Σάββατο 24 Ιουνίου 2017

Molecular composition of organic aerosol over an agricultural site in North China Plain: Contribution of biogenic sources to PM2.5

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Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Xingru Li, Yusi Liu, Dong Li, Guoan Wang, Yu Bai, Heling Diao, Rongrong Shen, Bo Hu, Jinyuan Xin, Zirui Liu, Yuesi Wang, Xueqing Guo, Lili Wang
Sugars and biogenic secondary organic aerosols (BSOAs) are substantial components of particulate organic matter, which affects regional and global air quality and climate. Fine particulate matter (PM2.5) samples were collected from 20 June to 30 July 2015 on a diurnal/nocturnal cycle in Yucheng, China in the North China Plain. The PM2.5 samples were analyzed for sugars and SOA tracers derived from biogenic volatile organic compounds (BVOCs) and other compounds, such as water soluble ions, element carbon (EC), organic carbon (OC) and water soluble organic carbon (WSOC). The quantified organic components accounted for 4.7% and 0.4% of the OC and PM2.5, respectively. SOA tracer concentrations were weakly higher during the day (101.6 ± 61.7 ng m−3) than at night (90.2 ± 41.5 ng m−3)(t = 0.610, P > 0.05), whereas sugar showed higher concentrations at night (227.0 ± 196.9 ng m−3) than during the day (177.9 ± 145.4 ng m−3)(t = −1.329, P > 0.05). Anhydro sugar (mannosan, galactosan, and levoglucosan) were the main components of the measured sugars and accounted for 58.5% and 75.6% of the daytime and nighttime measurements. The levoglucosan/mannosan ratios were 20.2 ± 12.9 and 17.6 ± 9.1 for the daytime and nighttime samples, respectively, indicating that crop residues, herbaceous plants and hardwood were the dominant types of biomass burned in the Yucheng region. Isoprene SOA tracers exhibited the highest levels among the measured SOA tracers, followed by α-pinene SOA tracers. The concentration of BSOC estimated using the tracer method was 3.9–1817.5 ng C m−3 and accounted for 0.1–26.0% of the OC. A clear negative correlation (r = 0.53) between isoprene-derived SOA and in-situ pH demonstrated that acid-catalyzed heterogeneous reactions can significantly enhance SOA mass. In addition, isoprene-derived SOA increased with the relative humidity (RH) when the RH was lower than 50%, whereas it decreased when the RH was higher than 50%.



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Gene-by-environment interactions of the CLOCK, PEMT and GHRELIN loci with average sleep duration in relation to obesity traits using a cohort of 643 New Zealand European children

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Mohanraj Krishnan, Andrew N. Shelling, Clare R. Wall, Edwin A. Mitchell, Rinki Murphy, Lesley M.E. McCowan, John M.D. Thompson
ObjectivesModern technology may have desensitised the ‘biological clock’ to environmental cues, disrupting the appropriate co-ordination of metabolic processes. Susceptibility to misalignment of circadian rhythms may be partly genetically influenced and effects on sleep quality and duration could predispose to poorer health outcomes. Shorter sleep duration is associated with obesity traits, which may be due to more opportunity to eat and/or a shift of hormonal profiles promoting hunger. We hypothesised that increased sleep duration will offset susceptible genetic effects, resulting in reduced obesity risk.MethodsWe recruited 643 (male: 338; female: 305) European children born to participants in the New Zealand centre of the International Screening for Pregnancy Endpoints sleep study. Ten genes directly involved in the circadian rhythm machinery and a further 20 genes hypothesised to be driven by cyclic oscillations were evaluated by Sequenom assay. Multivariable egression was performed to test the interaction between gene variants and average sleep length (derived from actigraphy), in relation to obesity traits (body mass index (BMI) z-scores and percentage body fat (PBF)).ResultsNo association was found between average sleep length and BMI z-scores (p=0.056) or PBF (p=0.609). Uncorrected genotype associations were detected between STAT-rs8069645 (p=0.0052) and ADIOPQ-rs266729 (p=0.019) with differences in average sleep duration. Evidence for uncorrected gene-by-sleep interactions of the CLOCK-rs4864548 (p=0.0039), PEMT-936108 (p=0.016) and GHRELIN-rs696217 (p=0.046) were found in relation to BMI z-scores but not for PBF.ConclusionOur results indicate that children may have different genetic susceptibility to the effects of sleep duration on obesity. Further confirmatory studies are required in other population cohorts of different age groups.



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Validation of the screening tool ApneaLink® in comparison to polysomnography for the diagnosis of sleep-disordered breathing in children and adolescents

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Florian Stehling, Judith Keull, Margarete Olivier, Jörg Große-Onnebrink, Uwe Mellies, Boris A. Stuck
ObjectiveWhile out-of-center testing was introduced as an alternative for the diagnosis of obstructive sleep apnea in adults, polysomnography (PSG) is still considered mandatory in the diagnosis of sleep-disordered breathing (SDB) in children. The purpose of this study was to validate the outpatient screening device ApneaLink® in comparison to PSG in children and adolescents for the diagnosis of SDB.MethodsSixty consecutive children and adolescents (10.4±6.2, 0–22 years) with suspected SDB admitted to the sleep laboratory underwent simultaneous recording with full PSG and the screening device ApneaLink® based on flow measurement and oxygen saturation.ResultsThe mean apnea–hypopnea index (AHI) was 11.8±19.7 in PSG and 10.3±12.0 in ApneaLink®. When the AHI threshold was set to 5/h to diagnose SDB, the overall sensitivity for ApneaLink® was 79% and the specificity was 63%. After reducing the AHI threshold to 1/h, the sensitivity and specificity were 94% and 29%. In children older than 10 years, the performance of ApneaLink® improved (AHI 5/h: sensitivity 80%, specificity 64%; AHI 1/h: sensitivity 100%, specificity 50%).ConclusionThese results show that the outpatient screening device ApneaLink® reliably identifies SDB in preselected children older than 10 years. In contrast, it may not be used for the exclusion of SDB.



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Severity of individual obstruction events increases with age in patients with obstructive sleep apnea

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Timo Leppänen, Juha Töyräs, Esa Mervaala, Thomas Penzel, Antti Kulkas
BackgroundAge is a risk factor of obstructive sleep apnea (OSA). It has been shown that OSA progresses over time, although conflicting results have been reported. However, the effect of age on the severity of OSA and individual obstruction events has not been investigated within different OSA severity categories by taking the most prominent confounding factors (ie, body mass index, gender, smoking, daytime sleepiness, snoring, hypertension, heart failure, and proportion of supine sleep) into account.MethodsPolygraphic data of 1090 patients with apnea–hypopnea index (AHI) ≥5 were retrospectively reanalyzed. The effect of age on the severity of OSA and obstruction events was investigated in general, within different OSA categories, and between different age groups (age <40, 40 ≤age <50, 50 ≤age <60, and age ≥60 years).ResultsIn the whole population, AHI and durations of apneas, hypopneas, and desaturations increased with increasing age (B≥0.108, p≤0.010). In more detailed analysis, AHI increased with age only in the moderate OSA category (B=0.075, p=0.022), although durations of apneas increased in mild and severe OSA categories (B≥0.076, p≤0.038). Furthermore, durations of hypopneas increased with age in mild and moderate OSA categories (B≥0.105, p≤0.038), and durations of desaturations (B≥0.120, p≤0.013) in all OSA severity categories.ConclusionAHI was not statistically significantly different between the age groups, although durations of obstruction events tended to increase towards older age groups. Therefore, as obstruction event severity was more strongly dependent on the age than it was dependent on AHI, considering the severity of obstruction events could be beneficial while estimating the long-term effects of the treatments and prognosticating the disease progression.



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Can the analysis of built-in software of CPAP devices replace polygraphy in children?

