Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο 23 Δεκεμβρίου 2017

Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen

Publication date: Available online 23 December 2017
Source:Radiotherapy and Oncology
Author(s): Lauren Henke, Rojano Kashani, Clifford Robinson, Austen Curcuru, Todd DeWees, Jeffrey Bradley, Olga Green, Jeff Michalski, Sasa Mutic, Parag Parikh, Jeffrey Olsen
Purpose/objectivesSBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT's therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies.Materials/methodsTwenty patients with oligometastatic or unresectable primary liver (n = 10) and non-liver (n = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR "anatomy-of-the-day" to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded.ResultsOnline adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (<6 months) treatment-related toxicities were observed.DiscussionSMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT.



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MRI evaluation of sacral chordoma treated with carbon ion radiotherapy alone

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Publication date: Available online 23 December 2017
Source:Radiotherapy and Oncology
Author(s): Lorenzo Preda, Davide Stoppa, Maria Rosaria Fiore, Giulia Fontana, Sofia Camisa, Roberto Sacchi, Michele Ghitti, Gisela Viselner, Piero Fossati, Francesca Valvo, Viviana Vitolo, Maria Bonora, Alberto Iannalfi, Barbara Vischioni, Alessandro Vai, Edoardo Mastella, Guido Baroni, Roberto Orecchia
Background and purposeTo compare RECIST 1.1 with volume modifications in patients with sacral chordoma not suitable for surgery treated with carbon ions radiotherapy (CIRT) alone. To evaluate patients pain before and after CIRT. To detect if baseline Apparent Diffusion Coefficient values (ADC) from Diffusion Weighted sequences could predict response to treatment.Material and methodsPatients included had one cycle of CIRT and underwent MRI before and after treatment. For each MRI, lesion maximum diameter and volume were obtained, and ADC values were analyzed within the whole lesion volume. Patients pain was evaluated with Numerical Rating Scale (NRS), considering the upper tumor level at baseline MRIs.Results39 patients were studied (mean follow-up 18 months). Considering RECIST 1.1 there was not a significant reduction in tumor diameters (p = 0.19), instead there was a significant reduction in tumor volume (p < 0.001), with a significant reduction in pain (p = 0.021) if the tumors were above vertebrae S2–S3 at baseline MRIs. The assessment of baseline ADC maps demonstrated higher median values and more negative skewness values in progressive disease (PD) patients versus both partial response (PR) and stable disease (SD).ConclusionsLesion volume measurement is more accurate than maximum diameter to better stratify the response of sacral chordoma treated with CIRT. Preliminary results suggest that baseline ADC values could be predictive of response to CIRT.



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Editorial Board

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Publication date: January 2018
Source:Critical Reviews in Oncology/Hematology, Volume 121





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Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets

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Publication date: Available online 24 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Suresh Sulekha Dhanisha, Chandrasekharan Guruayoorappan, Sudarsanan Drishya, Prathapan Abeesh
Mucins are the main structural components of mucus that create a selective protective barrier for epithelial surface and also execute wide range of other physiological functions. Mucins can be classified into two types, namely secreted mucins and membrane bounded mucins. Alterations in mucin expression or glycosylation and mislocalization has been seen in various types of pathological conditions such as cancers, inflammatory bowel disease and ocular disease, which highlight the importance of mucin in maintaining homeostasis. Hence mucins can be used as attractive target for therapeutic intervention. In this review, we discuss in detail about the structural diversity of mucins; their biosynthesis; its role in pathogenesis; regulation and as possible therapeutic targets.



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The ethical plausibility of the ‘Right To Try’ laws

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Publication date: Available online 24 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): D. Carrieri, F.A. Peccatori, G. Boniolo
'Right To Try' (RTT) laws originated in the USA to allow terminally ill patients to request access to early stage experimental medical products directly from the producer, removing the oversight and approval of the Food and Drug Administration. These laws have received significant media attention and almost equally unanimous criticism by the bioethics, clinical and scientific communities. They touch indeed on complex issues such as the conflict between individual and public interest, and the public understanding of medical research and its regulation. The increased awareness around RTT laws means that healthcare providers directly involved in the management of patients with life-threatening conditions such as cancer, infective, or neurologic conditions will deal more frequently with patients' requests of access to experimental medical products.This paper aims to assess the ethical plausibility of the RTT laws, and to suggest some possible ethical tools and considerations to address the main issues they touch.



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Non pharmacological interventions and non-fentanyl pharmacological treatments for breakthrough cancer pain: a systematic and critical review

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Publication date: Available online 23 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sebastiano Mercadante
Background: Oral opioids or other pharmacological or non-pharmacological interventions are often suggested in the management of breakthrough cancer pain (BTcP). The aim of this systematic and critical review was to analyse and critically comment the evidence of any non-fentanyl therapies proposed for BTcP.MethodsA systematic literature search was carried out to find studies providing clinical data on any treatment excluding fentanyl products.ResultsNo data exist about the use of oral opioids. Some information is available on parenteral morphine in a large sample of patients and episodes of BTcP. For other treatments, including methadone, nitrous oxide, anti-inflammatory drugs, samarium, and gabapentin the existing data, observational and obtained in a small number of patients do not provide useful information to be generalized. Only ketamine, a drug difficult to use for many physicians, particularly in determined setting, provided some evidence according a randomized controlled double-blind study.ConclusionsRecommendations suggesting the use of oral opioids or other pharmacological and non-pharmacologic interventions for BTcP, are not based on any, even minimal evidence. These treatments are worthwhile of further investigation, particularly in determined conditions that should fit the pharmacokinetics of oral opioids.



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Effects of maxillary protraction appliances on airway dimensions in growing class III maxillary retrognathic patients: A systematic review and meta-analysis

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Ye Ming, Yun Hu, Yuyue Li, Jinfeng Yu, Haojue He, Leilei Zheng
ObjectivesThe purpose of this study was to assess, through a systematic review and meta-analysis, the efficacy of maxillary protraction appliances (MPAs) on improving pharyngeal airway dimensions in growing class III patients with maxillary retrognathism.MethodsAn electronic search in PubMed, Cochrane Library, Web of Science, and EMBASE was until September 2nd, 2017. The assessments of methodological quality of the selected articles were performed using the Newcastle-Ottawa Scale. Review Manager 5.3 (provided by the Cochrane Collaboration) was used to synthesize the effects of MPAs on pharyngeal airway dimensions.ResultsFollowing full-text articles evaluation for eligibility, 6 studies (168 treated subjects and 140 untreated controls) were included in final quantitative synthesis and they were all high-quality. Compared to untreated control groups, the treatment groups had increased significantly nasopharyngeal airway dimensions with the following measurements: PNS-AD1 (fixed: mean difference, 1.33 mm, 95% CI, 0.48mm-2.19 mm, P = .002), PNS-AD2 (random: mean difference, 1.91 mm, 95% CI, 0.02mm-3.81 mm, P = .05), aerial nasopharyngeal area (fixed: mean difference, 121.91 mm2, 95% CI, 88.70 mm2-155.11 mm2, P < .00001) and total nasopharyngeal area (fixed: mean difference, 142.73 mm2, 95% CI, 107.90 mm2-177.56 mm2, P < .00001). Meanwhile, McNamara's upper pharynx dimension (fixed: mean difference, 0.96 mm, 95% CI, 0.29mm-1.63 mm, P = .005), which was highly related to post-palatal airway dimension, was also improved significantly. However, no statistically significant differences in adenoidal nasopharyngeal area (P > .05) and McNamara's lower pharynx dimension (P > .05) existed.ConclusionsMPAs can increase post-palatal and nasopharyngeal airway dimensions in growing skeletal class III subjects with maxillary retrusion. It may be suggested that MPAs have the potential to reduce the risk of obstructive sleep apnea syndrome in children with maxillary retrusion by enlarging airway space.



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Cochlear implant symmetry via template

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): A.J. Hallwachs, J.E. Weinstein, B.K. Reilly
Current trends in bilateral cochlear implantation (CI) favor a minimally invasive subperiosteal pocket technique. Symmetric receiver-stimulator (R/S) placement is an important goal for bilateral CI, especially with regard to patient satisfaction. In this article, we describe a method easily adopted to achieve optimal symmetry. Upon reviewing the Senior Author's 11 bilateral CI cases using the direct subperiosteal pocket technique with the proposed "mirror template," we found improved symmetry, which translated into high patient and family satisfaction regarding the aesthetics of the symmetric R/S placement.



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Mature and immature pediatric head and neck teratomas: A 15-year review at a large tertiary center

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Harish Dharmarajan, Noémie Rouillard-Bazinet, Binoy M. Chandy
IntroductionPediatric head and neck teratomas account for less than 4% of congenital teratomas. The distinct presentations and outcomes of mature and immature head and neck teratomas have not been well established.ObjectivesTo review the management and outcomes of pediatric head and neck teratomas. To distinguish differences between mature and immature tumors with respect to the age at presentation and surgery, tumor size and location, alpha fetoprotein (AFP) levels, airway management, and recurrence.MethodsA 15-year retrospective chart review of patients treated for head and neck teratomas at Texas Children's Hospital was performed. A total of 20 patients were included. Wilcoxon rank and Fisher's exact tests were used for statistical analysis.ResultsImmature teratomas were associated with both higher AFP levels (80800 ng/ml, p = 0.02) and maximum tumor dimensions (14.4 cm, p = 0.0034) than mature teratomas (24400 ng/ml and 6.44 cm). Patients with immature tumors were younger at the time of surgical resection (19.8 days, p = 0.025) compared to those with mature tumors (348 days). 89% of immature teratomas involved anterior neck localization compared to 27% for mature teratomas (p = 0.0098); 88% of the immature teratomas required an EXIT (Ex Utero Intrapartum Treatment) procedure compared with 40% of the mature teratomas (p = 0.0656). Recurrence was noted in only two cases: an immature teratoma 51 months after incomplete resection and a mature teratoma 33 months after complete resection. Long-term consequences of surgical resection included cleft palate (38.9%), dysphagia (33.3%), facial nerve paresis/paralysis (16.7%) and tracheotomy (16.7%).ConclusionImmature teratomas had higher AFP levels, tumor dimensions, frequency of anterior neck localization, and requirement of EXIT than mature teratomas. Given that there was no significant difference between the recurrence rates of immature and mature teratomas, follow-up vigilance should be maintained equally regardless of tumor maturity.



