Sleep Characteristics Associated With Drowsy Driving

Publication date: Available online 7 October 2017
Source:Sleep Medicine
Author(s): Jun-Sang Sunwoo, Young Hwangbo, Won-Joo Kim, Min Kyung Chu, Chang-Ho Yun, Kwang Ik Yang
ObjectiveThe aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population.MethodsThe study subjects consisted of 1675 adults aged 19 years or older who completed a population-based questionnaire survey on sleep habits. Experiences of drowsy driving were obtained from self-reported data. We investigated sleep-related variables including sleep duration, sleep efficiency, chronotype, subjective sleep perception, daytime sleepiness, sleep quality, and snoring. We performed multivariate logistic regression analysis to determine sleep characteristics independently associated with drowsy driving.ResultsThe mean age of the subjects was 43.2 years, and 66.3% were men. The prevalence of self-reported drowsy driving was 23.6% (396 of 1675), and 33.1% of subjects experienced dozing at the wheel at least once a month. Multivariate analysis demonstrated that men, office and manual workers, excessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were independently associated with drowsy driving. Subgroup analyses revealed that reduced weekday sleep duration was a risk factor of drowsy driving in adults with perceived sufficient sleep. On the other hand, frequent alcohol drinking significantly increased risk of drowsy driving in the subgroup with perceived sleep insufficiency. Furthermore, ordinal regression analyses confirmed the association between sleep characteristics and drowsy driving across different drowsy driving frequencies.ConclusionExcessive daytime sleepiness, depression, habitual snoring, and perceived insufficient sleep were sleep-related risk factors for drowsy driving. In addition to maintaining healthy sleep habits, individuals at high risk should be encouraged to evaluate underlying sleep disorders or psychiatric problems to prevent drowsy driving.



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Specific motor patterns of arousal disorders in adults: A video-polysomnographic analysis of 184 episodes

Publication date: Available online 7 October 2017
Source:Sleep Medicine
Author(s): Giuseppe Loddo, Elisa Sessagesimi, Francesco Mignani, Fabio Cirignotta, Susanna Mondini, Laura Licchetta, Francesca Bisulli, Paolo Tinuper, Federica Provini
ObjectiveTo compile an objective accurate description of the motor patterns of adult arousal disorders (ADs).MethodsWe reviewed 59 nocturnal video-polysomnographic (VPSG) recordings of 30 adult patients (>15 years) with a history of sleepwalking (SW). We scrutinized the semeiology of all 184 episodes recorded, classifying them into three groups according to three semeiological motor patterns characterized by increasing intensity and complexity: simple arousal movements (pattern I), characterized by head flexion/extension, head flexion/extension and limb movement or head flexion/extension and partial trunk flexion/extension; rising arousal movements (pattern II), characterized by a complete trunk flexion with patient sitting up in bed; and complex arousal with ambulatory movements (pattern III) characterized by SW. The VPSG recordings were compared to those of 10 healthy controls.ResultsAD patients presented with 169 pattern I, 37 pattern II, and nine pattern III episodes. Pattern I developed into pattern II in 17 cases and into pattern II followed by pattern III in five patients. Pattern II developed into pattern III in four patients. Onset was abrupt in 55% of the episodes. Episodes lasted a mean (±standard deviation) of 33 ± 35 seconds. Movements tended to halt temporarily during 72% of the episodes. We recorded 248 movements during sleep in the healthy controls, none of whom presented with AD patterns.ConclusionWe identified three specific motor patterns in AD patients not previously reported and not observed in healthy controls. Identification of these patterns could be important for diagnosis and serve as the basis for a new definition of AD in adults.



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Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy

Publication date: Available online 7 October 2017
Source:Sleep Medicine
Author(s): Yves Dauvilliers, Thomas Roth, Diane Guinta, Sarah Alvarez-Horine, Efim Dynin, Jed Black
ObjectiveTo assess the effects of three narcolepsy treatment modalities on sleep stage shifts associated with disrupted nighttime sleep (DNS) using data from a clinical trial.MethodsPolysomnograms were reviewed from 155 patients (who had these data available at baseline and 8 weeks) of the 278 patients who were randomized to placebo, 9-g sodium oxybate (SXB)/nightly, 200−600 mg/d modafinil, or SXB+modafinil. Major outcomes of these post hoc analyses, analyzed using analysis of covariance, were change from baseline in number of shifts from Stages N2/3/rapid eye movement (REM) to Stage N1/Wake, and from Stage N1/Wake to REM. Sleep quality was evaluated using the sleep-quality question from the Pittsburgh Sleep Quality Index.ResultsSXB alone or in combination with modafinil significantly decreased the number of shifts from Stage N2/3/REM to Stage N1/Wake (p < 0.01); least-squares mean change in number of shifts from baseline was –0.6, –16.5, 1.8, and –13.7 in the placebo, SXB, modafinil and SXB+modafinil groups, respectively. A similar pattern was observed for changes in shifts from REM to Stage N1/Wake and from Stage N1/Wake to REM. Relative to placebo, sleep quality significantly improved with SXB and SXB+modafinil (p ≤ 0.05) but not with modafinil alone.ConclusionThese results show that SXB with and without modafinil significantly consolidated sleep and improved patient-reported sleep quality relative to placebo. In contrast, no such effects were observed with modafinil alone, suggesting a specific effect of SXB on DNS in addition to its effect on daytime sleepiness.Clinicaltrials.gov identifierNCT00066170.