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Sonia Khirani, Vincent Delord, Jorge Olmo Arroyo, Livio De Sanctis, Annick Frapin, Alessandro Amaddeo, Brigitte Fauroux
ObjectivesPolysomnography (PSG) is the gold standard for the scoring of residual respiratory events during continuous positive airway pressure (CPAP). Studies comparing PSG scoring with automatic scoring by the built-in software of CPAP devices have reported acceptable agreements except for the hypopnea index (HI) in adult patients, but no study has yet been conducted in children. The aim of the present study was to compare the automatic scoring by CPAP device and manual scoring using the software tracings of the CPAP device integrating pulse oximetry (SpO2) with in-lab polygraphy (PG).MethodsConsecutive clinically stable children treated with constant CPAP (ResMed) for at least 1 month and scheduled for a nocturnal PG were recruited. A pulse oximeter was connected to the CPAP device. The PG apnea-hypopnea index (AHIPG), scored according to modified AASM guidelines, was compared with the automatic AHI reported by the CPAP device (AHIA CPAP) and the manual scoring of the AHI on the CPAP software (AHIM CPAP).ResultsFifteen children (1.5-18.6 years) were included. Mean residual AHIPG was 0.9±1.2/hour (0.0-4.6/hour) vs. AHIA CPAP of 3.6±3.6/hour (0.5-14.7/hour) (p<0.001), and AHIM CPAP of 1.2±1.6/hour (0.0-5.1/hour) (p=0.01). Correlation between AHIPG and AHIA CPAP was good (r=0.667; p=0.007), and improved when considering AHIM CPAP (r=0.933; p<0.001). Strong correlations were also observed between the PG apnea index (AI) and HI, and the manually scored AI and HI on CPAP, respectively.ConclusionsManual scoring of respiratory events on the built-in software tracings of CPAP devices integrating SpO2 signal may be helpful. These results have to be confirmed in patients with higher AHI.



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Relationship between stress coping and sleep disorders among the general Japanese population: a nationwide representative survey

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Yuichiro Otsuka, Yoshitaka Kaneita, Osamu Itani, Sachi Nakagome, Maki Jike, Takashi Ohida
ObjectiveTo clarify the prevalence of stress, and examine the relationship between sleep disorders and stress coping strategies among highly stressed individuals in the general Japanese population.MethodsA cross-sectional nationwide survey was undertaken in November 2007. Men and women were randomly selected from 300 districts throughout Japan. Data from 7671 (3532 men (average age 53.5±17.0 years) and 4139 women (average age 53.9±17.7 years)) were analyzed. Participants completed a self-reported questionnaire on stress, sleep disorders, and stress coping strategies in the previous month.ResultsHighly stressed individuals comprised 16.6% (95% confidence interval 15.8-17.5%) of the total sample, and most were aged 20-49 years. In multiple logistic regression, symptoms of insomnia (ie, difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening), excessive daytime sleepiness, nightmares, daytime malfunction, and lack of rest due to sleep deprivation were more prone to occur in highly stressed individuals. In addition, logistic regression analysis controlling for other adjustment factors revealed that stress coping strategies such as ‘giving up on problem-solving’,’ enduring problems patiently’, ‘smoking’ and ‘drinking alcohol’ were positively associated with the above-mentioned sleep disorders. On the other hand, stress coping strategies such as ‘exercising’, ‘enjoying hobbies’ and ‘sharing worries’ were inversely associated with the above-mentioned sleep disorders.ConclusionsDistraction-based stress coping (eg, hobbies, exercise and optimistic thinking) was found to be preferable to problem-based stress coping in a highly stressed Japanese general population.



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Utility of new-generation pacemakers in sleep apnea screening

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Margarida Dias, Inês Gonçalves, Bruno Amann, Pedro Marques, Cristina Martinho, Catarina Leitão, Rita Pinto Basto, João de Sousa, Paula Pinto, Cristina Bárbara
ObjectivePatients with cardiac pacemakers present a high prevalence of undiagnosed sleep apnea syndrome (SAS). New-generation pacemakers have algorithms that identify sleep respiratory events. Our aim was to evaluate their accuracy in the diagnosis of SAS.MethodsWe performed a prospective study that included patients with new-generation pacemakers (Reply 200). All patients underwent a polysomnography (PSG). On the same night, the respiratory disturbance index of the PSG (RDI-PSG) and of the pacemaker (RDI-PM) were recorded. The agreement between methods was assessed using the kappa coefficient, Bland and Altman statistics and receiver operating characteristic (ROC) curves.ResultsSixty patients were recruited but the RDI-PM for the PSG night was not available in six patients. PSG diagnosed SAS in 74% of patients (20% severe, 19% moderate, 35% mild). Besides snoring (63%), most patients had no SAS symptoms.There was a strong positive correlation between RDI-PSG and RDI-PM (r=0.522, p<0.001). but the level of agreement between methods regarding SA diagnosis/severity was poor (k=0.167). ROC curves identified a RDI-PM of 10 events/h as the optimal cut-off point for diagnosing SAS (area under the curve (AUC): 0.81, sensitivity: 80%, specificity: 79%, positive predictive value: 91%, negative predictive value: 58%). The best cut-off for identifying moderate/severe SAS was at 13 events/h (AUC: 0.86, sensitivity: 100%, specificity: 70%, positive predictive value: 68%, negative predictive value: 100%).ConclusionsSAS prevalence in patients with pacemakers is high (74%). Most are asymptomatic, which could delay the diagnosis. Patients with clinical indication for a pacemaker may benefit from a device with sleep apnea monitoring.



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Moving into poverty during childhood is associated with later sleep problems

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Publication date: Available online 24 June 2017
Source:Sleep Medicine
Author(s): Børge Sivertsen, Tormod Bøe, Jens Christoffer Skogen, Keith J. Petrie, Mari Hysing
ObjectiveA social gradient in sleep has been demonstrated across the life span, but previous studies have been cross-sectional and used self-reported socioeconomic status (SES) indicators. Using registry-based data on family income trajectories, the current study examined the association between relative poverty in childhood and subsequent sleep in adolescence.MethodsData on family income during 2004-2010 was obtained from the National Income Registry. Poverty was defined as household income <60% of the mean national income. Information on self-reported sleep was based the youth@hordaland-survey (n=8873) conducted in 2012 when the adolescents were 16-19 years old. Latent class analysis (LCA) was used to identify trajectories of family household poverty, and analysis of variance and general linear models were used to examine associations between income trajectories and sleep, adjusting for confounders.ResultsLatency class analysis identified four classes: ‘never poor’, two classes characterized by moving in or out of poverty, and ‘chronically poor’. Compared to the ‘never poor’ group, adolescents from families in the ‘moving into poverty’ group displayed worse sleep across most sleep measures, including shorter sleep, lower sleep efficiency, and more nocturnal wake time (but not sleep onset latency). Neither adolescents from families who had moved out of poverty by increasing family income, nor the ‘chronically poor’ group differed significantly from the reference group.ConclusionsThe study found that downward socioeconomic mobility was associated with increased adolescent sleep problems. More studies are required on the mechanisms that may account for the association, to find targeted and effective strategies to prevent short sleep duration in adolescents from families with unstable financial circumstances.



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Intraoperative sialendoscopy to assist with and confirm repair of Stensen’s duct

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Publication date: Available online 24 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): C.-B. Man, R. Patel, K. Karavidas




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Effect of exercising at minimum recommendations of the multiple sclerosis exercise guideline combined with structured education or attention control education – secondary results of the step it up randomised controlled trial

Recent exercise guidelines for people with multiple sclerosis (MS) recommend a minimum of 30 min moderate intensity aerobic exercise and resistance exercise twice per week. This trial compared the secondary ou...

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Novel approach to the maxillary sinusitis after sinus graft

Abstract

Background

Postoperative infection occurs when bone graft material is dislodged into the maxillary sinus cavity and most of the patients are often uncomfortable with the drainage and irrigation procedures to eradicate the infection. In this case report, we share a technique in treating patients with such condition.

