OtoLaryngology New Articles

Comparison of effects of OSA treatment by MAD and by CPAP on cardiac autonomic function during daytime Abstract Purpose The present study compared the effects of mandibular advancement therapy (MAD) with continuous positive airway pressure therapy (CPAP) on daytime cardiac autonomic modulation in a wide range of obstructive sleep apnea (OSA) patients under controlled conditions in a randomized, two-period crossover trial. Methods Forty OSA patients underwent treatment with MAD and with CPAP for 12 weeks each. At baseline and after each treatment period, patients were assessed by polysomnography as well as by a daytime cardiac autonomic function test that measured heart rate variability (HRV), continuous blood pressure (BP), and baroreceptor sensitivity (BRS) under conditions of spontaneous breathing, with breathing at 6, 12, and 15/min. Results Both CPAP and MAD therapy substantially eliminated apneas and hypopneas. CPAP had a greater effect. During daytime with all four conditions of controlled breathing, three-minute mean values of continuous diastolic BP were significantly reduced for both MAD and CPAP therapy. At the same time, selective increases due to therapy with MAD were found for HRV high frequency (HF) values. No changes were observed for BRS in either therapy mode. Conclusions These findings indicate that both MAD and CPAP result in similar beneficial changes in cardiac autonomic function during daytime, especially in blood pressure. CPAP is more effective than MAD in eliminating respiratory events. Read More » Predictors and patterns of melanoma recurrence following a negative sentinel lymph node biopsy. To analyse the patient demographics, tumour characteristics and follow-up data of patients with recurrence of melanoma following a negative sentinel lymph node biopsy. A retrospective review of a prospectively maintained melanoma database was conducted. Melanoma patients who had a negative sentinel lymph node were identified and we performed statistical analysis on their respective demographics, tumour histology characteristics and follow-up data. Of 164 patients studied, 40 (24%) had a recurrence of melanoma at a median of 39.5 months following diagnosis (range 1-92 months). Distant metastases were the most common form of disease recurrence (40% of all recurrences). Increasing tumour thickness was an independent predictor of recurrence on multivariate analysis while nodular histology approached significance. Median survival of 6 months was seen following disease recurrence (range 1-126 months). In the setting of a negative sentinel lymph node biopsy, there remains a risk of melanoma recurrence. Distant metastases were the most common form of recurrence. Disease recurrence occurred more frequently in those with thick primary tumours. Recurrences occurred at long intervals from diagnosis indicating the need to consider prolonged patient follow-up. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Graves' disease precipitated by rickettsial infection Read More » Fractionated stereotactic radiotherapy: an interesting alternative to stereotactic radiosurgery in acromegaly Read More » Update Skills in Head and Neck Surgery and Oncology 2015 Read More » Chemotherapie mit Paclitaxel führt zu microRNA-Freisetzung Zusammenfassung Hintergrund In den vergangenen Jahren gewinnen microRNA (griech. „micros": klein; miRNA) zunehmen an Bedeutung. miRNA sind konservierte, nichtcodierende, 17–28 Nukleotide lange einzelsträngige RNA-Moleküle. Von Tumorzellen sezerniert regulieren miRNA eine Vielzahl von biologischen Prozessen und sind auch bei der Ausbildung von Chemoresistenzen involviert. So werden durch die klassischen Therapieformen verschiedene miRNA freigesetzt. Welche miRNA mit Kopf-Hals Karzinomen und deren Resistenz gegenüber einem Zytostatikum wie Paclitaxel beteiligt sind, ist bisher unklar. Ziel der Arbeit Ziel war die Identifizierung der miRNA in Kopf-Hals-Karzinomen und Ermittlung jener miRNA, die an der Ausbildung von Resistenz gegenüber Paclitaxel beteiligt sind. Material und Methoden Für die Änderung der Genexpression wurden verschiedene HNSCC-Zelllinien mit 10 µM Paclitaxel für 48 h behandelt und mittels Microarray-Analyse untersucht. Anschließend wurde die Änderung der Expression von den einzelnen miRNA (miR221*, miR222 und miR222*) nach Paclitaxelbehandlung mittels quantitativer Echtzeit-Polymerasekettenreaktion (RT-PCR) bestimmt. Ergebnisse Therapie mit Paclitaxel setzt verschiedene miRNA frei. Die dominanteste Veränderung ist die erhöhte Genexpression des Gens MIR222. Die Regulation der miRNA miR222* scheint im Vergleich zwischen den HPV-negativen und den HPV-positiven HNSCC-Zelllinien unter Paclitaxelbehandlung unterschiedlich reguliert zu sein. Diskussion Die Expression von miR221/miR222 wurde mit der Regulation des Zellzyklus, der Onkogenese und der Resistenz gegenüber Krebsmedikamenten in Verbindung gebracht. Die Identifizierung der genauen Wirkweise von miRNA und ihren Regulationsmechanismen ist essenziell für das Ziel, miRNA als Krebsmarker zu verwenden und die Effizienz von Krebstherapien zu erhöhen. Read More » Endoskopietechniken in der ästhetischen Chirurgie Zusammenfassung Hintergrund Das Bestreben eines Chirurgen ist es, mit möglichst wenig Narben, Schwellungen, Blutungen und kurzer postoperativer Heilungsphase, ein für Patienten akzeptables Behandlungsergebnis zu erzielen. Ziel der Arbeit Der vorliegende Beitrag stellt Endoskopietechniken vor, die sich für Eingriffe eignen, bei denen ästhetischen Komponenten wesentliche Bedeutung zukommt. Material und Methoden Anwendungsbeispiele für Endoskopietechniken im Kopf-Hals-Bereich sind das endoskopische Augenbrauen- und Wangen-Lift sowie die anteriore Platysmamuskelplastik bei extendierten Gesichts- und Halsstraffungsoperationen. Beispielhaft für ästhetische oder rekonstruktive Operationen an der Körperoberfläche werden die endoskopische Bauchdeckenreduktionsplastik und die endoskopisch-assistierte Hebung eines Perforator-Fett-Faszien(PFF)-Lappens der vorderen Bauchwand beschrieben. Ergebnisse Das endoskopische Stirn-Lift stellt bei gegebener Indikation eine minimalinvasive Methode zur Hebung der Augenbrauenregion dar. Das Endobrow-Lift lässt sich idealerweise mit einem endoskopischen Mittelgesicht-Lift verbinden. Die Einführung einer 30°-Optik über die seitlichen Inzisionen im Rahmen ausgedehnter Gesichts- und Halsstraffungen kann die Darstellung der vorderen Platysmabänder und die kontrollierte Naht in der Medianebene, ohne zusätzliche submentale Hautinzision, ermöglichen. Auch bei einigen wenigen ästhetisch begründeten Bauchdeckenreduktionsplastiken besteht die Möglichkeit der endoskopischen Durchführung. Schlussfolgerungen In der ästhetischen Chirurgie ergeben sich verschiedene Indikationen für die Endoskopietechnik. Unter günstigen Bedingungen kann hierdurch auf zusätzliche Hautschnitte zur offenen Darstellung von anatomischen Strukturen verzichtet werden. Read More » Evaluation of Role of Mastoid Surgery in the Management of Safe Chronic Suppurative Otitis Media Abstract This study evaluates the outcome of type 1 tympanoplasty with and with out mastoidectomy. The comparative study comprises of 40 patients with CSOM safe type in dry ear. All cases were operated during a period of one and a half years. 20 of these cases were selected for tympanoplasty alone (Group A) and 20 cases were selected for Tympanoplasty with cortical mastoidectomy (Group B). Patients were reviewed after 3 weeks for inspection of the operated ear. The second and third postoperative reviews were done 6 and 12 weeks respectively for clinical assessment of the operated ear with respect to graft status, ear discharge and hearing improvement. The postoperative audiograms were recorded after 3 months. Type I tympanoplasty with cortical mastoidectomy has better graft uptake (100 %) as compared to without mastoidectomy (95 %). Post-operative A–B gap closure is better in tympano-mastoidectomy (20.48 dB) than tympanoplasty (15.75 dB) with p value <0.05. Post-operative hearing gain and graft uptake were both better with tympano-mastoidectomy and tympanoplasty. Read More » Investigation of the Source of Snoring Sound by Drug-Induced Sleep Nasendoscopy Objective: To investigate the source of snoring sound in patients with simple snoring (SS) and different degrees of obstructive sleep apnea syndrome (OSAS) in order to provide a basis for the surgical treatment of snoring. Methods: Fifty-two patients with either SS or OSAS (with an apnea-hypopnea index ≤40) underwent drug-induced sleep nasendoscopy (DISN). Vibration sites in the pharyngeal cavity were observed. Results: Vibration of the soft palate, pharyngeal lateral wall, epiglottis, and tongue base appeared in 100, 53.8, 42.3, and 26.9% of the patients, respectively. The source of snoring sound was divided into two types: palatal fluttering only (type I) and multisite vibration (type II). The latter was divided into 3 subtypes: palatal fluttering with epiglottis vibration (type IIa), palatal fluttering with lateral wall vibration (type IIb), and palatal fluttering with vibration of the lateral wall, epiglottis, and tongue base together (type IIc). The distribution of type I snoring was the highest in SS patients. Type IIb was more common in patients with medium and severe OSAS. Type IIc was most common in patients with severe OSAS. Conclusion: The source of snoring sound is diverse, with SS and OSAS patients showing different features. DISN is a very effective method of identifying the snoring source. ORL 2015;77:359-365 Read More » Assessment of vinyl polysiloxane as an innovative injection material for the anatomical study of vasculature Abstract There are numerous injection materials for the study of vasculature in anatomical specimens, each having its own advantages and disadvantages. Latex and resins are the most widely used injection materials but need several days to set. The development of new materials taking shorter time to polymerize might be very useful to improve anatomic specimen study conditions. The aim of the present study was to evaluate vinyl polysiloxane (VPS), a silicon material widely used for dental impressions with the advantage to set very rapidly, as an injection material. We assessed the preparation, use, diffusion and setting time of the product in different anatomical regions (central nervous system, external carotid/jugular, lower limb) to observe its behavior in variably sized vessels. Our results suggest that VPS might be of interest for the study of vessels in anatomical specimens. The main strengths of the product are represented by (1) simplicity of use, as it is a ready-to-use material, (2) very rapid polymerization, (3) availability in a range of viscosities making easier the exploration of small vessels, (4) its better elasticity compared to resines, (5) and finally its availability in a range of colors making it a material of choice for vascular system dissections including those with very small caliber vessels. Read More » How to determine the bone mineral density of the distal humerus with radiographic tools? Abstract Introduction The aim of this study was to investigate three methods of prediction of the bone quality of the distal humerus: dual-energy X-ray absorptiometry (DEXA), Ct-Scan and plain radiographs. Materials and methods The bone mineral density (BMD) of 21 cadaveric distal humerus was determined using DEXA at two levels. Then a CT-scan and anteroposterior radiographs were taken. The cancellous density was estimated with the CT-scan. The cortico-medullar index (CMI) was calculated as cortical thickness divided by total bone thickness on AP views. Results A significant positive correlation was found between the BMD of the epiphysis and the CMI of r = 0.61. The mean BMD of the distal humerus was 0.559 g/cm2. Male specimens showed a significantly higher BMD than females. The mean CMI of diaphysis was 1.431 and the mean BMD of the metaphysis region was 0.444 g/cm2. Discussion More than a direct evaluation of the bone density with a CT-scan, the CMI of the distal humerus diaphysis is a predictor of the bone quality of the distal humerus. This should be of great help for the surgeon's decision making in case of fracture of the distal humerus, as open Reduction and Internal Fixation (ORIF) of fractures of the distal humerus can lead to failure due to poor bone quality. Level of evidence Basic Science Study, Anatomic Cadaver Study. Read More » Coracobrachialis muscle: morphology, morphometry and gender differences Abstract Purpose Coracobrachialis (CBM) is a complex muscle with a wide range of variations in its morphology and innervation. The goal of this study was to elucidate the morphology, morphometry, gender differences of CBM and precise anatomical position of the musculocutaneous nerve (MCN) with reference to surrounding anatomical landmarks in an adult Sri Lankan population. Method Cadaveric upper limbs (n = 312) were examined for the proximal and distal attachments, length, width, thickness of CBM and its relationship with the MCN. Results The CBM originated from the tip of the coracoid process of the scapula and lateral, posterior and medial aspects of the tendon of short head of biceps brachii. Gender differences were observed in all morphometrical parameters of CBM. In 83.33 %, MCN perforated the CBM. In 50 % the MCN pierced the middle one-third of CBM while none pierced the lower one-third. The distance from the coracoid process to the point of entry of MCN into CBM (distance P) was 50.62 mm. A positive correlation was observed between the arm length and distance P indicating that arm length provides an accurate and reliable means of gauging the distance P of an individual. Conclusion The present study provides new evidence pertaining to the origin of CBM. Further, it was revealed that the predicted distance P of any upper extremity can be calculated by dividing the arm length by 5. Precise anatomical location of MCN in relation to CBM using unequivocal and well-defined anatomical landmarks will be imperative in modern surgical procedures. Read More » Finding the mental foramen Abstract The mental foramen and mental nerve are clinically important landmarks for clinicians across various disciplines including dentists, oral maxillofacial surgeons, emergency physicians and plastic and reconstructive surgeons. To minimize complications related to procedures in the vicinity of the mental foramen and nerve, knowledge of its anatomy and anatomical variations is cardinal to concerned clinicians. In this review, basic anatomy, procedural complications, hard and soft tissue relations, variations between population groups, asymmetry, accessory mental foramina and the use of various radiological modalities to determine the position of the mental foramen are reviewed to provide a more thorough understanding of this important landmark. Read More » Nasal Floor Mucosa: New Donor Site for Mucous Membrane Grafts. Purpose: Mucous membrane grafts are used for various indications in oculoplastics. The authors report the use of nasal floor mucosa as a new donor site for mucous membrane grafts. Methods: Following adequate anesthesia and vasoconstriction, the nasal floor is visualized with a 30[degrees] endoscope. Next, the interior turbinate is medialized, and the nasolacrimal duct is identified and preserved. Anterior, posterior, medial, and lateral incisions are made through the nasal mucosa to the nasal bone. The mucosa is dissected off the nasal bone with a periosteal elevator. Nasal saline irrigation is used postoperatively to aid healing. Histologic analysis of the harvested graft and mucosa from the inferior and middle turbinates were analyzed histologically for the number of mucin-producing cells per high power field and compared. Results: Nasal floor mucosa provides ample tissue for grafting with little donor site morbidity. The surgery is technically easy to learn and perform. There is less risk for blood loss compared with harvesting tissue from the turbinates and less postoperative discomfort compared with buccal mucosal grafts. The grafts have been used in 9 different patients for a variety of ocular indications. Histologically, the nasal floor mucosa contains statistically more mucin-secreting cells than other nasal site, which can be helpful especially in cases of ocular surface disease. In 1 case, biopsy of the grafted tissue at postoperative year 2 showed survival of the respiratory mucin-secreting cells under histologic examination. Conclusions: Nasal floor mucosa should be considered a donor site when a mucous membrane graft is needed. The surgery is safe, easy to perform, and has less morbidity than either a nasal turbinate graft or a buccal mucosal graft. (C) 2015 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved. Read More » TGF-β1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG 2 cells Abstract Liver cancer is one of the most common human malignancies, and transforming growth factor-beta (TGF-β) pathway plays a key role in its pathogenesis. To study the relationship between TGF-β pathway and the related protein expression of many signaling pathway, markers of stem cells, CK family, and others, liver cancer HepG2 cells were transfected with siRNA directed against TGF-β1 or were treated with exogenous TGF-β1. Then, these protein levels were measured by Western blotting. After siRNA transfection, TGF-β1 protein level was decreased, indicating that the siRNA against it was effective. In exogenous TGF-β1 group, the expression of smad4, smad2/3, and β-catenin proteins was increased, whereas that of p-smad2/3, CD133, cleaved Notch1, and epithelial cell adhesion molecule (EpCAM) proteins at 48 h was decreased. The expression of CK8 and CK18 proteins was increased at 24 h and was decreased at 48 and 96 h. In TGF-β1-silenced group, the expression of smad2/3, β-catenin, cleaved-notch1, and CK18 proteins was decreased, while that of smad4, p-smad2/3, CD133, EpCAM, and CK8 proteins was increased. TERT protein expression was slightly increased in exogenous TGF-β1 group at 48 h and in TGF-β1-silenced group at 96 h. TGF-β1 did not affect the protein expression of CK19 and HIF-1. Thus, TGF-β1 pathway plays an important role in cell regulation of liver cancer through the modulation of these proteins. These data will contribute to the understanding of the pathogenesis of liver cancer and the role of TGF-β pathway in this process. Read More » The role of miRNAs in the pheochromocytomas Abstract Pheochromocytoma (PCC) is a catecholamine-producing and neuroendocrine tumor, which originates from chromaffin cells in adrenal medulla or at extra-adrenal sites. The clinical symptoms of PCC patients were