal carpals are completely fused together into a single unit. Several differences between the manus of C. bauri and M. rhodesiensis are also identified. We review the evolution of the archosauromorph manus more broadly in light of these new data, and caution against incorporating carpal characters in phylogenetic analyses of fine-scale relationships of Archosauromorpha, in light of the high degree of observed polymorphism in taxa for which large sample sizes are available, such as the theropod Coelophysis and the sauropodomorph Plateosaurus. We also find that the reduction of the carpus and ultimate loss of the fourth and fifth digits among early dinosaurs did not proceed in a neat, stepwise fashion, but was characterized by multiple losses and possible gains of carpals, metacarpals and phalanges. Taken together, the high degree of intra- and interspecific variability in the number and identities of carpals, and the state of reduction of the fourth and fifth digits suggest the presence of a 'zone of developmental variability' in early dinosaur manus evolution, from which novel avian-like morphologies eventually emerged and became channelized among later theropod clades.

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Potential utility of a longitudinal relative dose intensity of molecularly targeted agents in phase 1 dose-finding trials

Abstract

Phase 1 trials of molecularly targeted agents (MTA) often do not use toxicity data beyond the first cycle of treatment to determine a recommended phase 2 dose (RP2D). We investigated the potential utility of longitudinal relative dose intensity (RDI) that may be a better new way of determining a more accurate RP2D as a lower dose that is presumably more tolerable over the long term without compromising efficacy. All consecutive patients who initially were treated using a single MTA at the conventional RP2D or at one level lower dose (OLLD) of that RP2D in nine phase 1 trials sponsored by the National Cancer Institute were included. The associations between longitudinal RDI, time to first progression, and response rate were analyzed. The RDIs of the conventional RP2D group were maintained a rate of ≥70% throughout 10 cycles, and were higher than those of the OLLD group, although in both groups the RDI gradually decreased with additional treatment cycles. The RP2D group was similar to the OLLD group with respect to time to first progression and response rate. In the both groups, however, the decreasing relative dose intensity (RDI) over time was significantly associated with shorter time to first disease progression; therefore, the longitudinal RDI, which takes into account lower grade toxicity occurrences, may be useful in determining a more desirable dose to use in phase 2 and 3 studies.

This article is protected by copyright. All rights reserved.

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Prevalence of papular urticaria caused by flea bites and associated factors in children 1–6 years of age in Bogotá, D.C.

Papular urticaria is a chronic inflammatory disease caused by exposure to arthropod bites. The disease has been reported in children attending medical centers, but the causes as the risk factors associated wit...

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A shared decision-making tool for obstructive sleep apnea without tonsillar hypertrophy: A randomized controlled trial

Objectives/Hypothesis

Shared decision-making is a process whereby patients and clinicians jointly establish a treatment plan integrating clinical evidence and patient values and preferences. Although this approach has been successfully employed in numerous medical disciplines, often using shared decision-making tools, otolaryngologic research assessing its use is scant. Our primary objective was therefore to determine if the tools we developed reduced decisional conflict for children with obstructive sleep apnea without tonsillar hypertrophy.

Study Design

Prospective, single-blind, randomized controlled trial.

Methods

We enrolled consecutive patients meeting inclusion criteria who were referred to our multidisciplinary upper airway center. Study patients used a shared decision-making tool whereas controls did not. Measures of decisional conflict (SURE [Sure of myself, Understanding information, Risk benefit ratio, Encouragement], CollaboRATE, and the Decisional Conflict Scale [DCS]) were obtained pre- and postvisit.

Results

We assessed 50 families (study group = 24, controls = 26). The mean age was 8.8 ± 6.6 years, 44% were female, 86% were white, and the mean obstructive apnea-hypopnea index was 12.7 ± 15.6 events/hour. The previsit mean DCS score was similar for controls (42.7) and study patients (40.8) (P = .38). The postvisit mean DCS score for controls was 13.3 and for study patients 6.1 (P = .034). Improvement in this score was greater in the study group (P = .03). At previsit evaluation, 63% of controls and 58% of study patients were unsure about their options. Postvisit, this improved to 4.1% and 0%, respectively.

Conclusions

Families counseled regarding treatment options using shared decision-making tools had significantly less decisional conflict than those who did not use these tools. These positive outcomes suggest that clinicians should consider integrating this approach into clinical practice.

Level of Evidence

1b Laryngoscope, 2017

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Total septal perforation repair with a pericranial flap: Radio-anatomical and clinical findings

Objectives/Hypothesis

Endonasal surgeries are the primary cause of septal perforation (SP). However, trauma, inflammation, infections, neoplasms, or abuse of inhaled drugs can also cause SP. Septal repair is indicated in patients who experience nasal obstruction, crusting, intermittent epistaxis, purulent discharge, or nasal whistling and in those who fail conservative treatment. Multiple approaches have been suggested to repair the SP; however, none has been universally adopted. This study explores the feasibility of repairing a total SP using the pericranial flap (PCF).

Study Design

Anatomical cadaver and radiological study plus case study.

Methods

Total nasal septectomy and endoscopic reconstruction with a PCF was performed in 12 injected cadaveric specimens. Maximum length and area of the nasal septum and the PCF were measured in 75 computed tomography scans. Based on the anatomical study and the radiological measurements of the cadavers, one patient underwent total nasal septum repair.

Results

Anatomic measurements showed that the nasal septum has a mean length of 5.8 ± 0.7 cm, whereas the PCF was on average 18.4 ± 1.3 cm long (mean surface area 121.6 ± 17.7 cm²). Radiological measurements revealed that the PCF should provide a surface area of 40.9 ± 4.2 cm² to account for the total septal area and an additional 30% to account range for potential scar retraction. For total septum repair, the distal edge of the PCF had to be placed 0.8 ± 2.0 cm (3.4 ± 8.7°) from the adopted reference point (vertical projection of the external ear canal). Total septal reconstruction was performed successfully in one patient without complications.

Conclusions

Radio-anatomical data and a case study demonstrate that a PCF allows complete endoscopic repair of the nasal septum.

Level of Evidence

NA Laryngoscope, 2017

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Three-dimensional endoscopy for endoscopic salvage nasopharyngectomy: Preliminary report of experience

Background

Prospective, observational study to assess the efficacy of salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma (NPC) via the endoscopic endonasal approach using a three-dimensional (3D) high-definition endoscopic system.

Methods

Between 2016 and 2017, 30 patients with recurrent NPC were recruited. Patient demographics, tumor characteristics, and perioperative data were recorded. Instrument ergonomics and perceived advantages were assessed by the operating, assisting, and observing surgeons.

Results

The majority (70%) of patients received radiotherapy alone as the initial treatment for NPC, and tumor recurred after a mean interval of 16.8 months. The tumor (T) classifications of the recurrent (R) tumors were: RT1: 46.7%; RT2: 33.3%; and RT3: 20.0%. The mean operative time was 293.3 minutes, and no conversion to open approach was necessary. Internal carotid artery dissection was required in nine patients, and the resection and repair of dura was required in six patients. The most common method of reconstruction was free vastus lateralis flap (46.7%). Microscopically clear resection margins were achieved in 73.3% of patients. The mean hospital stay was 6.8 days. There was no hospital mortality. One patient developed minor secondary hemorrhage, whereas the other developed transient contralateral vocal cord paralysis. On quantitative assessment, surgeons noticed a significant advantage of the 3D system with regard to depth and size perception, anatomy identification, and hand–eye coordination, whereas there was no significant difference in terms of strain sensation and dizziness.

Conclusion

The 3D high-definition endoscopic system improves the precision of endoscopic nasopharyngectomy, particularly when dissection of the internal carotid artery and dura is required.

Level of Evidence

4. Laryngoscope, 2017

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Telemedicine in laryngology: Remote evaluation of voice disorders-setup and initial experience

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The contribution of cochlear implants to postural stability

Objectives

To determine whether spatial auditory cues provided by cochlear implants can improve postural balance in adults with severe deafness.