Material and methods

A 47-year-old patient was referred after sinus elevation using the crestal socket osteotome, bone graft, and implant insertion at a local clinic. Clinical and radiographic findings confirmed the diagnosis of right maxillary sinusitis. A surgical and medical treatment regimen was applied.

Results

By using this technique for irrigation, we were able to achieve successful results, and the patient was satisfied due to less discomfort during the irrigation process.

Conclusion

This method is a patient-friendly technique for sinus irrigation. It is not only limited to sinus grafted patients, but also maxillary sinusitis patients in any other type of odontogenic infection.



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A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy

Abstract

Background

Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion.

Methods

In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws.

Results

We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device.

Conclusions

The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.



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Book review for “Orthognathic Surgery: Principles, Planning and Practice”



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Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population

Abstract

Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1–85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes—c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)—were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.



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Novel approach to the maxillary sinusitis after sinus graft

Abstract

Background

Postoperative infection occurs when bone graft material is dislodged into the maxillary sinus cavity and most of the patients are often uncomfortable with the drainage and irrigation procedures to eradicate the infection. In this case report, we share a technique in treating patients with such condition.

Material and methods

A 47-year-old patient was referred after sinus elevation using the crestal socket osteotome, bone graft, and implant insertion at a local clinic. Clinical and radiographic findings confirmed the diagnosis of right maxillary sinusitis. A surgical and medical treatment regimen was applied.

Results

By using this technique for irrigation, we were able to achieve successful results, and the patient was satisfied due to less discomfort during the irrigation process.

Conclusion

This method is a patient-friendly technique for sinus irrigation. It is not only limited to sinus grafted patients, but also maxillary sinusitis patients in any other type of odontogenic infection.



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A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy

Abstract

Background

Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion.

Methods

In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws.

Results

We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device.

Conclusions

The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.



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Book review for “Orthognathic Surgery: Principles, Planning and Practice”



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Paget's Disease of the Temporal Bone: A Single-Institution Contemporary Review of 27 Patients

imageObjectives: To report a contemporary review from a single-institution series on Paget's disease of the temporal bone (PDTB). Study Design: Retrospective chart review of patients evaluated from 1998 to 2016. Setting: Quaternary referral center. Patients: Patients with radiographically confirmed PDTB. Main Outcome Measures: Clinical, audiological, and radiological features and management strategies of PDTB. Results: A total of 50 temporal bones in 27 patients (15 men) were diagnosed with PDTB. Symptoms at presentation included hearing loss (n = 23, 85%), headache (n = 18, 67%), dizziness (n = 14, 52%), tinnitus (n = 5, 19%), chronic otitis media (n = 2, 7%), hemifacial spasm without facial paralysis (n = 1, 4%), multiple cranial neuropathies (n = 1, 4%), and neoplastic transformation (n = 1, 4%). Of the 23 ears with audiometric data available for review, 65% exhibited sensorineural hearing loss, and 35% mixed hearing loss. Long-term audiometric follow-up was available on two patients, both of whom demonstrated hearing loss at a rate greater than would be expected for normal aging. Two patients underwent successful cochlear implantation, achieving open-set speech recognition. Radiographic features of temporal bone involvement are reviewed and illustrated. Conclusion: This is the largest single-institution clinical series examining patients with PDTB in the English literature. Variable patterns of temporal bone involvement by Paget's disease are observed leading to a diverse set of clinical symptoms, including slowly progressive hearing loss, tinnitus, compressive cranial neuropathies, and benign or malignant tumorigenesis. Involvement typically begins in the petrous apex and progresses laterally. Otic capsule bone demineralization occurs late in the disease process. Cochlear implantation appears to be an effective management strategy for patients with severe-to-profound hearing loss.

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Surgical Management of a Persistent Stapedial Artery: A Review

imageObjective: To evaluate the outcome and per- and postoperative complications of the surgical management of patients with a persistent stapedial artery (PSA). Methods: A systemic literature search for reports on patients treated for pulsatile tinnitus and/or conductive hearing loss caused by a PSA was conducted of the PubMed and Embase databases using the terms “stapedial” and “artery.” Inclusion criteria were adequate description of the intervention and pre- and postoperative signs and symptoms. In addition, one case of a PSA, treated at VU University Medical Center Amsterdam, The Netherlands, was included in this series. Intervention: Middle ear surgery consisting of stapedotomy or stapedectomy, and/or transection of the PSA. Main Outcome Measures: Pre- and postoperative hearing levels, pre- and postoperative pulsatile tinnitus, and per- and postoperative complications. Results: Seventeen patients and 18 operated ears were evaluated (16 patients described in 14 articles and our case). Twelve out of 14 ears in which a stapedotomy or stapedectomy was initiated experienced improvement in hearing. In four cases pulsatile tinnitus was described pre- and postoperatively. In all four, pulsatile tinnitus subsided after transection of the PSA. Peroperative bleeding from the PSA was described in four patients, which could be controlled during the procedure. No significant postoperative sequelae were reported. Conclusions: In case of a PSA, improvement of conductive hearing loss is best achieved by stapes surgery, while pulsatile tinnitus is effectively treated with transection of the PSA. To date no long-term postoperative complications have been reported.

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Preliminary Model for the Design of a Custom Middle Ear Prosthesis

imageHypothesis: Custom prostheses could be used to recreate the ossicular chain and improve hearing. Background: Ossicular discontinuity or fixation occurs in 55% of cases of conductive hearing loss, with most cases involving the incus. Reconstruction has been achieved by a variety of methods; however, there has been little improvement in hearing outcomes in decades. Methods: Precise measurements of anatomic dimensions, weight, and center of gravity were taken from 19 cadaveric incudes. These measurements were combined with measurements from the medical literature and micro-computed tomography (micro-CT) of cadaveric temporal bones to generate a rasterizable incus model. As a proof of concept, incudal replacements including possible anatomic variations were then three-dimensionally (3-D) printed and inserted into a cadaveric temporal bone. Results: Our measurements of cadaveric incudes corresponded well with those from the medical literature. These measurements were combined with anatomical information from micro-CT allowing identification of critical features of the incus, which remained constant. Other model features were modified to increase stability and facilitate synthesis, including broadening and thickening of the lenticular process and the incudomalleolar articulation. 3-D printed incudal replacements based on this model readily fit into a cadaveric temporal bone and successfully bridged the gap between malleus and incus. Conclusion: We have generated a model for custom 3-D synthesis of incudal prostheses. While current 3-D printing in biocompatible materials at the size required is limited, the technology is rapidly advancing, and 3-D printing of incudal replacements with polylactic acid (PLA) is of the correct size and shape.

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Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT

imageHypothesis: The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. Background: An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. Methods: Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. Results: Interobserver variability was good (average absolute difference: 0.77 ± 0.42 mm) using standard views and fair (average absolute difference: 0.90 ± 0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ± 0.09 mm for the standard views and 0.38 ± 0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. Conclusion: There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.

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Pilot Electroacoustic Analyses of a Sample of Direct-to-Consumer Amplification Products

imageObjective: Recent national initiatives from the White House and Institute of Medicine have focused on strategies to increase the accessibility and affordability of hearing loss treatment given the average cost of $4700 for bilateral hearing aids. More affordable direct-to-consumer hearing technologies are increasingly gaining recognition, but the performance of these devices has been poorly studied. We investigated the technical and electroacoustic capabilities of several direct-to-consumer hearing devices to inform otolaryngologists who may be asked by patients to comment on these devices. Patients/Intervention: Nine direct-to-consumer hearing devices ranging in retail cost from $144.99 to $395.00 and one direct-to-consumer hearing device with a retail cost of $30.00. Main Outcome Measure: Electroacoustic results and simulated real-ear measurements. Main electroacoustic measures are frequency response, equivalent input noise, total harmonic distortion, and maximum output sound pressure level at 90 dB. Results: Five devices met all four electroacoustic tolerances presented in this study, two devices met three tolerances, one device met two tolerances, one device met one tolerance, and one device did not meet any tolerances. Nine devices were able to approximate five of nine National Acoustics Laboratories (NAL) targets within 10 dB while only three devices were able to approximate five of nine NAL targets within a more stringent 5 dB. Conclusion: While there is substantial heterogeneity among the selection of devices, certain direct-to-consumer hearing devices may be able to provide appropriate amplification to persons with mild-to-moderate hearing loss and serve as alternatives for hearing aids in specific cases.

