Head and Neck Diseases by Alexandros G.Sfakianakis: 12/13/16

Τρίτη 13 Δεκεμβρίου 2016

F-FDG PET/CT versus Human Papillomavirus, p16, and Epstein-Barr Virus Detection in Cervical Metastatic Lymph Nodes for identifying primary tumors.

F-FDG PET/CT versus Human Papillomavirus, p16, and Epstein-Barr Virus Detection in Cervical Metastatic Lymph Nodes for identifying primary tumors.

Int J Cancer. 2016 Dec 10;:

Authors: Park GC, Roh JL, Cho KJ, Kim JS, Jin MH, Choi SH, Nam SY, Kim SY

Abstract
Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16, and Epstein-Barr virus (EBV), in metastatic lymph nodes versus (18) F-fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16, and EBV analyses of lymph node fine-needle aspirates and (18) F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and (18) F-FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of (18) F-FDG PET/CT (P < 0.05). The area under the ROC curve of HPV was higher than that of (18) F-FDG PET/CT (0.857 vs. 0.666, P = 0.007). The disease-free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients (P < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment, and predict patient survival. This article is protected by copyright. All rights reserved.

PMID: 27943271 [PubMed - as supplied by publisher]

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Minimally invasive surgery versus radiotherapy/chemoradiotherapy for small-volume primary oropharyngeal carcinoma.

Minimally invasive surgery versus radiotherapy/chemoradiotherapy for small-volume primary oropharyngeal carcinoma.

Cochrane Database Syst Rev. 2016 Dec 11;12:CD010963

Authors: Howard J, Masterson L, Dwivedi RC, Riffat F, Benson R, Jefferies S, Jani P, Tysome JR, Nutting C

Abstract
BACKGROUND: More than 400,000 cases of oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed each year worldwide and the incidence is rising, partly as a result of human papillomavirus. Human papillomavirus-associated OPSCC affects younger patients and often presents at a higher stage; however, it is associated with a better prognosis.Until recently, first-line management of OPSCC involved chemoradiotherapy, as research had demonstrated comparable survival outcomes when compared with open surgery, with significantly decreased morbidity. However, interventions have now evolved with computerised planning and intensity-modulated radiotherapy, and the advent of endoscopic head and neck surgery, which provide the potential for decreased treatment-associated morbidity.The oropharynx plays an essential role in swallowing, speech and protecting the airway as it is situated at the bifurcation of the respiratory and digestive tracts. Treatment modality recommendations are based on survival outcomes. Given the younger patient demographic, establishing the safety of modalities that potentially have better functional outcome is becoming increasingly important.
OBJECTIVES: To assess the efficacy of endoscopic head and neck surgery (transoral robotic surgery or transoral laser microsurgery) for small-volume, primary (T1-2, N0-2) oropharyngeal squamous cell carcinoma (OPSCC) in comparison to radiotherapy/chemoradiotherapy.
SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 10); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 8 November 2016.
SELECTION CRITERIA: Randomised controlled trials in patients with carcinoma in the oropharynx subsite (as defined by the World Health Organization classification C09, C10). Cancers included were primary squamous cell carcinomas arising from the oropharyngeal mucosa. The tumours were classified as T1-T2 with or without nodal disease and with no evidence of distant metastatic spread. The intervention was transoral, minimally invasive surgery with or without adjuvant radiotherapy or adjuvant chemoradiotherapy. The comparator was primary radiotherapy with or without induction or concurrent chemotherapy for the tumour. The treatments received and compared were of curative intent and patients had not undergone prior intervention, other than diagnostic biopsy.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related mortality was to be studied where possible), locoregional control, disease-free survival and progression-free survival or time to recurrence. All outcomes were to be measured at two, three and five years after diagnosis. Our secondary outcomes included quality of life, harms associated with treatment, patient satisfaction and xerostomia score.
MAIN RESULTS: No completed studies met the inclusion criteria for the review. Two ongoing trials fulfilled the selection criteria, however neither are complete.'Early-stage squamous cell carcinoma of the oropharynx: radiotherapy versus trans-oral robotic surgery (ORATOR)' is a phase II randomised controlled trial comparing primary radiation therapy with primary transoral robotic surgery for small-volume primary (T1-2, N0-2) OPSCC. It is currently in progress with an estimated completion date of June 2021.'European Organisation for Research and Treatment of Cancer 1420 (EORTC 1420-HNCG-ROG)' is a phase III, randomised study assessing the "best of" radiotherapy compared to transoral robotic surgery/transoral laser microsurgery in patients with T1-T2, N0 squamous cell carcinoma of the oropharynx and base of tongue. It was due to start accrual mid-2016.
AUTHORS' CONCLUSIONS: The role of endoscopic head and neck surgery in the management of OPSCC is clearly expanding as evidenced by its more overt incorporation into the current National Comprehensive Cancer Network guidelines. Data are mounting regarding its outcomes both in terms of survival and lower morbidity. As confidence increases, it is being used in the management of more advanced OPSCC.Based on this review, there is currently no high-quality evidence from randomised controlled trials regarding clinical outcomes for patients with oropharyngeal cancer receiving endoscopic head and neck surgery compared with primary chemoradiotherapy.

PMID: 27943254 [PubMed - as supplied by publisher]

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Salivary biomarkers in cancer detection.

Salivary biomarkers in cancer detection.

Med Oncol. 2017 Jan;34(1):7

Authors: Wang X, Kaczor-Urbanowicz KE, Wong DT

Abstract
Cancer is the second most common cause of death in the USA. Its symptoms are often not specific and absent, until the tumors have already metastasized. Therefore, there is an urgent demand for developing rapid, highly accurate and noninvasive tools for cancer screening, early detection, diagnostics, staging and prognostics. Saliva as a multi-constituent oral fluid comprises secretions from the major and minor salivary glands, extensively supplied by blood. Molecules such as DNAs, RNAs, proteins, metabolites, and microbiota, present in blood, could be also found in saliva. Recently, salivary diagnostics has drawn significant attention for the detection of specific biomarkers, since the sample collection and processing are simple, cost-effective, and precise and do not cause patient discomfort. Here, we review recent salivary candidate biomarkers for systemic cancers by dividing them according to their origin into: genomic, transcriptomic, proteomic, metabolomic and microbial types.

PMID: 27943101 [PubMed - in process]

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Influence of aqueous humor convection current on IOL opacification.

Influence of aqueous humor convection current on IOL opacification.