Methods

In the presence of spatial white noise, 13 adult cochlear implantees wore head and lumbar-mounted inertial sensors while standing in the dark for 30 seconds in two auditory conditions: hearing assistive devices on and off.

Results

Stability was improved with implants on (aided condition) compared to off (unaided condition) with respect to differences in mean head velocity (Cohen's d = 0.912, P = 0.006) as well as to root mean square (RMS) acceleration (Cohen's d = 0.456, P = 0.048). This was particularly evident in measures of anteroposterior accelerations (mean difference = 0.034 m/s²; Cohen's d = 0.612; P = 0.011).

Conclusion

The decrease in RMS head acceleration and velocity while wearing cochlear implants suggests that they could be recognized as balance implants in addition to auditory implants. The clinical importance of this finding in various patient populations remains to be determined.

Level of Evidence

4. Laryngoscope, 2017

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When should therapeutic anticoagulation be restarted following major head and neck surgery?

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In reference to intervention for elevated intracranial pressure improves success rate after repair of spontaneous cerebrospinal fluid leaks

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Proton density–weighted laryngeal magnetic resonance imaging in systemically dehydrated rats

Objectives/Hypothesis

Dehydrated vocal folds are inefficient sound generators. Although systemic dehydration of the body is believed to induce vocal fold dehydration, this causative relationship has not been demonstrated in vivo. Here we investigate the feasibility of using in vivo proton density (PD)–weighted magnetic resonance imaging (MRI) to demonstrate hydration changes in vocal fold tissue following systemic dehydration in rats.

Study Design

Animal study.

Methods

Sprague-Dawley rats (n = 10) were imaged at baseline and following a 10% reduction in body weight secondary to withholding water. In vivo, high-field (7 T), PD-weighted MRI was used to successfully resolve vocal fold and salivary gland tissue structures.

Results

Normalized signal intensities within the vocal fold decreased postdehydration by an average of 11.38% ± 3.95% (mean ± standard error of the mean [SEM], P = .0098) as compared to predehydration levels. The salivary glands experienced a similar decrease in normalized signal intensity by an average of 10.74% ± 4.14% (mean ± SEM, P = .0195) following dehydration. The correlation coefficient (percent change from dehydration) between vocal folds and salivary glands was 0.7145 (P = .0202).

Conclusions

Ten percent systemic dehydration induced vocal fold dehydration as assessed by PD-weighted MRI. Changes in the hydration state of vocal fold tissue were highly correlated with that of the salivary glands in dehydrated rats in vivo. These preliminary findings demonstrate the feasibility of using PD-weighted MRI to quantify hydration states of the vocal folds and lay the foundation for further studies that explore more routine and realistic magnitudes of systemic dehydration and rehydration.

Level of Evidence

NA Laryngoscope, 2017

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Development and external validation of a risk-prediction model to predict 5-year overall survival in advanced larynx cancer

Objectives/Hypothesis

TNM-classification inadequately estimates patient-specific overall survival (OS). We aimed to improve this by developing a risk-prediction model for patients with advanced larynx cancer.

Study Design

Cohort study.

Methods

We developed a risk prediction model to estimate the 5-year OS rate based on a cohort of 3,442 patients with T3T4N0N+M0 larynx cancer. The model was internally validated using bootstrapping samples and externally validated on patient data from five external centers (n = 770). The main outcome was performance of the model as tested by discrimination, calibration, and the ability to distinguish risk groups based on tertiles from the derivation dataset. The model performance was compared to a model based on T and N classification only.

Results

We included age, gender, T and N classification, and subsite as prognostic variables in the standard model. After external validation, the standard model had a significantly better fit than a model based on T and N classification alone (C statistic, 0.59 vs. 0.55, P < .001). The model was able to distinguish well among three risk groups based on tertiles of the risk score. Adding treatment modality to the model did not decrease the predictive power. As a post hoc analysis, we tested the added value of comorbidity as scored by American Society of Anesthesiologists score in a subsample, which increased the C statistic to 0.68.

Conclusions

A risk prediction model for patients with advanced larynx cancer, consisting of readily available clinical variables, gives more accurate estimations of the estimated 5-year survival rate when compared to a model based on T and N classification alone.

Level of Evidence

2c Laryngoscope, 2017

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Cricothyroid joint type as predictor for vocal fold elongation in professional singers

Objective

Vocal fold (VF) elongation vocal folds depends on two factors: the activity of the laryngeal muscles and the cricothyroid joint (CTJ). The aim of the study was to show the influence of the CTJ on VF elongation while singing a sustained vowel at different pitches.

Study Design

Prospective study.

Methods

Forty-nine female professional singers (25 sopranos, 24 altos) were recruited. Three-dimensional images of the larynx derived from high-resolution computed tomography scanning were obtained at the mean speaking fundamental frequency (F0) and one (F1) and two octaves (F2) above this pitch.

Results

From F0 to F1, all three CTJ types showed equal elongation of the VF (type A: 14%, type B/C: 13%). From F1 to F2, VF elongation was 8% in singers with type A and 4% in those with type B/C (P < 0.0001).

Conclusion

The stability of the CTJ directly influences VF during singing. This is the first study to show this relationship in vivo.

Level of Evidence

4. Laryngoscope, 2017

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Lack of long-term add-on effect by montelukast in postoperative chronic rhinosinusitis patients with nasal polyps

Objectives/Hypothesis

Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking.

Study Design

Prospective, randomized, open-label trial.

Methods

In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy.

Results

After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months.

Conclusions

These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients.

Level of Evidence

1b Laryngoscope, 2017

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Cough strength and expiratory force in aspirating and nonaspirating postradiation head and neck cancer survivors

Objective

Expiratory functions that clear aspiration from the airway are compromised in patients with neurogenic dysphagia for whom cough and expiratory force may be impaired by the primary disease process. The relationship between expiratory function, cough, and aspiration is less clear in head and neck cancer (HNC) survivors for whom the disease process does not directly impact the lower respiratory system. Our objective was to compare mechanisms of airway clearance (expiratory force and cough) with aspiration status in postradiated HNC survivors.

Study Design

Cross-sectional study.

Methods

One hundred and three disease-free HNC survivors ≥ 3-months postradiotherapy referred for modified barium swallow studies were prospectively enrolled regardless of dysphagia status. Maximum expiratory pressures (MEPs) and peak cough flow (PCF) measures were taken at enrollment and examined as a function of aspiration status using generalized linear regression methods.

Results

Thirty-four (33%) patients aspirated. Maximum expiratory pressure and PCF demonstrated a moderate positive correlation (Pearson's r = 0.35). Adjusting for sex and age, MEPs were on average 19.2% lower (21.1 cm H₂O, 95% confidence interval [CI] 5.3, 36.8) among aspirators. Peak cough flow was also 14.9% lower (59.6 L/minute, 95% CI 15.8, 103.3) among aspirators after adjusting for age and sex.

Conclusion

Expiratory functions were depressed in postradiated HNC aspirators relative to nonaspirators, suggesting that airway protection impairments may extend beyond disrupted laryngopharyngeal mechanisms in the local treatment field. Exercises to strengthen subglottic expiratory force-generating capacity may offer an adjunctive therapeutic target to improve airway protection in chronic aspirators after head and neck radiotherapy.

Level of Evidence

2b. Laryngoscope, 2017

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Examination of olfactory training effectiveness in relation to its complexity and the cause of olfactory loss

Objective

Although the effectiveness of olfactory training (OT) had already been documented, the optimal regimen for such training remains unexplored. We examined whether the complexity of OT, namely alteration of odor quantity and quality, increases its effectiveness.

Design

One-hundred eight patients (M_age = 60.1 ± 1) with postinfectious (n = 57) or idiopathic (n = 51) olfactory dysfunction underwent OT preceded and followed by examination of olfactory function.