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The Normal Adult Human Internal Auditory Canal: A Volumetric Multidetector Computed Tomography Study

imageObjective: The purpose of this study was to demonstrate that volumetric analysis of multidetector computed tomography (CT) images can be used to calculate the volume of the adult human internal auditory canal (IAC) reproducibly, and to describe the range of normal IAC volumes in the adult population with subgroup analysis of sex, age, and laterality. Background: Previous studies of the IAC have typically used measurements in two dimensions or by using casts of cadavers to measure IAC volumes. This study is the first to report the normal ranges of IAC volumes measured by CT. Methods: Two hundred eighty-one CT scans were assessed. Of the CT scans that met the inclusion criteria, a software package was used to manually contour the IACs in each subject to calculate the volumes in cubic millimeters. Subgroup analysis of laterality, sex, and age was evaluated. Interobserver agreement was calculated for the first 59 patients (118 canals). Results: Two hundred fifty-nine scans (518 canals) met the inclusion criteria. The volumes ranged from 74 to 502 mm3, with no statistically significant difference between left and right (p value = 0.69). In males, the range of volumes measured 74 to 502 mm3 while in females it ranged from 78 to 416 mm3. Males had larger IAC volumes than females (Wilcoxon rank-sum test: S = 14,845.0, p value = 0.01 on the right, and S = 14,646, p value = 0.004 on the left). No correlation was found with age (Spearman: −0.10, p value = 0.09 on the right and −0.04, p value = 0.50 on the left). Excellent interobserver agreement was found. Conclusion: IAC volumes of normal adult subjects, measured by CT, were larger in males and not significantly different with respect to age or laterality.

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Transcanal Endoscopic Ear Surgery for Excision of a Facial Nerve Venous Malformation With Interposition Nerve Grafting: A Case Report

imageObjective: To illustrate a novel approach for the surgical management of a venous malformation of the facial nerve, including interposition nerve grafting, via an exclusively transcanal endoscopic ear surgery (TEES) approach. Patient: Thirty nine-year-old woman with a preoperative House–Brackmann (HB) grade IV facial paresis secondary to a facial nerve tumor. Intervention(s): Surgical excision and interposition nerve graft via a transcanal endoscopic approach. Main Outcome Measure(s): Completeness of resection, approach morbidities, and facial nerve outcome. Results: The TEES approach provided wide exposure of the facial nerve from the geniculate ganglion through the mastoid segment. This visualization facilitated gross total tumor resection, incus interposition ossicular reconstruction, and placement of an interposition nerve graft. The nerve graft was positioned in the fallopian canal and was secured at both ends with surgicel. The patient had no postoperative complications. At 11-month follow-up her facial function had returned to HB grade IV. Conclusions: This is the first report of resecting a venous malformation of the facial nerve with concomitant interposition nerve graft reconstruction via an exclusively endoscopic approach. This report adds to the growing body of evidence that TEES can manage diverse middle ear and lateral skull base pathology. Additional studies are needed to fully elucidate the risk-benefit profile of this technique.

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Endoscopic Infracochlear Approach for Drainage of Petrous Apex Cholesterol Granulomas: A Case Series

imageObjective: To describe the feasibility and technical nuances of a transcanal endoscopic infracochlear approach for drainage of petrous apex cholesterol granulomas. Study Design: Retrospective case review. Setting: Tertiary care university hospital. Patients: A 32-year-old man with bilateral petrous apex cholesterol granulomas and a 54-year-old man with a left-sided petrous apex granuloma each with symptoms necessitating surgical intervention. Interventions: Transcanal endoscopic infracochlear approach for drainage of the cholesterol granulomas. Main Outcome Measures: Operation efficacy, corridor size, and perioperative morbidity. Results: All three cholesterol granulomas were successful drained without violating the cochlea, jugular bulb, or carotid artery. The dimensions of the infracochlear surgical corridor measured 5 mm × 6 mm, 3.5 mm × 3.5 mm, and 6 mm × 4 mm, respectively. All corridors facilitated visualization within the cyst and allowed lyses of adhesions for additional cyst content eradication. All patients had resolution of their acute symptoms. Two of the three subjects had serviceable hearing before and after their procedures. One patient required revision surgery 2-months after their initial procedure secondary to recurrent symptoms from acute hemorrhage within the cyst cavity. The infracochlear tract in this patient was noted to be patent. Conclusions: A transcanal endoscopic infracochlear approach is feasible for the management of cholesterol granuloma. The surgical access was wide enough to introduce the endoscope into the petrous apex cavity in each case. Further studies are needed to compare the efficacy and perioperative morbidity versus the traditional postauricular transtemporal approaches.

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Epidemiology of Dizzy Patient Population in a Neurotology Clinic and Predictors of Peripheral Etiology

imageObjective: To compare the proportion of peripheral versus nonperipheral dizziness etiologies among all patients, inclusive of those presenting primarily or as referrals, to rank diagnoses in order of frequency, to determine whether or not age and sex predict diagnosis, and to determine which subgroups tended to undergo formal vestibular testing. Study Design: Retrospective cohort. Setting: Academic neurotology clinic. Patients: Age greater than 18 neurotology clinic patients with the chief complaint of dizziness. Intervention(s): None. Main Outcome Measure(s): Age, sex, diagnosis, record of vestibular testing. Results: Two thousand seventy-nine patients were assigned 2,468 diagnoses, of which 57.7 and 42.3% were of peripheral and nonperipheral etiologies, respectively. The most common diagnoses were Ménière's (23.0%), vestibular migraine (19.3%), benign paroxysmal positional vertigo (BPPV) (19.1%), and central origin, nonmigraine (16.4%). Peripheral diagnoses are more likely to be found in men than in women (odds ratio [OR] 1.59). Peripheral diagnoses were most likely to be found in the 60 to 69 age group (OR 3.82). There was not a significant difference in rate of vestibular testing between women and men. Among patients with two diagnoses, the most common combinations were vestibular migraine and BPPV then vestibular migraine and Ménière's. Conclusions: A large proportion of patients seen for the chief complaint of dizziness in the neurotology clinic were found not to have a peripheral etiology of their symptoms. These data challenge a prevalent dogma that the most common causes of dizziness are peripheral: BPPV, vestibular neuritis, and Ménière's disease. Age and sex are statistically significant predictors of peripheral etiology of dizziness.

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Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis

imageObjective: To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis. Setting: Tertiary pediatric referral center. Patients: Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database. Interventions: Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented. Main Outcome Measure: Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average. Results: One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up. Conclusion: Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.

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Single-Center Study Investigating Foreign Language Acquisition at School in Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants in the Swiss German Population

imageObjective: To evaluate foreign language acquisition at school in cochlear implant patients. Study Design: Cohort study. Setting: CI center. Patients: Forty three cochlear implants (CI) patients (10–18 yr) were evaluated. CI nonusers and patients with CI-explantation, incomplete datasets, mental retardation, or concomitant medical disorders were excluded. Intervention(s): Additional data (type of schooling, foreign language learning, and bilingualism) were obtained with questionnaires. German-speaking children with foreign tuition language (English and/or French) at school were enrolled for further testing. Main Outcome Measure(s): General patient data, auditory data, and foreign language data from both questionnaires and tests were collected and analyzed. Results: Thirty seven out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream education. Twenty-seven CI users (73%) have foreign language learning at school. Fifteen of these were in mainstream education (55%), others in special schooling. From 10 CI users without foreign language learning, one CI user was in mainstream education (10%) and nine patients (90%) were in special schooling. Eleven German-speaking CI users were further tested in English and six additionally in French. For reading skills, the school objectives for English were reached in 7 of 11 pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11 pupils (27%) reached the school norm in English and none in French. Conclusions: Almost 75% of our CI users learn foreign language(s) at school. A small majority of the tested CI users reached the current school norm for in English and French in reading skills, whereas for hearing skills most of them were not able to reach the norm.