Int Ophthalmol. 2016 Dec 10;

Authors: Agresta A, Giudiceandrea A, Salgarello T, Manganelli C, Fasciani R, Caporossi A

Abstract
BACKGROUND AND PURPOSE: The opacification of Akreos Adapt (Bausch & Lomb, Rochester; NY) intraocular lens (IOL) has been previously reported in Literature. A metabolic change in aqueous humour was considered as the main trigger factor to IOL opacification. We report our case and discuss the association with Ex-PRESS, highlighting the particular pattern of IOL opacification and its possible relation with the intraocular convective motions of the aqueous.
MATERIAL AND METHODS: We analyzed our case using both digital slit lamp acquisition and OCT Visante (Zeiss, Germany) images. A literature review was conducted to evaluate our results with that previously reported.
CONCLUSION: The role of a relative stationary flow was reported as suggested concurrent mechanism in IOL opacification phenomenon.

PMID: 27942981 [PubMed - as supplied by publisher]

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LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.

Cancer Chemother Pharmacol. 2016 Dec 09;

Authors: Takahashi S, Kobayashi T, Tomomatsu J, Ito Y, Oda H, Kajitani T, Kakizume T, Tajima T, Takeuchi H, Maacke H, Esaki T

Abstract
PURPOSE: Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients.
METHODS: LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status.
RESULTS: The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected.
CONCLUSIONS: LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed.
CLINICAL TRIAL INFORMATION: ClinicalTrials.gov NCT01911936.

PMID: 27942917 [PubMed - as supplied by publisher]

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Assessment of endolymphatic hydrops and otolith function in patients with Ménière's disease.

Assessment of endolymphatic hydrops and otolith function in patients with Ménière's disease.

Eur Arch Otorhinolaryngol. 2016 Dec 10;

Authors: Okumura T, Imai T, Takimoto Y, Takeda N, Kitahara T, Uno A, Kamakura T, Osaki Y, Watanabe Y, Inohara H

Abstract
Ménière's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière's disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière's disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière's disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière's disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear vestibulo-ocular reflexes.

PMID: 27942898 [PubMed - as supplied by publisher]

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Predictive and prognostic factors for patients with locoregionally advanced laryngeal carcinoma treated with surgical multimodality protocol.

Predictive and prognostic factors for patients with locoregionally advanced laryngeal carcinoma treated with surgical multimodality protocol.

Eur Arch Otorhinolaryngol. 2016 Dec 10;

Authors: Eskiizmir G, Tanyeri Toker G, Celik O, Gunhan K, Tan A, Ellidokuz H

Abstract
The prognosis is suboptimal in patients with locoregionally advanced laryngeal carcinoma even after multimodality protocols. The purpose of this study was to determine the potential influential factors that have an impact on the development of locoregional recurrence, distant metastasis, and oncological outcomes in patients with locoregionally advanced laryngeal carcinoma who had surgical multimodality protocols. A sample size of 85 cases was determined based on a power of 90% and an effect size of α 2 = 0.05. A retrospective analysis of 357 patients with a diagnosis of laryngeal cancer between 2002 and 2015 was performed. Eighteen variables based on sociodemographic, clinical, histopathological and treatment data were analyzed. Medical records of 85 consecutive patients with locoregionally advanced laryngeal carcinoma who underwent surgical multimodality protocols were reviewed. Five-year overall, disease-specific, disease-free, locoregional recurrence-free and distant metastasis-free survival were 68.7, 78.0, 69.6, 68.9 and 69.2%, respectively. Extracapsular extension was an independent predictive factor for locoregional recurrence. Pathologic tumor volume was an independent predictive factor for distant metastasis. pT-stage was an independent prognostic factor for 5-year overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis-free survival. High volume, pT4a laryngeal tumors with extracapsular extension are associated with a high risk of locoregional recurrence and distant metastasis; and have poor oncological outcomes in patients with locoregionally advanced laryngeal carcinoma treated with surgical multimodality protocols.

PMID: 27942895 [PubMed - as supplied by publisher]

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Recurrent oropharyngeal cancer after organ preserving treatment: pattern of failure and survival.

Recurrent oropharyngeal cancer after organ preserving treatment: pattern of failure and survival.

Eur Arch Otorhinolaryngol. 2016 Dec 09;

Authors: de Ridder M, Gouw ZA, Sonke JJ, Navran A, Jasperse B, Heukelom J, Tesselaar ME, Klop WM, van den Brekel MW, Al-Mamgani A

Abstract
The objectives is to thoroughly analyze the pattern of failure and oncologic outcome in recurrent oropharyngeal cancer (OPC) after (chemo)radiotherapy and correlate the site of failure to the planned radiation dose. Between January 2010 and April 2014, 57 patients with recurrent OPC after (chemo)radiotherapy were analyzed. Endpoints were pattern of failure and overall survival (OS). Local (LF) and regional failure (RF) were classified as in-field [>50% within gross tumor volume (GTV)], marginal [<50% within GTV but >50% within clinical target volume (CTV)], or out-of-field (>50% outside CTV) recurrences. In the whole group, 70 recurrences were reported. Of the 31 LF, 29 (93.5%) were in-field and 2 (6.5%) were marginal. No out-field LF was reported. Of the 21 RF, 13 RF (62%) were in-field, 6 (28.5%) marginal, and 2 (9.5%) out-of-field recurrences. Forty-three percent of RF was developed in an electively treated neck level, and 2 of them were contralateral. OS at 2 years in recurrent HPV positive, compared to HPV-negative OPC, were 66 and 18%, respectively (p = 0.011). OS was also significantly better in patients that were salvage treatment which was possible (70 vs. 6%, p < 0.001). Median survival after distant failure was 3.6 months. The great majority of LFs were located within the GTV and 43% of RFs developed in an electively treated neck level. The currently used margins and dose recipe and the indication for bilateral nodal irradiation need to be reevaluated. OS was significantly better in recurrent HPV-positive OPC and in patients, where salvage treatment was possible.

PMID: 27942891 [PubMed - as supplied by publisher]

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A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma.

A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma.