Methods

Subjects were randomly assigned to one of the three experimental conditions: 1) simple training comprising four basic, single-molecule substances; 2) complex training involving four odor mixtures; and 3) odor-altering training in which patients changed sets of mixtures every 2 months.

Results

The analysis of variance revealed that the benefit seen in this sample was not affected by the complexity of OT with regard to odor mixtures or alteration of odor type. The highest increase of the Sniffin' Sticks (Burghardt GmbH; Wedel, Germany) threshold, discrimination, and identification (and overall TDI) score was observed in postinfectious patients.

Conclusion

We conclude that the outcomes of OT are not strongly influenced by the training regimen. However, further investigation of OT regimens is required, particularly with regard to training duration.

Level of Evidence

2b. Laryngoscope, 2017

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ABO Blood Group and Cochlear Status: Otoacoustic Emission Markers.

Objectives: There are an increasing number of research studies examining the effects of ABO blood group on susceptibility to disease. However, little is known regarding the potential relationship between blood group and hearing. Higher risk of noise-induced hearing loss was linked to blood group O in several occupational health studies. Based on this finding, a recent study of cochlear status was conducted with normal-hearing female participants representing equal numbers of the four blood groups in the ABO blood group system. ABO blood group was associated with cochlear characteristics, including the prevalence of spontaneous otoacoustic emissions (SOAEs) and the amplitudes of transient-evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs). Females with blood group O showed significantly lower amplitudes of DPOAEs at some frequencies and lower prevalence of SOAEs compared with participants with blood group B. There was a general trend of reduced TEOAE and DPOAE amplitudes in blood group O individuals compared with participants with non-O blood groups. Following from this finding, and based on known sex differences in otoacoustic emission characteristics, the present study examined the possible effects of blood group on otoacoustic emission status in males. Design: Sixty clinically normal-hearing males aged between 18 and 26 years, with equal numbers of participants in each of the ABO blood groups, were recruited by purposive sampling. SOAE, DPOAE, and linear and nonlinear TEOAE recordings were collected from all participants, as well as tympanometric data related to external and middle ear characteristics. Results: The male blood group O participants exhibited significantly lower SOAE prevalence and reduced amplitudes of DPOAEs on average, and in the midfrequency range, than participants with blood group B, and lower nonlinear and linear TEOAE amplitudes at a number of frequencies when compared with participants with blood groups A and B. A consistent trend of lower TEOAE and DPOAE response amplitudes was observed in participants with blood group O. No significant difference was noted among blood groups for outer or middle ear characteristics. Conclusions: These results were consistent with previous findings of reduced otoacoustic emission responses in female blood group O individuals. Results support the hypothesis that blood group O individuals may be at increased risk of cochlear damage from noise exposure. Further investigation on the potential link between ABO blood group and auditory status, including potentially differential effects of noise exposure on cochlear function, is needed. The possible effects of ABO blood group on other aspects of audition, such as hearing sensitivity, speech understanding, and auditory processing, should be evaluated. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Speech in Noise Perception as a Marker of Cognitive Impairment in HIV Infection.

Objectives: Human immunodeficiency virus positive (HIV+) individuals report hearing difficulties, but standard audiological tests show no, or small, changes in peripheral hearing ability. The hearing complaints may reflect central nervous system (CNS) auditory processing deficits, rather than middle or inner ear problems, and may result from CNS damage due to HIV infection or treatment. If central auditory task performance and cognitive deficits in HIV+ individuals are shown to be related, then central auditory tests might serve as a "window" into CNS function in these patients. Design: We measured cognitive performance (Mandarin Montreal Cognitive Assessment [MoCA]) and speech in noise perception (Mandarin hearing-in-noise test [HINT]) in 166 normal-hearing HIV+ individuals (158 men, 8 women, average age 36 years) at the Shanghai Public Health Clinical Center in Shanghai, China. Data collection included audiometry, tympanometry, and the Amsterdam Inventory of Auditory Handicap (AIAH), which assesses the subjective ability to understand speech and localize sound. Results: Subjects had no middle ear disease and met criteria for normal-hearing sensitivity (all thresholds 20 dB HL or less). A significant negative relationship between speech reception thresholds (SRT) and MoCA scores (r2 = 0.15, F = 28.2, p

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From bench to clinical trials the EORTC experience in biology-based clinical cancer research

Publication date: Available online 6 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Konstantinos Tryfonidis, Katherine Hartmann, Marie Morfouace, Denis Lacombe
For over 50years the European Organization for Research and Treatment of Cancer (EORTC) has delivered major advances in cancer clinical research and cancer therapeutics. The introduction of molecularly targeted agents has led to significant improvements in outcome for patients with specific tumor types; however conventional chemotherapy remains the mainstay of treatment for the majority of patients. Due to increasing knowledge about the diversity of molecular pathways driving malignant progression, strategies to integrate biology into clinical research and development are continuously evolving. The challenges and the experience of the EORTC regarding how translational research is to be an indispensable component of the clinical research environment, which aims to deliver more sophisticated treatment approaches will be discussed in this perspective article.



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Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density

Publication date: Available online 7 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Duaa S. Helal, Dina M. El-Guindy
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.



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Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Experimental studies have revealed that phytoestrogens may modulate the risk of certain sites of cancer due to their structural similarity to 17β-estradiol. The present study investigates whether intake of these compounds may influence prostate cancer risk in human populations. During a median follow up of 11.5 years, 2,598 cases of prostate cancer (including 287 advanced cases) have been identified among 27,004 men in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dietary intake of phytoestrogens (excluding lignans) was assessed with a food frequency questionnaire. Cox proportional hazards regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary isoflavones and coumestrol in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer [HR (95% CI) for quintile (Q) 5 vs. Q1] was found for the dietary intake of total isoflavones [1.91 (1.25–2.92)], genistein [1.51 (1.02–2.22), daidzein [1.80 (1.18–2.75) and glycitein [1.67 (1.15–2.43)] (p-trend for all associations ≤0.05). For example, HR (95% CI) for comparing the Q2, Q3, Q4 and Q5 with Q1 of daidzein intake was 1.45 (0.93–2.25), 1.65 (1.07–2.54), 1.73 (1.13–2.66) and 1.80 (1.18–2.75), respectively (p-trend: 0.013). No statistically significant associations were observed between the intake of total isoflavones and individual phytoestrogens and non-advanced and total prostate cancer after adjustment for confounders. This study revealed that dietary intake of isoflavones was associated with an elevated risk of advanced prostate cancer.

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A New Substitute for Formalin: Application to Embalming Cadavers

Abstract

The development of formalin-free fixatives is an urgent issue in gross anatomy because of the health hazard and the tissue-hardening actions of formalin. We recently identified the fixative, antimicrobial, and preservative effects of N-vinyl-2-pyrrolidone (NVP), a precursor of the water-soluble macromolecular polymer polyvinylpyrrolidone, in animal experiments. The aim of the present study is to investigate whether NVP solution can be used as an alternative to formalin in human cadaveric dissection. Twelve donated cadavers were infused with NVP via the femoral and common carotid arteries using a peristaltic pump. Experienced teaching staff members in our department dissected the cadavers and examined their macroanatomical properties. The NVP-embalmed corpses showed no sign of decomposition or fungal growth. The bodies remained soft and flexible. Notably, the shoulder, elbow, wrist, phalangeal, hip, knee, cervical spine, and temporomandibular joints were highly mobile, almost equivalent to those of living individuals. The range of motion of most joints was greater in the NVP-fixed than formalin-fixed cadavers. Under the dermis, the subcutaneous fat was markedly reduced and the connective tissues were transparent, so the ligaments, cutaneous nerves, and veins were easily discernible. The abdominal wall and the visceral organs remained pliable and elastic, resembling those of fresh cadavers. The lungs, liver, and gastrointestinal tract were moveable in the thoracic and abdominal cavities and were readily isolated. NVP can be used successfully as a fixative and preservative solution for human cadavers; furthermore, NVP-embalmed bodies could be valuable for learning clinical skills and for training, and for developing innovative medical devices. This article is protected by copyright. All rights reserved.