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Lingual tonsillectomy in children with Down syndrome: Is it safe?

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Jonathan R. Skirko, Emily L. Jensen, Norman R. Friedman
ObjectiveEvaluate peri-operative course and morbidity in children with Down syndrome (DS) who underwent a lingual tonsillectomy (LT) for residual obstructive sleep apnea (rOSA).MethodsRetrospective case series for children with DS who underwent LT for rOSA from April 2011 to July 2016. Our primary outcomes were length of stay, readmission and complications. Surgical effectiveness was evaluated by change in the obstructive apnea-hypopnea-index(OAHI) and oxygen saturation nadir.ResultsThirty-nine patients underwent LT. The mean length of stay was 1.3 days with n = 21(72%) staying one night. One subject (2.6%) had a post-operative bleed that did not require operative intervention. No other major complications occurred. In terms of effectiveness of surgery, twenty–nine children had sufficient data for inclusion. Median OAHI did not appreciably change (p = 0.07) from before surgery. Five subjects (17%) were cured of OSA (OAHI < 2/hour) and a mix of improvement and worsening was identified. The lowest oxygen saturation improved from 78% (SD = 7) before surgery to 82% (SD = 6) after surgery (p = 0.003).ConclusionLT has a favorable post-operative course but its effectiveness at curing rOSA in the DS population has not been established/proven. Further research is indicated to determine optimal surgical management for DS children with LTH.Level of evidence4.



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How does a bilingual environment affect the results in children with cochlear implants compared to monolingual-matched children? An Italian follow-up study

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Francesca Forli, Giada Giuntini, Annalisa Ciabotti, Luca Bruschini, Ulrika Löfkvist, Stefano Berrettini
ObjectivesTo compare the results after cochlear implantation achieved by monolingual and bilingual deaf children implanted at our Institution, with the aim of understanding if there are any differences between the two groups and if there is a correlation between the outcomes and some patients' variables.MethodsThe study group was composed by 14 bilingual deaf children and the control group by the same number of monolingual children implanted at our Institution. The control group was obtained by matching to each bilingual child a monolingual one with a similar clinical history regarding age at hearing loss diagnosis, age at first hearing-aids fitting and age at CI procedure. Children received a speech perception and linguistic development evaluation through specific structured tests. The linguistic competence of the patients both in mainstream and native language was determined by the Student Oral Language Observation Matrix (SOLOM).ResultsWe did not find any statistically significant differences between bilingual and monolingual children in speech perception outcomes. Nevertheless, we obtained different results concerning language skills: bilingual implanted children scored lower at structured language tests, even if the difference was not statistically relevant. Bilingual children scored significantly lower than monolingual ones at the SOLOM scale for linguistic competence.ConclusionThe results reported in the present study show better language skills after cochlear implant in Italian monolingual cases than in bilingual ones. This seems to be related to the condition of bilingualism in Italy, mainly related to immigration, and frequently associated with low socio-economic levels, poor competence in the mainstream language and poor social integration, with a suboptimal exposure to the mainstream language and difficulties in following the rehabilitative program.



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Are validated patient-reported outcomes used on children in pediatric otolaryngology? A systematic review

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Kevin Wong, Jacquelyn Piraquive, Chelsea A. Troiano, Anita Sulibhavi, Kenneth M. Grundfast, Jessica R. Levi
ObjectivesReview the pediatric otolaryngology literature to 1) identify studies in which children completed patient-reported outcome (PRO) measures and 2) appraise the psychometric quality and validity of these PROs as they apply to pediatrics.MethodsIn October 2016, a systematic review was performed by two reviewers on PubMed/MEDLINE and EMBASE for all otolaryngology-related studies that utilized PROs in children. Inclusion criteria included articles that required children (age<18) to complete PROs. Exclusion criteria included validation studies, reviews, and abstracts. Interreviewer agreement was determined using Cohen's kappa. Quality and rigor of validation testing for included PROs was determined using the COnsensus-based Standards for selection of health status Measurement Instruments.ResultsInterrater agreement was very good (κ = 0.91; 95% CI, 0.85–0.98). Out of 316 articles retrieved, 11 met inclusion criteria. Eight PROs were identified. Six PROs were tested for validity and three of these PROs were tested for validity specifically within children. The most frequently utilized PRO was the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire. Two studies (18.2%) utilized PROs within the scope of their validation. Seven studies (63.6%) used PROs outside the scope of their validation. Two studies (18.2%) used non-validated PROs.ConclusionsPatient-reported outcomes have become an integral part of research and quality improvement. There is a relative paucity of PROs directed towards children in pediatric otolaryngology and some studies utilized PROs that were not validated or not validated for use in this age group. Future efforts to design and validate more instruments may be warranted.



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EXIT (ex utero intrapartum treatment) in a growth restricted fetus with tracheal atresia

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): S. Kyle Gonzales, Steven Goudy, Kara Prickett, Jane Ellis
Congenital high airway obstruction syndrome (CHAOS) encompasses a heterogeneous group of pathologies leading to poor lung development and difficulty oxygenating the newborn after delivery. While previously uniformly fatal, the ex utero intrapartum therapy (EXIT) procedure has provided a method to treat these patients and provide an airway to potentiate survival. We present a patient diagnosed prenatally with CHAOS secondary to tracheal atresia complicated by severe intra-uterine growth restriction (IUGR) who was successfully delivered via an EXIT procedure at 33-weeks. Multidisciplinary care and planning is paramount.



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Profilactic role of simvastatin and mitomycin C in tracheal stenosis after tracheal damage: Study in rats

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Adnan Ekinci, Sema Koc, Ahmet Serhat Erdoğan, Hakan Kesici
ObjectivesWe aimed to investigate the prophylactic effect simvastatin of and mitomycin C (MMC) on laryngeal and tracheal stenosis in tracheotomised rats by histopathological evaluation of laryngotracheal segment. Randomized prospective single-blind.Material and methodStandard vertical tracheotomy was performed on 24 rats. Then the animals were randomly divided into three groups as A, B and C. In group A 0.4 mg/day once daily mitomycin C was injected to the paratracheal region for 14 days. In group B daily 30 mg/kg/day simvastatin was given via gavage to rats for 14 days. In group C 2 cc/day intraperitoneal saline given to rats and the created control group by 14 days follow up. After 10 days, tracheal cannulas were removed. Three weeks later, all animals were euthanized and trachea specimens were harvested. The present study investigates the effects of MMC and Simvastatin on fibrosis, inflammation, stenosis index and tracheal wall thickness in a tracheal injury model.ResultsThe difference between the groups in terms of degree of inflammation scores was statistically insignificant (P = 0,187). Differences between the groups were found to be insignificant in terms of the preventionof fibrosis (P = 0,993). There was no significant difference between groups in terms of stenosis index (P = 0.645). In terms of wall thickness, control, simvastatin and mitomycin C groups were statistically different (p = 0.038). The difference between post-hoc test results was between Mitomycin C and control groups (p = 0.036).Maximum wall thickness in the MMC group (0,299 mm) was significantly lower compared to the control group (0,382 mm)(P < 0,0001). Maximum wall thickness was statistically lower in the simvastatin (0.324 mm) group compared with the control group (0.382 mm) (P < 0.0001). There was no statistically significant difference between the simvastatin group (0,198 mm) and control group (0,200 mm) with respect to minimum wall thickness (P = 0.982). Minimum wall thickness was significantly lower in the mitomycin-C group (0,160 mm) comparison to the control group (0,200 mm) (P < 0.0001).ConclusionIt was detected that the simvastatin and MMC is not effective in preventing the tracheal stenosis, inflammation and fibrosis formation.



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Iatrogenic Cushing's syndrome and adrenal insufficiency in infants on intranasal dexamethasone drops for nasal obstruction – Case series and literature review

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Rohan R. Joshi, Alison Maresh
The use of intranasal steroid drops for nasal obstruction in infants is common practice and can prevent more invasive surgical procedures; however, it is not without complication. We describe 2 cases of iatrogenic Cushing's secondary to nasal steroids in infants with nasal obstruction, discuss the etiology of this unusual complication, and review previous literature reports. While reporting in the literature is sparse, these cases highlight the risk of development of adrenal insufficiency with usage of nasal steroid drops in infants as well as the need for close monitoring of administration and tapering of the drops. Additionally, we suggest an approach to the infant with symptomatic nasal obstruction that addresses the usage of intranasal steroid drops and emphasizes the need for quick tapering and possible endocrine consultation when appropriate.