including paroxysmal hypertension and cardiovascular crises. Despite the identification of many molecular-level basics involved in these pathogenesis processes, the 5-year survival of advanced stage PCC is <40 %. The 5-year survival of advanced stage PCC is <40 %. microRNAs (miRNAs) are a class of single-strand, highly conserved, small, non-coding RNAs which inhibit gene expression by binding to the target messenger RNA (mRNA) 3′UTR to induce translational repression or their degradation. Increasing data have shown that the deregulated expression of miRNAs has been implicated in the diagnosis and treatment of tumors including PCC. In this review, we summarized the expressions and roles of miRNAs in PCC and comment on the potential role of miRNAs in improving diagnosis, prognosis, and treatment of PCC. Read More » An integrative transcriptomic analysis reveals p53 regulated miRNA, mRNA, and lncRNA networks in nasopharyngeal carcinoma Abstract It has been reported that p53 dysfunction is closely related to the carcinogenesis of nasopharyngeal carcinoma (NPC). Recently, an increasing body of evidence has indicated that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) participate in p53-associated signaling pathways and, in addition to mRNAs, form a complex regulation network to promote tumor occurrence and progression. The aim of this study was to elucidate the p53-regulated miRNAs, mRNAs, and lncRNAs and their regulating networks in NPC. Firstly, we overexpressed p53 in the NPC cell line HNE2 and performed transcriptomic gene expression profiling (GEP) analysis, which included miRNAs, mRNAs, and lncRNAs, using microarray technology at 0, 12, 24, and 48 h after transfection. There were 38 miRNAs (33 upregulated and 5 downregulated), 2107 mRNAs (296 upregulated and 1811 downregulated), and 1190 lncRNAs (133 upregulated and 1057 downregulated) that were significantly dysregulated by p53. Some of the dysregulated molecules were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Then, we integrated previously published miRNAs, mRNAs, and lncRNAs GEP datasets from NPC biopsies to investigate the expression of these p53 regulated molecules and found that 7 miRNAs, 218 mRNAs, and 101 lncRNAs regulated by p53 were also differentially expressed in NPC tissues. Finally, p53-regulated miRNA, mRNA, and lncRNA networks were constructed using bioinformatics methods. These miRNAs, mRNAs, and lncRNAs may participate in p53 downstream signaling pathways and play important roles in the carcinogenesis of NPC. Thorough investigations of their biological functions and regulating relationships will provide a novel view of the p53 signaling pathway, and the restoration of p53 functioning or its downstream gene regulating network is potentially of great value in treating NPC patients. Read More » Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway Abstract The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells. Read More » An Unusual Case of Extranodal Rosai-Dorfman Disease Manifesting as an Epibulbar Mass Purpose: To report an unusual presentation of a 48-year-old man with a salmon-colored epibulbar mass, whose pathology was consistent with extranodal Rosai-Dorfman disease (RDD). Method: We conducted a retrospective and interventional case report. Results: A 48-year-old white man presented with progressive left eye irritation, redness, and multiple large subcutaneous nodules on his arms and torso over the past year. He did not have any lymphadenopathy, lymphocytosis, or fever. Visual acuity and intraocular pressures were normal in both eyes. He had mild vertical diplopia on downward gaze. Slit lamp examination revealed a non-tender salmon-colored epibulbar mass of 1.0 × 1.2 cm. Incisional biopsy was performed. Histopathologic evaluation revealed emperipolesis, with positive CD68, positive S100, and negative CD1a staining. These findings were consistent with extranodal RDD. At the 24-month follow-up, there were no signs of recurrence, and his diplopia resolved. Conclusions: This case of RDD is rare because of the concurrent epibulbar mass with subcutaneous nodules on the torso and arms. Extranodal RDD with epibulbar mass involvement tends to be unilateral, occurring mainly in males, and evenly among people of white and black race. An epibulbar mass of any color should raise concern for systemic lymphoma and RDD. The clinical course for extranodal RDD is typically benign. Excisional biopsy is often done for diagnosis and treatment. Recurrence of the unilateral epibulbar mass after biopsy is rare, but common with bilateral epibulbar masses. Case Rep Ophthalmol 2015;6:351-355 Read More » Delayed Correction of Hypotony Maculopathy in a Patient with Glaucoma and Thyroid-Related Orbitopathy Hypotony maculopathy is a condition that may result in visual deterioration from choroidal folds or optic disc edema. Optic disc edema can result from altered translaminar pressure gradients (lowered intraocular pressure, increased cerebrospinal fluid pressure, or increased orbital pressure). We report a case of bilateral optic disc edema in a patient with glaucoma and thyroid-related orbitopathy. The patient's disc edema was initially presumed to be secondary to her orbitopathy, but persisted after bilateral orbital decompression. Ultimately, disc edema and choroidal folds in the right eye resolved after trabeculectomy revision and an increase in intraocular pressure. This case serves as a reminder of the causes of optic disc edema and demonstrates delayed reversal of hypotony maculopathy. Case Rep Ophthalmol 2015;6:356-360 Read More » The Norwegian Hearing in Noise Test for Children. Objectives: The aims of this study were to create 12 10-sentence lists for the Norwegian Hearing in Noise Test for children, and to use these lists to collect speech reception thresholds (SRTs) in quiet and in noise to assess speech perception in normal hearing children 5 to 13 years of age, to establish developmental trends, and to compare the results with those of adults. Data were collected in an anechoic chamber and in an audiometric test room, and the effect of slight room reverberation was estimated. Design: The Norwegian Hearing in Noise Test for children was formed from a subset of the adult sentences. Selected sentences were repeatable by 5- and 6-year-old children in quiet listening conditions. Twelve sentence lists were created based on the sentences' phoneme distributions. Six-year-olds were tested with these lists to determine list equivalence. Slopes of performance intensity (PI) functions relating mean word scores and signal to noise ratios (SNRs) were estimated for a group of 7-year-olds and adults. HINT normative data were collected for 219 adults and children 5 to 13 years of age in anechoic and audiometric test rooms, using noise levels 55, 60, or 65 dBA. Target sentences always originated from the front; whereas, the noise was presented either from the front, noise front (NF), from the right, noise right (NR) or from the left, noise left (NL). The NR and NL scores were averaged to yield a noise side (NS) score. All 219 subjects were tested in the NF condition, and 95 in the NR and NL conditions. Retest of the NF at the end of the test session was done for 53 subjects. Longitudinal data were collected by testing 9 children as 6, 8, and 13 years old. Results: NF and NS group means for adults were -3.7 and -11.8 dB SNR, respectively. Group means for 13-year-olds were -3.3 and -9.7, and for the 6-year-olds group means were -0.3 and -5.7 dB SNR, as measured in an anechoic chamber. NF SRTs measured in an audiometric test room were 0.7 to 1.5 higher (poorer) than in the anechoic chamber. Developmental trends were comparable in both rooms. PI slopes were 8.0% dB SNR for the 7-year-olds and 10.1% for the adults. NF SRTs in the anechoic chamber improved by 0.7 dB per year over an age range of 5 to 10 years. Using a PI slope 8 to 10% per dB, the estimated increase in percent intelligibility was 4 to 7% per year. Adult SRTs were about 3 dB lower than those for 6-year-olds, corresponding to 25 to 30% better intelligibility for adults. Conclusions: Developmental trends in HINT performance for Norwegian children with normal hearing are similar to those seen in other languages, including American English and Canadian French. SRTs approach adult normative values by the age of 13; however, the benefits of spatial separation of the speech and noise sources are less than those seen for adults. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Factors Predicting Postoperative Unilateral and Bilateral Speech Recognition in Adult Cochlear Implant Recipients with Acoustic Hearing. Objectives: The first objective was to examine factors that could be predictive of postoperative unilateral (cochlear implant alone) speech recognition ability in a group of subjects with greater degrees of preoperative acoustic hearing than has been previously examined. Second, the study aimed to identify factors predictive of speech recognition in the best-aided, bilateral listening condition. Design: Participants were 65 postlinguistically hearing-impaired adults with preoperative phoneme in quiet scores of greater than or equal to 46% in one or both ears. Preoperative demographic and audiometric factors were assessed as predictors of 12-month postoperative unilateral and bilateral monosyllabic word scores in quiet and of bilateral speech reception threshold (SRT) in babble. Results: The predictive regression model accounted for 34.1% of the variance in unilateral word recognition scores in quiet. Factors that predicted better scores included: a shorter duration of severe to profound hearing loss in the implanted ear; and poorer pure-tone-averaged thresholds in the contralateral ear. Predictive regression models of postimplantation bilateral function accounted for 36.0% of the variance for word scores in quiet, and 30.9% of the variance for SRT in noise. A shorter duration of severe to profound hearing loss in the implanted ear, a lower age at the time of implantation, and better contralateral hearing thresholds were associated with higher bilateral word recognition in quiet and SRT in noise. Conclusions: In this group of cochlear implant recipients with preoperative acoustic hearing, a shorter duration of severe to profound hearing loss in the implanted ear was shown to be predictive of better unilateral and bilateral outcomes. However, further research is warranted to better understand the impact of that factor in a larger number of subjects with long-term hearing impairment of greater than 30 years. Better contralateral hearing was associated with poorer unilateral word scores with the implanted ear alone, but better absolute bilateral speech recognition. As a result, it is clear that different models would need to be developed to predict unilateral and bilateral postimplantation scores. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Effects of Reverberation and Compression on Consonant Identification in Individuals with Hearing Impairment. Objectives: Hearing aids are frequently used in reverberant environments; however, relatively little is known about how reverberation affects the processing of signals by modern hearing-aid algorithms. The purpose of this study was to investigate the acoustic and behavioral effects of reverberation and wide-dynamic range compression (WDRC) in hearing aids on consonant identification for individuals with hearing impairment. Design: Twenty-three listeners with mild to moderate sloping sensorineural hearing loss were tested monaurally under varying degrees of reverberation and WDRC conditions. Listeners identified consonants embedded within vowel-consonant-vowel nonsense syllables. Stimuli were processed to simulate a range of realistic reverberation times and WDRC release times using virtual acoustic simulations. In addition, the effects of these processing conditions were acoustically analyzed using a model of envelope distortion to examine the effects on the temporal envelope. Results: Aided consonant identification significantly decreased as reverberation time increased. Consonant identification was also significantly affected by WDRC release time. This relationship was such that individuals tended to perform significantly better with longer release times. There was no significant interaction between reverberation and WDRC. The application of the acoustic model to the processed signal showed a close relationship between trends in the behavioral performance and distortion to the temporal envelope resulting from reverberation and WDRC. The results of the acoustic model demonstrated the same trends found in the behavioral data for both reverberation and WDRC. Conclusions: Reverberation and WDRC release time both affect aided consonant identification for individuals with hearing impairment, and these condition effects are associated with alterations to the temporal envelope. There was no significant interaction between reverberation and WDRC release time. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Factors Predicting Postoperative Unilateral and Bilateral Speech Recognition in Adult Cochlear Implant Recipients with Acoustic Hearing. Objectives: The first objective was to examine factors that could be predictive of postoperative unilateral (cochlear implant alone) speech recognition ability in a group of subjects with greater degrees of preoperative acoustic hearing than has been previously examined. Second, the study aimed to identify factors predictive of speech recognition in the best-aided, bilateral listening condition. Design: Participants were 65 postlinguistically hearing-impaired adults with preoperative phoneme in quiet scores of greater than or equal to 46% in one or both ears. Preoperative demographic and audiometric factors were assessed as predictors of 12-month postoperative unilateral and bilateral monosyllabic word scores in quiet and of bilateral speech reception threshold (SRT) in babble. Results: The predictive regression model accounted for 34.1% of the variance in unilateral word recognition scores in quiet. Factors that predicted better scores included: a shorter duration of severe to profound hearing loss in the implanted ear; and poorer pure-tone-averaged thresholds in the contralateral ear. Predictive regression models of postimplantation bilateral function accounted for 36.0% of the variance for word scores in quiet, and 30.9% of the variance for SRT in noise. A shorter duration of severe to profound hearing loss in the implanted ear, a lower age at the time of implantation, and better contralateral hearing thresholds were associated with higher bilateral word recognition in quiet and SRT in noise. Conclusions: In this group of cochlear implant recipients with preoperative acoustic hearing, a shorter duration of severe to profound hearing loss in the implanted ear was shown to be predictive of better unilateral and bilateral outcomes. However, further research is warranted to better understand the impact of that factor in a larger number of subjects with long-term hearing impairment of greater than 30 years. Better contralateral hearing was associated with poorer unilateral word scores with the implanted ear alone, but better absolute bilateral speech recognition. As a result, it is clear that different models would need to be developed to predict unilateral and bilateral postimplantation scores. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Effects of Reverberation and Compression on Consonant Identification in Individuals with Hearing Impairment. Objectives: Hearing aids are frequently used in reverberant environments; however, relatively little is known about how reverberation affects the processing of signals by modern hearing-aid algorithms. The purpose of this study was to investigate the acoustic and behavioral effects of reverberation and wide-dynamic range compression (WDRC) in hearing aids on consonant identification for individuals with hearing impairment. Design: Twenty-three listeners with mild to moderate sloping sensorineural hearing loss were tested monaurally under varying degrees of reverberation and WDRC conditions. Listeners identified consonants embedded within vowel-consonant-vowel nonsense syllables. Stimuli were processed to simulate a range of realistic reverberation times and WDRC release times using virtual acoustic simulations. In addition, the effects of these processing conditions were acoustically analyzed using a model of envelope distortion to examine the effects on the temporal envelope. Results: Aided consonant identification significantly decreased as reverberation time increased. Consonant identification was also significantly affected by WDRC release time. This relationship was such that individuals tended to perform significantly better with longer release times. There was no significant interaction between reverberation and WDRC. The application of the acoustic model to the processed signal showed a close relationship between trends in the behavioral performance and distortion to the temporal envelope resulting from reverberation and WDRC. The results of the acoustic model demonstrated the same trends found in the behavioral data for both reverberation and WDRC. Conclusions: Reverberation and WDRC release time both affect aided consonant identification for individuals with hearing impairment, and these condition effects are associated with alterations to the temporal envelope. There was no significant interaction between reverberation and WDRC release time. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » The Norwegian Hearing in Noise Test for Children. Objectives: The aims of this study were to create 12 10-sentence lists for the Norwegian Hearing in Noise Test for children, and to use these lists to collect speech reception thresholds (SRTs) in quiet and in noise to assess speech perception in normal hearing children 5 to 13 years of age, to establish developmental trends, and to compare the results with those of adults. Data were collected in an anechoic chamber and in an audiometric test room, and the effect of slight room reverberation was estimated. Design: The Norwegian Hearing in Noise Test for children was formed from a subset of the adult sentences. Selected sentences were repeatable by 5- and 6-year-old children in quiet listening conditions. Twelve sentence lists were created based on the sentences' phoneme distributions. Six-year-olds were tested with these lists to determine list equivalence. Slopes of performance intensity (PI) functions relating mean word scores and signal to noise ratios (SNRs) were estimated for a group of 7-year-olds and adults. HINT normative data were collected for 219 adults and children 5 to 13 years of age in anechoic and audiometric test rooms, using noise levels 55, 60, or 65 dBA. Target sentences always originated from the front; whereas, the noise was presented either from the front, noise front (NF), from the right, noise right (NR) or from the left, noise left (NL). The NR and NL scores were averaged to yield a noise side (NS) score. All 219 subjects were tested in the NF condition, and 95 in the NR and NL conditions. Retest of the NF at the end of the test session was done for 53 subjects. Longitudinal data were collected by testing 9 children as 6, 8, and 13 years old. Results: NF and NS group means for adults were -3.7 and -11.8 dB SNR, respectively. Group means for 13-year-olds were -3.3 and -9.7, and for the 6-year-olds group means were -0.3 and -5.7 dB SNR, as measured in an anechoic chamber. NF SRTs measured in an audiometric test room were 0.7 to 1.5 higher (poorer) than in the anechoic chamber. Developmental trends were comparable in both rooms. PI slopes were 8.0% dB SNR for the 7-year-olds and 10.1% for the adults. NF SRTs in the anechoic chamber improved by 0.7 dB per year over an age range of 5 to 10 years. Using a PI slope 8 to 10% per dB, the estimated increase in percent intelligibility was 4 to 7% per year. Adult SRTs were about 3 dB lower than those for 6-year-olds, corresponding to 25 to 30% better intelligibility for adults. Conclusions: Developmental trends in HINT performance for Norwegian children with normal hearing are similar to those seen in other languages, including American English and Canadian French. SRTs approach adult normative values by the age of 13; however, the benefits of spatial separation of the speech and noise sources are less than those seen for adults. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Increased frequency and severity of restless legs syndrome in patients with neuromyelitis optica spectrum disorder • The frequency and severity of RLS were significantly higher in NMOSD patients than in healthy controls.• NMOSD patients with RLS had a longer disease duration and more severe disability than those without RLS. Read More » Response to letter to the editor: "ferritin deficiency may deteriorate the symptoms of restless legs syndrome" We appreciate Drs. Tasdemir and Oz's interest in our paper, "Restless legs syndrome and central nervous system gammaaminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity" published in Sleep Medicine (1). We did not obtain iron indices in the subjects of that neuroimaging study. Central nervous system iron may certainly be essential to the pathophysiology of both primary and secondary RLS (2). However, we know of no evidence that directly implicates CNS or serum iron in GABA, glutamate or NAA levels in patients with RLS. Read More » Composition of inflammatory cells regulating the response to concurrent chemoradiation therapy for HPV (+) tonsil cancer Prognostic factors for head and neck squamous cell carcinomas (HNSCCs), such as tonsillar squamous cell cancer (TSCC), include age, smoking, TNM stage, margin status, metabolic status, and extracapsular spread [1–3]. Recently, rather than these factors, human papillomavirus (HPV) infection in combination with p16 expression in TSCC has also been significantly associated with TSCC prognosis [4]. HPV infection-related TSCC is frequently encountered, and it presents different patient characteristics and better treatment results than HPV (−) TSCC [5]. Read More » A prospective study of electronic quality of life assessment using tablet devices during and after treatment of head and neck cancers Patient-reported outcomes are increasingly important endpoints not only in clinical trials but also in routine clinical practice. There is growing interest in transitioning to electronic qualify of life (eQOL) data collection to improve efficiency, accuracy, and accessibility of information. This is especially crucial within the realm of head and neck oncology, where practice is constantly advancing to improve not only cancer survival but also quality of life, and outcomes need to be measured efficiently. Read More » Application of C-Shaped Osteotomy and Distraction Osteogenesis for Correction of Radial Angulation Deformities of the Hand in Children With Apert Syndrome: Review of 10 Years of Experience Abstract: Apert syndrome is characterized by short, radially deviated thumbs, leading to difficulties in daily life such as holding a fork or a spoon and buttoning up. The main goal of surgery is to achieve thumb to index finger pinch to overcome these difficulties. Seven patients (14 extremities) followed up with Apert syndrome underwent distraction after a C-shaped osteotomy to simultaneously correct the brachydactyly and the angulation deformity of the bilateral thumbs. The patients ranged in age from 4 to 7 years at the distraction operation, with a mean (SD) of 4.7 (1.7) years, and the mean (SD) length of follow-up was 100.6 (14.95) months. The mean (SD) length of the phalanges at the beginning of distraction was 19.1 (3.26) mm, and the mean (SD) length of the distracted phalanx at long-term follow-up visit was 26.2 (5.63) mm. The mean (SD) correction of radial angulation was calculated as 42.6 (9.95) degrees, and the difference was considered as being statistically significant (P Read More » Comparison of Delayed and Immediate Tissue Expander Breast Reconstruction in the Setting of Postmastectomy Radiation Therapy Background: Despite the continued demand for immediate prosthetic breast reconstruction, some suggest that delayed reconstruction may reduce complications. However, with limited comparative data available, the extent of this benefit is unclear, particularly in the setting of postmastectomy radiation therapy (PMRT). This study evaluates outcomes after mastectomy and delayed tissue expander reconstruction (DTER) or immediate tissue expander reconstruction (ITER). Methods: A retrospective review of 893 consecutive patients (1201 breasts) who underwent mastectomy with DTER or ITER at one institution during a 10-year period was performed. Relevant patient factors, including the use of PMRT and complication rates, were recorded. Complications were categorized by type and end-outcome, including nonoperative (no further surgery), operative (further surgery except explantation), and explantation. Statistics were done using Student t test and Fisher exact test. Results: There were no differences in clinical risk factors between ITER (n = 1127 breasts) and DTER (n = 74 breasts) patients. Delayed tissue expander reconstruction breasts had lower rates of mastectomy flap necrosis (P = 0.003), and nonoperative (P = 0.01) and operative (P = 0.001) complications relative to ITER. In ITER breasts, PMRT increased operative complications (P = 0.02) and explantation (P = 0.0005), resulting in a decrease in overall, 2-stage success rate (P Read More » Reconstruction of a Large External Hemipelvectomy Defect After Chordoma Resection Using a 5-Component Chimeric Rotational Flap No abstract available Read More » Orbital Floor Restoration Using the Transnasal Balloon Technique for Inferior Orbital Wall Fracture Background: Restoring the volume of orbital fracture is a challenge to the surgeons. We combined the transnasal balloon technique and the transorbital approach during orbital floor reconstruction, and compared the outcomes of this technique with those of the conventional transorbital approach. Methods: Patients with unilateral pure orbital floor fracture were divided according to the surgical method: the direct transconjunctival approach (group A, 20 patients, control group) or the combination approach with the transnasal balloon technique (group B, 20 patients, experimental group). The orbital volume ratio (OVR) was measured with the use of computed tomographic scans, and enophthalmos was checked with a Hertel exophthalmometer. Results: The orbital volume ratios in both groups decreased after surgery: it was more effectively decreased in group B (7.88%) than that in group A (1.69%) (P Read More » Book Review: Silicon on Trial: Breast Implants and the Politics of Risk No abstract available Read More » Improvement of Split Skin Graft Quality Using a Newly Developed Collagen Scaffold as an Underlayment in Full Thickness Wounds in a Rat Model Introduction: Frequently, full thickness skin defects were treated through split skin graft (SSG) transplantation. However, this is usually associated with a reduction of skin quality and scarring. In this context, a newly developed collagen cell carrier (CCC) has been evaluated as an underlayment in SSG transplantations in a rat model. Materials and Methods: Twenty-eight standardized full thickness skin defects were generated on the back of 28 adult male Lewis rats. The wounds were randomized and treated with SSG transplantation solitarily (n = 14) or SSG transplantation using CCC as an underlayment (n = 14). For skin quality analysis, a histological evaluation was performed 3 months postoperative in regard to epidermal cell count and epidermal and dermal thickness. Results: Wounds treated with SSG and CCC demonstrated a thicker epidermis and significantly higher epidermal cell count compared to SSG solitarily. At the time of evaluation, epidermal thickness of SSG and CCC was comparable to untreated, healthy skin (no statistically significant differences). Discussion: As split skin grafting is frequently associated with skin quality reduction, the presented results reveal the beneficial effects of CCC in terms of skin graft quality improvement. This may offer unique opportunities in wound management and encourages further evaluation of CCC in surgical applications and regenerative medicine. Read More » Comparison of Effects of Pulsed Electromagnetic Field Stimulation on Platelet-Rich Plasma and Bone Marrow Stromal Stem Cell Using Rat Zygomatic Bone Defect Model Background: Reconstruction of bone defects that occur because of certain reasons has an important place in plastic and reconstructive surgery. The objective of the treatments of these defects was to reinstate the continuity of tissues placed in the area in which the defect has occurred. In this experimental study, the effect of pulsed electromagnetic field stimulation on platelet-rich plasma (PRP) and bone marrow stromal cell, which propounded that they have positive impact on bone regeneration, was evaluated with the bone healing rate in the zygomatic bone defect model enwrapped with superficial temporal fascia. Methods: After creating a 4-mm defect on the zygomatic bone of the experiments, the defect was encompassed with a superficial temporal fascial flap and a nonunion model was created. After surgery, different combinations of the PRP, bone marrow stromal cell, and electromagnetic field applications were implemented on the defective area. All the experiments were subjected to bone density measurement. Results: The result revealed that the PRP and pulsed electromagnetic field implementation were rather a beneficial and an effective combination in terms of bone regeneration. Conclusions: It was observed that the superficial temporal fascial flap used in the experiment was a good scaffold choice, providing an ideal bone regeneration area because of its autogenous, vascular, and 3-dimensional structures. As a result, it is presumed that this combination in the nonhealing bone defects is a rather useful treatment choice and can be used in a reliable way in clinical applications. Read More » Cosmetic Comparison Between the Modified Uchida Method and the Mustarde Method for Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome Purpose: Blepharophimosis–ptosis–epicanthus inversus syndrome (BPES) is a rare, congenital, surgically challenging disease. We undertook an objective, functional, and cosmetic comparison between the modified Uchida procedure and the Mustarde procedure on Asian patients with BPES. Design: This is a retrospective, comparative, interventional case series with the description of 2 surgical techniques. Participants: Twenty consecutive Japanese patients with BPES were studied. Methods: The patients were assigned to either the modified Uchida or the Mustarde procedure on the basis of preoperative intercanthal distance (ICD) ratio (ICD/palpebral fissure width). Intercanthal distance and margin reflex distance were measured from photographs before and after surgery. Classifications were made according to epicanthal fold score and cosmetic score using a visual analog scale (VAS). Main Outcome Measures: The main outcome measures were postoperative improvement in ICD ratio and the VAS. Results: Of the 20 patients, 5 underwent the modified Uchida procedure and the other 15 underwent the Mustarde procedure. The preoperative median ICD ratio was 2.0 (range, 1.9–2.5) and 2.5 (range, 2.0–3.4) for the modified Uchida and Mustarde procedures, respectively, and decreased to 1.5 (range, 1.5–1.7) and 1.6 (range, 1.5–1.8) postoperatively. The mean ICD reduction rate was 35.7% (SD, 1.0%) in the Mustarde group and 22.1% (SD, 1.3%) in the modified Uchida group (P Read More » The Institute of Surgery and Innovation Trunk Flap Dissection Course Abstract: The Institute of Surgery and Innovation Trunk Flap Dissection Course is a biannual two day course, which covers dissection of flaps in the anterior and posterior trunk on fresh-frozen cadavers. The event is run by the Institute of Surgery and Innovation, and it was held for the first time in November 2013, at the Nottingham City Hospital Training Centre. The course was taught in English by senior faculty from the Department of Plastic Surgery of Nottingham University. The first day was dedicated to raising 8 flaps in the anterior chest and abdomen, while the second day was dedicated to 6 flaps in the posterior trunk and buttocks. There were 3 participants per dissection table and the faculty to participant ratio was 2:1, allowing close supervision and one-on-one teaching. Each flap was briefly introduced by a 10-minute presentation, followed by a live demonstration of how to raise the flap by one of the faculty. The main advantage of this course is that the focus is on practical dissection, rather than lectures. The presentations that were given had a very personal feel, describing real cases encountered in the faculty's previous experience. This served as a platform to discuss dissection tips, tricks, and common pitfalls. Flaps represent the basis of reconstructive surgery; however, they are often taught late in the professional course of a residency as they are technically challenging. This course offers the opportunity to practice skills and receive very comprehensive feedback from experienced faculty. The event is open to trainees of all levels, and it attracted very junior as well as senior trainees from across Europe, thus offering an international prospective. The course's affordability is a luring feature and the excellent content and quality of teaching makes it a highly valuable experience, which I would widely recommend to trainees of all levels. Read More » Study to Assess Outcome After Open and Closed Carpal Tunnel Decompression Abstract: Carpal tunnel decompression (CTD) is the most commonly performed surgical procedure within a hand unit. We have analyzed data on outcomes after carpal decompression performed by both open and closed techniques to assess whether outcomes differed between the 2 procedures. Data were jointly gathered from 2 units. The aim was to assess the outcome after CTD. Completed data were gathered from 621 CTD procedures performed on 484 patients. Of the procedures, 358 were performed via a standard open CTD technique and 263 procedures were performed via a closed single-port Agee technique. Assessments were performed by means of the Levine-Katz questionnaire, Semmes-Weinstein monofilament testing, grip strength, and pinch-grip strength testing. Assessments were performed both preoperatively and 6 months postoperatively. A randomly selected 10% of patients were also assessed at 12 months. The results were statistically better after closed CTD at the 6-month postoperative stage. However, the difference became less marked by 12-month postoperative stage. Our results show that CTD whether performed by an open or closed technique resulted in a similar outcome at the 12-month postoperative stage. However, those procedures performed by a closed technique offered a more rapid recovery in the first 6 months postoperative than by an open technique. Read More » Vascularized Partial Free Toe Tissue Transfer Under Local Anesthesia Background: This study was designed to introduce free toe soft tissue transfer using local infiltration anesthesia in patients not suitable for general anesthesia and local tissue coverage. Methods: From January 2006 to August 2012, a total of 11 traumatic fingertip defects were reconstructed by toe soft tissue transfer. All procedures except 1 were done as primary reconstructions, with either the lateral side of the great toe (5 cases) or the medial side of the second toe (6 cases) used as a donor. Postoperative follow-up periods were between 8 months to 2 years and 6 months. Results: Flap sizes varied from 1.0 × 2.0 to 2.0 × 3.5 cm. The mean operative times were 4 hours 29 minutes for cases done by a single team and 3 hours 21 minutes for cases done by a 2-team approach. Approximately 5.8 mL of local anesthetic agent was used in each finger and 5.9 mL was used in the toes for a total of 11.7 mL. All flaps survived and were fully taken without complications, except 1 case that presented partial necrosis. Conclusions: Fingertip soft tissue reconstruction by free toe tissue transfer under local anesthesia uses a more limited operative field, with a shorter operative time, enabling reconstruction in patients not suitable for general anesthesia. This is even more so with a microsurgical 2-team approach, which reduces the volume of anesthetic agent needed, making this method a sufficiently realistic option for fingertip soft tissue reconstruction. Read More » Mjölnir No abstract available Read More » A Simple Technique to Create Cheek Dimples Background: Cheek dimple is a commonly requested aesthetic procedure, especially in the Arabian Gulf area. Aim: This work describes the authors' experience in creation of cheek dimples using simple rapid technique. Patients and Methods: This study included 116 dimples in 74 patients. The dimple is done through an intraoral stab incision and prolene suture to fix the dermis of the cheek skin to the underlying buccinator muscle. Results: Eighty-six percent of patients had satisfactory results. The most common complications were fading or complete disappearance of the dimple in 14 