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Cochlear Implantation in Adults With Asymmetric Hearing Loss: Benefits of Bimodal Stimulation

imageObjective: This study addresses the outcome of cochlear implantation in addition to hearing aid use in patients with asymmetric sensorineural hearing loss. Study Design: Prospective longitudinal study. Setting: Tertiary referral center. Patients: Seven adults with asymmetric sensorineural hearing loss, i.e., less than 30% aided speech recognition in their worst hearing ear and 60 to 85% speech recognition in their best hearing ear. All patients had a postlingual onset of their hearing loss and less than 20 years of auditory deprivation of their worst hearing ear. Intervention: Cochlear implantation in the functionally deaf ear. Main Outcome Measures: Speech recognition in quiet, speech recognition in noise, spatial speech recognition, localization abilities, music appreciation, and quality of life. Measurements were performed before cochlear implantation and 3, 6, and 12 months after cochlear implantation. Results: Before cochlear implantation, the average speech recognition of the ear fitted with a hearing aid was 74%. Cochlear implantation eventually resulted in an average speech recognition of 75%. Bimodal stimulation yielded speech recognition scores of 82, 86, and 88% after 3, 6, and 12 months, respectively. At all time intervals, bimodal stimulation resulted in a significantly better speech recognition as compared with stimulation with only hearing aid or only cochlear implant (CI). Speech recognition in noise and spatial speech recognition significantly improved as well as the ability to localize sounds and the quality of life. Conclusion: This study demonstrated that patients are able to successfully integrate electrical stimulation with contralateral acoustic amplification and benefit from bimodal stimulation. Therefore, we think that cochlear implantation should be considered in this particular group of patients, even in the presence of substantial residual hearing on the contralateral side.

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Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population

Abstract

Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1–85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes—c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)—were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.



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Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate

Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Ginila T. Raju, Bhaskar V.K.S. Lakkakula, Jyotsna Murthy, Munirajan Arasambattu Kannan, Solomon F.D. Paul
ObjectivesTransforming growth factor beta1 (TGF-β1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-β1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- β1 towards non-syndromic cleft lip or palate (NSCL/P).MethodsUsing allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-β1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated.ResultsThe TGF-β1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r2 = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293).ConclusionTransmission of minor alleles were not observed from either parent indicating that the TGF-β1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-β1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.



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Study of the effects of hearing on static and dynamic postural function in children using cochlear implants

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Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Malihah Mazaheryazdi, Abdollah Moossavi, Javad Sarrafzadah, Saeed Talebian, Shohreh Jalaie
ObjectiveThe present study aimed to evaluate the postural control perturbations by the center of pressure parameters in two main approaches, cochlear implant turned “on” and “off”.MethodsWe included 25 children aged 8–10 years with unilateral cochlear implants and bilateral vestibular hypofunction deficit. To evaluate the postural function, each children was asked to stand on the force plate under 3 different conditions and cochlear implant turned “on” and “off”: Condition (A) double stance from open eyes to closed eyes, Condition (B) double stance with open eyes engaging in the dual task and Condition (C) From double leg stance to one leg stance with open eyes for assessment of dynamic postural control. Also to calculate the center of pressure parameters, we designed new software for the force plateResultsIn condition A: although the results demonstrated an overall reduction in the mean of center of pressure parameters when the cochlear implant was “on”, only the significant differences were seen in mean and standard deviations for anterior-posterior displacement, mediolateral displacement, area and mean velocity (P =0.00, P=0.04, P=0.02 and P=0.00, respectively) in open eyes In condition B: no significant difference was found between “on” and “off” cochlear implant in single or dual-task situations. In condition C: mean velocity variable demonstrated a significant difference (P=0.00) in the cochlear implant “on” condition in double leg stance only. Also, anterior-posterior displacement demonestrated a significant difference (P=0.00) when the cochlear implant was turned “on” in one leg stance situation.ConclusionThe results of our study show that auditory information can improve postural stability and reduce body sways in different situations as an underlying system for reinforcement of the postural control in children without complete normal balance subsystems.



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Auditory, visual and auditory-visual memory and sequencing performance in typically developing children

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Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Roshni Pillai, Asha Yathiraj
ObjectiveThe study evaluated whether there exists a difference/relation in the way four different memory skills (memory score, sequencing score, memory span, & sequencing span) are processed through the auditory modality, visual modality and combined modalities.MethodsFour memory skills were evaluated on 30 typically developing children aged 7 years and 8 years across three modality conditions (auditory, visual, & auditory-visual). Analogous auditory and visual stimuli were presented to evaluate the three modality conditions across the two age groups.ResultsThe children obtained significantly higher memory scores through the auditory modality compared to the visual modality. Likewise, their memory scores were significantly higher through the auditory-visual modality condition than through the visual modality. However, no effect of modality was observed on the sequencing scores as well as for the memory and the sequencing span. A good agreement was seen between the different modality conditions that were studied (auditory, visual, & auditory-visual) for the different memory skills measures (memory scores, sequencing scores, memory span, & sequencing span). A relatively lower agreement was noted only between the auditory and visual modalities as well as between the visual and auditory-visual modality conditions for the memory scores, measured using Bland-Altman plots.ConclusionsThe study highlights the efficacy of using analogous stimuli to assess the auditory, visual as well as combined modalities. The study supports the view that the performance of children on different memory skills was better through the auditory modality compared to the visual modality.



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Absence of KCNQ4 mutation in Bengali families with ADNSHL originated from West Bengal, India

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Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Bidisha Adhikary, Biswabandhu Bankura, Subhradev Biswas, Silpita Paul, Madhusudan Das
ObjectiveAutosomal Dominant Non-Syndromic Hearing Loss (ADNSHL) is extremely heterogeneous in nature. More than 60 loci with 30 different genes have been identified linked to ADNSHL. Mutation in KCNQ4 is considered as one of the most common causative factor responsible for ADNSHL. No study focused on the genetic alteration of KCNQ4 gene among hearing loss patients in India. The present study for the first time was carried out to determine the mutation spectrum of KCNQ4 gene in ADNSHL patients of West Bengal state, India.MethodTwenty nine individuals from 10 independent ADNSHL family (with two or more generation affected) were studied both clinically and genetically. Most of the patients showed moderate progressive sensorineural hearing loss. Mutation analysis was conducted for KCNQ4 gene using polymerase chain reaction followed by direct sequencing.ResultsNeither any reported nor a novel pathogenic mutation in KCNQ4was detected in our studied group, in contrast to the findings among East Asians.ConclusionThe result of the present study suggests that mutations in KCNQ4 gene are unlikely to be a major causative factor of ADNSHL in our studied patients from West Bengal, India, pointing to other genes might be responsible for ADNSHL in our studied patients.