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Prevalence of sleep apnea at the acute phase of ischemic stroke with or without thrombolysis

Publication date: Available online 7 October 2017
Source:Sleep Medicine
Author(s): Jaana K. Huhtakangas, Juha Huhtakangas, Risto Bloigu, Tarja Saaresranta
ObjectiveThe aim of the study was to compare the prevalence, type, and severity of sleep apnea during the acute phase of ischemic stroke among patients either receiving or not receiving thrombolysis.MethodsWe recruited 246 consecutive adult ischemic stroke patients. Patients underwent cardiorespiratory sleep study with portable 3-channel device during the first 48 hours after the symptom onset of ischemic stroke.ResultsWe enrolled 110 (65.5% male) stroke patients in the thrombolysis group and 94 (59.6% male) in the nonthrombolysis group. In the thrombolysis group, the median National Institutes of Health Stroke Scale (NIHSS) score was higher (5.5) compared to the nonthrombolysis group (2.0) (p < 0.001). There was a lower incidence of lacunar (17.3% vs 36.2%, p = 0.002) and cerebellar (2.7% vs 16.0%, p < 0.001) strokes and a higher frequency of middle cerebral artery syndrome (60.9% vs 33.0%, p < 0.001) in the thrombolysis group compared to the nonthrombolysis group. Sleep apnea defined as an apnea−hypopnea index (AHI) ≥ 5/h was diagnosed in 186 (91.2%) patients, its prevalence being higher in the thrombolysis (96.4%) compared to the nonthrombolysis (85.1%) group (p = 0.007). The mean baseline AHI was 33.7/h in the thrombolysis group compared to 26.8/h in the nonthrombolysis group (p = 0.017).ConclusionSleep apnea was present in the vast majority of ischemic stroke patients. The stroke patients treated with thrombolysis were more likely to have sleep apnea, to have elevated NIHSS score at admission, and to be younger. Sleep apnea was more severe among those receiving thrombolysis as compared to those who were not.Clinical Trial RegistrationURL: http://ift.tt/2y3J4iO. Unique identifier: NCT01861275.



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Re: Heat generation and drill wear during dental implant site preparation: systematic review

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): Stephan Christian Möhlhenrich, Ali Modabber, Timm Steiner, David A. Mitchell, Frank Hölzle




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Re: Heat generation and drill wear during dental implant site preparation

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Koopaie, S. Kolahdouz




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Chronic recurrent dislocation of the temporomandibular joint secondary to a complex facial tic disorder

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K.E. French, M.H. Wilson, P.J. Revington




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Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals

Publication date: Available online 5 October 2017
Source:Brain Stimulation
Author(s): L. Angius, A.R. Mauger, J. Hopker, A. Pascual-Leone, E. Santarnecchi, S.M. Marcora
BackgroundTranscranial direct current stimulation (tDCS) has been used to enhance endurance performance but its precise mechanisms and effects remain unknown.ObjectiveTo investigate the effect of bilateral tDCS on neuromuscular function and performance during a cycling time to task failure (TTF) test.MethodsTwelve participants in randomized order received a placebo tDCS (SHAM) or real tDCS with two cathodes (CATHODAL) or two anodes (ANODAL) over bilateral motor cortices and the opposite electrode pair over the ipsilateral shoulders. Each session lasted 10 min and current was set at 2 mA. Neuromuscular assessment was performed before and after tDCS and was followed by a cycling time to task failure (TTF) test. Heart rate (HR), ratings of perceived exertion (RPE), leg muscle pain (PAIN) and blood lactate accumulation (ΔB[La⁻]) in response to the cycling TTF test were measured.ResultsCorticospinal excitability increased in the ANODAL condition (P < 0.001) while none of the other neuromuscular parameters showed any change. Neuromuscular parameters did not change in the SHAM and CATHODAL conditions. TTF was significantly longer in the ANODAL (P = 0.003) compared to CATHODAL and SHAM conditions (12.61 ± 4.65 min; 10.61 ± 4.34 min; 10.21 ± 3.47 min respectively), with significantly lower RPE and higher ΔB[La⁻] (P < 0.001). No differences between conditions were found for HR (P = 0.803) and PAIN during the cycling TTF test (P = 0.305).ConclusionOur findings demonstrate that tDCS with the anode over both motor cortices using a bilateral extracephalic reference improves endurance performance.