J Audiol Otol. 2016 Dec;20(3):183-186

Authors: Nam SJ, Yang CJ, Chung JW

Abstract
Carcinoma in the external auditory canal (EAC) is a rare malignancy with an annual incidence of one per one million people, accounting for less than 0.2% of all head and neck cancers. The most common histopathological type of EAC cancer is squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, low-grade variant of squamous cell carcinoma. It is a locally destructive, invasive, and slow growing tumor that rarely metastasizes. Verrucous carcinoma occurs predominantly in the oral cavity and larynx, and its occurrence in the EAC is extremely rare. In this report, we present a histologically confirmed case of verrucous carcinoma in the EAC and temporal bone, which for several years had been classified as epithelial hyperplasia. Two-and-a-half years after diagnosis of verrucous carcinoma, a recurrent mass was found and the lesion was then confirmed to be squamous cell carcinoma.

PMID: 27942606 [PubMed - in process]

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Neuroglial Choristoma of the Middle Ear with Massive Tympanosclerosis: A Case Report and Literature Review.

Neuroglial Choristoma of the Middle Ear with Massive Tympanosclerosis: A Case Report and Literature Review.

J Audiol Otol. 2016 Dec;20(3):179-182

Authors: Shim HJ, Kang YK, An YH, Hong YO

Abstract
Neuroglialchoristoma is a rare cerebral heterotopia typically involving extracranial midline structures of the head and neck, including the nose, nasopharynx and oral cavity. It rarely involves non-midline structures, such as the middle ear, mastoid and orbit. We report the case of a 63-year-old woman with right-sided hearing loss and aural fullness who was diagnosed with neuroglialchoristoma of the middle ear and mastoid. To our knowledge, this is the first report on neuroglialchoristomawith massive tympanosclerosis. The presence of combination supported the inhalation theory of neuroglialchoristoma, given that tympanosclerosis is typically caused by Eustachian tube dysfunction.

PMID: 27942605 [PubMed - in process]

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Clinical Analysis of Dizzy Patients with High Levels of Depression and Anxiety.

Clinical Analysis of Dizzy Patients with High Levels of Depression and Anxiety.

J Audiol Otol. 2016 Dec;20(3):174-178

Authors: Kim SK, Kim YB, Park IS, Hong SJ, Kim H, Hong SM

Abstract
BACKGROUND AND OBJECTIVES: Some patients experiencing dizziness also report psychological distress. However, the association between vestibular deficits and psychological symptoms remains controversial. Thus, the aim of this paper is to report the proportion of patients who complained of dizziness who also had high depression and anxiety indices. Also we investigated the severity of their dizziness and the distribution of the diseases underlying this symptom.
SUBJECTS AND METHODS: We assessed the dizziness and psychological distress of 544 patients experiencing dizziness using the Korean versions of the Dizziness Handicap Inventory (DHI), the Beck Depression Inventory (BDI), and the Spielberger State-Trait Anxiety Inventory (STAI). We also reviewed the audio-vestibular symtoms of patients with high levels of depression and anxiety.
RESULTS: The incidences of high depression and anxiety scores were 11% (60/544) and 18% (98/544), respectively. Patients with vestibular migraine were most likely to have high depression and anxiety indices. Patients in the high-BDI or high-STAI groups (117/544) obtained significantly higher DHI scores than those in neither the high-BDI nor the high-STAI group (427/544). We noticed that about 20% of the patients experiencing dizziness had high levels of psychological distress in this study; this group also suffered from various vestibular diseases and more symptoms of dizziness.
CONCLUSIONS: The results of the study suggest that psychological evaluation should be considered when assessing patients with vertigo.

PMID: 27942604 [PubMed - in process]

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Clinical Aspects and Surgical Outcomes of Congenital Cholesteatoma in 93 Children: Increasing Trends of Congenital Cholesteatoma from 1997 through 2012.

Clinical Aspects and Surgical Outcomes of Congenital Cholesteatoma in 93 Children: Increasing Trends of Congenital Cholesteatoma from 1997 through 2012.

J Audiol Otol. 2016 Dec;20(3):168-173

Authors: Cho HS, Kim HG, Jung DJ, Jang JH, Lee SH, Lee KY

Abstract
BACKGROUND AND OBJECTIVES: The recent increase in the reported incidence of congenital cholesteatoma (CC) may be secondary to the widespread use of otoendoscopy as well as an increased awareness of these lesions among primary care physicians. However, little research about CC has been conducted in a large group of patients. This study aimed to analyze the clinical characteristics of CC including the annual number of patients, symptoms, age at diagnosis, stage and type of disease, surgical techniques, recurrence, and postoperative complications.
SUBJECTS AND METHODS: Retrospective chart review was performed for patients who met the inclusion criteria between January 1997 and June 2012.
RESULTS: Ninety-three patients underwent surgery for CC. The age at operation ranged from 12 months to 17 years (mean age, 6.1 years). The number of patients was less than 4 per year until 2005, but increased to more than 10 per year since 2008. CC was most commonly reported as an incidental finding (58.1%). The operative procedures included the transcanal myringotomy approach (46.2%), canal wall up mastoidectomy (37.6%), tympanoplasty (8.6%), and canal wall down mastoidectomy (7.5%). The recurrence rate was 20.4% and the complication rate was 12.9%. No patients with stage I CC had complications.
CONCLUSIONS: This study showed that the incidence of CC has recently increased notably. Most patients with stage I and II CC were completely cured by transtympanic surgery, and complication and recurrence rates increased according to the extent of disease. Early detection of CC is important to facilitate minimally invasive surgery and to reduce complication and recurrence rates.

PMID: 27942603 [PubMed - in process]

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Fibrinogen-Based Collagen Fleece Graft Myringoplasty for Traumatic Tympanic Membrane Perforation.

Fibrinogen-Based Collagen Fleece Graft Myringoplasty for Traumatic Tympanic Membrane Perforation.

J Audiol Otol. 2016 Dec;20(3):139-145

Authors: Choi SH, Song HY, Song CI

Abstract
BACKGROUND AND OBJECTIVES: The aim of this study was to investigate how fibrinogen-based collagen fleece (Tachocomb®) graft myringoplasty (FCGM), performed under microscopic guidance, improves both hearing and tympanic membrane tissue repair in patients with traumatic tympanic membrane perforation (TMP).
SUBJECTS AND METHODS: Between August 2009 and March 2015, a total of 52 patients with traumatic TMP visited the department of otorhinolaryngology at a secondary medical center. Twenty-nine of these underwent FCGM under microscopic guidance in our outpatient clinic. For each patient, we recorded the location and size of the perforation, the time elapsed from the onset of TMP until the myringoplasty, and the hearing level both before and after myringoplasty.
RESULTS: The TMP closed completely in all cases (29 of 29 patients). After myringoplasty, the postoperative air-bone gap (ABG) differed significantly from the preoperative ABG. Three of the 29 patients (10.3%) experienced complications. Specifically, 2 presented with otorrhea after FCGM, but conservative management led to improvement without recurrence of perforation. One patient showed delayed facial palsy 1 week after the procedure. The condition of this patient also improved and the palsy was not permanent.
CONCLUSIONS: FCGM may be an effective treatment option in case of traumatic TMP. The procedure requires no hospitalization, and can be used to avoid traditional tympanoplasty.