dimples and infection in 5 patients. Conclusions: This technique is very simple, very rapid, easy to execute, and gives satisfactory results in up to 86% of patients. This article also highlights the important information that must be discussed with the patients preoperatively. Read More » Posttraumatic Midface Pain: Clinical Significance of the Anterior Superior Alveolar Nerve and Canalis Sinuosus Background: Posttraumatic midface pain secondary to injury of the anterior superior alveolar nerve (ASAN) is characterized as pain localized to the central and lateral incisors, canines, and maxilla. This nerve is susceptible to injury and subsequent formation of neuromas after midface trauma. Surgical intervention requires an accurate and precise understanding of the course of the ASAN. Methods: Dissections of 12 human cadaver heads were conducted to identify the course of the ASAN through the canalis sinuosus (CS). Fifty 1-mm slice face computed tomographic scans were evaluated to document the dimensions and course of the CS. Results: The ASAN branched laterally from the infraorbital nerve before reaching the infraorbital rim in all cadavers. The bifurcation occurred 18 mm posterior to the infraorbital rim (range, 10–30 mm). At a point 25 mm inferior to the infraorbital rim, the ASAN is found 3.4 mm lateral to the piriform aperture (range, 3–4 mm). Radiographic analysis demonstrated a 12.9-mm horizontal length of the CS across the anterior maxilla (SD, 2.2 mm), a distance of 4.8 mm between the piriform aperture and the CS (SD, 1.2 mm), and 11.7 mm vertical length of the CS along the piriform aperture (SD, 3.0 mm). Conclusions: The ASAN maintains consistent coordinates at specific points along its course through the midface. An improved understanding of the course of the ASAN will guide future diagnosis of injury to this nerve and surgical intervention for patients with posttraumatic midface pain secondary to ASAN injury. Read More » An Updated View of the Integrated Plastic Surgery Match Background: Plastic surgery is one the most competitive residency programs. Data on match trends for plastic surgery residencies and traits of successful applicants are necessary for individuals applying into this highly desirable specialty. Aim: Analyze recent trends in the independent and integrated match as well as to describe attributes of successful applicants. Methods: Data from National Resident Matching Program and San Francisco Match Program for 2007 to 2014 were compiled and analyzed. Statistical analysis and figure creation were performed using the R software package. For bivariate associations, χ2 or Fisher's exact test was used. Results: The number of available integrated plastic surgery positions through National Resident Matching Program has increased since 2007, whereas the number of independent residencies offered through the SF Match has steadily decreased. The average Step 2 scores, The number of research presentations, publications, abstracts, and the percent of students ranking plastic surgery only have increased. In a break from previous trends, percent of applicants with Alpha Omega Alpha (AOA) membership and mean Step 1 board scores decreased. United States medical school applicants who matched were more likely to be AOA members and graduates from a top 40 medical school. There was no significant association between having an additional academic degree and successfully matching into integrated plastic surgery. Conclusions: Integrated plastic surgery residency programs continue to be highly competitive, with overall increasing research experience, but slightly lower Step 1 scores and AOA membership than that in previous years. If the trend of decreasing independent and increasing integrated positions continues, the applicant only interested in plastic surgery may find the integrated pathway a more feasible option. Read More » Expanded Flaps in Surgical Treatment of Pressure Sores: Our Experience for 25 Years Background: Because the ischial region is the main weight-bearing area in sitting, it is one of the areas most frequently affected by pressure ulcers in paraplegic patients resuming the sitting position during the subacute and chronic stages. The techniques described to date have not been able to reduce the high rates of recurrence and flap dehiscence. Other groups have described successful tissue expansion in the treatment of pressure ulcers, but to date, the long-term results of the procedure have not been reported. Methods: The long-term follow-up of 138 reconstructions of the ischial region in patients with pressure ulcers types III to IV treated with posterior thigh expanded rotation flaps is reported. Results: All patients achieved complete resolution, with adequate coverage of deeper layers, although 15.94% presented minor complications. None of these complications impeded full repair of the lesion. The 28 lesions that recurred were all reconstructed with the re-expansion of the same flap. There were no cases of flap dehiscence. Conclusions: The use of tissue expanders to treat ischial pressure ulcers, especially in patients with long life expectancy, offers important advantages over other approaches. The procedure provides abundant, high-quality tissue and may be repeated many times without creating new scars. With the use of tissue expanders, other reconstructive options can be reserved for the future. Read More » A Simple Method for Proper Placement of the Inframammary Fold Incision in Primary Breast Augmentation Background: The inframammary incision is a very common access in breast augmentation. The incision must be positioned well to place the resulting scar in the new inframammary fold. Aim: This article presents a simple marking on patients for proper localization of the inframammary incision. Materials and Methods: Ninety-six patients who underwent primary breast augmentation were divided into 3 groups according to the volume of the used implants. Results: A total of 90.6% of the patients had excellent postoperative scar location, and 9.4% had good results, with overall 100% patient satisfaction. Conclusions: Our preoperative markings offer simple, easy, and fixed measurements that facilitate proper postoperative location of the inframammary incision and hide the scar significantly. Read More » Flap Preconditioning by Electrical Stimulation as an Alternative to Surgical Delay: Experimental Study Abstract: Partial flap failures are unpredictable complications of reconstructive surgery. Electrical stimulation increases blood flow, capillary density, angiogenesis and vascular endothelial growth factor, anti-inflammatory effects while decreasing oxygen tension in tissues. In this study, we investigated these effective properties of electrical stimulation preoperatively on flap surgery instead of the surgical delay procedure. Modified McFarlane flaps were raised on the backs of 50 Sprague-Dawley rats. In the control group, a skin flap was made and flap survival rate was assessed on the seventh day. In the surgical delay group, 14 days after creating the bipedicled flap, the flap was totally elevated and flap survival rate was assessed on the 21st day. In the preconditioning by electrical stimulation group, the flap was created after application of electrical stimulation for 7 days. Flap survival rate was assessed on the 14th day. In the electrically stimulated ischemic flap group, the flap was created and afterward, electrical stimulation was applied for 7 days. After that, flap survival rate was assessed on the seventh day. In the surgical delay plus electrical stimulation group, following the elevation and suturing of the bipedicled flap back into its bed, electrical stimulation was applied in the first 7 days of delay, the flap was created on the 14th day, and then flap survival rate was assessed on the 21st day. In all groups, blood flow was evaluated at particular times. After completing these procedures, the flap vascularities of 5 animals from each group were assessed with microangiography. The flap survival rate of the preconditioning by electrical stimulation group was significantly higher than those of the other groups (P Read More » Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Angiogenesis No abstract available Read More » Hardware Removal in Craniomaxillofacial Trauma: A Systematic Review of the Literature and Management Algorithm Background: Craniomaxillofacial (CMF) fractures are typically treated with open reduction and internal fixation. Open reduction and internal fixation can be complicated by hardware exposure or infection. The literature often does not differentiate between these 2 entities; so for this study, we have considered all hardware exposures as hardware infections. Approximately 5% of adults with CMF trauma are thought to develop hardware infections. Management consists of either removing the hardware versus leaving it in situ. The optimal approach has not been investigated. Thus, a systematic review of the literature was undertaken and a resultant evidence-based approach to the treatment and management of CMF hardware infections was devised. Materials and Methods: A comprehensive search of journal articles was performed in parallel using MEDLINE, Web of Science, and ScienceDirect electronic databases. Keywords and phrases used were maxillofacial injuries; facial bones; wounds and injuries; fracture fixation, internal; wound infection; and infection. Our search yielded 529 articles. To focus on CMF fractures with hardware infections, the full text of English-language articles was reviewed to identify articles focusing on the evaluation and management of infected hardware in CMF trauma. Each article's reference list was manually reviewed and citation analysis performed to identify articles missed by the search strategy. There were 259 articles that met the full inclusion criteria and form the basis of this systematic review. The articles were rated based on the level of evidence. There were 81 grade II articles included in the meta-analysis. Result: Our meta-analysis revealed that 7503 patients were treated with hardware for CMF fractures in the 81 grade II articles. Hardware infection occurred in 510 (6.8%) of these patients. Of those infections, hardware removal occurred in 264 (51.8%) patients; hardware was left in place in 166 (32.6%) patients; and in 80 (15.6%) cases, there was no report as to hardware management. Finally, our review revealed that there were no reported differences in outcomes between groups. Conclusions: Management of CMF hardware infections should be performed in a sequential and consistent manner to optimize outcome. An evidence-based algorithm for management of CMF hardware infections based on this critical review of the literature is presented and discussed. Read More » Composition of inflammatory cells regulating the response to concurrent chemoradiation therapy for HPV (+) tonsil cancer Prognostic factors for head and neck squamous cell carcinomas (HNSCCs), such as tonsillar squamous cell cancer (TSCC), include age, smoking, TNM stage, margin status, metabolic status, and extracapsular spread [1–3]. Recently, rather than these factors, human papillomavirus (HPV) infection in combination with p16 expression in TSCC has also been significantly associated with TSCC prognosis [4]. HPV infection-related TSCC is frequently encountered, and it presents different patient characteristics and better treatment results than HPV (−) TSCC [5]. Read More » A prospective study of electronic quality of life assessment using tablet devices during and after treatment of head and neck cancers Patient-reported outcomes are increasingly important endpoints not only in clinical trials but also in routine clinical practice. There is growing interest in transitioning to electronic qualify of life (eQOL) data collection to improve efficiency, accuracy, and accessibility of information. This is especially crucial within the realm of head and neck oncology, where practice is constantly advancing to improve not only cancer survival but also quality of life, and outcomes need to be measured efficiently. Read More » Enhancement of Odor-Induced Activity in the Canine Brain by Zinc Nanoparticles: A Functional MRI Study in Fully Unrestrained Conscious Dogs Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected. Read More » Maltodextrin Acceptance and Preference in Eight Mouse Strains Rodents are strongly attracted to the taste(s) of maltodextrins. A first step toward discovery of the underlying genes involves identifying phenotypic differences among inbred strains of mice. To do this, we used 5-s brief-access tests and 48-h 2-bottle choice tests to survey the avidity for the maltodextrin, Maltrin M040, of mice from 8 inbred strains (129S1/SvImJ, A/J, CAST/EiJ, C57BL/6J, NOD/ShiLTJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). In brief-access tests, the CAST and PWK strains licked significantly less maltodextrin than equivalent concentrations of sucrose, whereas the other strains generally licked the 2 carbohydrates equally. Similarly, in 2-bottle choice tests, the CAST and PWK strains drank less 4% maltodextrin than 4% sucrose, whereas the other strains had similar intakes of these 2 solutions; the CAST and PWK strains did not differ from the C57, NOD, or NZO strains in 4% sucrose intake. In sum, we have identified strain variation in maltodextrin perception that is distinct from variation in sucrose perception. The phenotypic variation characterized here will aid in identifying genes responsible for maltodextrin acceptance. Our results identify C57 x PWK mice or NZO x CAST mice as informative crosses to produce segregating hybrids that will expose quantitative trait loci underlying maltodextrin acceptance and preference. Read More » Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2 Abstract SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2 Δ/Δ) resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2 Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven (N7) (99 % FVB). Slc44a2 Δ/Δ mice produced abnormally spliced Slc44a2 transcripts that contain a frameshift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2 Δ/Δ mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2 Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age, Slc44a2 Δ/Δ mice exhibited hearing loss at 32 kHz, but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2 +/+ and heterozygous +/Slc44a2 Δ mice. After 6 months of age, Slc44a2 Δ/Δ mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2 Δ mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2 Δ/Δ mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing. Read More » Validation of the Brazilian Version of the Voice Disability Coping Questionnaire To perform the validation of the Brazilian version of the Voice Disability Coping Questionnaire (B-VDCQ) using procedures according to the Scientific Advisory Committee of Medical Outcomes Trust and psychometric analyses to determine the scales validity and reliability. Read More » Analysis and Classification of Voice Pathologies Using Glottal Signal Parameters The classification of voice diseases has many applications in health, in diseases treatment, and in the design of new medical equipment for helping doctors in diagnosing pathologies related to the voice. This work uses the parameters of the glottal signal to help the identification of two types of voice disorders related to the pathologies of the vocal folds: nodule and unilateral paralysis. The parameters of the glottal signal are obtained through a known inverse filtering method, and they are used as inputs to an Artificial Neural Network, a Support Vector Machine, and also to a Hidden Markov Model, to obtain the classification, and to compare the results, of the voice signals into three different groups: speakers with nodule in the vocal folds; speakers with unilateral paralysis of the vocal folds; and speakers with normal voices, that is, without nodule or unilateral paralysis present in the vocal folds. Read More » An Objective Parameter for Quantifying the Turbulent Noise Portion of Voice Signals Currently, there are no objective measures capable of distinguishing between all four voice signal types proposed by Titze in 1995 and updated by Sprecher in 2010. We propose an objective metric that distinguishes between voice signal types based on the aperiodicity present in a signal. Read More » Application of Pattern Recognition Techniques to the Classification of Full-Term and Preterm Infant Cry Scientific and clinical advances in perinatology and neonatology have enhanced the chances of survival of preterm and very low weight neonates. Infant cry analysis is a suitable noninvasive complementary tool to assess the neurologic state of infants particularly important in the case of preterm neonates. This article aims at exploiting differences between full-term and preterm infant cry with robust automatic acoustical analysis and data mining techniques. Read More » Voice Disorders in Teacher Students—A Prospective Study and a Randomized Controlled Trial Teachers are at risk of developing voice disorders, but longitudinal studies on voice problems among teachers are lacking. The aim of this randomized trial was to investigate long-term effects of voice education for teacher students with mild voice problems. In addition, vocal health was examined prospectively in a group of students without voice problems. Read More » Spectrographic Acoustic Vocal Characteristics of Elderly Women Engaged in Aerobics This study was carried out to characterize the voice of the elderly women engaged in aerobics through spectrographic analysis. Read More » The Low Mandible Maneuver and Its Resonential Implications for Elite Singers Many elite singers appear to frequently drop the posterior mandible while singing to optimize resonance production. This study investigated the physiology of the Low Mandible Maneuver (LMM) through the use of magnetic resonance imaging (MRI), ultrasound (US), and spectrographic analysis.The study of elite singers has been hampered by the paucity of internal imagery. We have attempted to address this problem by using portable US equipment that we could transport to the homes, studios, or dressing rooms of such ranking singers. Read More » Acoustical and Perceptual Voice Profiling of Children With Recurrent Respiratory Papillomatosis Respiratory papillomatosis is a condition characterized by benign papillomatous (wart-like) growths in the respiratory tract. The condition tends to recur after treatment, requiring multiple procedures to control growth of the lesions. In such cases, the condition is known as recurrent respiratory papillomatosis (RRP). This study aims at