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Bilateral congenital cholesteatoma: Surgical treatment and considerations

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Daniele Marchioni, Alessia Rubini, Mauricio Gonzalez-Navarro, Matteo Alicandri-Ciufelli, Adrian James, Livio Presutti
ObjectivesTo describe a multicenter study regarding surgical management of bilateral congenital cholesteatoma (BCC) and underline the importance of endoscopes in the management of this condition. In BCC, hearing preservation is more crucial than in unilateral cases. The endoscopic approach allows complete removal of cholesteatoma via a minimally invasive technique offering low residual disease rates while preserving the normal physiology of the middle ear and possibly the ossicular chain.Study designRetrospective chart and surgical video review of patients with BCC who underwent surgery at Otolaryngology Department of Modena and Verona University Hospitals and the Hospital for Sick Children, Toronto.MethodsFrom 2002 to November 2016, six patients were identified with bilateral congenital cholesteatoma and included in this study. Pre-operative assessments, surgical treatments and outcomes were collected and described.ResultsThe median age at presentation was 4 years (range 2–7 years). A microscopic post auricular tympanoplasty was performed in two ears, four underwent a canal wall up mastoidectomy procedure and in the other six a transcanal endoscopic approach (TEA) was used. No intra- or post-operative complications were observed in any patients. The mean follow up period was 54.5 months.ConclusionsWhen both ears are involved with congenital cholesteatoma, it is particularly important to use a minimally invasive technique that preserves normal ossicular and mastoid structure and function whenever possible. In many cases this can be achieved with TEA, even in young children. In addition the endoscope allows good surgical control of cholesteatoma removal from hidden recesses.



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Laerdal SimMan 3G Patient Simulator

EMS Education, -Norwegian StyleExEMTNor

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Laerdal SimMan 3G Patient Simulator

EMS Education, -Norwegian StyleExEMTNor

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Ultrastructure of bioscaffolds derived from bovine articular cartilage as an experimental model to support blastema cells

Abstract

Decellularized cartilage extracellular matrix (ECM)-derived bioscaffolds have been designed as they provide a unique opportunity to carry out research on the mechanisms of chondrogenesis and its regulation. These scaffolds are used as a model in order to emulate different aspects relating to the formation, degeneration, and regeneration of the cartilage. This project has studied the interaction between the decellularized bovine articular cartilage and the blastema cells derived from the punched rabbit’s ear. Articular cartilage was dissected in fragments with 10 mm length and 2 mm thickness. Then, they were chemically decellularized with 2% sodium dodecyl sulfate (SDS) for 2 h. The tissue rings derived from the rabbit’s ear were assembled with the decellularized scaffolds and they were placed in a culture media for 30 days. These samples were fixed, sectioned, and microscopically studied. Micrographs of SEM electron microscopy and DAPI staining confirmed the decellularization of the scaffolds. FTIR analysis confirmed the preservation of ECM components including collagen II and proteoglycans. The optical microscopy observations confirmed migration, adherence, and penetration of the blastema cells into the scaffolds. The electron microscopy studies demonstrated that the blastema cells beside the scaffolds have triggered mutual interactions and merely progressed toward chondrogenic differentiation. The main objective is to identify and comprehend the interaction between cartilage matrix and blastema cells. The proposed model is an ideal model for fundamental studies in cartilage tissue engineering. The principles of tissue engineering must be taken in to account while studying such interactions.



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Laerdal SimMan 3G Patient Simulator

EMS Education, -Norwegian StyleExEMTNor

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Laerdal SimMan 3G Patient Simulator

EMS Education, -Norwegian StyleExEMTNor

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Clinical and pathological factors related to brain relapse–free survival in breast cancer patients—reply

Publication date: Available online 24 June 2017
Source:Human Pathology
Author(s): Rong Li, Kui Zhang, Gene P. Siegal, Shi Wei




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Markerless motion capture systems as training device in neurological rehabilitation: a systematic review of their use, application, target population and efficacy

Client-centred task-oriented training is important in neurological rehabilitation but is time consuming and costly in clinical practice. The use of technology, especially motion capture systems (MCS) which are...

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Inflammatory cell infiltrates in advanced metastatic uveal melanoma

Publication date: Available online 24 June 2017
Source:Human Pathology
Author(s): Yamini Krishna, Conni McCarthy, Helen Kalirai, Sarah E. Coupland
Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few, and to-date have demonstrated only marginal success. High densities of tumour-associated-macrophages (TAMs) and infiltrating T-lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole tissue-sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal-antibodies (mAbs) against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial-distribution of TILs were highlighted using Abs against CD3 (pan-lymphocyte marker), CD4 (T-helper cells) and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumour in all 35 specimens; their density was ‘moderate’ in 50% of cases, ‘few’ in 43% and the majority showed an ‘indeterminate’ phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumour. Of these CD8+ TILs were ‘few’ in number within mUM but were predominantly seen peri-tumourally at the tumour/normal liver interface, whilst CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of ‘indeterminate’ morphology were observed in mUM, suggesting a tendency towards the pro-tumourigenic M2-phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peri-tumoural. The biological and functional roles of inflammatory cells in mUM requires further investigation, to determine if they represent potential targets for future therapies in mUM.



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Clinical and pathological factors related to brain relapse–free survival in breast cancer patients

Publication date: Available online 24 June 2017
Source:Human Pathology
Author(s): Kadri Altundag




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High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma

Publication date: Available online 24 June 2017
Source:Human Pathology
Author(s): Xiaoxian Li, Bo Wei, Ceyda Sonmez, Zaibo Li, Limin Peng
This study is to address the significance of tumor budding (TB) in breast carcinoma. Totally 244 estrogen receptor-positive (ER+)/HER2-negative (HER2-) and 131 triple-negative breast carcinoma (TNBC) diagnosed from 2004 to 2014 were analyzed. TB (cluster of up to 5 tumor cells at the invasive front) was evaluated using five 200x high power field (HPF) at the hotspot. The highest TB (H-TB) in 1 HPF and average TB (A-TB) in 5 HPFs were correlated with lymph node and distant metastasis, lymphovascular invasion (LVI), local recurrence, overall survival (OS), disease-free survival (DFS). In ER+/HER2- cancer, H-TB and A-TB were significantly associated with distant metastasis. In TNBC, H-TB was associated with distant metastasis by univariate but not multivariate analysis; H-TB and A-TB were associated with LVI and worse OS (all P<.05). TB is associated with poor prognosis in ER+/HER2- and TNBC cancer. Evaluation of H-TB may be sufficient in breast carcinoma.



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Postprandial hyperinsulinemic hypoglycemia in a child as a late complication of esophageal reconstruction

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Impact of discontinuation of growth hormone treatment on lipids and weight status in adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Clinical evaluation and mutational analysis of GALK and GALE genes in patients with galactosemia in Greece: one novel mutation and two rare cases

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Markerless motion capture systems as training device in neurological rehabilitation: a systematic review of their use, application, target population and efficacy

Client-centred task-oriented training is important in neurological rehabilitation but is time consuming and costly in clinical practice. The use of technology, especially motion capture systems (MCS) which are...

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Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: A systematic review

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Publication date: September 2017
Source:European Journal of Cancer, Volume 82
Author(s): Aisha A. Hussein, Marco N. Helder, Jan G. de Visscher, C. René Leemans, Boudewijn J. Braakhuis, Henrica C.W. de Vet, Tymour Forouzanfar
Head and neck squamous cell carcinoma (HNSCC) is typically regarded as a disease of elderly people. However, increasing numbers of patients worldwide with HNSCC at younger age (defined as <45 years old) have been reported in recent years.To assess geographical variations and trends worldwide in incidence of oral and oropharyngeal cancer in young patients, a systematic review was conducted in PubMed and Google scholar databases from 1975 to June 2016. Seventy-eight studies were selected for further study.Nineteen population-based studies on incidence rate were available from 13 countries, showing a prominent increase over time except for the Netherlands. A notable rise of oral (mobile) tongue cancer among white women and oropharyngeal cancer in white men was observed. Data suggest that cancer in young patients may be a distinct clinical entity and characterised by different aetiology and pathogenesis. Additionally, the relative proportion of oral and oropharyngeal cancer in young patients to total incidence revealed a significant difference between estimates from North America (5.5%) and both Africa (17.2%) and Middle East (14.5%).It is concluded that (i) a rising trend in oral and oropharynx cancers is observed in young patients worldwide; (ii) incidence studies should properly define outcomes in age cohorts and use a consensus cut-off for young patients; (iii) more population-based studies should be performed in non-Western regions to get accurate global measures of incidence for these cancers in young subpopulations and (iv) there is an urge to identify new aetiological factors in these young patients.