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Impact of age on the anatomy of the pediatric pterygopalatine fossa and its relationship to the suprazygomatic maxillary nerve block

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Alexander P. Marston, Glenn Merritt, Jonathan M. Morris, Shelagh A. Cofer
ObjectivesThe suprazygomatic maxillary nerve block is associated with improved post-operative pain management after select craniofacial surgical procedures. This study's objective is to better define the impact of pediatric facial skeletal growth on techniques for accessing the pterygopalatine fossa (PPF).MethodsPediatric patients with prior thin-slice maxillofacial computed tomography imaging were identified in an institutional radiology database. Aquarius image-processing software (Ver. 4.4.11, TeraRecon, Inc., Foster City, CA) was used to measure from the suprazygomatic skin to the greater wing of the sphenoid where the needle is then re-oriented in an anterior and inferior trajectory allowing it to advance into the PPF.ResultsA total of 90 patients ranging from 0 to ≤18 years of age were included in the study. The mean distance from the suprazygomatic skin to the foramen rotundum in patients 0 to ≤12 months of age and >13 to ≤18 years of age was 38.6 (SD ± 4.7) and 47.1 (SD ± 3.2) mm, respectively (p < .0001). The statistical analysis demonstrated a positive correlation between age in years and all of the measured distances (p = .0001). With respect to the plane of the needle entry site, the anterior and inferior angles required for passage into the PPF in the 0 to ≤12 months age group were 11 (SD ± 2.1) and 9.0 (SD ± 2.5) degrees, respectively, compared to those in the >13 to ≤18 years of age group at 12.4 (SD ± 1.9) and 12.1 (SD ± 3.2) degrees, respectively. These data reveal that patients in the oldest compared to the youngest pediatric age groups require significantly greater needle insertion, yet the angles of needle re-orientation are clinically similar between these two pediatric age groups varying by up to only 3°.ConclusionAs expected, the distance from the skin to the foramen rotundum increases significantly with age; however, the angles of re-orientation with respect to the original needle entry site demonstrated up to only 3° of variability between the youngest and oldest age groups evaluated in this pediatric cohort.



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A novel approach for comparing patterns of foreign body injuries across countries: A case study comparing European Countries and Bosnia and Herzegovina

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Giulia Lorenzoni, Sekib Umihanić, Danila Azzolina, Emiliano Manza, Fuad Brkić, Dario Gregori
ObjectivesThe present study aimed at analyzing the characteristics of FB injuries from Bosnia and Herzegovina (B&H), a rapidly growing newly industrialized country, and to compare them with cases from European countries.MethodsThe analysis is based on FB injury cases included in the Susy Safe registry. Cases from the Ear-Nose-Throat (ENT) Clinic, University Clinical Center of Tuzla (B&H) were compared with cases from European countries participating in the Susy Safe project. Multiple Correspondence Analysis (MCA) was performed to elucidate differences within a large data set regarding mechanisms and objects causing injuries.ResultsThe results of the MCA showed that the first three dimensions explained 43% of the variability. The first dimension was identified by children hospitalized for FB ingestion, the second one by children hospitalized for FB aspiration (lower airways), and the third one by children with an FB in the ear or in the upper airways. The analysis of the median of coordinates of factors contributing to each dimension showed that the greatest difference between B&H and European countries regarded the third one. Looking at the profile of these patients, it might be suggested that the proportion of males and females and the type of activity in which they were involved at time of injury occurrence are different among the countries consideredConclusionsThis study proposes a simple tool for assessing differences among countries in the distribution of FB injuries. This case study shows that B&H has different patterns of FB injuries in the upper respiratory tract.



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Validity of automated threshold audiometry in school aged children

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): S.M. Govender, M. Mars
BackgroundAutomated hearing tests have the potential to reduce the burden of disease amongst learners by introducing such services within the school context.MethodsThe aim of the study was to conduct a validation study on normal and hearing impaired learners, comparing air and bone conduction automated test results to conventional test results in 50 school aged learners (n = 100 ears) within a noise controlled school environment using a cross sectional comparative study design. The KuduWave 5000 (Emoyo.net) was used in this study.Data analysisThe spearman's correlation coefficient was calculated to determine test-retest reliability. The mean and standard deviation (SD) was measured for each frequency. The absolute mean difference (AMD) and SD was calculated for both air and bone conduction testing at each frequency for automated testing. A paired sampled t-test and a one way ANOVA was used to identify any significant differences. Alpha was set as 0.05.ResultsThere was significant correlation between thresholds obtained for automated test one and test two for normal hearing and hearing impaired group. The spearmans correlation coefficient was high (close to +1) for majority of the results for both groups across the frequency range. Both air and bone conduction testing across the frequency range of 250 Hz–2000 Hz and at 8000 Hz were not statistically signfiicant (p < .005) for both groups, however at 4000 Hz for bone conduction testing in the hearing impaired group, there was a statisticially signficant difference (p = .003). This was attirubted to the variaibilty in bone conduction test results often due to force and placement of the bone vibrator.ConclusionThe findings indicate that automated audiometry can yield relaible results that are comparable to conventional test results. Key clinical considerations include extending the response time, regular rest periods, improving instructions and comfort levels.



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Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Razieh Alemi, Masoud Motassadi Zarandy, Mohammad Taghi Joghataei, Ali Eftekharian, Mohammad Reza Zarrindast, Nasim Vousooghi
IntroductionSensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array.MethodsHere we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds.ResultsPlasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes.ConclusionIt is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation.



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Reliability and validity of the Chinese pediatric voice handicap index

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Kena Liu, Shaofeng Liu, Zhou Zhou, Qinyi Ren, Jie Zhong, Renzhong Luo, Huabiao Qin, Siyi Zhang, Pingjiang Ge
ObjectivesTo evaluate the reliability and validity of the Chinese version of pediatric voice handicap index (pVHI).Material and methodsThe original English version-pVHI was translated into Chinese. Parents of 52 children with voice dysphonia and 43 children with no history or symptoms of voice problems were asked to fill the Chinese pVHI questionnaires twice with an interval of 2 weeks. GRB (Grade, Roughness, Breathiness) scale was used for perceptual assessment by two otolaryngologists and one speech pathologist for each child's voice. The internal consistency was assessed using Cronbach's alpha coefficient. Pearson's correlation coefficient was used to evaluate the test-retest reliability. The Kendall's coefficient of concordance W was used to assess the consistency of GRB scores of 3 voice specialists. The nonparametric Mann-Whitney test was used to assess the differences between the dysphonia group and controls. The correlation between pVHI and GRB scores were assessed using Pearson's correlation coefficient.ResultsThe internal consistency of total score and three subscales scores of Chinese pVHI were 0.788–0.944. The test-retest reliability was 0.631–0.887(P < .001). The pVHI scores of control group significantly were lower than the pathological group (P = .000). The GRB scores of 3 voice specialists have an excellent consistency (W = 0.694–0.807, P = .000). The pVHI scores positively correlated with GRB assessment (P < .01).ConclusionsThe Chinese version of pVHI had a good reliability and validity. It can be applicable and useful supplementary tool for evaluating parents' perception of their children's dysphonia.



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A clinical pathway for the postoperative management of hypocalcemia after pediatric thyroidectomy reduces blood draws

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Neha A. Patel, Randall A. Bly, Seth Adams, Kristen Carlin, Sanjay R. Parikh, John P. Dahl, Scott Manning
ObjectivesPostoperative calcium management is challenging following pediatric thyroidectomy given potential limitations in self-reporting symptoms and compliance with phlebotomy. A protocol was created at our tertiary children's institution utilizing intraoperative parathyroid hormone (PTH) levels to guide electrolyte management during hospitalization.The objective of this study was to determine the effect of a new thyroidectomy postoperative management protocol on two primary outcomes: (1) the number of postoperative calcium blood draws and (2) the length of hospital stay.Study designInstitutional review board approved retrospective study (2010–2016).MethodsConsecutive pediatric total thyroidectomy and completion thyroidectomy ± neck dissection cases from 1/1/2010 through 8/5/2016 at a single tertiary children's institution were retrospectively reviewed before and after initiation of a new management protocol. All cases after 2/1/2014 comprised the experimental group (post-protocol implementation). The pre-protocol control group consisted of cases prior to 2/1/2014. Multivariable linear and Poisson regression models were used to compare the control and experimental groups for outcome measure of number of calcium lab draws and hospital length of stay.Results53 patients were included (n = 23, control group; n = 30 experimental group). The median age was 15 years. 41 patients (77.4%) were female. Postoperative calcium draws decreased from a mean of 5.2 to 3.6 per day post-protocol implementation (Rate Ratio = 0.70, p < .001), adjusting for covariates. The mean number of total inpatient calcium draws before protocol initiation was 13.3 (±13.20) compared to 7.2 (±4.25) in the post-protocol implementation group. Length of stay was 2.1 days in the control group and 1.8 days post-protocol implementation (p = .29). Patients who underwent concurrent neck dissection had a longer mean length of stay of 2.32 days compared to 1.66 days in those patients who did not undergo a neck dissection (p = .02). Hypocalcemia was also associated with a longer mean length of stay of 2.41 days compared to 1.60 days in patients who did not develop hypocalcemia (p < .01).ConclusionsThe number of calcium blood draws was significantly reduced after introduction of a standardized protocol based on intraoperative PTH levels. The hospital length of stay did not change. Adoption of a standardized postoperative protocol based on intraoperative PTH levels may reduce the number of blood draws in children undergoing thyroidectomy.



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Central xanthoma of the mandible associated with hyperlipidemia: A rare presentation

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Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): John K. Brooks, Behzad Mostoufi, Ahmed S. Sultan, Zaid H. Khoury, Jeffery B. Price, John C. Papadimitriou, John R. Basile, Cinthia B. Drachenberg, Rania H. Younis
Xanthoma is a common, self-limiting cutaneous lesion of non-Langerhans cell, lipid-laden foamy histiocytes that is often concomitant with hyperlipidemia. The intraosseous counterpart is rarely encountered and typically presents as a painless, expansile osteolytic process in the context of hyperlipidemia or normolipidemia. Only a scant number of gnathic xanthomas have been reported in the otolaryngologic literature. We report the clinical, laboratory, radiographic, histopathologic, immunohistochemical, and ultrastructural studies of a mandibular lesion discovered in an asymptomatic 16-year-old male, and associated with 2 previously unreported comorbidities, namely hyperlipidemia and vitamin D deficiency.