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Correlation of lysosome-associated protein transmembrane-4β gene overexpression with the malignant phenotypes of hepatocellular carcinoma

Publication date: Available online 7 October 2017
Source:Pathology - Research and Practice
Author(s): Hongying Su, Tao Xu, Xiongfei Huang, Shengbing Zang, Bin Wang, Yang Huang, Jingfeng Liu, Aimin Huang
Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies, for which hepatitis B virus (HBV) chronic infection constitutes a major risk factor. The lysosome-associated protein transmembrane-4 β gene (LAPTM4B) is a recently identified gene that was found to be overexpressed in several types of cancer. However, the role of LAPTM4B in HCC tumorigenesis and progression has not been clearly determined. The present study demonstrated that the mRNA as well as the protein levels of LAPTM4B were significantly upregulated in HCC specimens. Patients with higher levels of LAPTM4B mRNA in their HCC tissues tended to be of a younger age, HBsAg+, with an advanced Barcelona Clinic Liver Cancer stage. Moreover, LAPTM4B mRNA expression was positively associated with serum α −fetoprotein levels. We also observed that LAPTM4B was able to promote HCC cell proliferation, migration and invasion in vitro. In conclusion, our results indicated that LAPTM4B plays an important role in the promotion of hepatocarcinogenesis and cancer progression and may serve as a biomarker for the diagnosis and monitoring of HCC.



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A TERT-CLPTM1 locus polymorphism (rs401681) is associated with EGFR mutation in non-small cell lung cancer

Publication date: Available online 7 October 2017
Source:Pathology - Research and Practice
Author(s): Deok Heon Lee, Yu-Ran Heo, Won-Jin Park, Jae-Ho Lee
Telomere length is associated with lung carcinogenesis, and recent studies have focused on telomere-maintaining genes and their polymorphisms. Cancer susceptibility of the rs401681 polymorphism, located in the TERT-CLPTM1L locus, has been studied in many cancers. We examined the clinicopathological and prognostic value of rs401681 variants in lung cancer. The relationship between rs401681 variants and telomere length was analyzed in 134 non-small cell lung cancers (NSCLCs). The rs401681 polymorphism had the following genotype frequencies: C/C in 52.2% of the samples, C/T in 30.6%, and T/T in 17.2%. The T allele showed a strong correlation with EGFR mutation (p=0.037). Telomeres in the tumor samples were 3.26-fold longer, on average, than telomeres in matched normal samples (SD=0.48), and there were no differences in telomere length according to rs401681 polymorphism. Smoking was associated with telomere shortening (p=0.01). Survival analysis showed no prognostic value for rs401681 polymorphisms or telomere length in NSCLC. These results suggested that the rs401681 polymorphism contributes to lung carcinogenesis only in patients harboring an EGFR mutation. However, the polymorphism was not associated with survival; therefore, further comprehensive analysis should be performed.



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Association between Morphological Patterns of Myometrial Invasion and Cancer Stem Cell Markers in Endometrial Endometrioid Carcinoma

Abstract

In endometrial endometrioid adenocarcinoma (EEC), the depth of myometrial invasion (MI) is an important parameter for determining whether additional treatment is warranted. The present study investigated the association between MI patterns, cancer stem cell (CSC) phenotypes, and their clinicopathological significance in EEC. A total of 73 cases of EEC with MI were examined in this study. Haematoxylin and eosin-stained tissue specimens were analysed for MI pattern, which was categorised as infiltrating; expansile; adenomyosis (AM)-like; or microcystic, elongated, and fragmented (MELF)-type. The expression of CSC markers such as cluster of differentiation (CD)44, CD133, and Nanog1, as well as oestrogen receptor (ER) and progesterone receptor (PR) was examined by immunohistochemistry. Clinicopathological features including age, DOI, MI pattern, LVI, lymph node (LN) metastasis, disease progression, and survival outcome were recorded. Most examined cases (45/73) were International Federation of Gynecology and Obstetrics (FIGO) stage I. MI showed infiltrating (49.3%), AM-like (26.3%), MELF (15.1%), and expansile (9.6%) patterns. Tumours with the infiltrating pattern were associated with high FIGO grade (P = 0.002), reduced ER and PR, and CD44 expression (P = 0.014, 0.026, and 0.030, respectively); those with a MELF pattern showed LN metastasis (P < 0.001), lymphovascular invasion (P = 0.011), and reduced ER, CD44, and CD133 expression (P = 0.036, 0.006, and 0.016, respectively). EEC with infiltrating/MELF patterns of MI is associated with worse prognosis. These results suggest that CSC expression profiles are an unfavourable indicator of EEC.