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HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be ...

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A Comprehensive Health Profile of Guyanese Immigrants Aged 18–64 in Schenectady, New York

Abstract

Guyanese immigrants are the 5th largest foreign-born group in NY State, but sparse literature is available on their health status and health needs. A community-based health interview survey of Schenectady NY residents aged 18–64 (N = 1861) was analyzed. Bivariate comparisons between Guyanese respondents and White, Black, and Hispanic respondents were made for each variable to identify disparities. As predominantly low SES immigrants, Guyanese adults were less likely to be covered by health insurance, have a usual place for care, and receive cancer screenings. They were more likely to engage in alcohol binge drinking, but generally in good overall physical and mental health and less likely to smoke or report disability. Stable family structure and supportive interpersonal relationships are major assets of this group. Improved access to affordable health insurance, linkages to primary care, targeted cancer screening programs, and culturally-sensitive behavioral health services are recommended for Guyanese immigrants.



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MD-2 regulates LPS-induced NLRP3 inflammasome activation and IL-1beta secretion by a MyD88/NF-κB-dependent pathway in alveolar macrophages cell line

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Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Man Luo, Lijuan Hu, Dandan Li, Yanying Wang, Yuting He, Lei Zhu, Weiying Ren
Myeloid differentiation protein 2 (MD-2) is required in the recognition of lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and participates in LPS-induced alveolar macrophage (AM) inflammation during acute lung injury (ALI). Activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome aggravates inflammation in LPS-induced ALI. However, there is currently little known about the relationship between MD-2 signaling and the NLRP3 inflammasome. This study showed that NLRP3 expression, IL-1beta (IL-1β) secretion, and pyroptosis were up-regulated after LPS stimulation in the NR8383 AM cell-line. MD-2 gene knock-down reduced LPS-induced mRNA and protein expression of NLRP3 and IL-1β secretion in NR8383 cells, and inhibited the MyD88/NF-κB signaling pathway. Conversely, over-expression of MD-2 not only heightened NLRP3, MyD88, and NF-κB p65 protein expression, it also aggravated the LPS-induced inflammatory response. Furthermore, the NF-κB inhibitor SN50 had a beneficial role in decreasing NLRP3 and caspase-1 mRNA and protein expression. The observations suggest that MD-2 helps to regulate LPS-induced NLRP3 inflammasome activation and the inflammatory response in NR8383 cells, and likely does so by affecting MyD88/NF-κB signaling.



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Autophagy and multidrug resistance in cancer

Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative sy...

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Chronometric investigations of the Middle to Upper Paleolithic transition in the Zagros Mountains using AMS radiocarbon dating and Bayesian age modelling

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Publication date: August 2017
Source:Journal of Human Evolution, Volume 109
Author(s): Lorena Becerra-Valdivia, Katerina Douka, Daniel Comeskey, Behrouz Bazgir, Nicholas J. Conard, Curtis W. Marean, Andreu Ollé, Marcel Otte, Laxmi Tumung, Mohsen Zeidi, Thomas F.G. Higham
The Middle to Upper Paleolithic transition is often linked with a bio-cultural shift involving the dispersal of modern humans outside of Africa, the concomitant replacement of Neanderthals across Eurasia, and the emergence of new technological traditions. The Zagros Mountains region assumes importance in discussions concerning this period as its geographic location is central to all pertinent hominin migration areas, pointing to both east and west. As such, establishing a reliable chronology in the Zagros Mountains is crucial to our understanding of these biological and cultural developments. Political circumstance, coupled with the poor preservation of organic material, has meant that a clear chronological definition of the Middle to Upper Paleolithic transition for the Zagros Mountains region has not yet been achieved. To improve this situation, we have obtained new archaeological samples for AMS radiocarbon dating from three sites: Kobeh Cave, Kaldar Cave, and Ghār-e Boof (Iran). In addition, we have statistically modelled previously published radiocarbon determinations for Yafteh Cave (Iran) and Shanidar Cave (Iraqi Kurdistan), to improve their chronological resolution and enable us to compare the results with the new dataset. Bayesian modelling results suggest that the onset of the Upper Paleolithic in the Zagros Mountains dates to 45,000–40,250 cal BP (68.2% probability). Further chronometric data are required to improve the precision of this age range.



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Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 mice

The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the...

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Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis

In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. I...

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Alzheimer’s disease related genes during primate evolution

Abstract

During primate evolution, the neuronal and cognition-related genes have evolved rapidly. These genes seem to induce neurological illnesses such as Alzheimer's disease (AD). In this study, we analyzed genes APOE, TOMM40, and PICALM known as the risk factors of AD. We performed bioinformatics analyses in relation to evolution, phylogeny, and protein structure for those genes in humans, Neanderthals, chimpanzees, bonobos, gorillas, orangutans, crab-eating monkeys, and rhesus monkeys. Cholesterol-related genes showed relatively rapid evolution toward a lower risk of AD. Neanderthals showed relatively higher polymorphism in genes APOE, TOMM40, and PICALM than humans did. Phylogeny indicated different topologies in the trichotomy of humans, chimpanzees, and gorillas in terms of genes APOE, TOMM40, and PICALM. These results provide to hominin-specific patterns in three genes, and give clues to the modern human-specific traits of AD and shed light on further functional research helping to understand AD.



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Editorial



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Autophagy and multidrug resistance in cancer

Abstract

Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.



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Targeting metabolic reprogramming in KRAS-driven cancers

Abstract

Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect. The role of KRAS signaling in the regulation of aerobic glycolysis has been reported in several types of cancer. KRAS-driven cancers are characterized by altered metabolic pathways involving enhanced nutrients uptake, enhanced glycolysis, enhanced glutaminolysis, and elevated synthesis of fatty acids and nucleotides. However, Just how mutated KRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis of KRAS-driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data on KRAS-related metabolic alterations in cancer cells. Given that cancer cells rely on changes in metabolism to support their growth and survival, the targeting of metabolic processes may be a potential strategy for treating KRAS-driven cancers.



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HOXB7 accelerates the malignant progression of hepatocellular carcinoma by promoting stemness and epithelial-mesenchymal transition

Abstract

Background

Homeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined.

Methods

Immunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and wound-healing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo.

Results

Higher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated.

Conclusion

Overexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC.



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PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

Abstract

Background

Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown.

Methods

Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma.

Results

PRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway.

Conclusions

This investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development.



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Efficacy of e.coli-derived rhBMP-2 in posterolateral lumbar fusion: an open, active-controlled, randomized, multicenter trial

The efficacy and safety of recombinant human bone morphogenetic protein-2 as a bone graft substitute in spinal fusion has been widely researched. However, no study of the efficacy and safety of E.coli-derived rhBMP-2 (E.BMP-2) with a hydroxyapatite (HA) carrier has been proposed.

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Coffee consumption and risk of renal cell carcinoma

Abstract

Background

Studies have suggested an inverse association between coffee consumption and risk of renal cell carcinoma (RCC); however, data regarding decaffeinated coffee are limited.

Methods

We conducted a case–control study of 669 incident RCC cases and 1,001 frequency-matched controls. Participants completed identical risk factor questionnaires that solicited information about usual coffee consumption habits. The study participants were categorized as non-coffee, caffeinated coffee, decaffeinated coffee, or both caffeinated and decaffeinated coffee drinkers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for multiple risk factors for RCC.