PMID: 27942599 [PubMed - in process]

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Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1^asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1^asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1^asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

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Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

by Dylan K. Chan, Stephanie L. Rouse

Ca²⁺ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca²⁺ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca²⁺ changes in response to sound. We find that both slow monotonic changes in intracellular Ca²⁺ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.

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False Belief Performance of Children Adopted Internationally

Purpose

The purpose of this study was to explore relationships among adoption, individual, and family variables on false belief performance of children adopted internationally (CAI).

Method

Using a quasiexperimental design, thirty-five 4-year-old children adopted from Asian and Eastern European countries before age 2 years were compared with a U.S. group of 33 nonadopted 4-year-old children on a standardized English-language measure, 3 false belief tasks, and a go/no-go inhibition measure.

Results

The adopted group differed significantly from the U.S. nonadopted group in expressive language and false belief performance. For the adopted group, inhibition measures were significantly correlated with core language scores. Core language scores and number of older siblings predicted false belief performance.

Conclusions

Similar to children who are not adopted, language competence and living with older siblings positively influenced social understanding in CAI. Because CAI experience interrupted language acquisition and live with fewer older siblings, they are at risk of having weaker language competence and social understanding in their adopted language. When working with CAI, practitioners should assess social communication, language competence, and inhibition skills. They should assist adoptive families in providing socially mentored opportunities for their children to observe and interact with older children.

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Long-term consequences of acute kidney injury in the perioperative setting.

Purpose of review: Recent studies indicate that acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected syndromes. Although the majority of patients who suffer an episode of AKI will recover laboratory indices suggesting complete or near complete recovery of renal function, a significant portion of post-AKI survivors will develop major kidney events, including development of late-stage CKD, need for renal replacement therapies, and death. Recent findings: Our review highlights epidemiology of adverse post-AKI events, association of AKI with late development of nonrenal adverse outcomes, use of bedside equations that facilitate prognostication of adverse renal outcomes of AKI, and how variability in serum creatinine values in individual patients, even among those with normal baseline renal function may indicate risk for the development of CKD. Use of common laboratory parameters such as serum creatinine and albumin, along with certain clinical and demographic markers, individualize patients at high risk of complications and in need of close postdischarge follow-up. Evidence that 'organ crosstalk' following a major AKI episode may increase the risk of heart failure, stroke, and hypertension, places its survivors in a special patient category deserving active efforts to minimize risk for cardiovascular events. Summary: AKI is a major cause for acute in-hospital mortality and development of both late-stage CKD and cardiovascular events. Perioperative care to prevent AKI must challenge the notion that a single normal point of contact serum creatinine value substantially reduces the likelihood of its occurrence. Copyright (C) 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Synthesis, crystal structure and DFT studies of a Zinc(II) complex of 1,3-diaminopropane (Dap), [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]n. The additional stabilizing role of S⋯π chalcogen bond

Publication date: 5 April 2017
Source:Journal of Molecular Structure, Volume 1133
Author(s): Mshari A. Alotaibi, Abdulrahman I. Alharthi, Wiktor Zierkiewicz, Muhammad Akhtar, Muhammad Nawaz Tahir, Muhammad Mazhar, Anvarhusein A. Isab, Saeed Ahmad
A zinc(II) complex of 1,3-diaminopropane (Dap), [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]n (1) has been prepared and characterized by elemental analysis, IR, ¹H & ¹³C NMR spectroscopy, and its crystal structure was determined by X-ray crystallography. The crystal structure of 1 consists of two types of molecules, a discrete monomer and a polymeric one. In the monomeric unit, the zinc atom is bound to one terminal Dap molecule and to two N-bound thiocyanate ions, while in the polymeric unit, Dap acts as a bridging ligand forming a linear chain. The Zn(II) ions in both assume a slightly distorted tetrahedral geometry. The structures of two systems: the [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]3 complex as a model of 1 and [Zn(Dap)(NCS)2]4 as a simple polymeric structure were optimized with the B3LYP-D3 method. The DFT results support that the experimentally determined structure (1) is more stable in comparison to a simple polymeric structure, [Zn(Dap)(NCS)2]n (2). The interaction energies (ΔE) for NCS anions obtained by B3LYP-D3 method are about −145 kcal mol⁻¹, while the calculated ΔE values for neutral organic ligands are about twice smaller. The X-ray structure of 1 shows that the complex is stabilized mainly by hydrogen bonds. We also found that weak chalcogen bonds play an additional role in stabilization of compound 1. Some of the intermolecular S⋯N distances are smaller than the sum of the van der Waals radii of the corresponding atoms. To the best of our knowledge, this is the first study that shows the structure where the trivalent sulfur is involved in formation of a S⋯π chalcogen bond. The NBO and NCI analyses confirm the existence of this kind of interactions.

Graphical abstract

http://ift.tt/2gX8RQj

The evolution of medical care: from the beginnings to personalized medicine

http://ift.tt/2hs4D42

Exploratory analysis of local gene groups in breast cancer guided by biological networks

Abstract

The path to personalized medicine requires the stratification of patients based on their genetic, molecular, and other characteristics to achieve the individualized treatment of complex diseases such as the breast cancer. The identification of single "biomarkers" as the driving forces for the appearance of cancer has therefore been widely pursued in the last fifteen years but with no robust results across different studies. The use of existing biological knowledge such as the gene interaction networks and regulatory pathways can be of great help, since it has been argued that cancer is caused by the deregulation of multiple biological processes in the cell. In this study we explore the usage of such biological knowledge for the tuning and adaptation of the breast cancer classification tasks both in a supervised (classifying unknown samples according to a predetermined taxonomy) and unsupervised setting (clustering of new data towards identifying new categories). The proposed methodology starts from an initial list of "seed" genes and proceeds to the expansion of their "neighborhoods" according to the topology of a given biological network. The expansion process operates in a supervised manner for the construction of the first level in a two level classification scheme. The first level base classifiers are built using the network structure and a "random walk" search strategy for the selection of the genes used in these classifiers. At the second level, a meta-classifier is trained to combine in the best possible way the results of the base classifiers. The proposed approach therefore aims to strengthen the predictive ability of the initial list of genes and provide more robust generalization guarantees. Proceeding to the unsupervised setting, the extracted gene neighborhoods around the initial "seeds" are considered as modules of highly interacting genes within the same group but of strong independence across groups. This consideration allows the introduction of a sparse Gaussian mixture model for the assignment of breast cancer samples into a set of unknown clusters. Our methodology is explained in full detail and promising results in Breast Cancer related scenarios are obtained.

http://ift.tt/2hq6gBL

Understanding Risk for Reading Difficulties in Children With Language Impairment

Purpose

The purpose of this study was to retrospectively examine the preschool language and early literacy skills of kindergarten good and poor readers, and to determine the extent to which these skills predict reading status.