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Conditional survival of pediatric, adolescent, and young adult soft tissue sarcoma and bone tumor patients

Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Judy Y. Ou, Holly Spraker-Perlman, Andrew C. Dietz, Rochelle R. Smits-Seemann, Sapna Kaul, Anne C. Kirchhoff
BackgroundSurvival estimates for soft tissue sarcomas (STS) and malignant bone tumors (BT) diagnosed in pediatric, adolescent, and young adult patients are not easily available. We present survival estimates based on a patient having survived a defined period of time (conditional survival). Conditional survival estimates for the short-term were calculated for patients from diagnosis to the first five years after diagnosis and for patients surviving in the long-term (up to 20 years after diagnosis).MethodsWe identified 703 patients who were diagnosed with a STS or BT at age ≤25 years from January 1, 1986 to December 31, 2012 at a large pediatric oncology center in Salt Lake City, Utah, United States. We obtained cancer type, age at diagnosis, primary site, and demographic data from medical records, and vital status through the National Death Index. Cancer stage was available for a subset of the cohort through the Utah Cancer Registry. Cox proportional hazards models, adjusted for age and sex, calculated survival estimates for all analyses.ResultsShort-term survival improves over time for both sarcomas. Short-term survival for STS from diagnosis (Year 0) did not differ by sex, but short-term survival starting from 1-year post diagnosis was significantly worse for male patients (Survival probability 1-year post-diagnosis [SP1]:77% [95% CI:71-83]) than female patients (SP1:86% [81–92]). Survival for patients who were diagnosed at age ≤10 years (Survival probability at diagnosis [SP0]:85% [79–91]) compared to diagnosis at ages 16–25 years (SP0:67% [59–75]) was significantly better at all time-points from diagnosis to 5-years post-diagnosis. Survival for axial sites (SP0:69% [63–75]) compared to extremities (SP0:84% [79–90]) was significantly worse from diagnosis to 1-year post-diagnosis. Survival for axial BT (SP0: 64% [54–74] was significantly worse than BT in the extremities (SP0:73% [68–79]) from diagnosis to 3-years post diagnosis. Relapsed patients of both sarcoma types had significantly worse short-term survival than non-relapsed patients. Long-term survival for STS in this cohort is 65% at diagnosis, and improves to 86% 5-years post-diagnosis. BT survival improves from 51% at diagnosis to 78% at 5-years post-diagnosis.ConclusionConditional survival for short- and long-term STS and BT improve as time from diagnosis increases. Short-term survival was significantly affected by patients' sex, age at diagnosis, cancer site, and relapse status.



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Re: “Lesson Learned with the Use of Iliac Branch Devices: Single Centre 10 Year Experience in 157 Consecutive Procedures”

Publication date: Available online 7 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Iain N. Roy, Richard G. McWilliams, Robert K. Fisher




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Radical espontânea

Radical espontânea

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A Hierarchical Structure for Human Behavior Classification using STN Local Field Potentials

Publication date: Available online 7 October 2017
Source:Journal of Neuroscience Methods
Author(s): Hosein M. Golshan, Adam O. Hebb, Sara J. Hanrahan, Joshua Nedrud, Mohammad H. Mahoor
BackgroundClassification of human behavior from brain signals has potential application in developing closed-loop deep brain stimulation (DBS) systems. This paper presents a human behavior classification using local field potential (LFP) signals recorded from subthalamic nuclei (STN).MethodA hierarchical classification structure is developed to perform the behavior classification from LFP signals through a multi-level framework (coarse to fine). At each level, the time-frequency representations of all six contacts of the DBS leads are combined through an MKL-based SVM classifier to classify five tasks (speech, finger movement, mouth movement, arm movement, and random segments). To lower the computational cost, we alternatively use the inter-hemispheric synchronization of the LFPs to make three pairs out of six bipolar signals. Three classifiers are separately trained at each level of the hierarchical approach, which lead to three labels. A fusion function is then developed to combine these three labels and determine the label of the corresponding trial.ResultsUsing all six LFPs with the proposed hierarchical approach improves the classification performance. Moreover, the synchronization-based method reduces the computational burden considerably while the classification performance remains relatively unchanged.Comparison with existing methodsOur experiments on two different datasets recorded from nine subjects undergoing DBS surgery show that the proposed approaches remarkably outperform other methods for behavior classification based on LFP signals.ConclusionThe LFP signals acquired from STNs contain useful information for recognizing human behavior. This can be a precursor for designing the next generation of closed-loop DBS systems.