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Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma

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Publication date: February 2018
Source:Oral Oncology, Volume 77
Author(s): Rebecca Hoesli, Andrew C. Birkeland, Andrew J. Rosko, Mohamad Issa, Kelsey L. Chow, Nicole L. Michmerhuizen, Jacqueline E. Mann, Steven B. Chinn, Andrew G. Shuman, Mark E. Prince, Gregory T. Wolf, Carol R. Bradford, Jonathan B. McHugh, J. Chad Brenner, Matthew E. Spector
Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma.Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014. Demographic and clinical data were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31, Vimentin, EGFR, and p53.Elevated levels of either CD8 or CD4 positive TILs were associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24–0.88, CD4: HR 0.43; 95% CI 0.21–0.89) and disease free survival (CD8: HR 0.53, 95% CI 0.29–0.94, CD4: HR 0.52; 95% CI 0.27–0.99). Levels of CD8 (HR 0.74; 95% CI 0.47–1.17) or CD4 (HR 0.66; 95% CI 0.40–1.08) TILs were not significantly associated with overall survival. In bivariate analysis, patients with elevated CD4 and/or CD8 TILs had significantly improved disease specific survival (HR 0.42; 95% CI 0.21–0.83) and disease free survival (HR 0.45; 95% CI 0.24–0.84) compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin, EGFR, and p53 were not significant prognostic factors. On multivariate analysis, elevated CD8 TILs were associated with improved disease specific survival (HR 0.35; 95% CI 0.14–0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17–0.96, p = .04).CD8, and possibly CD4, positive TILs are associated with favorable disease free and disease specific survival for recurrent/persistent laryngeal cancer.



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In situ shrinking fibers enhance strain hardening and foamability of linear polymers

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Eric S. Kim, Heon E. Park, Patrick C. Lee
The strain hardening behavior of polymers has important roles in processing such as foaming, film formation, and fiber spinning. The most common method to enhance strain hardening is to introduce a long-chain branching structure on the backbone of a linear polymer, but this method is costly and challenging to tailor the behavior. We hypothesized that in situ shrinking fibers can increase the strain hardening of linear polymers, and the degree can be efficiently controlled. In this study, we show that heat-activated shrinking fibers compounded in linear polypropylene enhance strain hardening and foamability. Moreover, changing processing conditions, such as temperature, can amplify the degree of enhancement. Rheological measurements and physical foaming tests are shown to support our hypothesis.

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NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening

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Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Aaron Katzman, Cristina M Alberini
The prefrontal cortex (PFC) is critical for memory formation, but the underlying molecular mechanisms are poorly understood. Clinical and animal model studies have shown that changes in PFC excitation and inhibition are important for cognitive functions as well as related disorders. Here, we discuss recent findings revealing the roles of the excitatory and inhibitory synaptic proteins neuroligin 1 (NLGN1) and NLGN2 in the PFC in memory formation and modulation of memory strength. We propose that shifts in NLGN1 and NLGN2 expression in specific excitatory and inhibitory neuronal subpopulations in response to experience regulate the dynamic processes of memory consolidation and strengthening. Because excitatory/inhibitory imbalances accompany neuropsychiatric disorders in which strength and flexibility of representations play important roles, understanding these mechanisms may suggest novel therapies.



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Intracranial high-γ connectivity distinguishes wakefulness from sleep

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Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Ezequiel Mikulan, Eugenia Hesse, Lucas Sedeño, Tristán Bekinschtein, Mariano Sigman, María del Carmen García, Walter Silva, Carlos Ciraolo, Adolfo M. García, Agustín Ibáñez
Neural synchrony in the γ-band is considered a fundamental process in cortical computation and communication and it has also been proposed as a crucial correlate of consciousness. However, the latter claim remains inconclusive, mainly due to methodological limitations, such as the spectral constraints of scalp-level electroencephalographic recordings or volume-conduction confounds. Here, we circumvented these caveats by comparing γ-band connectivity between two global states of consciousness via intracranial electroencephalography (iEEG), which provides the most reliable measurements of high-frequency activity in the human brain. Non-REM Sleep recordings were compared to passive-wakefulness recordings of the same duration in three subjects with surgically implanted electrodes. Signals were analyzed through the weighted Phase Lag Index connectivity measure and relevant graph theory metrics. We found that connectivity in the high-γ range (90–120 Hz), as well as relevant graph theory properties, were higher during wakefulness than during sleep and discriminated between conditions better than any other canonical frequency band. Our results constitute the first report of iEEG differences between wakefulness and sleep in the high-γ range at both local and distant sites, highlighting the utility of this technique in the search for the neural correlates of global states of consciousness.



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Non-invasive estimation of [11C]PBR28 binding potential

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Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Martin Schain, Francesca Zanderigo, R. Todd Ogden, William C. Kreisl
[11C]PBR28 is a PET radioligand used to estimate densities of the 18 kDa translocator protein (TSPO) in vivo. Since there is no suitable reference region, arterial blood samples are required for full quantification. Here, we evaluate a methodology for full quantification of [11C]PBR28 PET data that does not require either a reference region or blood samples.Simultaneous estimation (SIME) uses time-activity curves from several brain regions to estimate binding potential (BPND), a theoretically more sensitive outcome measure than total distribution volume. SIME can be employed with either a measured arterial input function (AIF) or a template input function (tIF) that has similar shape as the AIF, but with arbitrary amplitude.We evaluated the ability of SIME to detect group differences in TSPO densities using PET and arterial plasma data from 21 Alzheimer's disease (AD) patients and 15 controls that underwent [11C]PBR28 imaging. Regional BPND obtained with tIFs were compared to those obtained using measured AIFs. Standard kinetic modeling was also employed for comparison. The sensitivity of each method to detect group differences in TSPO densities were assessed by comparing estimated effect sizes between AD patients and controls. For this purpose, BPND estimated for one region with high pathological burden (inferior temporal cortex), and for one region with low pathological burden (cerebellum) was used.BPND estimates obtained with SIME and tIFs were close to identical to those obtained with AIF (3.0 ± 21% difference, r2 = 0.78). In this dataset, the effect sizes between AD patients and controls for both SIME with AIF and SIME with tIF were similar (30.3%, p = 0.001 and 31.0%, p = 0.004, respectively) and were each greater than the effect size observed using the two-tissue compartment model (16.1%, p = 0.12). None of the tested methods showed difference in TSPO binding in cerebellum.These results demonstrate that BPND can be estimated for [11C]PBR28 using SIME, and may be useful in clinical studies. In addition, arterial sampling may not be necessary if tIFs can be reliably estimated.



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Evaluating the hematological and clinical-chemistry parameters of kratom (Mitragyna speciosa) users in Malaysia

Publication date: 25 March 2018
Source:Journal of Ethnopharmacology, Volume 214
Author(s): Darshan Singh, Christian P. Müller, Vikneswaran Murugaiyah, Shahrul Bariyah Sahul Hamid, Balasingam K. Vicknasingam, Bonnie Avery, Nelson Jeng Yeou Chear, Sharif Mahsufi Mansor
Ethnopharmacological relevanceKratom (Mitragyna speciosa Korth.) from the Rubiaceae family is an indigenous tropical medicinal tree of Southeast Asia. Kratom leaves have been used for decades in Malaysia and Thailand in traditional context for its perceived vast medicinal value, and as a mild stimulant among manual labourers. Kratom consumption has been reported to cause side-effects in kratom users.Aim of the studyTo evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia.MethodsA total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users.ResultsFindings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3–114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users.ConclusionThese data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.

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Cytokine/chemokine elevation during the transition phase from HSV encephalitis to autoimmune anti-NMDA receptor encephalitis

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Publication date: Available online 23 December 2017
Source:Brain and Development
Author(s): Takanori Omae, Yoshiaki Saito, Hirokazu Tsuchie, Koyo Ohno, Yoshihiro Maegaki, Hiroshi Sakuma
A 3-year-old girl suffered from anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis after resolution of herpes simplex virus encephalitis (HSE). Methylprednisolone pulse and immunoglobulin therapies showed little effect, but the patient completely recovered after six courses of monthly cyclophosphamide pulse therapy and successive maintenance on mycophenolate mofetil for one year. Anti-NMDA receptor antibody in the cerebrospinal fluid (CSF) was minimally detected during the prodromal febrile period and then was seen to be markedly elevated at the onset of second encephalopathy phase. CSF interleukin (IL)-6, and 10, tumor necrosis factor-α, interferon gamma, C-X-C motif ligands (CXCL)10 and 13, chemokine ligand 2, and migration inhibitory factor showed a second peak during the prodromal period and were reduced at the onset of anti-NMDA receptor encephalitis. These suggest the presence of cytokine/chemokine phase between the initial HSE and the secondary autoimmune encephalitis phases. Treatment strategy during the early stage of this entity should be further explored.