Method

Participants were 136 children with language impairment enrolled in early childhood special education classrooms. On the basis of performance on a word recognition task given in kindergarten, children were classified as either good or poor readers. Comparisons were made across these 2 groups on a number of language and early literacy measures administered in preschool, and logistic regression was used to determine the best predictors of kindergarten reading status.

Results

Twenty-seven percent of the sample met criterion for poor reading in kindergarten. These children differed from good readers on most of the skills measured in preschool. The best predictors of kindergarten reading status were oral language, alphabet knowledge, and print concept knowledge. Presence of comorbid disabilities was not a significant predictor. Classification accuracy was good overall.

Conclusion

Results suggest that risk of reading difficulty for children with language impairment can be reliably estimated in preschool, prior to the onset of formal reading instruction. Measures of both language and early literacy skills are important for identifying which children are likely to develop later reading difficulties.

http://ift.tt/2hj9SW7

Experiments on Auditory-Visual Perception of Sentences by Users of Unilateral, Bimodal, and Bilateral Cochlear Implants

Purpose

Five experiments probed auditory-visual (AV) understanding of sentences by users of cochlear implants (CIs).

Method

Sentence material was presented in auditory (A), visual (V), and AV test conditions to listeners with normal hearing and CI users.

Results

(a) Most CI users report that most of the time, they have access to both A and V information when listening to speech. (b) CI users did not achieve better scores on a task of speechreading than did listeners with normal hearing. (c) Sentences that are easy to speechread provided 12 percentage points more gain to speech understanding than did sentences that were difficult. (d) Ease of speechreading for sentences is related to phrase familiarity. (e) Users of bimodal CIs benefit from low-frequency acoustic hearing even when V cues are available, and a second CI adds to the benefit of a single CI when V cues are available. (f) V information facilitates lexical segmentation by improving the recognition of the number of syllables produced and the relative strength of these syllables.

Conclusions

Our data are consistent with the view that V information improves CI users' ability to identify syllables in the acoustic stream and to recognize their relative juxtaposed strengths. Enhanced syllable resolution allows better identification of word onsets, which, when combined with place-of-articulation information from visible consonants, improves lexical access.

http://ift.tt/2htZGrL

Writing Process Products in Intermediate-Grade Children With and Without Language-Based Learning Disabilities

Purpose

Difficulties with written expression are an important consideration in the assessment and treatment of school-age children. This study evaluated how intermediate-grade children with and without written language difficulties fared on a writing task housed within the Hayes and Berninger (2014) writing process framework.

Method

Sixty-four children completed a writing task whereby they planned, wrote, and revised a narrative story across 3 days. Children had extended time to produce an outline, first draft, and final copy of their story. Language transcription approaches were used to obtain measures reflecting writing productivity, complexity, accuracy, and mechanics, in addition to measures of planning and revision.

Results

Results indicated that children with writing difficulties produced poorer quality stories compared with their peers yet were not significantly different across all measures. Children with typical development produced longer stories with better spelling accuracy. Writing process measures predicted significant amounts of variance in writing quality across the sample.

Discussion

Writing should be considered as part of language assessment and intervention, whether as the sole language difficulty or alongside difficulties with speaking, listening, or reading in children with language-based learning difficulties. Implications for translation of research to practice and service delivery are provided.

http://ift.tt/2hj2mKM

Literate Language Intervention With High-Need Prekindergarten Children: A Randomized Trial

Purpose

The present article reports on the implementation and results of a randomized intervention trial targeting the literate language skills of prekindergarten children without identified language disorders but with low oral language skills.

Method

Children (N = 82; 45 boys and 37 girls) were screened-in and randomized to a business-as-usual control or to the pull-out treatment groups in which they received 4 instructional units addressing different sentence-level syntactic and semantic features: prepositions, conjunctions, adverbs, and negations. The intervention was delivered by paraprofessionals in small groups in the form of 20-min lessons 4 times a week for 12 weeks.

Results

Overall, children receiving the supplemental instruction showed educationally meaningful gains in their oral language skills, relative to children in the control group. Significant group differences were found on researcher-designed oral language measures, with moderate to large effect sizes ranging from .44 to .88 on these measures.

Conclusions

The intervention holds the potential to positively affect understanding and production of syntax and semantic features, such as prepositions and conjunctions, in young children with weak oral language skills.

http://ift.tt/2hjdqaz

Vocabulary Development in European Portuguese: A Replication Study Using the Language Development Survey

Purpose

Our objective was to replicate previous cross-linguistic findings by comparing Portuguese and U.S. children with respect to (a) effects of language, gender, and age on vocabulary size; (b) lexical composition; and (c) late talking.

Method

We used the Language Development Survey (LDS; Rescorla, 1989) with children (18–35 months) learning European Portuguese (n = 181) and English (n = 206).

Results

In both languages, girls had higher vocabulary scores than boys and vocabulary scores increased with age. Portuguese LDS scores were significantly lower than English scores, but the effect size was small. Cross-linguistic concordance of percentage use scores yielded a Q correlation of .50, with 64 of the "top 100" words being exact matches. Cross-linguistic concordance was highest for the youngest age group. In both languages, vocabulary composition in late talkers (children ≥ 24 months with Conclusions

http://ift.tt/2htXaS5

Estimating Subglottal Pressure From Neck-Surface Acceleration During Normal Voice Production

Purpose

The purpose of this study was to evaluate the potential for estimating subglottal air pressure using a neck-surface accelerometer and to compare the accuracy of predicting subglottal air pressure relative to predicting acoustic sound pressure level (SPL).