providing comparative measures of acoustic as well as perceptual voice analysis of children with RRP. Read More » The Effect of Experience on Response Time When Judging Synthesized Voice Quality The purpose of this study was to determine the effect of level and type of experience on response time and the number of replays needed when judging voice quality. Read More » Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence Although there is considerable literature pertaining to IgE and non IgE-mediated food allergy, there is a paucity of information on non-immune mediated reactions to foods, other than metabolic disorders such as lactose intolerance. Food additives and naturally occurring 'food chemicals' have long been reported as having the potential to provoke symptoms in those who are more sensitive to their effects. Diets low in 'food chemicals' gained prominence in the 1970s and 1980s, and their popularity remains, although the evidence of their efficacy is very limited. This review focuses on the available evidence for the role and likely adverse effects of both added and natural 'food chemicals' including benzoate, sulphite, monosodium glutamate, vaso-active or biogenic amines and salicylate. Studies assessing the efficacy of the restriction of these substances in the diet have mainly been undertaken in adults, but the paper will also touch on the use of such diets in children. The difficulty of reviewing the available evidence is that few of the studies have been controlled and, for many, considerable time has elapsed since their publication. Meanwhile dietary patterns and habits have changed hugely in the interim, so the conclusions may not be relevant for our current dietary norms. The conclusion of the review is that there may be some benefit in the removal of an additive or a group of foods high in natural food chemicals from the diet for a limited period for certain individuals, providing the diagnostic pathway is followed and the foods are reintroduced back into the diet to assess for the efficacy of removal. However diets involving the removal of multiple additives and food chemicals have the very great potential to lead to nutritional deficiency especially in the paediatric population. Any dietary intervention, whether for the purposes of diagnosis or management of food allergy or food intolerance, should be adapted to the individual's dietary habits and a suitably trained dietitian should ensure nutritional needs are met. Ultimately a healthy diet should be the aim for all patients presenting in the allergy clinic. Read More » Bimodal Hearing Aid Retention after Unilateral Cochlear Implantation The goal of this study was to investigate contralateral hearing aid (HA) use after unilateral cochlear implantation and to identify factors of influence on the occurrence of a unilateral cochlear implant (CI) recipient becoming a bimodal user. A retrospective cross-sectional chart review was carried out among 77 adult unilateral CI recipients 1 year after implantation. A bimodal HA retention rate of 64% was observed. Associations with demographics, hearing history, residual hearing and speech recognition ability were investigated. Better pure-tone thresholds and unaided speech scores in the non-implanted ear, as well as a smaller difference in speech recognition scores between both ears, were significantly associated with HA retention. A combined model of HA retention was proposed, and cut-off points were determined to identify those CI recipients who were most likely to become bimodal users. These results can provide input to clinical guidelines concerning bimodal CI candidacy. Audiol Neurotol 2015;20:383-393 Read More » Hospital Anxiety and Depression Scale: Factor Structure, Internal Consistency and Convergent Validity in Patients with Dizziness Psychiatric comorbidities, particularly anxiety-related pathologies, are often observed in dizzy patients. The Hospital Anxiety and Depression Scale (HADS) is a widely used self-report instrument used to screen for anxiety and depression in medical outpatient settings. The purpose of this study was to assess the factor structure, internal consistency and convergent validity of the HADS in an unselected group of patients with dizziness. The HADS and the Dizziness Handicap Inventory (DHI) were administered to 205 dizzy patients. An exploratory factor analysis was conducted and indicated a 3-factor structure, inconsistent with the 2-subscale structure (i.e. anxiety and depression) of the HADS. The total scale was found to be internally consistent, and convergent validity, as assessed using the DHI, was acceptable. Overall findings suggest that the HADS should not be used as a tool for psychiatric differential diagnosis, but rather as a helpful screener for general psychiatric distress in the two domains of psychiatric illness most germane in dizzy patients. Audiol Neurotol 2015;20:394-399 Read More » Auditory Development Series: Auditory Development Hierarchy One of the first things we need to know when we are working with children is how to play, so we should know play milestones that are appropriate for young children. The two key things we need to know when we are developing listening skills are auditory strategies that we can use to facilitate the listening hierarchy and the current level of a child's skill and where we want them to go to. We also need to know appropriate goals at each level that will help facilitate acquisition of that skill. Then I will talk about these levels and goals with purposeful play activities. Read More » Auditory Development Series: Factors that Impact Listening Outcomes This text course is an edited transcript of a live webinar. Download supplemental course materials.Learning ObjectivesBy the end of this course, you will be able to understand the intrinsic and extrinsic factors that impact listening and spoken langu Read More » Form Follows Function in Quality Patient Care I have been involved with the identification and treatment of obstructive sleep apnea for over 25 years. I have seen a multitude of different products and strategies to provide patient care. It is not enough to simply identify a patient with sleep apnea. In my opinion this is when the work really starts. The medical professionals that treat these patients are required to consider many variables including lifestyle, concurrent disease and the patients willingness to comply with therapy. I am convinced that the best therapy is the one the patient will use. I have a close friend Dr Bradley Eli DDS who often says " the first night a patient goes without therapy is the first night of the rest of their life". It is therefore imperative when considering combination therapies to understand the importance of fit and function of CPAP patient interfaces. In spite of the millions of dollars and countless hours of engineering invested in cpap mask design, each patient is in fact different. Which leads me to a note by Bob Rutan who deserves recognition as perhaps the nations most avid CPAP patient advocate. Bob and Debbie Rutan have spent over 5 years travelling the country one DME provider to the next advocating for a simple enhancement to current thinking about CPAP masks…treat the patient as an individual- ed Bob Rutan's NoteBook One of the most interesting things I have observed over the last five years of traveling the country meeting CPAP patients, is that CPAP has a magical effect on patients who can wear the mask all night long. In spite of the millions of dollars spent on designing new patient interfaces the one thing that is most often over looked is that all patient's are different. Co morbidities, sensitivities and genetics sometimes allow a patient interface to be acceptable to one person, yet intolerable to the next. RemZzzs® is a product that works like a gasket to provide a soft hypo allergenic pad between the mask and the patients face, providing a better fit and reducing skin breakdown and allergic interactions. Robert G. sent us the following letter.  We were really happy he got a good result.  "Due to rising blood pressure, being borderline diabetic and suffering from sleep apnea, it is mandatory for me to use a CPAP machine.  Due to restricted nasal passages, I also breathe through my mouth, so a full face mask is required. Because of a skin allergy, my nose and cheeks break out from the mask cushion.  The Remzzz's liner is the only way that I can use my cpap effectively. Prior to using the Remzzz's liners, it was difficult to use the cpap the full 4 hours per night.  Since I started using them, I'm now averaging 7.5 hours per night.  In order for me to stay Medicare compliant with the CPAP, I have no choice but to use the liners.  Being totally dependent on Social Security for income and Medicare and my supplement insurance, I desperately need the Remzzz's face mask liners to be covered by Medicare." Robert G. Billings, MT. Read More » Pediatric Severe Chronic Upper Airway Disease (P-SCUAD) Abstract The term SCUAD (severe chronic upper airway disease) has been previously introduced to describe cases with upper airway disorders and symptoms not adequately controlled despite correct diagnosis and management. It has been so far applied mainly in adults and no specific focus has been given on the pediatric population. When the term SCUAD is considered for children specifically, a series of issues may arise. These issues involve accurate definition, epidemiology, clinical characteristics, pathophysiology, and socioeconomic implications. These issues seem to clearly differentiate adult from pediatric SCUAD. We attempt to shed light on these issues in an effort to provide directions for future guideline development and research. In this context, P-SCUAD (pediatric severe chronic upper airway disease) is hereby introduced. Read More » Different Approaches for Treating Multilevel Cervical Spondylotic Myelopathy: A Retrospective Study of 153 Cases from a Single Spinal Center by Xiumao Li, Liang Jiang, Zhongjun Liu, Xiaoguang Liu, Hua Zhang, Hua Zhou, Feng Wei, Miao Yu, Fengliang Wu Objective The optimal surgical treatment for multilevel cervical spondylotic myelopathy (MCSM) remains controversial. This study compared the outcomes of three surgical approaches for MSCM treatment, focusing on the efficacy and safety of a combined approach. Methods This retrospective study included 153 consecutive MCSM patients (100 men, 53 women; mean age ± standard deviation, 55.7 ± 9.4 years) undergoing operations involving ≥3 intervertebral segments. The patients were divided into three groups according to surgical approach: anterior (n = 19), posterior (n = 76), and combined (n = 58). We assessed demographic variables, perioperative parameters, and clinical outcomes ≥12 months after surgery (20.5 ± 7.6 months), including Japanese Orthopaedic Association (JOA) score, improvement, recovery rate, and complications. Results The anterior group had the most favorable preoperative conditions, including the highest preoperative JOA score (12.95 ± 1.86, p = 0.046). In contrast, the combined group had the highest occupancy ratio (48.0% ± 11.6%, p = 0.002). All groups showed significant neurological improvement at final follow-ups, with JOA recovery rates of 59.7%, 54.6%, and 68.9% in the anterior, posterior, and combined groups, respectively (p = 0.163). After multivariable adjustments, the groups did not have significantly different clinical outcomes (postoperative JOA score, p = 0.424; improvement, p = 0.424; recovery rate, p = 0.080). Further, subgroup analyses of patients with occupancy ratios ≥50% showed similar functional outcomes following the posterior and combined approaches. Overall complication rates did not differ significantly among the three approaches (p = 0.600). Occupancy ratios did not have a significant negative influence on postoperative recovery following the posterior approach. Conclusions If applied appropriately, all three approaches are effective for treating MCSM. All three approaches had equivalent neurological outcomes, even in subgroups with high occupancy ratios. Further investigations of surgical approaches to MCSM are needed, particularly prospective multicenter studies with long-term follow-up. Read More » The effect of ofloxacin otic drops on the regeneration of human traumatic tympanic membrane perforations Abstract Objective To investigate the effects of direct application of ofloxacin otic drops on human traumatic tympanic membrane perforations (TMPs). Study design Prospective, sequential allocation, controlled clinical study. Setting Tertiary university hospital. Subjects and Methods In total, 149 patients with traumatic TMPs were recruited. They were allocated sequentially to two groups: a conservative observation group (n = 75) and a ofloxacin drops-treated group (n = 74). The closure rate, closure time, and rate of otorrhoea were compared between the groups at 6 months. Results In total, 145 patients were analysed. The closure rates of medium perforations between the groups were not significantly different (P = 0.35); however, the ofloxacin drops-treated group had a significantly shorter closure time for medium perforations than the observation group (P < 0.01). Additionally, the ofloxacin drops-treated group showed improvement in the closure rate of large perforations (P = 0.02) and a significantly shorter mean closure time (P < 0.01) than the observation group. However, purulent otorrhoea was not significantly different between the groups (P = 0.37). Conclusions The present findings indicate that the moist eardrum environment resulting from topical application of ofloxacin drops shortened the closure time and improved the closure rate, but did not affect hearing improvement or increase the rate of middle ear infection of large traumatic TMPs. Thus, although traumatic TMPs tend to heal spontaneously, moist therapy can be considered for traumatic, large TMPs in the clinic. This article is protected by copyright. All rights reserved. Read More » mTHPC mediated, systemic photodynamic therapy (PDT) for nonmelanoma skin cancers: Case and literature review Background and Objective Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.g., surgery or radiation) to these patients. Study Design A systemic search was carried out that focused on the main clinical studies using mTHPC-PDT on NMSCs in humans. This review describes some of the basic principles of the treatment, the most effective treatment parameters as well as its possible adverse outcomes, which is illustrated with a short description of our own experiences using this treatment modality on four patients with multiple NMSCs. Results To date, only four clinical studies have been published. It was demonstrated that mTHPC-PDT could be highly effective. On illuminating 1–2 days after drug administration, plasma drug levels were high and the tumor clearance rates were high (up to 100%), with relative few side effects and excellent cosmetic and functional outcomes. These results were obtained with a relatively low, patient friendly photosensitizer dose (0.04–0.05 mg/kg) as skin photosensitivity was shorter after the procedure. Although the patients personally experienced consistently good cure rates, the healing times varied greatly between anatomical areas. The head and neck areas heal well with good cosmesis, while the lower leg and foot areas show delayed, at times compromised, healing with scarring. Conclusions Although mTHPC-PDT is described in the literature as an interesting and promising therapeutic option, especially for multiple NMSCs, a randomized clinical trial is lacking and personal experiences warrant too much skepticism. With the recent introduction of the hedgehog pathway inhibitor vismodegib, mTHPC-PDT seems to be less suitable as a first line of treatment; it should be considered as a last resort therapy. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc. Read More » Objective assessment of intensive targeted treatment for solar lentigines using intense pulsed light with wavelengths between 500 and 635 nm Background and Objectives Solar lentigines are commonly found in sun-exposed areas of the body including hands, neck, or face. This study evaluates the efficacy of an intense pulsed light (IPL) device, with wavelengths between 500 and 635 nm and delivered with a targeted tip, for the treatment of solar lentigines on Japanese skin. Study Design/Materials and Methods Forty Japanese patients with solar lentigines received one IPL treatment with a targeted treatment tip that emits wavelengths between 500 and 635 nm and contact cooling. Pulses were delivered through a targeted tip to each lentigo until mild swelling and a gray color were observed. Digital photographs and gray level histogram values were taken pre- and post-treatment, and patient assessments were recorded post-treatment. Results Significant improvement was observed for all patients in digital photographs and mean values of gray level histograms (P < 0.0001). Ninety percent of patients reported satisfaction with the improvement of the treatment area and convenience of the procedure. Complications were minor and transitory, consisting of a slight burning sensation and mild erythema which resolved within 5 hours of treatment. No serious adverse events were observed. Conclusions A short-wavelength IPL, delivered with a targeted tip and contact cooling, offers a highly efficacious treatment for solar lentigines in Japanese skin with minimal downtime and complications. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc. Read More » Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing Abstract The extent to which microorganisms impair wound healing is an ongoing controversy in the management of chronic wounds. Because the high diversity and extreme variability of the microbiota between individual chronic wounds lead to inconsistent findings in small cohort studies, evaluation of a large number of chronic wounds by using identical sequencing and bioinformatics methods is necessary for clinicians to be able to select appropriate empiric therapies. In this study, we utilized 16S rDNA pyrosequencing to analyze the composition of the bacterial communities present in samples obtained from patients with chronic diabetic foot ulcers (N = 910), venous leg ulcers (N = 916), decubitus ulcers (N = 767), and nonhealing surgical wounds (N = 370). The wound samples contained a high proportion of Staphylococcus and Pseudomonas species in 63% and 25% of all wounds, respectively; however, a high prevalence of anaerobic bacteria and bacteria traditionally considered commensalistic was also observed. Our results suggest that neither patient demographics nor wound type influenced the bacterial composition of the chronic wound microbiome. Collectively, these findings indicate that empiric antibiotic selection need not be based on nor altered for wound type. Furthermore, the results provide a much clearer understanding of chronic wound microbiota in general; clinical application of this new knowledge over time may help in its translation to improved wound healing outcomes. This article is protected by copyright. All rights reserved. Read More » Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia Abstract Bone marrow-derived mesenchymal stem cells (BM-MSCs) have properties that make them promising for the treatment of chronic non-healing wounds. The major challenge is ensuring an efficient, safe and painless delivery of BM-MSCs. Tissue-engineered skin substitutes have considerable benefits in skin damage resulting from chronic non-healing wounds. Here, we have constructed a 3D biomimetic scaffold known as collagen/chitosan sponge scaffolds (CCSS) using the cross-linking and freeze-drying method. Scanning electron microscopy (SEM) images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve bio-stability using swelling and degradation assays. Furthermore, BM-MSCs were seeded in CCSS using the two-step seeding method to construct tissue-engineered skin substitutes. In addition, in this 3D biomimetic CCSS, BM-MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM-MSCs exhibited a significant upregulated expression of pro-angiogenesis factors, including HIF-1α, VEGF and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing. This article is protected by copyright. All rights reserved. Read More » Presepsin as a predictor of critical colonization in CLI hemodialysis patients Abstract Infection during critical limb ischemia (CLI) is a challenging issue. Plasma presepsin is a novel biomarker for infection, which is related to bacterial phagocytosis by macrophages. The purpose of the present study was to investigate the validity of presepsin as an indicator and predictor for early detection of infectious CLI. A retrospective observational study was conducted among 20 CLI patients (Rutherford 5 and 6) on hemodialysis (HD). Twenty CLI patients on HD (mean age 70.7±5.6 years, male 85%) and 15 healthy patients on HD without CLI and infection (control group) were analyzed. All CLI patients received appropriate revascularization and plastic surgical treatment. CLI patients were classified into two groups: the healing group with complete epithelialization without discharge and the non-healing group with infection signs. Plasma presepsin was measured and compared among the two groups and the control group using an automated immunoanalyzer, PATHFAST, based on a non-competitive chemiluminescent enzyme immunoassay. The median plasma presepsin and its interquartile range were 1,320 (1,055 ― 1,465) pg/mL in the control group, 1,320 (1,050 ― 1,613) pg/mL in the healing group and 3,193 (2,519 ―3,832) pg/mL in the non-healing group. The plasma presepsin concentrations were significantly higher in the non-healing group compared with the control group (P<0.001) and the healing group (P<0.01). A receiver operating characteristic curve analysis revealed that presepsin had highest accuracy (0.979) among various inflammatory markers, including C-reactive protein and the white blood cell count. The diagnostic cut-off value of 2,083 pg/mL was able to distinguish the non-healing group and healing group with a sensitivity of 100% and a specificity of 88.9%. Our results suggest that plasma presepsin may be useful for predicting "critical colonization" and "infection" in non-healing CLI in HD patients, therefore, the definitive cut-off value may be used for determinating the indication for reintervention and/or major limb amputation. This article is protected by copyright. All rights reserved. Read More » The voltage-gated sodium channel NaV1.9 in visceral pain Abstract Background Visceral pain is a common symptom for patients with gastrointestinal (GI) disease. It is unpleasant, debilitating, and represents a large unmet medical need for effective clinical treatments. Recent studies have identified NaV1.9 as an important regulator of afferent sensitivity in visceral pain pathways to mechanical and inflammatory stimuli, suggesting that NaV1.9 could represent an important therapeutic target for the treatment of visceral pain. This potential has been highlighted by the identification of patients who have an insensitivity to pain or painful neuropathies associated with mutations in SCN11A, the gene encoding voltage-gated sodium channel subtype 1.9 (NaV1.9). Purpose Here, we address the role of NaV1.9 in visceral pain and what known human NaV1.9 mutants can tell us about NaV1.9 function in gut physiology and pathophysiology. Visceral pain and hypersensitivity are symptoms of patients with gastrointestinal diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recent evidence implicates the voltage-gated sodium channel subtype 1.9 (NaV1.9) as a regulator of primary visceral nociceptor sensitivity and as a contributor to sodium current conductance in neurones of the enteric nervous system. Patients with painful and painless phenotypes associated with mutations in NaV1.9 have been identified, which, in some cases, possess complex gastrointestinal disorders. These studies have served to confirm a key role for NaV1.9 in visceral pain and suggest that NaV1.9 may contribute to gastrointestinal disorders. Read More » Claudin-1 as a Biomarker of Cervical Cytology and Histology Abstract Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing. A population of 352 women attending colposcopic referral visits resulting in cervical conisation and a second population of 150 women attending routine gynaecological visits with negative cervical cytology were enrolled in a multi-centre clinical study in Hungary. Cytology and HPV (Genoid Full Spectrum HPV Amplification and Detection System) testing were carried out along with immunocytochemistry for CLDN1, and as a reference, using CINtec p16 Cytology Kit. Three different evaluation protocols were used which assessed immunostaining characteristics with or without cytological readings. High correlation observable between p16INK4a and CLDN1 established CLDN1 as a competing marker in cervical cancer. Concordance of CLDN1 immunostaining of cervical intraepithelial neoplasia 2 and above (CIN2+) positives was 84.0 % (73.8–89.3); concordance of CIN2+ negatives was 69.0 % (59.6–75.8). In conclusion, CLDN1 has similar diagnostic potential as p16INK4a, our results established it as a histological and cytological biomarker with the potential to improve the clinical performance of cervical cytology and histology. Read More » Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis Abstract Early detection of colorectal cancer (CRC) is vital for the improvement of disease prognosis. However to date there are no blood-based biomarkers sensitive and specific enough for early diagnosis. We analysed the differences in serum protein expression of early stage CRC (Dukes' A and B) and late stage CRC (Dukes' C and D) against normal controls using 2D Fluorescence Difference Gel Electrophoresis (2D-DIGE). Analysis of the 2D maps showed that 23 proteins were differentially expressed between groups (p ≤ 0.05) and these proteins were identified with LC-MS/MS. Eight proteins were up-regulated and 2 down-regulated in patients with early CRC, whereas 14 proteins were up-regulated and 4 down-regulated in those with late CRC compared to normal controls (p ≤ 0.05). Five proteins, namely apolipoprotein A1 (APOA1), apolipoprotein E (APOE), complement factor H (CFH), galectin-7 (GAL7) and synaptojanin-2 (SYNJ2) were validated using ELISA and only APOA1 and GAL-7 showed consistent findings. Further validation using immunohistochemistry showed negative immunoreactivity for GAL-7 in CRC tissues, suggesting that GAL-7 detected in the serum did not originate from the CRC tumour. APOA1 showed positive immunoreactivity but its expression did not correlate with Dukes' staging (p = 0.314), tumour grading (p = 0.880) and lymph node involvement (p = 0.108). Differences in APOA1 isoforms and/or conformation between serum and tissue samples as well as tumour heterogeneity may explain for the discrepancies between DIGE and ELISA when compared to immunohistochemistry. Structural and functional studies of APOA1 in future would best describe the role of APOA1 in CRC. Read More » Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers Abstract Background In 2008, the European Respiratory Society Task Force proposed the terms multiple-trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24-month stability and predictiveness for asthma. Methods 565 preschoolers (1, 2 and 3-year olds) in primary care with respiratory symptoms were followed until the age of six years when asthma was diagnosed. MTW and EVW status was determined using questionnaire data collected at baseline and after one and two years. We distinguished 3 phenotypes and determined their 24-month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes' associations with asthma. Results 281 children had complete information. MTW and EVW were stable in 10/281 (3.6%) and 24/281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7-119) and 3.6 (1.2-11.3) times greater than for children free of wheeze (for at least one year). ICS was associated with increased stability of MTW and EVW. Conclusions Stable multiple-trigger and stable episodic viral wheeze are relatively uncommon. However, one to three year olds with stable MTW are at much increased risk of asthma. This article is protected by copyright. All rights reserved. Read More » Anti-OX40L alone or in combination with anti-CD40L and CTLA4Ig does not inhibit the humoral and cellular response to a major grass pollen allergen Abstract Background IgE-mediated allergy is a common disease characterized by a harmful immune response towards otherwise harmless environmental antigens. Induction of specific immunological non-responsiveness towards allergens would be a desirable goal. Blockade of costimulatory pathways is a promising strategy to modulate the immune response in an antigen-specific manner. Recently OX40 (CD134) was identified as a costimulatory receptor important in Th2 mediated immune responses. Moreover, synergy between OX40 blockade and 'conventional' costimulation blockade (anti-CD40L, CTLA4Ig) was observed in models of alloimmunity. Objective We investigated the potential of interfering with OX40 alone or in combination with CD40/CD28 signals to influence the allergic immune response. Methods The OX40 pathway was investigated in an established murine model of IgE-mediated allergy where BALB/c mice are repeatedly immunized with the clinically relevant grass pollen allergen Phl p 5. Groups were treated with combinations of anti-OX40L, CTLA4Ig and anti-CD40L. In selected mice Tregs were depleted with anti-CD25. Results Blockade of OX40L alone at the time of first or second immunization did not modulate the allergic response on the humoral or effector cell levels but slightly on T cell responses. Administration of a combination of anti-CD40L/CTLA4Ig delayed the allergic immune response but antibody-production could not be inhibited after repeated immunization even though the allergen-specific T cell response was suppressed in the long run. Notably, additional blockade of OX40L had no detectable supplementary effect. Immunomodulation partly involved regulatory T cells as depletion of CD25+ cells led to restored T cell proliferation. Conclusions and Clinical Relevance Collectively, our data provide evidence that the allergic immune response towards Phl p 5 is independent of OX40L, although reduction on T cell responses and slightly, on the asthmatic phenotype, were detectable. Besides, no relevant synergistic effect of OX40L blockade in addition to CD40L/CD28 blockade could be detected. Thus, the therapeutic potential of OX40L blockade for IgE-mediated allergy appears to be ineffective in this setting. This article is protected by copyright. All rights reserved. Read More » Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2 Abstract SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2 Δ/Δ) resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2 Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven (N7) (99 % FVB). Slc44a2 Δ/Δ mice produced abnormally spliced Slc44a2 transcripts that contain a frameshift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2 Δ/Δ mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2 Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age, Slc44a2 Δ/Δ mice exhibited hearing loss at 32 kHz, but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2 +/+ and heterozygous +/Slc44a2 Δ mice. After 6 months of age, Slc44a2 Δ/Δ mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2 Δ mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2 Δ/Δ mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing. Read More » Benign paroxysmal positional vertigo (BPPV): it may occur after dental implantology. A mini topical review OBJECTIVE: Benign Paroxysmal Positional Vertigo (BPPV) is one of the most frequent vestibular disorders. BPPV as a complication of Osteotome Sinus Floor Elevation (OSFE) is a complication that rarely occurs. The aim of this paper is to better understand the mechanisms underlying the BPPV after SFE with the osteotomes. This could be important for all the dental and maxillofacial surgeons that should know and manage this clinical occurrence. DISCUSSION: The osteotome sinus floor elevation (OSFE), firstly described by Summers requires the use of a surgical mallet for striking the bone, until the optimal depth is reached. The surgical mallet develops a mechanical trauma, even if the striking is performed with a gentle percussion. The recent literature describes an average occurrence of OSFE-induced BPPV quite low, but the symptoms show to be unpleasant and severe, often able to alter the patient's daily life. CONCLUSIONS: A successful remission of BPPV following treatment with a particle repositioning maneuver will be necessary and relatively urgent for the surgeons who have experienced this clinical complication. The surgeons, therefore, must be aware of these complications and about the ways to manage them. L'articolo Benign paroxysmal positional vertigo (BPPV): it may occur after dental implantology. A mini topical review sembra essere il primo su European Review. Read More » Effect of chewing speed on the detection of a foreign object in food Summary Accidentally biting hard on a piece of hard foreign object in food is among the causes of tooth fracturing and could be associated with oral sensibility. This study has investigated the effect of chewing speed on the ability to detect a foreign object in food in human. Fourteen healthy subjects were asked to randomly chew one of 10 cooked rice balls, five of which containing a foreign object made from a tiny uncooked rice grain, until they detected the rice grain. Each subject chewed the test foods both at 50 (slow) and 100 (fast) chews min−1. The accuracy of detection and the number of chews before detection (CBD) were recorded and compared between the two chewing speeds using paired t-tests. The results showed that almost all subjects detected the foreign object by biting. The accuracy of detection was more than 90% and not significantly different between slow and fast chewing but the mean CBD in slow chewing (11·7 ± 1·3 chews) was significantly different from that in fast chewing (20·7 ± 1·9 chews; P < 0·001). The study showed that slow chewers required less number of chews before a foreign object in food could be detected and was, presumably, more effective in detecting the object compared to fast chewers. If each chew bears equal probability of teeth encountering the foreign object, slow chewing might also reduce the chance of accidentally biting hard on the foreign object and fracturing the tooth. Read More » Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum , inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo Abstract Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies. Read More » The clinical significance of vascular endothelial growth factor in malignant ascites Abstract Ascites can be caused by many kinds of diseases. Patients with undetermined ascites represent a diagnostic challenge. The aims of this study were to determine the diagnostic value of vascular endothelial growth factor (VEGF) in differentiation of malignant ascites from benign ascites and to investigate the clinical value of ascitic VEGF as an independent prognostic parameter. The study included 462 consecutive patients with malignant ascites and 550 patients with benign ascites, VEGF level in ascites were determined by a sandwich enzyme-linked immunosorbent assay. The survival rate was calculated by the Kaplan-Meier method and the log-rank test. Multivariate survival analysis was performed using the Cox hazards model. In our study, we found VEGF levels in malignant ascites (676.59 ± 303.86 pg/ml) were significantly higher than those in benign ascites (218.37 ± 98.15 pg/ml) (P < 0.001). Meanwhile, we also found that VEGF levels in malignant ascites from patients with ovarian cancer were higher than those with other cancers. Areas under the receiver operating characteristic (ROC) curves of ascitic VEGF was 0.940. At a cutoff value of 319.5 pg/ml, VEGF yielded a sensitivity of 89.2 % and a specificity of 88.4 %. Patients associated with the high-level VEGF value (≥613.38 pg/ml) in malignant ascites exhibited poor mean survival rates (8.3 ± 0.52 vs 15.11 ± 0.66 months, P < 0.001). In a multivariate Cox regression model, higher ascitic VEGF was an independent prognostic factor for overall survival. Planned subgroup analysis was performed for patients with tumor node metastasis (TNM) stage I. In the univariate analysis, only ascitic VEGF was associated with overall survival. VEGF was found to have a highly accurate sensitivity and specificity, suggesting that it could be considered as a new biomarker to differentiate malignant ascites from the benign one. The high level of VEGF value in malignant ascites may be used as an independent prognostic factor in patients with all stages of cancer. Read More » Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness Abstract Radiofrequency ablation (RFA) represents a valuable choice in hepatocellular carcinoma (HCC); however, local recurrence of HCC is common after RFA. Here, 20 primary HCC patients treated by RFA were enrolled. Before (termed 0d) and after RFA treatment for 1 and 7 days (termed 1d and 7d, respectively), plasma and noncancerous tissue were collected. ELISA assay showed that plasma C-X-C motif chemokine 10 (CXCL10) was increased in ten patients (type I patients) but decreased in the other 10 patients (type II patients). The mean interval for HCC recurrence in type I patients was less than the mean interval in type II patients. Interestingly, a significant negative correlation between interval for HCC recurrence and fold change of plasma CXCL10 (1d/0d or 7d/0d) was identified, suggesting that RFA-induced CXCL10 is associated with earlier HCC recurrence. Immunofluorescence assay showed that the receptor of CXCL10, chemokine (C-X-C motif) receptor 3 (CXCR3), was significantly increased in type I, but not type II, patients after RFA. In vitro assay demonstrated that CXCL10 stimulus increased the rate of CD133+ cancer stem cells (CSCs) in HepG2 cells by binding to CXCR3 and then inducing c-Myc expression. Many studies have reported that induction of CD133+ CSCs contributes to HCC recurrence. Thus, CXCL10-increased CD133+ CSCs by activating CXCR3/c-Myc pathway might accelerate HCC recurrence after RFA. These data might have potential implications for HCC therapy. Read More » Protein Kinase CK2 Content in GL261 Mouse Glioblastoma Abstract Glioblastoma (GBM) is the most prevalent and aggressive human glial tumour with a median survival of 14–15 months. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment. Unfortunately, chemoresistence always ensues with concomitant tumour regrowth. Protein kinase CK2 (CK2) contributes to tumour development, proliferation, and suppression of apoptosis in cancer and it is overexpressed in human GBM. Targeting CK2 in GBM treatment may benefit patients. With this translational perspective in mind, we have studied the CK2 expression level by Western blot analysis in a preclinical model of GBM: GL261 cells growing orthotopically in C57BL/6 mice. The expression level of the CK2 catalytic subunit (CK2α) was higher in tumour (about 4-fold) and in contralateral brain parenchyma (more than 2-fold) than in normal brain parenchyma (p < 0.05). In contrast, no significant changes were found in CK2 regulatory subunit (CK2β) expression, suggesting an increased unbalance of CK2α/CK2β in GL261 tumours with respect to normal brain parenchyma, in agreement with a differential role of these two subunits in tumours. Read More » Making Sense of Cervical Cancer Screening Guidelines and Recommendations Opinion statement Since the publication of the American Cancer Society (ACS)/American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology (ASCP) clinical guidelines in 2012, the majority of practice organizations have reached a consensus on screening recommendations for a low-risk population. These guidelines were based on a thorough review of the evidence with reproducible methods to obtain high-quality, generalizable guidelines. Despite the strength of the evidence based recommendations comprising these guidelines, limitations in physician understanding and compliance remain with respect to reaching an unscreened population and defining and caring for women who are at "high risk." "High-risk" patients are poorly characterized but should include women with a history of a prior abnormal screening, as data has shown a subsequent increased risk of cervical intraepithelial neoplasia grade 2 (CIN2) or greater, even after treatment. These women warrant more intense screening than the general population—though there are no evidence-based guidelines for optimized screening protocols in this population. Emerging data in cervical cancer screening this year includes the FDA approval of primary high-risk human papillomavirus (HPV) testing. While the data is promising, its role in clinical practice, impact on rates of colposcopy in a non-study population, and long-term outcomes are not fully understood, and ongoing research is needed. Challenges remain in this shifting environment on the optimal interval and modality for cervical cancer screening to provide the greatest benefit in detection of precancerous lesions while minimizing the harm of overtreatment. While rapid advancements in research provide improved knowledge on how to treat and prevent this disease, it is often difficult for providers across multiple specialties to remain abreast of these changes and to educate their patients about the most current recommendations. Ultimately, provider and patient education is critical both for improving primary prevention with HPV vaccination, as well as for the uptake of evidence-based screening and management guidelines aimed at detecting and treating precancerous changes of the cervix. Read More » Oral impact on daily performance: need and use of dental prostheses among Brazilian adults Summary Although there is a large amount of evidence that demonstrates the relationship between oral health status and oral impact daily performance, there are few studies that have evaluated the impact of prosthetic status, particularly the need for a dental prosthesis. Therefore, the aim of this study was to investigate the relationship between need and use of dental prostheses and the prevalence of oral impact on daily performance. A sample of 720 subjects, aged between 50 and 74 years, was evaluated using a cross-sectional study. Participants were selected through a multistage proportional random sampling. The impact of oral health status on daily performance (oral impact on daily performance – OIDP) and socio-demographic data was assessed using a standardised questionnaire, and clinical data were assessed by oral examination. The outcome was the prevalence of impact. The association between the explanatory variables and the outcome was analysed through two models of multivariate Poisson regression. In the adjusted model, the variables need of upper and lower prosthesis and use of lower prosthesis maintained a statistically significant association. No statistically relevant relation between socio-demographic variables and outcomes was found. Findings show that the need and use and of a prosthesis are related to oral health quality of life. Read More » Airway Measurements in Tracheobronchial Stenosis Using Endobronchial Ultrasonography During Stenting Purpose : To assess airway measurements, endobronchial ultrasonography (EBUS) and multidetector, row computed tomography (MDCT) images were compared in patients with tracheal stenosis. Methods : Airway stenting was performed on 31 patients, 25 malignant and 6 benign. EBUS and MDCT images were compared before intervention to assess the degree of airway narrowing at 212 sites. Of these, 130 sites were considered normal and 82 abnormal. For malignant stenosis, airway measurements were taken at 160 sites including 112 normal and 48 abnormal. For benign stenosis, airway measurements were taken at 52 sites including 18 normal and 34 abnormal. This technique enables the EBUS probe to measure the distal end to the proximal end of the stenosis whereby the inflated balloon size changes according to the degree of stenosis. Results : The diameter and length of the stenotic sites measured by EBUS and MDCT were nearly equal in all patients. Significant correlation was seen at all 212 sites (r=0.805, P Read More » The march from early life food sensitisation to allergic disease: A systematic review and meta-analyses of birth cohort studies Abstract Background There is growing evidence for an increase in food allergies. The question of whether early life food sensitisation, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. Objectives We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitisation and allergic disease in birth cohorts. Methods MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitisation in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. Results The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitisation was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitisation is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95%CI 2.0-4.0), eczema (pooled OR 2.7; 95%CI 1.7-4.4), and allergic rhinitis (pooled OR 3.1; 95%CI 1.9-4.9) from 4 to 8 years. Conclusion Food sensitisation in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. This article is protected by copyright. All rights reserved. Read More » Hodgkin-Lymphom in Kindheit oder Jugend: Keine niedrigere Mutterschaftsrate nach Bestrahlungen außerhalb des Beckens Read More » Diabetes risk linked to Smoking Researchers analyzed data on almost 5.9 million people in 88 previous studies examining the connection between smoking, second-hand smoke exposure and diabetes. They estimated that roughly 28 million type 2 diabetes cases worldwide – or about 11.7 percent of cases in men and 2.4 percent in women – could be attributed to active smoking. The more cigarettes smokers consumed, the more their odds of getting diabetes increased. If they quit, ex-smokers initially faced an even higher risk of diabetes, but as more years pass without cigarette use their odds of getting the disease gradually diminished, the analysis found. "The diabetes risk remains high in the recent quitters," said lead study author An Pan, of Huazhong University of Science and Technology in China. Weight gain linked to smoking cessation may be at least partly to blame for the heightened diabetes risk in those first months after giving up cigarettes, Pan added. "However, the diabetes risk is reduced substantially after five years," Pan said by email. "The long-term benefits – including benefits for other diseases like cancer and heart disease – clearly outweigh the short-term higher risk." Worldwide, nearly one in 10 adults had diabetes in 2014, and the disease will be the seventh leading cause of death by 2030, according to the World Health Organization. Most of these people have type 2 diabetes, which is associated with obesity and aging and happens when the body can't properly use or make enough of the hormone insulin to convert blood sugar into energy. Left untreated, diabetes can lead to nerve damage, amputations, blindness, heart disease and strokes. Plenty of research has established a connection between smoking and diabetes, although the reason is still unclear. For the current analysis, Pan and colleges focused on exploring the link between the amount and type of smoke exposure and diabetes risk, as well as the potential for this risk to diminish with smoking cessation. Overall, the pooled data from all the studies showed the risk of diabetes was 37 percent higher for smokers than non-smokers, the study team reports in The Lancet Diabetes and Endocrinology. Exactly how smoking might lead to diabetes isn't firmly established, but it's possible smoking might cause inflammation, which in turn boosts the risk for diabetes, Dr. Abbas Dehghan, of Erasmus University Medical Center in Rotterdam, The Netherlands. "The more one smokes, the more chronic inflammation there will be, and the higher the risk of diabetes will be," Dehghan, who wasn't involved in the study, said by email. Occasional smokers were 21 percent more likely to have diabetes than people who never picked up the habit, while the increased risk was 57 percent for heavy smokers. People exposed to second-hand smoke were 22 percent more likely to develop diabetes than people who never smoked, the study also found. If smokers quit, their risk of diabetes over the next five years was 54 percent higher than for people who never smoked. After that, the increased risk dropped to 18 percent over the following five-year period. Remaining abstinent for a decade or more, however, reduced the extra risk to 11 percent. While the connection between smoking and diabetes is nowhere near as strong as the link between cigarettes and lung cancer, the findings still suggest that doctors should add diabetes to the list of risks they warn smokers about, Amy Taylor of the University of Bristol in the United Kingdom. and colleagues note in an accompanying editorial. The short-term increase in diabetes risk after quitting shouldn't deter smokers' cessation efforts, they argue. Instead, smokers should remember that cigarettes are tied to lower weight and cessation can lead some people to eat or drink more, leading to weight gain. References: http://www.mdspiro.com http://www.thelancet.com/journals/landia/article/PIIS2213-8587(15)00316-2/abstract http://www.phillyvoice.com/more-evidence-smoking-cessation-lowered-diabetes/  While smoking is linked to an increased risk of developing diabetes, this risk appears to drop over the long term once cigarette use stops, a review of evidence suggests. Read More » Issue information Read More » Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions BACKGROUND It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. METHODS In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). RESULTS GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). CONCLUSIONS GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions. Cancer (Cancer Cytopathol) 2015;123:576-81. © 2015 American Cancer Society. Read More » Digital dynamo, delayed: Despite progress, whole slide imaging faces more hurdles on the path to broader acceptance in primary diagnostics Read More » Effect of submucosal application of tramadol on postoperative pain after third molar surgery The aim of this study was to evaluate the effectiveness of submucosal application of tramadol, for acute postoperative facial pain, following the extraction of impacted third molar teeth. This prospective, double-blind, randomised placebo-controlled study included 60 ASA I-II patients undergoing impacted third molar surgery under local anaesthesia. Following the surgical procedure, patients were randomly divided into two groups; group T (1 mg/kg tramadol) and group S (2-mL saline). Treatments were applied submucosally after surgery. Pain after extraction was evaluated using a visual analogue scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 h postoperatively. The time at which the first analgesic drug was taken, the total analgesic dose used, and adverse tissue reactions were also evaluated. In group T, postoperative VAS scores were significantly lower compared to that in group S (p < 0.05). This study demonstrated that post-operative submucosal application of tramadol is an effective method for reducing acute post-operative facial pain after impacted third molar surgery. Read More » Effects of a novel magnetic orthopedic appliance (MOA-III) on the dentofacial complex in mild to moderate skeletal class III children IntroductionThe objective of this study was to evaluate the changes of skeletal and dental structures in mild to moderate skeletal Class III children following the use of a new magnetic orthopedic appliance (MOA-III). Methods: A total of 36 patients (14 boys and 22 girls, mean age 9 years and 5 months) who presented with a mild to moderate skeletal Class III jaw discrepancy were treated with MOA-III. Another group of 20 untreated patients (9 boys and 11 girls, mean age 9 years and 2 months) with the same level of deformity served as the control group. The average treatment time was 6.6 months. Radiographs were taken at the same time intervals for both groups. A paired t test was used to determine the significant differences before and after treatment, and a two-sample t test was used to analyze the differences between the treatment and control groups. Results: The anterior crossbite in all subjects was corrected after MOA-III therapy. The maxillomandibular relationship showed favorable changes (ANB, Wits, overjet increased significantly, P < 0.001). The maxilla was anteriorly positioned (SNA, ptm-A, ptm-S increased significantly, P < 0.001) with clockwise rotation (PP-FH increased, P < 0.001). The mandible showed a slight downward and backward rotation (SNB decreased, P < 0.05, MP-SN, Y-axis increased, P < 0.05). The length of the mandibular body showed no significant changes (Go-Pg, P > 0.05). Significant upper incisor proclination and lower incisor retroclination were observed (UI-NA increased, P < 0.001, LI-NB, FMIA decreased, P < 0.001). The upper lip moved forward, and the lower lip moved backward (UL-EP increased, P < 0.001, LL-EP decreased, P < 0.05). In the control group, most of the parameters showed normal growth, except for some unfavorable mandibular skeletal and soft tissue changes (Go-Pg, Go-Co, MP-SN, N′-SN-Pg′ increased, P < 0.001). Significant positive changes were induced with the MOA-III appliance compared to the untreated group. Conclusions: The MOA-III was effective for the early treatment of a mild to moderate Class III malocclusion in children. Read More » The relationship between aircraft noise exposure and day-use visitor survey responses in backcountry areas of national parks To evaluate the relationship between aircraft noise exposure and the quality of national park visitor experience, more than 4600 visitor surveys were collected at seven backcountry sites in four U.S. national parks simultaneously with calibrated sound level measurements. Multilevel logistic regression was used to estimate parameters describing the relationship among visitor responses, aircraft noise dose metrics, and mediator variables. For the regression models, survey responses were converted to three dichotomous variables, representing visitors who did or did not experience slightly or more, moderately or more, or very or more annoyance or interference with natural quiet from aircraft noise. Models with the most predictive power included noise dose metrics of sound exposure level, percent time aircraft were audible, and percentage energy due to helicopters and fixed-wing propeller aircraft. These models also included mediator variables: visitor ratings of the "importance of calmness, peace and tranquility," visitor group composition (adults or both adults and children), first visit to the site, previously taken an air tour, and participation in bird-watching or interpretive talks. The results complement and extend previous research conducted in frontcountry areas and will inform evaluations of air tour noise effects on visitors to national parks and remote wilderness sites. Read More » Automatic transcription of Turkish microtonal music Automatic music transcription, a central topic in music signal analysis, is typically limited to equal-tempered music and evaluated on a quartertone tolerance level. A system is proposed to automatically transcribe microtonal and heterophonic music as applied to the makam music of Turkey. Specific traits of this music that deviate from properties targeted by current transcription tools are discussed, and a collection of instrumental and vocal recordings is compiled, along with aligned microtonal reference pitch annotations. An existing multi-pitch detection algorithm is adapted for transcribing