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Intraoperative cortico-cortical evoked potentials shows disconnection of the motor cortex from the epileptogenic network during subtotal hemispherotomy

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Publication date: Available online 23 December 2017
Source:Clinical Neurophysiology
Author(s): Takeshi Inoue, Hisashi Kawawaki, Masataka Fukuoka, Kiyohiro Kim, Megumi Nukui, Ichiro Kuki, Shin Okazaki, Saya Koh, Noritsugu Kunihiro, Takehiro Uda, Yasuhiro Matsuzaka, Masao Matsuhashi, Yasushi Iimura, Hiroshi Otsubo




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Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Jen-Chyong Wang, Somayeh Alinaghi, Abbas Tafakhori, Elizabeth Sikora, Luis J. Azcona, Siamak Karkheiran, Alison Goate, Coro Paisán-Ruiz, Hossein Darvish
A subset of early-onset Alzheimer's disease is inherited as an autosomal-dominant trait and is associated with mutations in the genes encoding β-amyloid precursor protein, presenilin 1, or presenilin 2. In this study, we identified 2 PSEN1 mutations (1 novel and 1 known) in 2 unrelated Iranian families with autosomal-dominant Alzheimer's disease. The disease progressed rapidly with a mean age at onset of 33 and 42 years and an age at death ranging from 43 to 48 years.



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Contents continued

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Publication date: February 2018
Source:Neurobiology of Aging, Volume 62





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Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Daniela Galimberti, Giorgio G. Fumagalli, Chiara Fenoglio, Sara M.G. Cioffi, Andrea Arighi, Maria Serpente, Barbara Borroni, Alessandro Padovani, Fabrizio Tagliavini, Mario Masellis, Maria Carmela Tartaglia, John van Swieten, Lieke Meeter, Caroline Graff, Alexandre de Mendonça, Martina Bocchetta, Jonathan D. Rohrer, Elio Scarpini
We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarriers. In addition, we evaluated a possible role of TMEM106B rs1990622 as a genetic modifier and correlated progranulin plasma levels and gray-matter atrophy. Plasma progranulin mean ± SD plasma levels in patients and asymptomatic carriers were significantly decreased compared with noncarriers (30.5 ± 13.0 and 27.7 ± 7.5 versus 99.6 ± 24.8 ng/mL, p < 0.00001). Considering the threshold of >61.55 ng/mL, the test had a sensitivity of 98.8% and a specificity of 97.5% in predicting the presence of a mutation, independent of symptoms. No correlations were found between progranulin plasma levels and age, years from average age at onset in each family, or TMEM106B rs1990622 genotype (p > 0.05). Plasma progranulin levels did not correlate with brain atrophy. Plasma progranulin levels predict the presence of GRN null mutations independent of proximity to symptoms and brain atrophy.



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Editorial Advisory Board

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Publication date: February 2018
Source:Neurobiology of Aging, Volume 62





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Sex- and age-specific modulation of brain GABA levels in a mouse model of Alzheimer's disease

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Upasana Roy, Lara Stute, Corinna Höfling, Maike Hartlage-Rübsamen, Jörg Matysik, Steffen Roβner, A. Alia
Age and sex are risk factors of Alzheimer's disease (AD). Among the neurotransmitter systems, gamma-aminobutyric acid (GABA) has been implicated in AD pathogenesis but the relevance of sex-specific GABAergic dysfunction during AD progression remains unknown. In the present study, we utilized state-of-the-art high-resolution magic angle spinning nuclear magnetic resonance to systematically monitor the brain region-, age-, and sex-specific modulation of GABA levels in wild-type and Tg2576 mice with amyloid pathology. In addition, we followed the possible role of reactive astrocytes in sex-specific GABA modulation. In female Tg2576 mice, hippocampal GABA levels were significantly elevated, along with higher number of reactive astrocytes and amyloid deposition. The elevated GABA was found to be produced via the monoamine oxidase-B route from putrescine in reactive astrocytes, more substantially in female than male mice, thus suggesting a role of astrocytes in memory impairment and sex-related differences in AD. Our results paint a coherent model of memory impairment in AD and signify that dynamic changes in regional GABA may be at the root of marked sex disparities observed in AD.



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Early Alzheimer-type lesions in cognitively normal subjects

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Stergios Tsartsalis, Aikaterini Xekardaki, Patrick R. Hof, Enikö Kövari, Constantin Bouras
Amyloid deposits and tau-immunoreactive neurofibrillary tangles, together with neuronal and synaptic loss, are the neuropathological hallmarks of Alzheimer's disease (AD). Both proteins are present in the normal brain during aging. However, the temporal sequence of their involvement in the onset of AD pathology remains controversial. To define whether amyloid β protein deposits or tau protein lesions appear first during normal brain aging, we performed an immunohistological study on serial sections from 105 autopsy brains (age range: 40–104 years) from patients free of clinical signs of cognitive decline, using anti-tau (AT8) and anti-amyloid (4G8) antibodies in the hippocampus, entorhinal cortex, inferior temporal cortex (Brodmann area 20), prefrontal cortex (Brodmann area 9), occipital cortex (Brodmann areas 17 and 18), and in the brainstem. All cases older than 48 years displayed at least a few neurofibrillary tangles, which appeared more frequently in the entorhinal than in the transentorhinal cortex. Tau pathology in these areas preceded tau inclusions in the brainstem. Furthermore, the first site of the apparition of tau pathology is inconsistent, being the entorhinal cortex in most cases, and in fewer cases, the transentorhinal region. There was no case presenting with amyloid deposition in the absence of neurofibrillary tangles, lending evidence to the fact that neurofibrillary tangles appear earlier than amyloid plaques during normal brain aging. However, the role of amyloid in promoting tau deposition cannot be excluded in some cases but may not represent the sole mechanism of disease induction and progression.



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Genetic influence of plasma homocysteine on Alzheimer's disease

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Tina Roostaei, Daniel Felsky, Arash Nazeri, Philip L. De Jager, Julie A. Schneider, David A. Bennett, Aristotle N. Voineskos
Observational studies have consistently reported elevated plasma homocysteine as a risk factor for Alzheimer's disease (AD). However, results from clinical trials of homocysteine-lowering treatments are inconsistent. This discrepancy may be explained by a lack of causal association between homocysteine and AD. Mendelian randomization studies have the potential to provide insight into the causality of this association through studying the effect of genetic predisposition to high homocysteine on AD. Our analyses using summarized (n = 54,162) and individual participant (n = 6987) data from Caucasian participants did not show an effect of plasma homocysteine genetic risk on susceptibility to AD. Although with smaller sample sizes, further subanalyses also did not support an effect of genetically determined plasma homocysteine on cognitive impairment and decline, beta-amyloid and tau pathology and gray matter atrophy in AD. However, we found associations with tau tangle burden (n = 251) and gray matter atrophy (n = 605) in cognitively normal elderly. Our results do not support a causal association between elevated homocysteine and risk, severity, and progression of AD. However, the relationship between genetically determined homocysteine and brain pathology in cognitively normal elderly requires further exploration.



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Beyond ALS and FTD: the phenotypic spectrum of TBK1 mutations includes PSP-like and cerebellar phenotypes

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Carlo Wilke, Jonathan Baets, Jan L. De Bleecker, Tine Deconinck, Saskia Biskup, Stefanie N. Hayer, Stephan Züchner, Rebecca Schüle, Peter De Jonghe, Matthis Synofzik
Mutations in the TANK-binding kinase 1 gene (TBK1) are a rare, but recurrent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the complete phenotypic spectrum of syndromes associated with TBK1 mutations remains to be elucidated. Using next-generation panel-sequencing of neurodegenerative disease genes, we identified a TBK1 index patient presenting with a progressive supranuclear palsy–like syndrome. Consecutively, we screened the whole-exome sequencing data of 439 index subjects presenting with various neurodegenerative syndromes outside the ALS-FTD spectrum for TBK1 mutations. Based on this genetic screen, we identified another TBK1 index patient presenting with progressive cerebellar ataxia. Both index patients carried the established p.Glu643del TBK1 mutation (c.1928_1930delAAG). In the index patients' families, we identified mesencephalic and cerebellar atrophy as recurrent imaging findings of TBK1-associated neurodegeneration, with cerebellar atrophy occurring even in presymptomatic mutation carriers. Our findings demonstrate that the phenotypic spectrum of TBK1 mutations extends beyond ALS and FTD to include also progressive supranuclear palsy–like and cerebellar syndromes, with mesencephalon and cerebellum representing recurrent sites of TBK1-associated neurodegeneration.



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Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Jan Verheijen, Julie van der Zee, Ilse Gijselinck, Tobi Van den Bossche, Lubina Dillen, Bavo Heeman, Estrella Gómez-Tortosa, Albert Lladó, Raquel Sanchez-Valle, Caroline Graff, Pau Pastor, Maria A. Pastor, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Jordi Clarimon, Alexandre de Mendonça, Ellen Gelpi, Magda Tsolaki, Janine Diehl-Schmid, Benedetta Nacmias, Maria Rosário Almeida, Barbara Borroni, Radoslav Matej, Agustín Ruiz, Sebastiaan Engelborghs, Rik Vandenberghe, Peter P. De Deyn, Marc Cruts, Christine Van Broeckhoven, Kristel Sleegers
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13–1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts.



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Corrigendum to “Detrimental effects of arachidonic acid and its metabolites in cellular and mouse models of Alzheimer's disease: structural insight” [Neurobiol. Aging 33 (2012) 831.e21–831.e31]

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Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Zareen Amtul, Markus Uhrig, Lin Wang, Richard F. Rozmahel, Konrad Beyreuther




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Contents

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Publication date: February 2018
Source:Neurobiology of Aging, Volume 62





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Substernal thyroidectomy: the trans-cervical approach

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Publication date: Available online 23 December 2017
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Christine M. Dahlhausen, Nathaniel J. Walsh, David J. Terris
Substernal thyroid goiters that require surgery may pose unique challenges to thyroid surgeons based on the size and inferior extent of the disease. Consequently, there are multiple variations to the approach and additional considerations in operative planning and technique that are often required. While there is some debate on the precise definition of substernal thyroid, for the purposes of this manuscript it is considered to be thyroid tissue below the sternal notch or clavicle. This article aims to provide thyroid surgeons who encounter the challenges of substernal thyroid a straightforward algorithm for planning and operative techniques that have proven successful in the safe and effective management of this condition.