Method

Indirect estimates of subglottal pressure (P_sg′) were obtained from 10 vocally healthy speakers during loud-to-soft repetitions of 3 different /p/–vowel gestures (/pa/, /pi/, /pu/) at 3 pitch levels in the modal register. Intraoral air pressure, neck-surface acceleration, and radiated acoustic pressure were recorded, and the root-mean-square amplitude of the acceleration signal was correlated with P_sg′ and SPL.

Results

The coefficient of determination between accelerometer level and P_sg′ was high when data were pooled from all vowel and pitch contexts for each participant (r ² = .68–.93). These relationships were stronger than corresponding relationships between accelerometer level and SPL (r ² = .46–.81). The average 95% prediction interval for estimating P_sg′ using accelerometer level was ±2.53 cm H₂O, ranging from ±1.70 to ±3.74 cm H₂O across participants.

Conclusions

Accelerometer signal amplitude correlated more strongly with P_sg′ than with SPL. Future work is warranted to investigate the robustness of the relationship in nonmodal voice qualities, individuals with voice disorders, and accelerometer-based ambulatory monitoring of subglottal pressure.

http://ift.tt/2htUAvv

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Protective Factors, Correctional Treatment and Desistance

Publication date: Available online 12 December 2016
Source:Aggression and Violent Behavior
Author(s): Devon L.L. Polaschek
A confusing array of empirical and conceptual definitions has been offered for protective factors and related terms. This paper reviews these, and recent scales that include protective factors, for their treatment implications. The scales, and the small volume of treatment research on protective factors reveal a similar amount of confusion: most notably with regard to whether protective factors are really different from risk factors except in name. Next, I argue that research on desistance has also examined several protective factors, such as the relationship of release planning to various positive intermediate community outcomes that may mediate desistance effects. Three conceptualizations of protective factors in treatment and desistance are described, before I conclude that calling a factor protective may not automatically enhance treatment effectiveness or desistance support, and that more research is needed, including studies that examine the potential effects of correctional treatment on positive outcomes.

http://ift.tt/2gEQxPO

Problems in protective factor research and practice

Publication date: Available online 13 December 2016
Source:Aggression and Violent Behavior
Author(s): Clare-Ann Fortune, Tony Ward
The concept of protective factors and allied constructs such as strengths or resilience has been the focus of increased research and practice attention within the criminal justice domain over the last ten years or so. A major reason for this interest is that assisting individuals to desist from further offending means helping them to live their lives in fulfilling and prosocial social ways. While this is a laudable aim several research problems are now apparent in the literature that threatens to undermine this goal. In this paper we focus on four of these problems and thereby set the scene for the remaining papers of this special issue. The four problems are definitional ambiguity, practitioner uncertainty, explanatory confusion, and the dual nature of protective factors.

http://ift.tt/2gX1hoH

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

by Dylan K. Chan, Stephanie L. Rouse

In vivo digestomics of milk proteins in human milk and infant formula using a suckling rat pup model

Publication date: Available online 13 December 2016
Source:Peptides
Author(s): Yasuaki Wada, Brett S. Phinney, Darren Weber, Bo Lönnerdal
Human milk is the optimal mode of infant feeding for the first several months of life, and infant formulas serve as an alternative when breast-feeding is not possible. Milk proteins have a balanced amino acid composition and some of them provide beneficial bioactivities in their intact forms. They also encrypt a variety of bioactive peptides, possibly contributing to infant health and growth. However, there is limited knowledge of how milk proteins are digested in the gastrointestinal tract and bioactive peptides are released in infants. A peptidomic analysis was conducted to identify peptides released from milk proteins in human milk and infant formula, using a suckling rat pup model. Among the major milk proteins targeted, α-lactalbumin and β-casein in human milk, and β-lactoglobulin and β-casein in infant formula were the main sources of peptides, and these peptides covered large parts of the parental proteins' sequences. Release of peptides was concentrated to specific regions, such as residues 70–92 of β-casein in human milk, residues 39–55 of β-lactoglobulin in infant formula, and residues 57–96 and 145-161 of β-CN in infant formula, where resistance to gastrointestinal digestion was suggested. In the context of bioactive peptides, release of fragments containing known bioactive peptides was confirmed, such as β-CN-derived opioid and antihypertensive peptides. It is therefore likely that these fragments are of biological significance in neonatal health and development.

http://ift.tt/2gEO7k4

Review of "Preservation of the Nerves to the Frontalis Muscle During the Pterional Craniotomy" by Poblete T, Jiang X, Komune N, Matsushima K, Rhoton AL in J Neurosurg 122: 1274-1282, 2015.

No abstract available

http://ift.tt/2gERwj1

Are Three-Dimensional Monitors More Appropriate Than Two-Dimensional Monitors in the Three-Dimensional Analysis?.

In orthognathic surgery, three-dimensional (3D) program-based analysis of 3D reconstructions of computed tomography (CT) images is commonly used, and images viewed on a monitor. The authors compared the coordinates of facial landmarks on images in a 3D program displayed on a two-dimensional (2D) (standard) or 3D monitor. Facial bone CT data from 30 patients were reconstructed in 3D. Four researchers identified 33 facial landmarks, 3 times each on 2D and 3D monitors, for each patient, by their x-, y-, and z-coordinates. The time taken to complete these identifications was measured. For each set of coordinates, the average intraclass coefficient was >0.8 for 2D and 3D analyses, as well as among 4 readers. It took on average of 2 minutes 46 seconds to identify the landmarks on the 2D monitor, compared with 2 minutes 25 seconds on the 3D monitor. The variance of individual coordinates differed when measured on 2D or 3D monitor. The landmarks affected were located near the median region of the facial area, and are important for setting the reference sagittal plane during diagnosis for orthognathic surgery. Therefore, identifying facial landmarks using 3D monitors may be helpful for conducting accurate facial diagnoses. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2hrRZBJ

Off-Label Use of Bone Morphogenetic Protein 2 in the Reconstructions of Mandibular Continuity Defects.