Results

Compared with no coffee consumption, we found an inverse association between caffeinated coffee consumption and RCC risk (OR 0.74; 95% CI 0.57–0.99), whereas we observed a trend toward increased risk of RCC for consumption of decaffeinated coffee (OR 1.47; 95% CI 0.98–2.19). Decaffeinated coffee consumption was associated also with increased risk of the clear cell RCC (ccRCC) subtype, particularly the aggressive form of ccRCC (OR 1.80; 95% CI 1.01–3.22).

Conclusions

Consumption of caffeinated coffee is associated with reduced risk of RCC, while decaffeinated coffee consumption is associated with an increase in risk of aggressive ccRCC. Further inquiry is warranted in large prospective studies and should include assessment of dose–response associations.



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CT findings in patients with Cabazitaxel induced pelvic pain and haematuria: a case series

Abstract

Background

Haematuria and pelvic pain are recognized and documented adverse reactions related to Cabazitaxel use. To date there has not been any documentation of imaging findings in patients with this presentation.

Cases

We report a case series of five patients who experienced these symptoms while on Cabazitaxel and were all found to have very similar urothelial changes on CT. The patients were noted to have ureteric and renal pelvic dilatation along with urothelial enhancement (in those who had post contrast imaging). All of these changes were noted to be reversible in those who had follow up imaging after cessation of Cabazitaxel and initiation of a short course of steroids.

Conclusion

This case series helps demonstrate the pathological reversible urothelial inflammatory changes that may be occurring in patients experiencing haematuria and pelvic pain on Cabazitaxel therapy. These changes may relate to direct toxic effect of drug metabolites, a radiation recall type phenomenon or a combination of both.



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Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis

Abstract

Background

In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival.

Methods

Pubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival.

Results

Eight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32–1.09, I2: 3.35%, P-heterogeneity = 0.36, 3 studies), 1.09 for distant recurrence (95%-CI: 0.74–1.60, I2: 50.5%, P-heterogeneity = 0.13; 3 studies), and 2.99 for leptomeningeal disease (95% CI 1.55–5.76; I2: 14.4% p-heterogeneity: 0.28; 2 studies). For the same comparison, the risk ratio for median overall survival was 0.47 (95% CI: 0.41–0.54; I2: 79.1%, P-heterogeneity < 0.01; 4 studies) in a fixed-effect model, but was no longer significant (0.63; 95%-CI: 0.40–1.00) in a random-effect model. SRS was associated with a lower risk of leukoencephalopathy (RR: 0.15, 95% CI: 0.07–0.33, 1 study), yet with a higher risk of radiation-necrosis (RR: 19.4, 95% CI: 1.21–310, 1 study).

Conclusion

Based on retrospective cohort studies, the results of this study suggest that SRS of the resection cavity may offer comparable survival and similar local and distant control as adjuvant WBRT, yet may be associated with a higher risk for developing leptomeningeal disease. Future research on SRS should focus on achieving a better understanding of the various factors that may favor SRS over WBRT.



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Premonitory Symptoms of Migraine in Childhood and Adolescence

Abstract

Purpose of Review

Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future. Recognition of these symptoms by parents, guardians, teachers and carers is of importance in ensuring early and effective attack treatment.

Recent Findings

A previous clinic-based questionnaire study in 103 children found a prevalence of premonitory symptoms in paediatric migraine of 67%, with a mean number of reported symptoms of two. A recent study found that in a clinic population of 100 children or adolescents with a migraine diagnosis who were preselected as having at least one premonitory symptom associated with their attacks, two or more premonitory symptoms were reported by 85% of patients. The most common symptoms were fatigue, mood change and neck stiffness.

Summary

Although the population prevalence of premonitory symptoms in migraine within the paediatric population, or their ability to predict accurately the onset of an impending headache cannot be deduced from the retrospective studies performed to date, premonitory symptoms occur in children as young as 18 months old. Understanding the biological basis of these, and their heterogeneous phenotype may help future targeted therapeutic research, helping the development of drugs that act before the onset of pain, limiting the morbidity associated with the migraine attack.



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Premonitory Symptoms of Migraine in Childhood and Adolescence

Abstract

Purpose of Review

Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future. Recognition of these symptoms by parents, guardians, teachers and carers is of importance in ensuring early and effective attack treatment.

Recent Findings

A previous clinic-based questionnaire study in 103 children found a prevalence of premonitory symptoms in paediatric migraine of 67%, with a mean number of reported symptoms of two. A recent study found that in a clinic population of 100 children or adolescents with a migraine diagnosis who were preselected as having at least one premonitory symptom associated with their attacks, two or more premonitory symptoms were reported by 85% of patients. The most common symptoms were fatigue, mood change and neck stiffness.

Summary

Although the population prevalence of premonitory symptoms in migraine within the paediatric population, or their ability to predict accurately the onset of an impending headache cannot be deduced from the retrospective studies performed to date, premonitory symptoms occur in children as young as 18 months old. Understanding the biological basis of these, and their heterogeneous phenotype may help future targeted therapeutic research, helping the development of drugs that act before the onset of pain, limiting the morbidity associated with the migraine attack.



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Shifting the Physical Inactivity Curve Worldwide by Closing the Gender Gap

Abstract

Purpose

The aims of this study were to (i) examine gender differences in physical inactivity in countries with different levels of Human Development Index (HDI); and (ii) assess whether small changes in the prevalence of inactivity in women could achieve the World Health Organization's (WHO) global inactivity target.

Methods

Data on inactivity were extracted for 142 countries for the year 2010 from the WHO Data Repository. Data for HDI were obtained for the year 2010 from the United Nations Development Program. Absolute and relative gender differences were calculated for countries according to four HDI categories. The potential effects of increasing women's activity levels on achievement of the WHO physical inactivity target were computed.

Results

Overall inactivity prevalence was higher in women (27%) than in men (20%). Women were more inactive than men in all except eight countries. Absolute gender differences [median 7.5% (range −10.1 to 33.2)] did not vary by HDI category, but there was a small negative correlation between relative gender difference in inactivity and HDI (rho −0.19; p = 0.02), which was mostly influenced by three outlier countries with low HDI. A decrease in inactivity levels of 4.8% points among women across the world would achieve the WHO target of reducing global levels of inactivity by 10%.

Conclusion

Gender differences in the prevalence of physical inactivity were highly variable, both within and across categories of HDI. Interventions which result in small changes in inactivity prevalence in women would achieve the 2025 WHO global target for inactivity, without any change to the prevalence in men.



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Duration and cessation characteristics of heparinization after finger replantation: A retrospective analysis of outcomes

Abstract

Background

To prevent postoperative thrombosis, indications for anticoagulation in finger replantation have been described, but no consensus has yet been found for cessation protocols. The aim of this study is to investigate cessation methods of intravenous anticoagulation after finger replantation.

Methods

A retrospective review of all patients treated for a finger replantation between December 2014 and July 2016 was performed. Only those who required postoperative treatment with intravenous heparin were extracted. Primary outcome was survival of finger at hospital discharge and data collection focused on postoperative anticoagulation regimens.

Results

108 patients with replantation were treated with intravenous heparin and included in the analysis. When anticoagulated, survival rate was 60% (n = 65) at hospital discharge, wherein arterial and venous thrombosis accounted for 60 and 40% respectively. Descriptive analysis failed to demonstrate an increase in failure rates when tested for duration of intravenous heparin, fixed or variable infusion rates of anticoagulation and need for vascular grafts. However, there was a 2.8-fold (P = .009) increase in the survival rate with progressive weaning of anticoagulation rather than abrupt discontinuation. Subgroup analysis demonstrated similar findings when considering arterial thrombosis alone (OR 5.2, P = .012), but did not show any significant difference for venous thrombosis (OR 1.7, P = .344).

Conclusions

Progressive tapering of intravenous heparin is associated with an increased survival rate after finger replantation, particularly for arterial thrombosis. Further prospective and randomized trials are necessary to elucidate the optimal duration, method of infusion and indications for vascular grafts.



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