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Preface

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Publication date: Available online 23 December 2017
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Phillip Pellitteri




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Techniques for thyroid cancer involving extreme superior thyroid pole

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Publication date: Available online 23 December 2017
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Daniel Kwon, Alfred Simental
Standard operative techniques for thyroidectomy have become well refined and widely disseminated. However, special circumstances, such as superior pole thyroid cancers, can present unique difficulties for the unprepared surgeon. Appropriate workup and appreciation of the unique anatomic relationships in the superior-most extent of the thyroid gland is vital in surgical planning. The ability to anticipate and manage a variety of contingencies such as superior laryngeal nerve sacrifice, vascular isolation / repair, laryngectomy, and repair of pharyngeal defects are essential for safe surgery for cancers of the extreme superior thyroid pole.



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Operative Techniques in Otolaryngology-Head and Neck Surgery

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Publication date: Available online 23 December 2017
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): Joseph Scharpf
The worldwide incidence of thyroid cancer has increased and generated great debate and study concerning the proper evidence-based management strategies. Despite this increase, there has been no significant increase in advanced, invasive thyroid cancers, which continue to represent the primary cause of thyroid cancer specific death. This section provides an evidence-based management review for thyroid cancer invading the aero-digestive tract and addresses critical issues of diagnosis, preoperative evaluation, surgical management, and adjuvant treatment germane to this important subset of patients. Illustrative examples of complex patients will be presented in the context of evidence-based literature to help guide the practitioner in an area less frequently encountered by many surgeons.



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Surgery for fibro adherent inflammatory thyroid disease

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Publication date: Available online 23 December 2017
Source:Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): David Goldenberg, Warren Swegal, Mitchell Dunklebarger, Phillip K. Pellitteri
Inflammatory thyroid diseases include those which are mediated through autoimmune disorders such as Hashimoto′s thyroiditis and Grave′s disease, as well as inflammatory goiter and sub-acute thyroiditis. In patients with such disorders, the thyroid gland often becomes markedly enlarged with an associated fibro-vascular connective tissue reaction involving the thyroid capsule and surrounding soft tissues. This results in dense, adherent connective tissue which may compress and obscure critical central neck compartment structures and make capsular dissection challenging. Thyroid surgery in patients with fibro-adherent inflammatory thyroid disease are technically challenging and post-operative complication rates are higher for these procedures. Due to these increased risks for complications, operative procedures in these circumstances should be designed with careful consideration of the anatomic changes associated with the underlying inflammatory pathology. Elements important to successful surgical resection include appropriate patient preparation and surgical planning, together with execution of the operative procedure with adaptation to many of the changes induced by inflammation on both the thyroid gland and the surrounding central neck structures.



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Label-free sensor for automatic identification of erythrocytes using digital in-line holographic microscopy and machine learning

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Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103
Author(s): Taesik Go, Hyeokjun Byeon, Sang Joon Lee
Cell types of erythrocytes should be identified because they are closely related to their functionality and viability. Conventional methods for classifying erythrocytes are time consuming and labor intensive. Therefore, an automatic and accurate erythrocyte classification system is indispensable in healthcare and biomedical fields. In this study, we proposed a new label-free sensor for automatic identification of erythrocyte cell types using a digital in-line holographic microscopy (DIHM) combined with machine learning algorithms. A total of 12 features, including information on intensity distributions, morphological descriptors, and optical focusing characteristics, is quantitatively obtained from numerically reconstructed holographic images. All individual features for discocytes, echinocytes, and spherocytes are statistically different. To improve the performance of cell type identification, we adopted several machine learning algorithms, such as decision tree model, support vector machine, linear discriminant classification, and k-nearest neighbor classification. With the aid of these machine learning algorithms, the extracted features are effectively utilized to distinguish erythrocytes. Among the four tested algorithms, the decision tree model exhibits the best identification performance for the training sets (n = 440, 98.18%) and test sets (n = 190, 97.37%). This proposed methodology, which smartly combined DIHM and machine learning, would be helpful for sensing abnormal erythrocytes and computer-aided diagnosis of hematological diseases in clinic.



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Ferritin based bionanocages as novel biomemory device concept

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Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103
Author(s): Şükriye Nihan Karuk Elmas, Remziye Güzel, Mehmet Girayhan Say, Arzu Ersoz, Rıdvan Say
Ferritin is an iron cage having protein, capable of extracting metal ions in their cages and a consequence of the electron transfer of metal ions in their cage by reduction and oxidation processes, electrochemical information storage devices can be designed. In this work, ferritin based protein biomemory substrate has been synthesized by using Amino Acid (monomer) Decorated and Light Underpinning Conjugation Approach (ANADOLUCA) method, which utilizes photosensitive electron transfer based microemulsion co-polymerization as nanobead form of ferritin. Protein substrate contains metal ions such as silver and copper or metal ion pairs namely, silver-copper (Janus bionanocage) and co-polymeric shell of the photosensitive crosslinker protein. The redox behavior of bionanocages differentiates electrochemical "writing" and "erase" states depending on these metal ions (silver or copper) or metal ion pairs. The bionanocages based biomemory substrates have been immobilized using graphene modified glassy carbon electrodes and the memory functions of ferritin based bionanocages have been confirmed by chronoamperometry (CA) and open circuit potential amperometry (OCPA). The stability and durability of multi-state memory devices represent promising properties for future bioelectronic information technologies.



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Silk provides a new avenue for third generation biosensors: Sensitive, selective and stable electrochemical detection of nitric oxide

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Publication date: 30 April 2018
Source:Biosensors and Bioelectronics, Volume 103
Author(s): Mustafa M. Musameh, Christopher J. Dunn, Md Hemayet Uddin, Tara D. Sutherland, Trevor D. Rapson
Using heme entrapped in recombinant silk films, we have produced 3rd generation biosensors, which allow direct electron transfer from the heme center to an electrode avoiding the need for electron mediators. Here, we demonstrate the use of these heme-silk films for the detection of nitric oxide (NO) at nanomolar levels in the presence and absence of oxygen. The sensor was prepared by drop-casting a silk solution on a glassy carbon electrode modified with multiwalled carbon nanotubes (MWCNT) followed by infusion with heme. The sensor was characterized by cyclic voltammetry and showed well defined and reversible Fe+/ Fe3+ redox couple activity, with NO detection by oxidation at potentials above +0.45V or reduction at potentials below − 0.7V. Evaluation of the effect of pH on the sensor response to NO reduction indicated a maximum response at pH 3. The sensor showed good linearity in the concentration range from 19 to 190nM (R2 = 0.99) with a detection limit of 2nM. The sensor had excellent selectivity towards NO with no or negligible interference from oxygen, nitrite, nitrate, dopamine and ascorbic acid and retained 86% of response after 2 months of operation and storage at room temperature.



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Prediction of agenesis of the mandibular second premolar using the developmental stages of the mandibular canine, first premolar, and second molar

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Ji-Soo Song, Teo Jeon Shin, Young-Jae Kim, Jung-Wook Kim, Ki-Taeg Jang, Sang-Hoon Lee, Hong-Keun Hyun
ObjectiveThe aim in this study was to suggest a standard for early diagnosis of agenesis of the mandibular second premolars (L5) by estimating the developmental stages of the mandibular canines (L3), first premolars (L4), and second molars (L7).DesignAmong all 5136 pediatric patients aged 5–11 years who received panoramic radiographs between June 2008 and December 2009 at Seoul National University Dental Hospital, 215 control patients and 74 agenesis patients who met inclusion criteria were analyzed. The developmental stages of all L3, L4, L5, and L7 of control and agenesis patients were estimated using the method proposed by Demirjian. To identify the tooth (L3, L4, L7) with the developmental pattern most similar to that of L5, Kendall rank correlation coefficients and Bootstrap method were used. To verify that patients with agenesis of L5 show delayed development, Wilcoxon rank sum test was used. To identify the stages in which to diagnose agenesis of L5, we performed survival analysis.ResultsThere was a significant correlation between the developmental stages of L3, L4, L7 and L5. The developmental stages of those three teeth in the agenesis group were delayed compared with those in the control group at certain ages. If the developmental stages of at least two of those three teeth reach Demirjian stage D without the calcification of L5, agenesis of L5 can be confirmed.ConclusionsAgenesis of L5 can be confirmed when two of the three teeth (L3, L4, L7) reach Demirjian stage D.



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An improved synthesis of 1-methylcyclopropanol using the Kulinkovich reaction

Publication date: Available online 23 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Christine Delsarte, Guillaume Etuin, Laurent Petit
An improved process for the preparation of 1-methylcyclopropanol using the Kulinkovich reaction is described. The use of titanium tetramethoxide as catalyst resulted in minimal side product formation. The reaction, isolation and purification procedures were optimized so they can be easily implemented in multi-purpose equipment.

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Discovery of New Thienopyrimidine Derivatives as Potent and Orally Efficacious Phosphoinositide 3-Kinase Inhibitors

Publication date: Available online 23 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Songwen Lin, Chunyang Wang, Ming Ji, Deyu Wu, Yuanhao Lv, Li Sheng, Fangbin Han, Yi Dong, Kehui Zhang, Yakun Yang, Yan Li, Xiaoguang Chen, Heng Xu
A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.