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Can Corticotomy (with or without bone grafting) Expand the Limits of Safe Orthodontic Therapy?

Publication date: Available online 7 November 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Federico Brugnami, Alfonso Caiazzo, Pushkar Mehra
PurposeTo assess whether concomitant particulate bone grafting makes a difference in the ability to safely orthodontically reposition teeth outside the bony envelope after corticotomy.Material & MethodsRetrospective analysis of patients who underwent corticotomy as part of their orthodontic therapy for treatment of severe crowding. Patients were divided as: a) Group 1: corticotomy with bone grafting, and, b) Group 2: corticotomy without bone grafting. CT scan examinations were performed before and at the end of the treatment. Measurements of bone and tooth positions were obtained and differences between pre- and post-treatment values were calculated.ResultsThe study sample included 20 adult patients between the ages of 25 to 58 years. A total of 144 teeth were orthodontically repositioned outside their native bony envelope after corticotomy. Average follow-up was 9 months. Teeth that were repositioned after corticotomy and bone grafting maintained the alveolar bone volume around them while corticotomy without bone grafting was not successful in maintaining bone thickness around teeth that were moved outside the alveolar housing.ConclusionsCorticotomy in combination with guided bone regeneration has the potential to increase the scope of conventional orthodontic treatment by allowing for expansive movements beyond the traditional limits.



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Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Abstract

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer. However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and pancreatic cancer incidence in European populations.

We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident pancreatic cancer cases (EPIC n=626; HUNT2 n=112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D₂ and 25(OH)D₃ combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI).

Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53); and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with pancreatic cancer risk (p for trend = 0.23).

Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of pancreatic cancer risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant. This article is protected by copyright. All rights reserved.

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Risk of skin cancer among patients with myotonic dystrophy type 1 based on Primary care physician data from the United Kingdom Clinical Practice Research Datalink

Abstract

Myotonic dystrophy type 1 (DM1) is an inherited multisystem neuromuscular disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. Recent evidence documents that DM1 patients have an increased risk of certain cancers, but whether skin cancer risks are elevated is unclear. Using the U.K. Clinical Practice Research Datalink (CPRD), we identified 1,061 DM1 patients and 15,119 DM1-free individuals matched on gender, birth year (±2 years), attending practice, and registration year (±1 year). We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of DM1 diagnosis with skin cancer risk using Cox proportional hazards models, for all skin cancers combined and by histological subtype. Follow-up started at the latest of the age at practice registration, DM1 diagnosis/control selection or January 1st 1988, and ended at the earliest of the age at first skin cancer diagnosis, death, transfer out of the practice, last date of data collection or the end of the CPRD record (October 31, 2016). During a median follow-up of 3.6 years, 35 DM1 patients and 108 matched DM1-free individuals developed a skin cancer. DM1 patients had an increased risk of skin cancer overall (HR=5.44, 95% CI=3.33-8.89, p<.0001), and basal cell carcinoma (BCC) (HR=5.78, 95% CI=3.36-9.92, p<.0001). Risks did not differ by gender, or age at DM1 diagnosis (P-heterogeneity>0.5). Our data confirm suggested associations between DM1 and skin neoplasms with the highest risk seen for BCC. Patients are advised to minimize ultraviolet light exposure and seek medical advice for suspicious lesions. This article is protected by copyright. All rights reserved.

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Midlife metabolic factors and prostate cancer risk in later life

Abstract

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n=9,097, enrolled 1967-1987) were followed for incident (n=1,084 total; n=378 advanced; n=148 high-grade) and fatal (n=340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m²; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mmHg or taking anti-hypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dL or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides was associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs. 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p-trend=0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer. This article is protected by copyright. All rights reserved.

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Biweekly cisplatin and gemcitabine in patients advanced biliary tract cancer

Abstract

Treatment with cisplatin with gemcitabine (CG) demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1000mg/m²/min) and cisplatin 20mg/m² on days 1 and 15 of every 28-day cycle. Patients received treatment until time of progression, death or discontinuation due to intolerance. Collected data included demographics, clinico-pathologic features, toxicities and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). The study included 107 evaluable pts with unresectable ABTC who received the biweekly regimen. Sites of tumor included gallbladder (21.5%), ampullary (3.7%) and bile duct (74.8%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade ≥3 adverse events included neutropenia (11%), fatigue (10%) and thrombocytopenia (6.4%). Biweekly FDR GC in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many patients. Further prospective trials should consider evaluating the role of biweekly GC regimen in ABTC, including a potentially more favorable platform in novel experimental strategies. This article is protected by copyright. All rights reserved.

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A comprehensive analysis of polymorphic variants in steroid hormone and IGF-1 metabolism and risk of in situ breast cancer: results from the Breast and Prostate Cancer Cohort (BPC3) Consortium

Abstract

We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and IGF-1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was done using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (OR_hom=3.05, 95%CI = 1.72-5.44, P_hom= 1.47 × 10⁻⁴), MAST2-rs12124649 (OR_hom=1.73, 95% CI =1.18-2.54, P_hom= 5.24 × 10⁻³), and INSR-rs10500204 (OR_hom= 1.96, 95% CI =1.44-2.67, P_hom=1.68 × 10⁻⁵) were associated with increased risk of BCIS; however only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (OR_hom=1.78, 95% CI =1.30-2.44, P_hom= 3.23 × 10⁻⁴).

The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further. This article is protected by copyright. All rights reserved.

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Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses

The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses. All radiation settings induced pronounced persistent systemic effects in mice, which resulted from even short exposures of a small irradiated area. OCDLs were elevated in a wide variety of unirradiated normal tissues. In out-of-field duodenum, there was a trend for elevated apoptotic cell death under most irradiation conditions; however, DSBs were elevated only after exposure to lower doses. These genotoxic events were accompanied by changes in plasma concentrations of macrophage-derived cytokine, eotaxin, IL10, TIMP1, VEGF, TGFβ1, and TGFβ2, along with changes in tissues in frequencies of macrophages, neutrophils, and T lymphocytes. Overall, our findings have implications for the planning of therapeutic and diagnostic radiation treatments to reduce the risk of radiation-related adverse systemic effects. Cancer Res; 77(22); 1–11. ©2017 AACR.

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Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma

The incidence of cutaneous melanoma has continued to increase in recent years. For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis, with 5-year survival rates of 98% for stage I disease and 90% for stage II disease. However,…

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BAP1 is a novel target in HPV negative head and neck cancer.

Purpose: This study examined the potential role of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) in radioresistance in head and neck squamous cell cancer (HNSCC). Experimental Design: We overexpressed, knocked down, and rescued BAP1 expression in six HNSCC cell lines, three human papillomavirus (HPV) -negative and HPV-positive, and examined the effects on radiosensitivity in vitro and in HNSCC mouse xenograft models. Radiosensitivity was assessed by clonogenic cell survival and tumor growth delay assays; changes in protein expression were analyzed by immunofluorescence staining and western blotting. We also analyzed The Cancer Genome Atlas HNSCC database to test for associations between BAP1 expression and outcome in patients. Results. Overexpression of BAP1 induced radioresistance in both cell lines and xenograft models; conversely, BAP1 knockdown led to increased ubiquitination of histone H2A, which has been implicated in DNA repair. We further found that BAP1 depletion suppressed the assembly of constitutive BRCA1 foci, which are associated with homologous recombination (HR), but had minimal effect on -H2AX foci and did not affect proteins associated with nonhomologous end joining, suggesting that BAP1 affects radiosensitivity in HNSCC by modifying homologous recombination. Finally, in patients with HNSCCC, overexpression of BAP1 was associated with higher failure rates after radiation therapy. Conclusions. BAP1 can induce radioresistance in HNSCC cells, possibly via deubiquitination of H2Aub and modulation of HR, and was associated with poor outcomes in patients with HNSCC. BAP1 may be a potential therapeutic target in HNSCC.