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Neural electrode resilience against dielectric damage may be improved by use of highly doped silicon as a conductive material

Publication date: Available online 7 October 2017
Source:Journal of Neuroscience Methods
Author(s): Ryan Caldwell, Rohit Sharma, Pavel Takmakov, Matthew G. Street, Florian Solzbacher, Prashant Tathireddy, Loren Rieth
BackgroundDielectric damage occurring in vivo to neural electrodes, leading to conductive material exposure and impedance reduction over time, limits the functional lifetime and clinical viability of neuroprosthetics. We used silicon micromachined Utah Electrode Arrays (UEAs) with iridium oxide (IrOx) tip metallization and parylene C dielectric encapsulation to understand the factors affecting device resilience and drive improvements.New methodIn vitro impedance measurements and finite element analyses were conducted to evaluate how exposed surface area of silicon and IrOx affect UEA properties. Through an aggressive in vitro reactive accelerated aging (RAA) protocol, in vivo parylene degradation was simulated on UEAs to explore agreement with our models. Electrochemical properties of silicon and other common electrode materials were compared to help inform material choice in future neural electrode designs.ResultsExposure of silicon on UEAs was found to primarily affect impedance at frequencies >1 kHz, while characteristics at 1 kHz and below were largely unchanged. Post-RAA impedance reduction of UEAs was mitigated in cases where dielectric damage was more likely to expose silicon instead of IrOx. Silicon was found to have a per-area electrochemical impedance >10×higher than many common electrode materials regardless of doping level and resistivity, making it best suited for use as a low-shunting conductor.Comparison with existing methodsNon-semiconductor electrode materials commonly used in neural electrode design are more susceptible to shunting neural interface signals through dielectric defects, compared to highly doped silicon.ConclusionStrategic use of silicon and similar materials may increase neural electrode robustness against encapsulation failures.



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A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells

Publication date: Available online 7 October 2017
Source:Journal of Neuroscience Methods
Author(s): Tuomo Mäki-Marttunen, Geir Halnes, Anna Devor, Christoph Metzner, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll
BackgroundRecent progress in electrophysiological and optical methods for neuronal recordings provides vast amounts of high-resolution data. In parallel, the development of computer technology has allowed simulation of ever-larger neuronal circuits. A challenge in taking advantage of these developments is the construction of single-cell and network models in a way that faithfully reproduces neuronal biophysics with subcellular level of details while keeping the simulation costs at an acceptable level.New MethodIn this work, we develop and apply an automated, stepwise method for fitting a neuron model to data with fine spatial resolution, such as that achievable with voltage sensitive dyes (VSDs) and Ca²⁺ imaging.ResultWe apply our method to simulated data from layer 5 pyramidal cells (L5PCs) and construct a model with reduced neuronal morphology. We connect the reduced-morphology neurons into a network and validate against simulated data from a high-resolution L5PC network model.Comparison with Existing MethodsOur approach combines features from several previously applied model-fitting strategies. The reduced-morphology neuron model obtained using our approach reliably reproduces the membrane-potential dynamics across the dendrites as predicted by the full-morphology model.ConclusionsThe network models produced using our method are cost-efficient and predict that interconnected L5PCs are able to amplify delta-range oscillatory inputs across a large range of network sizes and topologies, largely due to the medium after hyperpolarization mediated by the Ca²⁺-activated SK current.



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A Brain-computer Interface based on Functional Transcranial Doppler Ultrasound Using Wavelet Transform and Support Vector Machines

Publication date: Available online 7 October 2017
Source:Journal of Neuroscience Methods
Author(s): Aya Khalaf, Matthew Sybeldon, Ervin Sejdic, Murat Akcakaya
BackgroundFunctional transcranial Doppler (fTCD) is an ultrasound based neuroimaging technique used to assess neural activation that occurs during a cognitive task through measuring velocity of cerebral blood flow.New methodThe objective of this paper is to investigate the feasibility of a 2-class and 3-class real-time BCI based on blood flow velocity in left and right middle cerebral arteries in response to mental rotation and word generation tasks. Statistical features based on a five-level wavelet decomposition were extracted from the fTCD signals. The Wilcoxon test and support vector machines (SVM), with a linear kernel, were employed for feature reduction and classification.ResultsThe experimental results showed that within approximately 3seconds of the onset of the cognitive task average accuracies of 80.29%, and 82.35% were obtained for the mental rotation versus resting state and the word generation versus resting state respectively. The mental rotation task versus word generation task achieved an average accuracy of 79.72% within 2.24seconds from the onset of the cognitive task. Furthermore, an average accuracy of 65.27% was obtained for the 3-class problem within 4.68seconds.Comparison with Existing methodsThe results presented here provide significant improvement compared to the relevant fTCD-based systems presented in literature in terms of accuracy and speed. Specifically, the reported speed in this manuscript is at least 12 and 2.5 times faster than any existing binary and 3-class fTCD-based BCIs, respectively.ConclusionsThese results show fTCD as a promising and viable candidate to be used towards developing a real-time BCI.