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Sex hormone levels and expression of their receptors in lactating and lactating pregnant rats

Publication date: Available online 23 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Ignacio Camacho-Arroyo, Aliesha González-Arenas, Carolina Jiménez-Arellano, Sumiko Morimoto, Agustín Galván-Rosas, Porfirio Gómora-Arrati, Marcos García-Juárez, Oscar González-Flores
Parturient rats show a postpartum estrus, a period of sexual receptivity that occurs from 6 to 15 h after the birth of a litter, which allows the mother to gestate a second litter while simultaneously nursing the first one (lactating and pregnant). The present study investigated hormone levels and the expression pattern of estrogen receptor α, and β, progesterone receptor isoforms and SRC1 in the hypothalamus and the preoptic area of lactating as well as in lactating-pregnant rats. In the latter, estradiol levels were 3-fold higher than those observed in lactating rats on day 14, meanwhile progesterone levels did not change in any condition. There were higher levels of prolactin in both lactating and lactating-pregnant rats on day 7 and decreased on the following days. In the hypothalamus of the lactating rat, the content of ERα increased during lactation meanwhile that of ERβ decreased 50% on day 10. The content of both estrogen receptor subtypes in the hypothalamus increased 3-fold on day 21 in lactating-pregnant rats. In the preoptic area, the content of ERα was higher in lactating-pregnant rats on days 14 and 21 while the content of progesterone receptor isoforms was lower as compared with those found in lactating animals on days 7 and 10. The content of SRC1 increased 2-fold in the preoptic area only in lactating rats at day 14 and 21. These findings suggest that lactating- pregnant animals should exhibit differential neuroendocrine and molecular characteristics as compared to lactating animals.



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Androgen excess is due to elevated 11-oxygenated androgens in treated children with congenital adrenal hyperplasia

Publication date: Available online 23 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Clemens Kamrath, Lisa Wettstaedt, Claudia Boettcher, Michaela F. Hartmann, Stefan A. Wudy
Adrenal androgen excess is the hallmark of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Recently, 11-oxygenated C19 steroids, a class of highly active adrenal-derived androgens, have been described in patients with CAH.The aim of our study was to elucidate the significance of 11-oxygenated androgens in children with CAH.We retrospectively analysed 190 daily urinary excretion rates of glucocorticoid-, 17α-hydroxyprogesterone (17OHP)-, and androgen metabolites determined by gas chromatography-mass spectrometry of 99 children aged 3.0 to 10.9 years with classic CAH on hydrocortisone and fludrocortisone treatment. Daily urinary steroid metabolite excretions were transformed into z-scores using references of healthy children. Androgen metabolite z-scores were separately calculated for androsterone (AN), the major urinary metabolite of androstenedione (A4), testosterone and 5α-dihydrotestosterone, for urinary metabolites of dehydroepiandrosterone (DHEA), and for 11β-hydroxyandrosterone (11OHAN), the major urinary metabolite of adrenal-derived 11-oxygenated androgens. Multivariate regression analysis was applied to analyse the precursors of 11OHAN synthesis.11OHAN, cortisol-, and 17OHP metabolite z-scores were elevated in treated children with CAH, whereas AN- and DHEA metabolite z-scores were normalized or suppressed. Multivariate regression analysis revealed that 11OHAN excretion was strongest associated with 21-deoxycortisol (β = 0.379; P =.0006), followed by A4 (β = 0.280; P =. 0008)) and 17OHP (β = 0.243; P =. 04) metabolite excretion.Androgen excess in treated children with CAH is solely due to elevated 11-oxygenated androgens that derive in addition to the known conversion from A4 also by direct conversion from 21-deoxycortisol. 11-Oxygenated androgens may represent better biomarkers of adrenal androgen status and treatment response than conventional androgens.

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Gastrocnemius fascicle and achilles tendon length at the end of the eccentric phase in a single and multiple countermovement hop

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Publication date: Available online 23 December 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Daniel E. Lidstone, Herman van Werkhoven, Alan R. Needle, Paige E. Rice, Jeffrey M. McBride
The purpose of this investigation was to compare fascicle and tendon length of the gastrocnemius at the end of the eccentric phase during a hop utilizing a single countermovement (sCM) versus multiple countermovement (mCM1, mCM2, mCM3) strategy. Seventeen healthy males performed nine hopping trials of sCM and nine trials of mCM. Ankle and knee joint angle and lower leg length from videography and muscle ultrasound were used to calculate muscle-tendon unit (MTU), fascicle and tendon length. Sacral marker data was used to determine hopping height. Force- and displacement-time curves were utilized to calculate work. Muscle activity of the lateral and medial gastrocnemius was also measured. Fascicle length was significantly shorter (mCM3: 6.2 ± 1.5 cm, sCM: 7.3 ± 2.0 cm) and tendon length was significantly longer (mCM3: 36.5 ± 3.6 cm, sCM: 35.5 ± 3.8 cm) at the end of the eccentric phase in mCM3 in comparison to sCM. Maximal hopping height (mCM: 14.6 ± 3.1 cm, sCM: 13.1 ± 2.5 cm), eccentric phase gastrocnemius muscle activity (mCM medial gastrocnemius: 0.10 ± 0.03 mV, mCM lateral gastrocnemius: 0.08 ± 0.04 mV, sCM medial gastrocnemius: 0.07 ± 0.03 mV, sCM lateral gastrocnemius: 0.05 ± 0.04 mV), and both eccentric (mCM3: 46.6 ± 19.4 J, sCM: 38.5 ± 15.9 J) and concentric work (mCM3: 87.6 ± 26.5 J, sCM: 80.9 ± 27.6 J) were significantly higher for mCM3 compared to sCM. The results indicate that a multiple countermovement hop strategy results in shorter fascicle length and longer tendon length at the end of the eccentric phase. In addition, greater eccentric phase muscle activity during the third countermovement (mCM3) in comparison to a single countermovement hop (sCM) was observed. A multiple countermovement strategy appears to result in higher hopping height and greater work done in both the eccentric and concentric phase indicating possible contribution of stored-elastic energy from the tendon.



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Estimating representative background PM2.5 concentration in heavily polluted areas using baseline separation technique and chemical mass balance model

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Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Shuang Gao, Wen Yang, Hui Zhang, Yanling Sun, Jian Mao, Zhenxing Ma, Zhiyuan Cong, Xian Zhang, Shasha Tian, Merched Azzi, Li Chen, Zhipeng Bai
The determination of background concentration of PM2.5 is important to understand the contribution of local emission sources to total PM2.5 concentration. The purpose of this study was to exam the performance of baseline separation techniques to estimate PM2.5 background concentration. Five separation methods, which included recursive digital filters (Lyne-Hollick, one-parameter algorithm, and Boughton two-parameter algorithm), sliding interval and smoothed minima, were applied to one-year PM2.5 time-series data in two heavily polluted cities, Tianjin and Jinan. To obtain the proper filter parameters and recession constants for the separation techniques, we conducted regression analysis at a background site during the emission reduction period enforced by the Government for the 2014 Asia-Pacific Economic Cooperation (APEC) meeting in Beijing. Background concentrations in Tianjin and Jinan were then estimated by applying the determined filter parameters and recession constants. The chemical mass balance (CMB) model was also applied to ascertain the effectiveness of the new approach. Our results showed that the contribution of background PM concentration to ambient pollution was at a comparable level to the contribution obtained from the previous study. The best performance was achieved using the Boughton two-parameter algorithm. The background concentrations were estimated at (27 ± 2) μg/m3 for the whole year, (34 ± 4) μg/m3 for the heating period (winter), (21 ± 2) μg/m3 for the non-heating period (summer), and (25 ± 2) μg/m3 for the sandstorm period in Tianjin. The corresponding values in Jinan were (30 ± 3) μg/m3, (40 ± 4) μg/m3, (24 ± 5) μg/m3, and (26 ± 2) μg/m3, respectively. The study revealed that these baseline separation techniques are valid for estimating levels of PM2.5 air pollution, and that our proposed method has great potential for estimating the background level of other air pollutants.



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Factors associated with NO2 and NOX concentration gradients near a highway

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): J. Richmond-Bryant, M.G. Snyder, R.C. Owen, S. Kimbrough
The objective of this research is to learn how the near-road gradient, in which NO2 and NOX (NO + NO2) concentrations are elevated, varies with changes in meteorological and traffic variables. Measurements of NO2 and NOX were obtained east of I-15 in Las Vegas and fit to functions whose slopes (dCNO2/dx and dCNOX/dx, respectively) characterize the size of the near-road zone where NO2 and NOX concentrations from mobile sources on the highway are elevated. These metrics were used to learn about the near-road gradient by modeling dCNO2/dx and dCNOX/dx as functions of meteorological variables (e.g., wind direction, wind speed), traffic (vehicle count), NOX concentration upwind of the road, and O3 concentration at two fixed-site ambient monitors. Generalized additive models (GAM) were used to model dCNO2/dx and dCNOX/dx versus the independent variables because they allowed for nonlinearity of the variables being compared. When data from all wind directions were included in the analysis, variability in O3 concentration comprised the largest proportion of variability in dCNO2/dx, followed by variability in wind direction. In a second analysis constrained to winds from the west, variability in O3 concentration remained the largest contributor to variability in dCNO2/dx, but the relative contribution of variability in wind speed to variability in dCNO2/dx increased relative to its contribution for the all-wind analysis. When data from all wind directions were analyzed, variability in wind direction was by far the largest contributor to variability in dCNOX/dx, with smaller contributions from hour of day and upwind NOX concentration. When only winds from the west were analyzed, variability in upwind NOX concentration, wind speed, hour of day, and traffic count all were associated with variability in dCNOX/dx. Increases in O3 concentration were associated with increased magnitude near-road dCNO2/dx, possibly shrinking the zone of elevated concentrations occurring near roads. Wind direction parallel to the highway was also related to an increased magnitude of both dCNO2/dx and dCNOX/dx, again likely shrinking the zone of elevated concentrations occurring near roads. Wind direction perpendicular to the road decreased the magnitude of dCNO2/dx and dCNOX/dx and likely contributed to growth of the zone of elevated concentrations occurring near roads. Thus, variability in near-road concentrations is influenced by local meteorology and ambient O3 concentration.