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Muscadine Grape Skin Extract in Men with Biochemically Recurrent Prostate Cancer: A Randomized, Multicenter, Placebo-Controlled Clinical Trial

Purpose: MPX, a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer (PCa) wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multi-center, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR PCa, powered to detect a prostate specific antigen doubling time (PSADT) difference of 6 months (low-dose) and 12 months (high-dose) relative to placebo. Participants were stratified (baseline PSADT, Gleason score) and randomly assigned 1:2:2 to receive placebo, 500mg MPX (low), 4000mg MPX (high) daily. Correlates included superoxide dismutase-2 (SOD2) genotype, lipid peroxidation and polyphenol pharmacokinetics. Results: The evaluable population included 112 patients, all treated for at least 6 months and 62% treated for 12 months. No significant difference was found in PSADT change between control and treatment arms (p=0.81): control 0.9 months (n=20, range -6.7 to 83.1), low-dose 1.5 months (n=52, range: -10.3 to 87.2), high-dose 0.9 months (n=40, range: -27.3 to 88.1). One high-dose patient experienced objective response. No drug-related CTCAE grade 3-4 adverse events were seen. In a preplanned exploratory analysis, PSADT pre-to-post increase was significant in the 27 (26%) genotyped patients with SOD2 Alanine/Alanine genotype (rs4880 T>C polymorphism) on MPX (pooled treatment arms) (6.4 months, p=0.02), but not in control (1.8 months, p=0.25). Conclusions: Compared with placebo, MPX did not significantly prolong PSADT in BCR patients over two different doses. Exploratory analysis revealed a patient population with potential benefit that would require further study.

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One-day low-intensity combined arm–leg (Cruiser) ergometer exercise intervention: cardiorespiratory strain and gross mechanical efficiency in one-legged and two-legged exercise

This study aims to research whether there is a difference in cardiorespiratory variables and gross mechanical efficiency (GE) in healthy individuals during low-intensity one-legged and two-legged exercise on the combined arm–leg (Cruiser) ergometer and whether motor learning occurs. The outcome of this study will support the use of the Cruiser ergometer in future as a testing and training instrument in the rehabilitation of patients with a lower limb amputation. Twenty-eight healthy men participated in this randomized-controlled trial. One group (n=14) used one leg and both arms during the exercise and the other group (n=14) used both legs and both arms. All participants performed a 1-day low-intensity exercise protocol. This included a standardized pretest and post-test of three bouts of 4 min exercise at 40 W and an exercise intervention of seven bouts of 2×4 min exercise at 40 W. The one-legged and two-legged group differed significantly in the heart rate and GE between the pretest and post-test. At the post-test, the one-legged group showed motor learning. GE improved significantly in both groups over the duration of the three exercise bouts of the pretest, but it did not improve during the post-test. There are differences in cardiorespiratory variables and GE between one-legged and two-legged exercise on the Cruiser ergometer. When using this ergometer in the rehabilitation of patients with a lower limb amputation, it is important to consider these differences and the occurrence of motor learning.

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Research on prevalence of secondary conditions in individuals with disabilities: an overview

Individuals with disabilities may be at increased risk of a number of secondary conditions. Secondary conditions influence health status and quality of life. Many of these conditions are preventable and their consequences can be managed. Knowledge of the prevalence, course, and association with age of secondary conditions is needed for better prevention and management. The aim of present study was to review the available literature on the prevalence of secondary conditions in individuals with disability. We performed searches of electronic databases for studies published between 1980 and 2017 that provided information on the prevalence of secondary conditions in individuals with disabilities. The reference list of all relevant citations was also reviewed for further material. Nineteen papers were included. The findings indicate that (i) studies were mainly population-based descriptive studies, (ii) researchers used different questionnaires, (iii) the most common studied population are patients with spinal cord injury, and (iv) even though secondary conditions are different in different patient populations, the main secondary conditions are pain, spasticity, urinary tract infections, fatigue, depression, and sleep problems. The prevalence of each condition varies widely depending on the studied population and research methodologies across studies. There is still much information that remains to be obtained on the prevalence, definition, and conceptual organization of secondary conditions. There is also a lack of longitudinal studies on the natural course of these conditions.

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Botulinum toxin use in rehabilitation clinics: a survey to highlight differences and similarities

Spasticity is a complex condition and its management is multifaceted, involving physical therapies as well as interventions with botulinum toxin. There is currently no standard for best practice and also wide variation in spasticity service set-ups and the background of clinicians involved in treatment. This could potentially cause large differences in practice. The aim of this survey was to attempt to identify some of the common elements of service delivery as well as highlight any significant variations in service models. It was hoped that the results would assist healthcare professionals working with toxins to gauge or improve their own service provision in the light of any findings. A survey of 48 botulinum toxin experts was conducted at a national conference in the UK. Questions included (i) numbers of patients referred and diagnostic groups, (ii) staff composition of each clinic, (iii) methods of spasticity assessment, (iv) outcome measures and treatment goals commonly used and (v) follow-up arrangements. There were broad areas of agreement between experts such as methods of assessment of spasticity, treatment, injection guidance and follow-up arrangements. However, there were differences in diagnostic groups seen, staff composition and in outcome measurement across a wide range of clinic settings. There are considerable variations in practice between toxin experts. This survey may help practitioners identify areas of improvement in their services or explore alternative service arrangements.

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Effects of physical exercise in older adults with reduced physical capacity: meta-analysis of resistance exercise and multimodal exercise

Older adults with reduced physical capacity are at greater risk of progression to care dependency. Progressive resistance strength exercise and multimodal exercise have been studied to restore reduced physical capacity. To summarize the best evidence of the two exercise regimes, this meta-analysis study appraised randomized-controlled trials from published systematic reviews. Medline, Embase, and the Cochrane Database of Systematic Review and Cochrane Central Register of Controlled Clinical Trials were searched for relevant systematic reviews. Two reviewers independently screened the relevant systematic reviews to identify eligible trials, assessed trial methodological quality, and extracted data. RevMan 5.3 software was used to analyze data on muscle strength, physical functioning, activities of daily living, and falls. Twenty-three eligible trials were identified from 22 systematic reviews. The mean age of the trial participants was 75 years or older. Almost all multimodal exercise trials included muscle strengthening exercise and balance exercise. Progressive resistance exercise is effective in improving muscle strength of the lower extremity and static standing balance. Multimodal exercise is effective in improving muscle strength of the lower extremity, dynamic standing balance, gait speed, and chair stand. In addition, multimodal exercise is effective in reducing falls. Neither type of exercise was effective in improving activities of daily living. For older adults with reduced physical capacity, multimodal exercise appears to have a broad effect on improving muscle strength, balance, and physical functioning of the lower extremity, and reducing falls relative to progressive resistance exercise alone.