This paper describes 3 patients of off-label use of bone morphogenetic protein 2 (rhBMP-2) in the reconstruction of mandibular continuity defects. In the first patient, rhBMP-2 was associated with iliac crest bone graft for late mandibular reconstruction after resection of osteosarcoma. In the 2 other patients, rhBMP-2 was used alone. In 1 patient the mandibular continuity defect was due to resection for treatment of osteomyelitis and in the other patient a continuity defect was created by unsuccessful osteogenic distraction for correction of mandibular hypoplasia. Despite the good results in those patients, the off-label use of rhBMP-2 is associated with increased rate of complications, so more studies are needed to assess the predictability of the use of rhBMP-2 in mandibular continuity defects. Therefore, at the moment the off-label use of rhBMP-2 should be restricted to complicated bone defects in which the conventional alternatives of reconstruction were unsuccessful. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2gEIOBm

Assessment of the Postoperative Stability of Mandibular Orthognathic Surgery for Correction of Class III Skeletal Malocclusion.

To assess the stability of mandible position after orthognathic surgery for correction of class III skeletal malocclusion. Twenty adult males, aged 18 to 40 years, with Angle class III skeletal malocclusion underwent preoperative orthodontic treatment for elimination of dental compensations followed by combined maxillomandibular surgery with rigid internal fixation. Lateral cephalograms from each patient, obtained in the natural head position before surgery, immediately after surgery, and at 6-month follow-up, were retrieved from the files of the Pontifical Catholic University of Rio Grande do Sul outpatient Oral and Maxillofacial Surgery clinic and compared. Comparison of craniometric landmark measurements showed that the precision of mandibular setback was compromised in the horizontal plane, with a mean mandibular relapse of 37.75% at point B and 45.85% at point Pg. Improved intercuspation and adaptation of the musculature to the new position of the jaws after orthognathic surgery lead to counterclockwise rotation of the mandible, ultimately displacing the mandible more anteriorly than desired. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2hrVZCu

Anatomical Study and Locating Nasolacrimal Duct on Computed Topographic Image.

Purpose: We performed a novel anatomical and radiological investigation to understand the structure of nasolacrimal duct (NLD) and to provide data to help surgeons locate the openings of NLD efficiently based on landmarks. Materials and methods: We examined the NLD region using computed tomography images of 133 individuals and 6 dry skull specimens. Multiplanar reconstruction of the computed tomography images was performed, and the anatomical features of the NLD were studied in the coronal, sagittal, and axial planes. The long and short diameters of NLD were measured along its cross-section. The position of NLD was localized using the nostril, concha nasalis media, and medial orbital corner as landmarks. The free and open source software, 3D Slicer, was used for the segmentation of the NLD and 3D visualization of the superior and inferior openings of the NLD. Results: The length, angle, and diameter of NLD were significantly influenced by the age in females compared to those in males. The inferior opening of the NLD could be located efficiently using the nostril and the midsagittal line while the superior opening of NLD could be located using the medial orbital corner. Third, 3D Slicer enabled us to measure the distance between the skin and the bony structure in the image. Conclusion: Our study indicates that the sex and age of the patient should be considered while selecting the optimal NLD stent for a patient, and that the precise location of NLD in reference to landmarks can simplify the surgical difficulties and reduce the risk of injury during the transnasal operation. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2gEIgeR

The Need for Overcorrection When Using a Suborbital Cervicofacial Hike Flap.

Background: The senior author has previously described a deep-plane cervicofacial hike flap as a workhorse for reconstruction mid-cheek defects. One important modification commonly used involves overcorrection of the defect in order to reduce the incidence of ectropion. This report outlines the senior author's experience in surgical treating complex cheek defects with an overcorrected deep-plane cervicofacial hike flap. Methods: The authors performed a retrospective review of the senior author's patients with cheek and eyelid reconstruction. The authors initially identified all patients who had undergone a deep-plane cervicofacial hike flap, then filtered those charts for patients who had overcorrection of their deformity in order to prevent ectropion. Results: A total of 3 patients had an overcorrected flap. Overcorrection was accomplished either by cheek advancement with suture fixation to the deep temporal fascia, or by placement of drill holes and bone anchors. Lower eyelid malposition was avoided in all 3 patients. Patient satisfaction at long term follow-up was very high, and no revision surgery was needed. Conclusion: If gravitational or cicatricial forces can potentially distort the eyelid in patients with cheek or eyelid reconstruction, it is necessary to overcorrect the cheek flap. This modification of the deep-plane cervicofacial flap is an important tool in reconstructing defects in this area. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2hpTaoi

Conjoined Twin Separation: Integration of Three-Dimensional Modeling for Optimization of Surgical Planning.

Conjoined twinning is a rare anomaly, with an incidence of approximately 1 in 100,000 live births. There is a high perinatal mortality rate, but twins who survive pose reconstructive challenges that require meticulous preoperative planning. The authors describe the senior surgeon's career experience with conjoined twin separation, and the evolution of medical modeling and 3-dimensional imaging as a critical component in presurgical planning. The authors performed a retrospective review of all consecutive patients of conjoined twin separation at a single institution from January 2004 to December 2013. Data were collected related to patient demographics, comorbidities, operative technique, perioperative complications, survival, long-term outcomes, and the type of medical modeling system used for preoperative planning. Five sets of conjoined twins underwent separation during the 10-year study period. There were 3 sets of thoraco-omphalopagus twins, 1 set of pyopagus twins, and 1 set of ischiopagus tetrapus twins. The mean age at separation was 70 days, with a mean of 3.5 surgical procedures performed per patient during the first year of life. One set of twins experienced postseparation complications that warranted immediate return to the operating room. The overall survival rate after separation was 70%. The imaging methods used were computed tomography scan with 3-dimensional reconstruction, plaster molds, medical modeling with composite printing, and virtual surgical planning. The use of imaging and medical modeling in presurgical planning has proven to be an important element in optimizing the outcomes for patients with this rare anomaly. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2hrQXWB

A Modified Approach to Extensive Oromandibular Reconstruction Using Free Fibula Flaps.

In select patients with advanced disease resulting in large composite tissue defects, consideration is often given to multiple flap reconstruction. The authors propose an alternative option. Using virtual surgical planning the authors demonstrate how modest sacrifice in projection translates into a substantial decrease in the volume and surface area of soft tissue needed, in turn maximizing soft tissue coverage with a single fibula free flap. The authors used 3-dimensional virtual surgery to simulate angle-to-angle reconstructions using free fibula flaps. The reference 3-segment reconstruction was done using symphyseal projection to the plane perpendicular to the anterior nasal spine, a customary landmark. Additional simulations were then performed using recessed projections 0.5 mm, 1 cm, 1.5 cm, and 2 cm posterior to anterior nasal spine plane. Program analytics were used to calculate the surface area and volume of the floor of mouth. With projection recessed by 1 cm, surface area decreased 22% to 14 cm2. With projection recessed by 2 cm, surface area decreased 44% to 10 cm2. With a 3-segment construct converted to a 2-segment construct, surface area decreased 22% to 14 cm2. This demonstrates for the first time an official analysis of an intraoperative modification that sacrifices little and gains a lot. Ultimately, 1 compound flap can be used in extensive reconstructions with increased confidence that it will not be overly stressed. (C) 2016 by Mutaz B. Habal, MD.

http://ift.tt/2hpKu12

Invasive Aspergillosis Mimicking Sphenoid Wing Meningioma.