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Response to the letter to the editor regarding “The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach”

We would like to thank Prof. Zheng-Cai Lou [1] for his interest in our study entitled "The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach" [2] and we appreciate the useful comments. His main concerns will be discussed below.

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Occlusal loading during biting from an experimental and simulation point of view

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Oliver Röhrle, Harnoor Saini, David C. Ackland
ObjectivesOcclusal loading during clenching and biting is achieved by the action of the masticatory system, and forms the basis for the evaluation of the functional performance of prosthodontic and maxillofacial components. This review provides an overview of (i) current bite force measurement techniques and their limitations and (ii) the use of computational modelling to predict bite force. A brief simulation study highlighting the challenges of current computational dental models is also presented.MethodsAppropriate studies were used to highlight the development and current bite force measurement methodologies and state-of-the-art simulation for computing bite forces using biomechanical models.ResultsWhile a number of strategies have been developed to measure occlusal forces in three-dimensions, the use of strain-gauges, piezo-electric sensors and pressure sheets remain the most widespread. In addition to experimental-based measurement techniques, bite force may be also estimated using computational models of the masticatory system. Simulations of different bite force models clearly show that the use of three-dimensional force measurements enriches the evaluation of masticatory functional performance.SignificanceHence, combining computational modelling with three-dimensional force measurement techniques can significantly improve the evaluation of masticatory system and the functional performance of prosthodontic components.



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Mixed-mode fracture toughness of texturized LS2 glass-ceramics using the three-point bending with eccentric notch test

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Renan Belli, Michael Wendler, Anselm Petschelt, Ulrich Lohbauer
Here we use the 3-point bending with eccentric notch test (3-PBEN) to investigate the fracture behavior of a pressable and a CAD/CAM lithium disilicate (LS2) glass-ceramics under combined mode-I and mode-II loading. The effect of the bulk texturization in the beams of the pressable LS2 is made visible through the fracture trajectory following the most energetically favorable path dictated by the crystallite alignment. The CAD/CAM LS2 shows an isotropic fracture mode but increasing fracture energy with mode-II contribution, similar to the pressable variant.



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Differential cytotoxic effects on odontoblastic cells induced by self-adhesive resin cements as a function of the activation protocol

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Paulo Henrique Perlatti D'Alpino, Gioconda Emanuella Diniz de Dantas Moura, Silvana Coelho de Arruda Barbosa, Lygia de Azevedo Marques, Marcos Nogueira Eberlin, Fábio Dupart Nascimento, Ivarne Luis dos Santos Tersariol
ObjectivesTo evaluate the cytotoxic effects of exposing odontoblast cells to a variety of commercial self-adhesive cements polymerized using different activation modes.MethodsFive cements: MaxCem Elite (MAX), Bifix SE (BSE), G-Cem LinkAce (GCE), Clearfil SA Luting (CAS), and RelyX U200 (U200) were mixed, dispensed into molds, and distributed in groups, according to polymerization protocols: immediate photoactivation; delayed photoactivation (10min self-curing plus light-activation); and chemical activation (no light exposure). Immortalized rat odontoblast cells (MDPC-23) were cultured. Cell viability was assessed by Trypan Blue staining and total cell death was assessed by annexin V-APC/7-AAD double staining and flow cytometry. Volatilized compounds from polymerized specimens of cements were evaluated by gas chromatography/mass spectrometry (GC–MS). Data was analyzed with 2-way ANOVA/Tukey tests (α=0.05).ResultsExposure to all of the cements tested significantly reduced the cell viability, irrespective of the activation protocol (p<0.05). The least harmful cements were CSA and U200. Total death of cells significantly increased when exposed to BSE, GCE, and MAX, especially when chemically activated (p<0.05). Characteristic apoptotic cells increased after exposure to cements, mainly for MAX, regardless of the activation mode. Chemical activation of MAX also induced necrosis. Moreover, GCE and MAX exhibited higher percentages of late apoptotic/dead cells. Chromatograms revealed 28 compounds released from the cements tested, some of them with known carcinogenic effects. Selection of self-adhesive cements and polymerization protocols affect the cytotoxicity and cell viability of odontoblastic cells.Clinical significanceDespite the simplified cementation protocol, care is needed when cementing indirect restorations with self-adhesive cements, especially on recently exposed dentin. This category of material may cause differential cytotoxic effects and should be considered when selecting a cement. This is particularly true in clinical cases of light attenuation, where the polymerization depends on chemical activation, inducing higher cytotoxic damages when using some of the cements tested.