music with 20 cent resolution, and a method for converting a multi-pitch heterophonic output into a single melodic line is proposed. Evaluation metrics for transcribing microtonal music are applied, which use various levels of tolerance for inaccuracies with respect to frequency and time. Results show that the system is able to transcribe microtonal instrumental music at 20 cent resolution with an F-measure of 56.7%, outperforming state-of-the-art methods for the same task. Case studies on transcribed recordings are provided, to demonstrate the shortcomings and the strengths of the proposed method. Read More » Erratum: Stimulus ratio dependence of low-frequency distortion-product otoacoustic emissions in humans [J. Acoust. Soc. Am. 137(2), 679–689 (2015)] Read More » Fast computation of seabed spherical-wave reflection coefficients in geoacoustic inversion This paper develops a fast numerical approach to computing spherical-wave reflection coefficients (SWRCs) for layered seabeds, which provides substantial savings in computation time when used as the forward model for geoacoustic inversion of broadband seabed reflectivity data. The approach exploits the Sommerfeld-integral representation of SWRCs as the Hankel transform of a function proportional to the plane-wave reflection coefficient (PWRC), and applies Levin integration to the rapidly oscillating integrand cast as the product of a (pre-computed) media-independent matrix and a vector involving PWRCs at a sparse sampling of integration angles. Compared to conventional Simpson's rule integration for computation of the SWRC, the Levin integration yields speed-up factors of an order of magnitude or more. Further, it results in reduced memory requirements for storage of pre-computed quantities, a desirable property when a graphics processing unit (GPU) is used for parallel computation of SWRCs. The paper applies trans-dimensional Bayesian inversion to investigate the impact of forward modeling in terms of PWRCs and SWRCs on the estimation of geoacoustic parameters and uncertainties. Model comparisons are quantified in simulated- and measured-data inversions by comparing the estimated geoacoustic parameters to the true parameters or core measurements, respectively, and by calculating the deviance information criterion for model selection. Read More » Prevalence and reversibility of lung hyperinflation in adult asthmatics with poorly controlled disease or significant dyspnea Abstract Background In asthma, inflammation affects both the proximal and distal airways, and may induce significant hyperinflation (HI). The present study sought to evaluate the prevalence of HI in asthmatic patients with poorly controlled disease and/or dyspnea. Methods Poor asthma control was defined by an Asthma Control Test (ACT) score <20 (n=287) and dyspnea was defined as a modified Medical Research Council score ≥1 (n=18). HI was defined as either a residual volume/total lung capacity (RV/TLC) above the upper limit of normal (RV-HI) or a functional residual capacity (FRC) >120% predicted (FRC-HI). HI reversibility after administration of salbutamol (400 μg) was defined as a decrease in RV >20% or a reduction in FRC >10%. Changes in dyspnea and chest tightness were evaluated on a visual analogue scale. Results Both RV-HI and FRC-HI were observed in 48% of the 305 patients (mean ± SD age: 49 ± 17; FEV1: 75 ± 18% predicted) included in the study. The prevalence of HI was higher in patients with a FEV1 <60% predicted (93% for RV-HI and 71% for FRC-HI, vs. 21% and 41% in patients with a FEV1 >80%). In patients with HI, the ACT score was lower and chest tightness higher. HI reversibility was obtained in 38% of the asthmatics with FRC-HI and 29% of the asthmatics with RV-HI whereas FEV1 reversibility was obtained in half of these patients. Conclusions HI is highly prevalent in poorly controlled asthmatics suggesting small airway dysfunction and may represent an additional criteria for evaluating responsiveness to bronchodilators. This article is protected by copyright. All rights reserved. Read More » House dust mite sublingual immunotherapy is safe in patients with mild-to-moderate, persistent asthma: a clinical trial Abstract Background The safety of allergen immunotherapy (AIT) in asthma has not always been sufficiently documented; accordingly, fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context. In a double-blind, placebo-controlled, randomized clinical trial, house dust mite (HDM) sublingual AIT was found to be efficacious in moderate, persistent asthma. The trial's safety results are now reported in detail. Methods Asthmatic adults were randomized 2:1 to twelve months of daily treatment with a sublingual solution of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. Adverse events (AEs) at least possibly related to the investigational product were classified by the investigators as adverse drug reactions (ADRs). Results Overall, the patients in the safety analysis set (n=484; active treatment: n=322; placebo: n=162) had mostly well-controlled, persistent asthma (mild in 290 patients (59.9%), moderate in 183 (37.8%) and severe in 11 (2.3%)). No treatment-related serious AEs were reported. Respectively 87.0% and 75.9% of the patients in the active and placebo groups experienced at least one AE (mostly mild), and 78.9% and 48.1% experienced an ADR (mostly mild or moderate oral reactions). The incidence of asthma exacerbations (symptoms requiring a short-course of oral corticosteroids) during the study was similar in the active treatment group (3.7%) and the placebo group (4.3%). There were no significant intergroup differences or intragroup changes over time in respiratory AEs, lung function or asthma-related quality of life. Conclusions HDM sublingual AIT was safe and well tolerated in adult patients with mild-to-moderate, persistent asthma (ClinicalTrials. gov: NCT00660452). This article is protected by copyright. All rights reserved. Read More » Allergic manifestation 15 years after early intervention with hydrolyzed formulas – the GINI Study Abstract Background Data on the long-term impact of hydrolyzed formulas on allergies are scarce. Objective To assess the association between early intervention with hydrolyzed formulas in high–risk children and allergic outcomes in adolescence. Methods GINI trial participants (N=2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow′s milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. Results Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (Risk Ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group or for sensitization. Conclusion In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence. This article is protected by copyright. All rights reserved. Read More » Eliciting Cervical Vestibular-Evoked Myogenic Potentials by Bone-Conducted Vibration via Various Tapping Sites. Objectives: This study compared bone-conducted vibration (BCV) cervical vestibular-evoked myogenic potentials (cVEMPs) via tapping at various skull sites in healthy subjects and patients with vestibular migraine (VM) to optimize stimulation conditions. Design: Twenty healthy subjects underwent a series of cVEMP tests by BCV tapping via a minishaker at the Fz (forehead), Cz (vertex), and inion (occiput) sites in a randomized order of tapping sites. Another 20 VM patients were also enrolled in this study for comparison. Results: All 20 healthy subjects had clear BCV cVEMPs when tapping at the inion (100%) or Cz (100%), but not at the Fz (75%). Mean p13 and n23 latencies from the Cz tapping were significantly longer than those from the Fz tapping, but not longer than those from the inion tapping. Unlike healthy subjects, tapping at the Cz (95%) elicited a significantly higher response rate of present cVEMPs than tapping at the inion (78%) in 20 VM patients (40 ears), because seven of nine VM ears with absent cVEMPs by inion tapping turned out to be present cVEMPs by Cz tapping. Conclusions: While both inion and Cz tapping elicited 100% response rate of cVEMPs for healthy individuals, Cz tapping had a higher response rate of cVEMPs than inion tapping for the VM group. In cases of total loss of saccular function, cVEMPs could not be activated by either inion or Cz tapping. However, if residual saccular function remains, Cz tapping may activate saccular afferents more efficiently than inion tapping. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Auditory Lexical Decision and Repetition in Children: Effects of Acoustic and Lexical Constraints. Objectives: The objective of this study was to identify factors that may detract from children's ability to identify words they do and do not know. Factors investigated were acoustic constraints stemming from the presence of hearing loss (HL) or an acoustic competitor, and lexical constraints due to an impoverished or cluttered vocabulary. Design: Eleven children with normal hearing (NH) and 11 children with bilateral, mild to moderately severe sensorineural HL were asked to categorize and repeat two-syllable real and nonsense words. Stimuli were amplified and frequency shaped for each child with HL and presented randomly at a level consistent with average conversational speech (65 dB SPL). About half of the children in each group listened in quiet while the other half listened in multitalker babble. In addition to overall performance, responses were judged based on the word category chosen by the child (real or nonsense), the category of the word produced by the child as judged by an examiner (real or nonsense), and the accuracy of the verbal response compared with the stimulus. From these judgments, 10 discrete types of errors were identified. Analyses were conducted for three different combinations of the 10 error categories to best characterize the effects of acoustic and lexical constraints. Results: Performance was highest for real words presented in quiet and poorest for nonsense words presented in multitalker babble. Also, the performance of the children with HL was poorer than that of the children with NH. Error analyses revealed strong effects of acoustic constraints on performance but few effects of lexical constraints. The two most frequently occurring errors were the same for both children with NH and the children with HL and entailed the misperception of nonsense words and the mistaking of nonsense words for real words. However, while both groups of children exhibited these errors in multitalker babble, the children with HL demonstrated these errors in quiet as well. Conclusions: These results suggest that children's interactions with real and nonsense words are significantly constrained when the acoustic signal is degraded by HL and/or an acoustic competitor. The children's tendency to repair unknown words into real words in the presence of acoustic interference may be beneficial when perceiving familiar speech, but could also be detrimental if that tendency causes them to miss opportunities to learn new words. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Eliciting Cervical Vestibular-Evoked Myogenic Potentials by Bone-Conducted Vibration via Various Tapping Sites. Objectives: This study compared bone-conducted vibration (BCV) cervical vestibular-evoked myogenic potentials (cVEMPs) via tapping at various skull sites in healthy subjects and patients with vestibular migraine (VM) to optimize stimulation conditions. Design: Twenty healthy subjects underwent a series of cVEMP tests by BCV tapping via a minishaker at the Fz (forehead), Cz (vertex), and inion (occiput) sites in a randomized order of tapping sites. Another 20 VM patients were also enrolled in this study for comparison. Results: All 20 healthy subjects had clear BCV cVEMPs when tapping at the inion (100%) or Cz (100%), but not at the Fz (75%). Mean p13 and n23 latencies from the Cz tapping were significantly longer than those from the Fz tapping, but not longer than those from the inion tapping. Unlike healthy subjects, tapping at the Cz (95%) elicited a significantly higher response rate of present cVEMPs than tapping at the inion (78%) in 20 VM patients (40 ears), because seven of nine VM ears with absent cVEMPs by inion tapping turned out to be present cVEMPs by Cz tapping. Conclusions: While both inion and Cz tapping elicited 100% response rate of cVEMPs for healthy individuals, Cz tapping had a higher response rate of cVEMPs than inion tapping for the VM group. In cases of total loss of saccular function, cVEMPs could not be activated by either inion or Cz tapping. However, if residual saccular function remains, Cz tapping may activate saccular afferents more efficiently than inion tapping. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Auditory Lexical Decision and Repetition in Children: Effects of Acoustic and Lexical Constraints. Objectives: The objective of this study was to identify factors that may detract from children's ability to identify words they do and do not know. Factors investigated were acoustic constraints stemming from the presence of hearing loss (HL) or an acoustic competitor, and lexical constraints due to an impoverished or cluttered vocabulary. Design: Eleven children with normal hearing (NH) and 11 children with bilateral, mild to moderately severe sensorineural HL were asked to categorize and repeat two-syllable real and nonsense words. Stimuli were amplified and frequency shaped for each child with HL and presented randomly at a level consistent with average conversational speech (65 dB SPL). About half of the children in each group listened in quiet while the other half listened in multitalker babble. In addition to overall performance, responses were judged based on the word category chosen by the child (real or nonsense), the category of the word produced by the child as judged by an examiner (real or nonsense), and the accuracy of the verbal response compared with the stimulus. From these judgments, 10 discrete types of errors were identified. Analyses were conducted for three different combinations of the 10 error categories to best characterize the effects of acoustic and lexical constraints. Results: Performance was highest for real words presented in quiet and poorest for nonsense words presented in multitalker babble. Also, the performance of the children with HL was poorer than that of the children with NH. Error analyses revealed strong effects of acoustic constraints on performance but few effects of lexical constraints. The two most frequently occurring errors were the same for both children with NH and the children with HL and entailed the misperception of nonsense words and the mistaking of nonsense words for real words. However, while both groups of children exhibited these errors in multitalker babble, the children with HL demonstrated these errors in quiet as well. Conclusions: These results suggest that children's interactions with real and nonsense words are significantly constrained when the acoustic signal is degraded by HL and/or an acoustic competitor. The children's tendency to repair unknown words into real words in the presence of acoustic interference may be beneficial when perceiving familiar speech, but could also be detrimental if that tendency causes them to miss opportunities to learn new words. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Comparative bactericidal activity of four fluoroquinolones against Pseudomonas aeruginosa isolated from chronic suppurative otitis media Background: The aim of the present study was to evaluate the bactericidal activity of four new fluoroquinolones against current isolates of Pseudomonas aeruginosa from the patients with chronic suppurative otitis media (CSOM). Methods: We examined bactericidal activity of four types of fluoroquinolones, garenoxacin (GRNX), levofloxacin (LVFX), ciprofloxacin (CPFX) and sitafloxacin (STFX) against current isolates of P. aeruginosa (50 strains). Results: STFX exhibited the most potent activity of both MIC 50 and MIC 90 , followed by CPFX, LVFX, and GRNX. The number of GRNX-resistant strains was significantly greater than those of LVFX, CPFX, and STFX (P < 0.05). Conclusion: STFX showed the most potent activity against P. aeruginosa for recent pathogens recovered from CSOM as compared with the others, suggesting that the clinical application of topical STFX would be useful to prevent the emergence of resistant mutants of P. aeruginosa. Read More » Making Sense of Cervical Cancer Screening Guidelines and Recommendations Opinion statement Since the publication of the American Cancer Society (ACS)/American Society for Colposcopy and Cervical Pathology (ASCCP)/American Society for Clinical Pathology (ASCP) clinical guidelines in 2012, the majority of practice organizations have reached a consensus on screening recommendations for a low-risk population. These guidelines were based on a thorough review of the evidence with reproducible methods to obtain high-quality, generalizable guidelines. Despite the strength of the evidence based recommendations comprising these guidelines, limitations in physician understanding and compliance remain with respect to reaching an unscreened population and defining and caring for women who are at "high risk." "High-risk" patients are poorly characterized but should include women with a history of a prior abnormal screening, as data has shown a subsequent increased risk of cervical intraepithelial neoplasia grade 2 (CIN2) or greater, even after treatment. These women warrant more intense screening than the general population—though there are no evidence-based guidelines for optimized screening protocols in this population. Emerging data in cervical cancer screening this year includes the FDA approval of primary high-risk human papillomavirus (HPV) testing. While the data is promising, its role in clinical practice, impact on rates of colposcopy in a non-study population, and long-term outcomes are not fully understood, and ongoing research is needed. Challenges remain in this shifting environment on the optimal interval and modality for cervical cancer screening to provide the greatest benefit in detection of precancerous lesions while minimizing the harm of overtreatment. While rapid advancements in research provide improved knowledge on how to treat and prevent this disease, it is often difficult for providers across multiple specialties to remain abreast of these changes and to educate their patients about the most current recommendations. Ultimately, provider and patient education is critical both for improving primary prevention with HPV vaccination, as well as for the uptake of evidence-based screening and management guidelines aimed at detecting and treating precancerous changes of the cervix. Read More »