No abstract available

http://ift.tt/2gI7WW9

Wall teichoic acid is an essential component of Staphylococcus aureus for the induction of human dendritic cell maturation

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Sung Jun Hong, Sun Kyung Kim, Eun Byeol Ko, Cheol-Heui Yun, Seung Hyun Han
Staphylococcus aureus is a Gram-positive pathogen that can cause chronic skin inflammation, pneumonia, and septic shock. The immunomodulatory functions of wall teichoic acid (WTA), a glycopolymer abundantly expressed on the Gram-positive bacterial cell wall, are poorly understood. Here, we investigated the role of WTA in the phenotypic and functional activation of human monocyte-derived dendritic cells (DCs) treated with ethanol-killed S. aureus. WTA-deficient S. aureus mutant (ΔtagO) exhibited attenuated binding and internalization to DCs compared to the wild-type. ΔtagO induced lower expression of maturation markers on and cytokines in DCs than the wild-type S. aureus. Furthermore, autologous human peripheral blood mononuclear cells cocultured with ΔtagO-treated DCs exhibited a marked reduction in T cell proliferative activity, the expression of activation markers, and the production of cytokines compared to the wild-type S. aureus-stimulated DCs. Collectively, these results suggest that WTA is an important cell wall component of S. aureus for the induction of DC maturation and activation.

http://ift.tt/2gWCOzR

Antibody-mediated targeting of antigen to C-type lectin-like receptors Clec9A and Clec12A elicits different vaccination outcomes

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Christophe Macri, Claire Dumont, Scott Panozza, Mireille H. Lahoud, Irina Caminschi, Jose A. Villadangos, Angus P.R. Johnston, Justine D. Mintern
Targeting antigen (Ag) to dendritic cell (DC) surface receptors is a potential new mode of vaccination. C-type lectin-like receptors Clec9A and Clec12A are attractive receptor targets however their targeting in vivo elicits significantly different outcomes for unknown reasons. To gain insight into the mechanisms responsible, we have examined the intrinsic capacity of Clec9A and Clec12A to elicit MHC I and MHC II Ag presentation following ex vivo targeting with primary murine DC. Both receptors exhibited high rates of internalization by CD8⁺ DCs, while Clec12A delivered a significantly higher Ag owing to its higher expression level. Targeting Ag to immature CD8⁺ DCs via both Clec9A and Clec12A failed to elicit MHC I cross-presentation above that of controls, while Clec12A was the superior receptor to target following CD8⁺ DC maturation. CD8⁻ DCs were unable to elicit MHC I cross-presentation regardless of the receptor targeted. For MHC II presentation, targeting Ag to Clec12A enabled significant responses by both immature CD8⁺ and CD8⁻ DCs, whereas Clec9A did not elicit significant MHC II Ag presentation by either DC subset, resting or mature. Therefore, Clec9A and Clec12A exhibit different intrinsic capacities to elicit MHC I and MHC II presentation following direct Ag targeting, though they can only elicit MHC I responses if the DC expressing the receptor is equipped with the capacity to cross-present. Our conclusions have consequences for the exploitation of these receptors for vaccination purposes, in addition to providing insight into their roles as Ag targets in vivo.

http://ift.tt/2gElbZL

Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Dibyendu Samanta, Haisu Guo, Rotem Rubinstein, Udupi A. Ramagopal, Steven C. Almo
In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells. Here we report the crystal structure of the human TIGIT ectodomain, which exhibits the classic two-layer β-sandwich topology observed in other immunoglobulin super family (IgSF) members. Biophysical studies indicate that TIGIT is monomeric in solution but can form a dimer at high concentrations, consistent with the observation of a canonical immunoglobulin-like dimer interface in the crystalline state. Based on existing structural data, we present a model of the TIGIT:nectin-2 complex and utilized complementary biochemical studies to map the nectin-binding interface on TIGIT. Our data provide important structural and biochemical determinants responsible for the recognition of nectin-2 by TIGIT. Defining the TIGIT:nectin-2 binding interface provides the basis for rational manipulation of this molecular interaction for the development of immunotherapeutic reagents in autoimmunity and cancer.

http://ift.tt/2gWHdmH

Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Xiaoxu Duan, Shuang Gao, Jinlong Li, Liuzhong Wu, Yang Zhang, Wei Li, Lu Zhao, Jinli Chen, Shan Yang, Guifan Sun, Bing Li
Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice were used as a model to systemically administration 2.5, 5 and 10mg/kg NaAsO2 intra-gastrically for 24h. We found that arsenic significantly decreased the spleen and thymus weights and indices, and flow cytometry revealed that arsenic decreased the relative frequency of CD4⁺ T cell subpopulation and the ratios of CD4/CD8 in spleen. In contrast, serum concentration of tumor necrosis factor α (TNF-α), IL-1β and IL-6 as well as the mRNA of key inflammatory mediators in spleen and thymus, including transforming growth factor β (Tgf-β), Tnf-α, Il-12, Il-1β and Il-6 were significantly increased in arsenic-treated mice compared to the control as assayed by ELISA and real time PCR, respectively. In addition, arsenic increased the expression of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) −associated transcription factors and cytokines as well as decreased Th17-associated transcription factors and cytokines. Moreover, arsenic enhanced oxidative stress and induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 and their downstream transcription factors nuclear factor kappa B (NF-kB) and nuclear factor E2-related factor 2 (Nrf2), which comprise important mechanistic pathways involved in immune-inflammatory manifestations. Together, these results provide a novel strategy to block the arsenic-dependent impairments in immune responses.

http://ift.tt/2htHcYb

Wall teichoic acid is an essential component of Staphylococcus aureus for the induction of human dendritic cell maturation

Antibody-mediated targeting of antigen to C-type lectin-like receptors Clec9A and Clec12A elicits different vaccination outcomes

Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2

Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 13 Δεκεμβρίου 2016

Graphical abstract

Abstract

Αρχειοθήκη ιστολογίου