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ADM guidance-ceramics: Fatigue principles and testing

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): J.R. Kelly, P.F. Cesar, S.S. Scherrer, A. Della Bona, R. van Noort, M. Tholey, A. Vichi, U. Lohbauer
BackgroundClinical failure of dental ceramics is usually reported as partial fracture of the restoration (chipping) or as catastrophic fracture of the whole structure. In contrast to metals, ceramics are linear-elastic, brittle materials exhibiting extremely low damage tolerance to failure. Well documented clinical and lab reports have shown this fracture event often occurs at loads far below their fracture strength due to intrinsic fatigue degradation via slow crack growth or cyclic fatigue mechanisms. The presence and development of surface flaws have a dominant role in damage accumulation and lifetime reduction of ceramic structures.AimsThis ADM guidance document aims to summarize the aspects related to fatigue degradation of dental ceramics, reviewing the concepts of fatigue testing and furthermore aims to provide practical guidance to young scientists entering into fatigue related research. The description of fatigue strength is always accompanied by a clear understanding of the underlying fracture mechanisms.



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Re: Heat generation and drill wear during dental implant site preparation

We studied with interest the paper "Heat generation and drill wear during dental implant site preparation: systematic review" by Möhlhenrich et al, which provides valuable data about drilling bone. They describe "drill material" as "zirconium coated with steel", whereas because of the mechanical and thermal stresses at the interface of the drill and the bone, the material's resistance to wear must be a coating for the drill.1

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Re: Heat generation and drill wear during dental implant site preparation: systematic review

We thank you for your interest in our study as well as your valuable comments. You are of course right that "zirconium coated with steel" does not make sense and, furthermore, that the material of the drills used by Harder et al.1 was zirconium oxide and not zirconium. We apologise for any inconvenience caused.

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Chronic recurrent dislocation of the temporomandibular joint secondary to a complex facial tic disorder

We report the case of a 14-year-old boy who presented to the emergency department with bilateral dislocation of the temporomandibular joint (TMJ) of unusual aetiology. He had recently developed a repetitive action that involved thrusting the jaw forwards, which involved maximal mouth opening. This had preceded the dislocation of the TMJ two hours previously.

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Eye movements in genetic parkinsonisms affecting the α-synuclein, PARK9, and manganese network

Specific saccadic abnormalities follow basal ganglia dysfunction. Eye movements are indeed often analyzed to differentiate parkinsonian syndromes and to provide new insights into the modulatory role of the basal ganglia. Nevertheless, the oculomotor description of most inherited parkinsonisms is still lacking. Here, we analyzed the eye movement characteristics of three inherited parkinsonian syndromes (genetic Parkinson's disease, PDG): Parkinson's disease 9 (or Kufor-Rakeb syndrome, PARK9, #606693), due to recessive mutations in ATP13A2 encoding the lysosomal P-type ATPase PARK9 (Ramirez et al., 2006; Gitler et al., 2009); hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMNDYT1, #613280) due to recessive mutations in SLC30A10 leading to manganese accumulation in the liver, bone marrow, and nervous system (Quadri et al., 2012), and Parkinson's disease 1 (PARK1, #168601) associated with dominant mutations in SNCA encoding α-synuclein (Golbe et al., 1990).

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Prevalence of sleep apnea at the acute phase of ischemic stroke with or without thrombolysis

The aim of the study was to compare the prevalence, type, and severity of sleep apnea during the acute phase of ischemic stroke among patients either receiving or not receiving thrombolysis.

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Sleep Characteristics Associated With Drowsy Driving

The aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population.

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Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy

To assess the effects of three narcolepsy treatment modalities on sleep stage shifts associated with disrupted nighttime sleep (DNS) using data from a clinical trial.

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Immediate reactions to iodinated contrast media

Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients.

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Small percentage of anaphylactic reactions treated with epinephrine during food challenges in Dutch children

Severe allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine.

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Successful perinatal management of hereditary angioedema with normal C1 esterase inhibitor and factor XII mutation using C1 esterase inhibitor therapy

Hereditary angioedema (HAE) is a rare, autosomal dominant condition that consists of a deficiency or dysfunction of C1 esterase inhibitor (C1-INH). Various triggers can lead to self-limiting or life-threatening airway edema.1 Owing to its nonhistaminergic pathophysiologic features, HAE subtypes do not respond to epinephrine, corticosteroids, or antihistamine. Supplementation of C1-INH is an accepted and common treatment for HAE attacks and HAE prophylaxis.