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Impact of chemical lateral boundary conditions in a regional air quality forecast model on surface ozone predictions during stratospheric intrusions

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Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Diane Pendlebury, Sylvie Gravel, Michael D. Moran, Alexandru Lupu
A regional air quality forecast model, GEM-MACH, is used to examine the conditions under which a limited-area air quality model can accurately forecast near-surface ozone concentrations during stratospheric intrusions. Periods in 2010 and 2014 with known stratospheric intrusions over North America were modelled using four different ozone lateral boundary conditions obtained from a seasonal climatology, a dynamically-interpolated monthly climatology, global air quality forecasts, and global air quality reanalyses. It is shown that the mean bias and correlation in surface ozone over the course of a season can be improved by using time-varying ozone lateral boundary conditions, particularly through the correct assignment of stratospheric vs. tropospheric ozone along the western lateral boundary (for North America). Part of the improvement in surface ozone forecasts results from improvements in the characterization of near-surface ozone along the lateral boundaries that then directly impact surface locations near the boundaries. However, there is an additional benefit from the correct characterization of the location of the tropopause along the western lateral boundary such that the model can correctly simulate stratospheric intrusions and their associated exchange of ozone from stratosphere to troposphere. Over a three-month period in spring 2010, the mean bias was seen to improve by as much as 5 ppbv and the correlation by 0.1 depending on location, and on the form of the chemical lateral boundary condition.



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Constraining the uncertainty in emissions over India with a regional air quality model evaluation

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Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Alexandra Karambelas, Tracey Holloway, Gregor Kiesewetter, Chris Heyes
To evaluate uncertainty in the spatial distribution of air emissions over India, we compare satellite and surface observations with simulations from the U.S. Environmental Protection Agency (EPA) Community Multi-Scale Air Quality (CMAQ) model. Seasonally representative simulations were completed for January, April, July, and October 2010 at 36  km × 36  km using anthropogenic emissions from the Greenhouse Gas-Air Pollution Interaction and Synergies (GAINS) model following version 5a of the Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants project (ECLIPSE v5a). We use both tropospheric columns from the Ozone Monitoring Instrument (OMI) and surface observations from the Central Pollution Control Board (CPCB) to closely examine modeled nitrogen dioxide (NO2) biases in urban and rural regions across India. Spatial average evaluation with satellite retrievals indicate a low bias in the modeled tropospheric column (−63.3%), which reflects broad low-biases in majority non-urban regions (−70.1% in rural areas) across the sub-continent to slightly lesser low biases reflected in semi-urban areas (−44.7%), with the threshold between semi-urban and rural defined as 400 people per km2. In contrast, modeled surface NO2 concentrations exhibit a slight high bias of +15.6% when compared to surface CPCB observations predominantly located in urban areas. Conversely, in examining extremely population dense urban regions with more than 5000 people per km2 (dense-urban), we find model overestimates in both the column (+57.8) and at the surface (+131.2%) compared to observations. Based on these results, we find that existing emission fields for India may overestimate urban emissions in densely populated regions and underestimate rural emissions. However, if we rely on model evaluation with predominantly urban surface observations from the CPCB, comparisons reflect model high biases, contradictory to the knowledge gained using satellite observations. Satellites thus serve as an important emissions and model evaluation metric where surface observations are lacking, such as rural India, and support improved emissions inventory development.



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Aerosols in Northern Morocco: Input pathways and their chemical fingerprint

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Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): A. Benchrif, B. Guinot, M. Bounakhla, H. Cachier, B. Damnati, B. Baghdad
The Mediterranean basin is one of the most sensitive regions in the world regarding climate change and air quality. Deserts and marine aerosols combine with combustion aerosols from maritime traffic, large urban centers, and at a larger scale from populated industrialized regions in Europe. From Tetouan city located in the North of Morocco, we attempted to better figure out the main aerosol transport pathways and their respective aerosol load and chemical profile by examining air mass back trajectory patterns and aerosol chemical compositions from May 2011 to April 2012. The back trajectory analysis throughout the sampling period led to four clusters, for which meteorological conditions and aerosol chemical characteristics have been investigated. The most frequent cluster (CL3: 39%) corresponds to polluted air masses coming from the Mediterranean Basin, characterized by urban and marine vessels emissions out of Spain and of Northern Africa. Two other polluted clusters were characterized. One is of local origin (CL1: 22%), with a marked contribution from urban aerosols (Rabat, Casablanca) and from biomass burning aerosols. The second (CL2: 32%) defines air masses from the near Atlantic Ocean, affected by pollutants emitted from the Iberian coast. A fourth cluster (CL4: 7%) is characterized by rather clean, fast and rainy oceanic air masses, influenced during their last 24 h before reaching Tetouan by similar sources with those affecting CL2, but to a lesser extent.The chemical data show that carbonaceous species are found in the fine aerosols fraction and are generally from local primary sources (low OC/EC) rather than long-range transported. In addition to fresh traffic and maritime vessel aerosols, our results suggest the contribution of local biomass burning.



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Guided episodic sampling for capturing and characterizing industrial plumes

Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Chang-Feng Ou-Yang, Wei-Cheng Liao, Chih-Chung Chang, Hsin-Cheng Hsieh, Jia-Lin Wang
An integrated sampling technique, dubbed trigger sampling, was developed to capture characteristic industrial emissions or plumes. In the field experiment, a hydrogen sulfide (H2S) analyzer was used as the triggering instrument at the boundary of a refinery plant due to frequent complaints of foul smell from local residents. Ten episodic samples were captured when the H2S level surpassed the prescribed trigger level of 8.5 ppbv over a three-day period. Three non-episodic (blank) samples and 23 road-side samples were also collected for comparison. All the 36 flask samples were analyzed by gas chromatography–mass spectrometry/flame ionization detection (GC–MS/FID) for 108 volatile organic compounds (VOCs). The total VOC abundance of the event samples was exceedingly higher than the non-episodic samples by over 80 times in the extreme case. Alkanes were found to be the dominant constituents in the event samples, amounting to over 90% of the total VOC concentrations vs. only 30–40% for the blank and metropolitan samples. In addition, light alkanes in the event samples were highly correlated with the trigger species H2S (R2 = 0.82), implying their common origin. The matrix of chemical composition vs. sample types permitted easy visualization of the dominance of light alkanes for the event samples compared to other types of samples. Principle component analysis (PCA) identified two major contributors to cover 93% of the total variance arising from the 36 samples, further quantifying the distinction of the triggered episodic samples from the contrast samples. The proposed trigger sampling is a coupling of fast-and-slow measurement techniques. In this example, the fast-response H2S analyzer served to "guide" sampling to capture industrial plumes which were then characterized by a relatively slow method of GC–MS/FID for detailed chemical composition representative of the prominent sources.

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Wet deposition of mercury in Qingdao, a coastal urban city in China: Concentrations, fluxes, and influencing factors

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Publication date: February 2018
Source:Atmospheric Environment, Volume 174
Author(s): Lufeng Chen, Yanbin Li, Chang Liu, Lina Guo, Xiulin Wang
Mercury (Hg) is a global pollutant of public concern because of its high toxicity and capability for worldwide distribution via long-range atmospheric transportation. Wet atmospheric deposition is an important source of Hg in both terrestrial and aquatic environments. Concentrations of various Hg species in precipitation were monitored from March 2016 to February 2017 in a coastal urban area of Qingdao, and their wet deposition fluxes were estimated. The results showed that the volume-weighted mean (VWM) concentrations of total mercury (THg), reactive mercury (RHg), dissolved THg (DTHg), particulate THg (PTHg), total methylmercury (TMeHg), and dissolved and particulate MeHg (DMeHg and PMeHg) in Qingdao's precipitation were 13.6, 1.5, 5.4, 8.2, 0.38, 0.15, and 0.22 ng L−1, respectively, and their annual deposition fluxes were estimated to be 5703.0 (THg), 666.6 (RHg), 2304.0 (DTHg), 3470.4 (PTHg), 161.6 (TMeHg), 64.0 (DMeHg), and 95.7 (PMeHg) ng m−2 y−1, respectively. A relatively high proportion of MeHg in THg was observed in precipitation (3.0 ± 2.6%) possibly due to higher methylation and contributions from an oceanic source to MeHg in the precipitation. Obvious seasonal variations in Hg concentrations and deposition fluxes were observed in the precipitation in Qingdao. Correlation analyses and multiple regression analyses showed that SO2, pH, and NO3 were the controlling factors for THg in precipitation, whereas the MeHg concentration was primarily controlled by the SO2, WS, Cl, and THg concentrations. PM2.5 and Cl were the major controlling factors for PMeHg/TMeHg, whereas the TMeHg/THg ratio was mainly influenced by Cl. The THg and MeHg fluxes were primarily controlled by precipitation, whereas Cl was also an important factor for the MeHg wet deposition flux. The results of a 72-h backward trajectory analysis in the study region with the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model indicated that Hg deposition in Qingdao mainly originated from four major sources, i.e., the local area, northwestern China, southeastern China and an oceanic source. This oceanic source is an important source of Hg (especially MeHg) in the precipitation in Qingdao.



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