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Gait analysis on force treadmill in children: comparison with results from ground-based force platforms

Gait analysis (GA) typically includes surface electromyographic (sEMG) recording from several lower limb muscles, optoelectronic measurement of joint rotations, and force recordings from ground-based platforms. From the latter two variables, the muscle power acting on the lower limb joints can be estimated. Recently, gait analysis on a split-belt force treadmill (GAFT) was validated for the study of adult walking. It showed high reliability of spatiotemporal, kinematic, dynamic, and sEMG parameters, matching those obtainable with GA on the basis of ground walking. GAFT, however, still needs validation in children. Potential differences with respect to adult GAFT relate to (a) possible high signal-to-noise ratio, given the lower forces applied; (b) higher differences between treadmill and over-ground walking; and (c) limited compliance with the experimental setup. This study aims at investigating whether GAFT provides results comparable with those obtainable from ground walking in children and consistent with results from GAFT in adults. GAFT was applied to three groups of healthy children aged 5–6 years (n=6), 7–8 years (n=6), and 9–13 years (n=8) walking at the same average speed spontaneously adopted overground. The results were compared with those obtained from another study applying GA to an age-matched and speed-matched sample of 47 children, and with those obtained from GAFT in adults. The reliability (as indicated by the SD) of both spatiotemporal and dynamic parameters was higher in GAFT compared with GA. In the 5–6-, 7–8-, and 9–13-year-old groups, at average speeds of 0.83, 1.08, and 1.08 m/s, step length was shorter by 9.19, 3.57, and 2.30% compared with GA in controls at comparable speeds, respectively. For the youngest group, a lower power generation from the plantar flexors (peak power: 1.35±0.32 vs. 2.11±1.02 W/kg) and a slightly more flexed posture of the hip, knee, and ankle joints were observed during GAFT compared with GA in controls. The other gait parameters were very similar between the GAFT and the GA groups. The shortening of step length during GAFT, relative to GA at superimposable speed, was on average of all children 6.8%, in line with the 8% decrease found in adults. The profiles of sEMG and joint rotations, and all of the weight-standardized joint power parameters, matched those recorded in adults. The entire experimental session lasted about 1 h. All children complied with the experimental setting and easily completed the requested tests. In conclusion, GAFT seems to be a promising alternative to conventional GA in children.

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The value of musculoskeletal ultrasound in geriatric care and rehabilitation

The WHO reports that one of the major chronic conditions affecting the elderly worldwide is musculoskeletal disorders that are associated with long-term pain and disability. Considering the healthcare needs of the elderly (i.e. comprehensive, accessible, efficient) and the advantages of ultrasound (US) use (patient-friendly, convenient, cost-effective, and does not require exposure to radiation or magnetic fields), there seems to be a 'gap' in the actual clinical practice. In this paper, we aimed to highlight the potential value of US imaging in the management of the elderly with a wide spectrum of musculoskeletal conditions (degenerative/rheumatic joint diseases, falls/trauma, nursing care, peripheral nerve problems, sarcopenia, and interventions). In this respect, electronic databases (ISI Web of Science, PubMed, Elsevier Science Direct) and reference lists of relevant articles/reviews were screened by two blinded investigators for each topic. The main medical subject heading terms selected to capture the most relevant papers on the topics in accordance with the literature were knee/hip/hand osteoarthritis, prevalence, rotator cuff injury, lateral epicondylitis, tendinopathy, rheumatoid arthritis, Sjogren's syndrome, polymyalgia rheumatica, crystal arthropathies, gout, pseudogout, carpal tunnel syndrome, fall, fractures, hematoma, pressure ulcer, ultrasonography, interventional, sarcopenia, body composition, rehabilitation, frail elderly, and aged. The search was limited to peer-reviewed full-text English journals starting from the earliest papers to May 2017. A study population (or part of the study population) of adults older than 65 years (if possible) was included. We especially underscore the use of US by clinicians as an extension of their physical examination or as a practical guide for an immediate intervention.

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Three-dimensional head-mounted gaming task procedure maximizes effects of vestibular rehabilitation in unilateral vestibular hypofunction: a randomized controlled pilot trial

Considering the emerging advantages related to virtual reality implementation in clinical rehabilitation, the aim of the present study was to discover possible (i) improvements achievable in unilateral vestibular hypofunction patients using a self-assessed head-mounted device (HMD)-based gaming procedure when combined with a classical vestibular rehabilitation protocol (HMD group) as compared with a group undergoing only vestibular rehabilitation and (ii) HMD procedure-related side effects. Therefore, 24 vestibular rehabilitation and 23-matched HMD unilateral vestibular hypofunction individuals simultaneously underwent a 4-week rehabilitation protocol. Both otoneurological measures (vestibulo-ocular reflex gain and postural arrangement by studying both posturography parameters and spectral values of body oscillation) and performance and self-report measures (Italian Dizziness Handicap Inventory; Activities-specific Balance Confidence scale; Zung Instrument for Anxiety Disorders, Dynamic Gait Index; and Simulator Sickness Questionnaire) were analyzed by means of a between-group/within-subject analysis of variance model. A significant post-treatment between-effect was found, and the HMD group demonstrated an overall improvement in vestibulo-ocular reflex gain on the lesional side, in posturography parameters, in low-frequency spectral domain, as well as in Italian Dizziness Handicap Inventory and Activities-specific Balance Confidence scale scores. Meanwhile, Simulator Sickness Questionnaire scores demonstrated a significant reduction in symptoms related to experimental home-based gaming tasks during the HMD procedure. Our findings revealed the possible advantages of HMD implementation in vestibular rehabilitation, suggesting it as an innovative, self-assessed, low-cost, and compliant tool useful in maximizing vestibular rehabilitation outcomes.

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Robot ZORA in rehabilitation and special education for children with severe physical disabilities: a pilot study

The aim of this study was to explore the potential of ZORA robot-based interventions in rehabilitation and special education for children with severe physical disabilities. A two-centre explorative pilot study was carried out over a 2.5-month period involving children with severe physical disabilities with a developmental age ranging from 2 to 8 years. Children participated in six sessions with the ZORA robot in individual or in group sessions. Qualitative and quantitative methods were used to collect data on aspects of feasibility, usability, barriers and facilitators for the child as well as for the therapist and to obtain an indication of the effects on playfulness and the achievement of goals. In total, 17 children and seven professionals participated in the study. The results of this study show a positive contribution of ZORA in achieving therapy and educational goals. Moreover, sessions with ZORA were indicated as playful. Three main domains were indicated to be the most promising for the application of ZORA: movement skills, communication skills and cognitive skills. Furthermore, ZORA can contribute towards eliciting motivation, concentration, taking initiative and improving attention span of the children. On the basis of the results of the study, it can be concluded that ZORA has potential in therapy and education for children with severe physical disabilities. More research is needed to gain insight into how ZORA can be applied best in rehabilitation and special education.

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Antivertiginous drug therapy does not hinder the efficacy of individualized vibrotactile neurofeedback training for vestibular rehabilitation – a randomized trial

Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ∼10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins.

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Effectiveness of the conductive educational approach added to conventional physiotherapy in the improvement of gait parameters of poststroke patients: randomized-controlled pilot study

Our objective was to assess the benefits of the conductive education (CE) approach added to conventional physiotherapy in gait functions of poststroke, hemiparetic patients. A randomized-controlled trial was designed in a rehabilitation clinic. Late and chronic poststroke patients with gait disturbances (n=17, median age: 55 years, range: 41–72 years) were enrolled in the study. All patients received conventional physiotherapy. However, patients of only one group took part in therapy on the basis of the CE approach. The gait parameters, semiobjective outcome measures, functional independence measure, and International Classification of Functioning, Disability and Health domains were collected. The effectiveness of the CE approach was underlined by those outcome measures that were only significant (P≤0.05) in the conductive group: functional independence measure motor subscale; maintaining body position and walking long distances; and muscle strength in some muscle groups. The results suggest that CE could have an additive effect on gait improvement of stroke patients.

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Localized muscle vibration reverses quadriceps muscle hypotrophy and improves physical function: a clinical and electrophysiological study

Quadriceps weakness has been associated with knee osteoarthritis (OA). High-frequency localized muscle vibration (LMV) has been proposed recently for quadriceps strengthening in patients with knee OA. The purpose of this study was (a) to investigate the clinical effectiveness of high-frequency LMV on quadriceps muscle in patients with knee OA and (b) to disentangle, by means of surface electromyography (sEMG), the underlying mechanism. Thirty patients, aged between 40 and 65 years, and clinically diagnosed with knee OA were included in this randomized, controlled, single-blinded pilot study. Participants were randomly assigned to two groups: a study group treated with LMV, specifically set for muscle strengthening (150 Hz), by means of a commercial device VIBRA, and a control group treated with neuromuscular electrical stimulation. Clinical outcome was measured using the Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, knee range of motion, Timed Up and Go test, and Stair climbing test. To assess changes in muscle activation and fatigue a subgroup of 20 patients was studied with the use of sEMG during a sustained isometric contraction. The LMV group showed a significant change in Western Ontario and McMaster Universities Osteoarthritis Index score, Visual Analogue Scale score, Timed Up and Go test, Stair Climbing Test, and knee flexion. These improvements were not significant in patients treated with neuromuscular electrical stimulation. sEMG analysis suggested an increased involvement of type II muscle fibers in the group treated with LMV. In conclusion, the present study supports the effectiveness of local vibration in muscle function and clinical improvement of patients with knee OA.

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Spinal cord injury following a mild trauma in homocystinuria-related bone frailty: neurorehabilitation and education on bone health management

Homocystinuria (HCU) is a rare autosomal recessive disease characterized by the deficiency of cystathionine β-synthetase, presenting with variable clinical features including micronutrient deficiency-related osteoporosis. Early-onset osteoporosis results in increased bone fragility, which is associated with low-impact fractures. To date, no traumatic myelopathy has ever been described in patients with HCU. This case report describes a 30-year-old male patient with HCU who was not aware that he was at high risk of sustaining debilitating bone fractures. After a mild trauma, he reported a T12 compression fracture with spinal cord injury. The patient underwent a tailored rehabilitation program, on the basis of multidisciplinary approach, and was educated about the increased risk of fractures, maintaining adherence to treatment and diet, having an active lifestyle, avoiding excessive weight loss, and preventing falls or other traumatic injury. To reduce the risk of fractures – with possible catastrophic consequences – patients with HCU, and their caregivers, should be educated about prevention of fractures.

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The effect of different dosage regimens of tranexamic acid on blood loss in bimaxillary osteotomy: a randomized, double-blind, placebo-controlled study

The purpose of this study was to compare the effects of three dosage regimens of intravenous tranexamic acid and normal saline placebo on blood loss and the requirement for transfusion during bimaxillary osteotomy. A prospective, randomized, double-blind, placebo-controlled study was performed. Eighty patients scheduled for elective bimaxillary osteotomy were divided into four groups: a placebo group and three groups receiving a single dose of tranexamic acid 10, 15, or 20mg/kg body weight after the induction of anaesthesia.

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Targeting de novo lipogenesis as a novel approach in anti-cancer therapy

Targeting de novo lipogenesis as a novel approach in anti-cancer therapy

Targeting <i>de novo</i> lipogenesis as a novel approach in anti-cancer therapy, Published online: 07 November 2017; doi:10.1038/bjc.2017.374

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CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma, Published online: 07 November 2017; doi:10.1038/bjc.2017.364

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Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer, Published online: 07 November 2017; doi:10.1038/bjc.2017.390

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Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response, Published online: 07 November 2017; doi:10.1038/bjc.2017.389

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Immunologic, microbial, and epithelial interactions in atopic dermatitis

To provide an overview of studies contributing to the understanding of immunologic, microbial, and epithelial interactions in atopic dermatitis.

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Home-based program of maintaining unresponsiveness in children with allergic reactions to larger amounts of peanuts

Allergists currently advise most patients with peanut allergy to observe life-long avoidance. This is in contrast to milk and egg allergy, where many children are partly tolerant to the food and tolerance induction with food ladders is routine.1 Twenty-one percent of children with proven peanut allergy at challenges appear to outgrow their clinical reactivity.2 Furthermore, clinical trials using oral, subcutaneous, and epicutaneous peanut immunotherapy have demonstrated that patients vary in the amount of peanut needed to trigger a reaction and that desensitization and to some extent sustained unresponsiveness can be achieved in children and adolescents.

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P237 Real world effects of reslizumab: a retrospective chart review

Reslizumab was recently approved for certain patients with asthma. This study compares asthma control before and during treatment in a California allergy clinic.

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Ask the Authors

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Ischemic Preconditioning Improves Time-Trial Performance at Moderate Altitude.

PURPOSE: Endurance athletes often compete and train at altitude where exercise capacity is reduced. Investigating acclimation strategies is therefore critical. Ischemic preconditioning (IPC) can improve endurance performance at sea level through improved O2 delivery and utilization, which could also prove beneficial at altitude. However, data are scarce and there is no study at altitudes commonly visited by endurance athletes. METHODS: In a randomized, crossover study, we investigated performance and physiological responses in thirteen male endurance cyclists during four 5-km cycling time trials (TT), preceded by either IPC (3x5-minutes ischemia/5-minutes reperfusion cycles at 220 mmHg) or SHAM (20 mmHg) administered to both thighs, at simulated low (FIO2 0.180, ~1200 m) and moderate (FIO2 0.154, ~2400 m) altitudes. Time to completion, power output, cardiac output (Q), arterial O2 saturation (SpO2), quadriceps tissue saturation index (TSI) and ratings of perceived exertion (RPE) were recorded throughout the TT. Differences between IPC and SHAM were analyzed at every altitude using Cohen's effect size (ES) and compared to the smallest worthwhile change. RESULTS: At low altitude, IPC possibly improved time to complete the TT (-5.2sec, -1.1%, Cohen's ES +/- 90% confidence limits -0.22, -0.44;0.01), power output (2.7%, ES 0.21, -0.08;0.51) and Q (5.0%, ES 0.27, 0.00;0.54), but did not alter SpO2, muscle TSI and RPE. At moderate altitude, IPC likely enhanced completion time (-7.3sec, -1.5%, ES -0.38, -0.55;-0.20) and power output in the second half of the TT (4.6%, ES 0.28, -0.15;0.72), increased SpO2 (1.0%, ES 0.38, -0.05;0.81), and decreased TSI (-6.5%, ES -0.27, -0.73;0.20) and RPE (-5.4%, ES -0.27, -0.48;-0.06). CONCLUSION: IPC may provide an immediate and effective strategy to defend SpO2 and enhance high-intensity endurance performance at moderate altitude. (C) 2017 American College of Sports Medicine

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Effects of ad libitum Low Carbohydrate High-Fat Dieting in Middle-Age Male Runners.

PURPOSE: This study examined the effects of a 3-week ad libitum high fat (~70% of calories), low carbohydrate (

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Impact of Blood Flow Restriction Exercise on Muscle Fatigue Development and Recovery.

Purpose: The present study was designed to provide mechanistic insight into the time-course and etiology of muscle fatigue development and recovery during and after low-intensity exercise when it is combined with blood flow restriction (BFR). Methods: Seventeen resistance-trained males completed four sets of low-intensity isotonic resistance exercise under two experimental conditions: knee extension exercise combined with (i) BFR and (ii) without BFR (CON). Neuromuscular tests were performed before, during (immediately after each set of knee extension exercise) and 1, 2, 4, and 8 min after each experimental condition. Maximal voluntary torque (MVT), quadriceps twitch torque in response to paired electrical stimuli at 10 Hz (PS10) and 100 Hz (PS100), PS10[BULLET OPERATOR]PS100-1 ratio as an index of low-frequency fatigue and voluntary activation were measured under isometric conditions. Perceptual and EMG data were recorded during each exercise condition. Results: After the first set of exercise, BFR induced significantly greater reductions in MVT, PS100 and PS10[BULLET OPERATOR]PS100-1 ratio compared to CON. These parameters progressively declined throughout the BFR protocol but recovered substantially within 2 min post-exercise when blood flow was restored. Neither a progressive decline in the course of the exercise protocol nor a substantial recovery of these parameters occurred during and after CON. Only at exercise termination, voluntary activation differed significantly between BFR and CON with greater reductions during BFR. Conclusion: At the early stage of exercise, BFR exacerbated the development of muscle fatigue mainly due to a pronounced impairment in contractile function. Despite the high level of muscle fatigue during BFR exercise, the impact of BFR on muscle fatigue was diminished after 2 min of reperfusion, suggesting that BFR has a strong but short-lasting impact on neuromuscular function. (C) 2017 American College of Sports Medicine

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Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle.

Purpose: This study aimed to determine protein arginine methyltransferase 1 (PRMT1), -4 (also known as coactivator-associated arginine methyltransferase 1; CARM1), and -5 expression and function during acute, exercise-induced skeletal muscle remodelling in vivo. Methods: C57BL/6 mice were assigned to one of three experimental groups: sedentary, acute bout of exercise, or acute exercise followed by 3 hours of recovery. The mice in the exercise groups performed a single bout of treadmill running at 15 m/min for 90 minutes. Hindlimb muscles were collected and quantitative real-time polymerase chain reaction and Western blotting were employed to examine exercise-induced gene expression. Results: PRMT gene expression and global enzyme activity were muscle-specific, generally being higher (P

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Maximal Exercise Alters the Inflammatory Phenotype and Response of Mononuclear Cells.

Purpose: Monocytes express the CD14 receptor that facilitates lipopolysaccharide (LPS) ligation to toll-like receptor 4 (TLR4) to elicit production of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-[alpha]). However, pro-inflammatory conditions, such as strenuous exercise, increase the percentage of monocytes expressing CD16, a receptor that enhances LPS stimulated TNF-[alpha] production. Therefore, we examined whether maximal treadmill exercise would alter the inflammatory phenotype of classical (CD14+/CD16-) and pro-inflammatory monocytes (intermediate [CD14++/CD16+] and non-classical [CD14+/CD16++]), evidenced by changes in TLR4, CD14, and CD16 receptor expression, and their inflammatory response to ex vivo LPS stimulation. Methods: Human mononuclear cells from 25 male participants (age: 24.2 +/- 4.0 yr.) were isolated prior to and following exercise to assess TLR4, CD14, and CD16 expression by flow cytometry and ex vivo production of LPS-stimulated inflammatory cytokines (IL-6, IL-10, and TNF-[alpha]). Results: Exercise reduced the percentage of classical monocytes and increased the percentage of intermediate and non-classical monocytes. In addition, TLR4 expression decreased on classical and intermediate monocytes, but not the non-classical monocyte subset. Furthermore, while CD14 expression decreased on all monocyte subsets, CD16 expression increased on intermediate monocytes only. In parallel with these phenotypic changes, the inflammatory milieu shifted towards a pro-inflammatory response following LPS stimulation (decreased IL-6 and IL-10 and increased IL-6 to IL-10 ratio and TNF-[alpha] production). Conclusion: These findings demonstrate that acute maximal exercise elicits a pro-inflammatory phenotype of isolated monocytes exposed to LPS and highlight potential mechanisms that will help elucidate the role of acute and chronic exercise on the innate immune response of circulating monocytes. (C) 2017 American College of Sports Medicine

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Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.

Purpose: To investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in ageing using large-scale longitudinal data. Methods: This study used the Survey of Health Ageing and Retirement in Europe (SHARE), a 10-year population-based cohort study with repeated measurements in 5 waves, every 2 years between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life SEC (wave 3) were collected in 22,846 individuals aged 50 to 95 years. Results: Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.20 to 1.86). With ageing, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR = 1.04, CI = 1.02 to 1.06 for women; OR = 1.02, CI = 1.00 to 1.05 for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Conclusions: Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy ageing trajectories, especially among women with disadvantaged early-life socioeconomic circumstances. (C) 2017 American College of Sports Medicine

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The anterolateral thigh flap with kiss technique for microsurgical reconstruction of oncological scalp defects

Defects after radical resection of scalp tumor feature extensive size, complexity of composite defect and poor elasticity of surrounding original tissue1. The anterolateral thigh (ALT) flap is one of the most frequently used workhorses for scalp reconstruction. However, most scalp defects are rounded instead of oval shaped and prone to be significantly wider than the maximal transverse diameter of classical ALT flap when direct closure of donor site is scheduled. Recently, Zhang et al.2 developed the concept of "economy in autologous flap transfer" and reported on the kiss technique in order to both reduce donor site morbidity and enable optimal soft tissue coverage.

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Event-related neuronal responses to acoustic novelty in single-sided deaf cochlear implant users: Initial findings

Cochlear implants (CIs) restore hearing to deaf and severely hard of hearing individuals. They bypass a non-functional inner ear by direct electrical stimulation of auditory nerves (Zeng et al., 2011). Compared to normal acoustic hearing CI-transmitted sounds are degraded (Drennan and Rubinstein, 2008). This makes speech understanding difficult, particularly in background noise (Baskent et al., 2016; Wilson and Dorman, 2008). Speech intelligibility with the CI is typically assessed via word or sentences tests in quiet or noise (Hahlbrock, 1953; Haumann et al., 2010; Hey et al., 2014, 2016; Hochmair-Desoyer et al., 1997; Zeng and Fay, 2013).

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Optimal use of EEG montages to identify inferior temporal epileptiform activity

The 10/20 EEG electrode position system recommended by Herbert Jasper at the 2nd International EEG Congress has remarkably stood the test of time (Klem et al., 1999). Image localization and studies of closely spaced electrode systems have generally confirmed that 10/20 electrode positions are located similarly, within 1 cm of major anatomic landmarks in individuals despite their varying head sizes and shapes (Homan et al., 1987). Silverman and other recognized, however, that interictal and ictal epileptiform discharges often originate in basal and anterior temporal regions that are poorly sampled by standard 10/20 leads and recommended T1/T2 electrodes for recording anterior inferior sources (Silverman, 1960).

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Electromagnetic Source Imaging Using Simultaneous Scalp EEG and Intracranial EEG: An Emerging Tool for Interacting with Pathological Brain Networks

Functional brain imaging aims at studying the function and dysfunction of the brain by monitoring its functional dynamics over time. Such modalities include, for instance, functional magnetic resonance imaging (fMRI) (Bandettini et al., 1992; Kwong et al., 1992; Ogawa et al., 1992), positron emission tomography (PET) (Ter-Pogossian et al., 1975), electroencephalography (EEG) (He et al., 1987; Michel and He, 2011; Niedermeyer and da Silva, 2005), and magnetoencephalography (MEG) (Cohen, 1972; Hämäläinen et al., 1993).

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It is vital to identify the underlying cause of chronic laryngopharyngeal neuropathy

We reviewed, with great interest, the paper entitled "Randomized double blind trial of amitriptyline versus placebo in treatment of chronic laryngopharyngeal neuropathy," by Jang et al. [1]. This is an excellent work. The authors found that subjective laryngopharyngeal symptoms improved in 67% patients of an amitriptyline group and in 44% patients of a placebo group. However, we believe that the inclusion criteria and exclusion criteria were somewhat inappropriate. Also, the measures of clinical outcomes could have been improved.

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Adenoidectomy and chronic nasal obstruction developing after failure of nasal steroid therapy

We reviewed, with great interest, the paper entitled "Role of adenoidectomy in chronic nasal obstruction after nasal steroid therapy failure" by Ciolek et al. [1]. This is excellent work. In the study, the authors document an average rate of respiratory allergies, but a high rate of asthma, among patients who fail nasal steroid therapy to treat chronic nasal obstructions. The authors suggest that adenoidectomy was highly efficacious in this subset of patients. However, adenoidectomy may not be necessary.

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Congratulations to SLHS Students Leilani Melendrez, Alyssa Pitts, and Olivia Carillo, Newly Inducted Mortar Board Members!

Mortar Board is a national honor society that recognizes college seniors for distinguished ability and achievement in scholarship, leadership, and service. 

The following SLHS students earned this distinction for 2017-2018 and are recognized below with their named "Most Influential Faculty Member":

• Leilani Melendrez, with Dr. Sonja Pruitt-Lord (1st picture)
• Alyssa Pitts, with Dr. Jessica Barlow (2nd picture)
• Olivia Carillo, with Dr. Peter Torre (unpictured)

Congratulations to all!

Check out all the newest Mortar Board members >>

[See image gallery at slhs.sdsu.edu]

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Table_of_Contents

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British_Society_of_Aesthetics

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Back_Cover

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