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Importin-β and exportin-5 are strong biomarkers of productive reoviral infection of cancer cells

Publication date: Available online 7 October 2017
Source:Annals of Diagnostic Pathology
Author(s): Gerard Nuovo, Hue Tran, Andres Gutierrez, Paolo Fadda, Flavia Pichiorri, Enrico Caserta, Craig C. Hofmeister, Marta Chesi, P. Leif Bergsagel, Don Morris, Qiao Shi, Matt Coffey, Chandini Thirukkumaran
Acute reoviral infection has been extensively studied given the virus's propensity to target malignant cells and activate caspase-3 mediated apoptosis. Reovirus infection of malignant N1E-115 mouse neuroblastoma cells led to significant increased expression of importin-β and exportin-5 mRNAs (qRTPCR) and proteins (immunohistochemistry) which was partially blocked by small interfering LNA oligomers directed against the reoviral genome. Co-expression analysis showed that the N1E-115 cells that contained reoviral capsid protein had accumulated importin-β and exportin-5, as well as activated caspase 3. Reoviral oncolysis using a syngeneic mouse model of multiple myeloma similarly induced a significant increase in importin-β and exportin-5 proteins that were co-expressed with reoviral capsid protein and caspase-3. Apoptotic proteins (BAD, BIM, PUMA, NOXA, BAK, BAX) were increased with infection and co-localized with reoviral capsid protein. Surprisingly the anti-apoptotic MCL1 and bcl2 were also increased and co-localized with the capsid protein suggesting that it was the balance of pro-apoptotic molecules that correlated with activation of caspase-3. In summary, productive reoviral infection is strongly correlated with elevated importin-β and exportin-5 levels which may serve as biomarkers of the disease in clinical specimens.



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Distinct high molecular weight organic compound (HMW-OC) types in aerosol particles collected at a coastal urban site

Publication date: Available online 7 October 2017
Source:Atmospheric Environment
Author(s): M. Dall'Osto, R.M. Healy, J.C. Wenger, C. O'Dowd, J. Ovadnevaite, D. Ceburnis, Roy M. Harrison, D.C.S. Beddows
Organic oligomers were discovered in laboratory-generated atmospheric aerosol over a decade ago. However, evidence for the presence of oligomers in ambient aerosols is scarce and mechanisms for their formation have yet to be fully elucidated. In this work, three unique aerosol particle types internally mixed with High molecular weight organic compounds (HMW-OC) species - likely oligomers - were detected in ambient air using single particle Aerosol Time-Of-Flight Mass Spectrometry (ATOFMS) in Cork (Ireland) during winter 2009. These particle types can be described as follows: (1) HMW-OCs rich in organic nitrogen - possibly containing nitrocatechols and nitroguaiacols - originating from primary emissions of biomass burning particles during evening times; (2) HMW-OCs internally mixed with nitric acid, occurring in stagnant conditions during night time; and (3) HMW-OCs internally mixed with sea salt, likely formed via photochemical reactions during day time. The study exemplifies the power of methodologies capable of monitoring the simultaneous formation of organic and inorganic particle-phase reaction products. Primary emissions and atmospheric aging of different types of HMW-OC contributes to aerosol with a range of acidity, hygroscopic and optical properties, which can have different impacts on climate and health.



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Response of greenhouse gas emissions from three types of wetland soils to simulated temperature change on the Qinghai-Tibetan Plateau

Publication date: Available online 7 October 2017
Source:Atmospheric Environment
Author(s): Yi Liu, Guihua Liu, Ziqian Xiong, Wenzhi Liu
Wetlands emit a large quantity of greenhouse gases into the atmosphere and contribute significantly to global warming. The Qinghai-Tibetan Plateau, known as the "Third Pole" of the earth, contains abundant and diverse wetlands. Due to increasing human-induced pressures such as reclamation, overgrazing and climate change, many plateau wetlands have been degraded or destroyed. Until now, the response of soil greenhouse gas emissions to extreme summer temperatures in the plateau wetlands remains unknown. In this study, we collected 36 soil samples from riverine, lacustrine and palustrine wetlands on the Qinghai-Tibetan Plateau. We compared the carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) emissions from soils incubated aerobically at 7, 12, and 19 °C. The results showed that the emissions of CH4 and N2O but not CO2 were significantly affected by the simulated temperature change. The N2O emission rate was considerably higher in palustrine wetlands compared with lacustrine and riverine wetlands. However, the CO2 and CH4 emissions did not differ significantly among the three wetland types. The ratio of CO2 to CH4 production increased with increasing incubation temperatures. The global warming potential of greenhouse gases at 19 °C was approximately 1.18 and 2.12 times greater than that at 12 and 7 °C, respectively. Our findings suggest that temperature change has a strong effect on soil greenhouse gas emissions and global warming potential of wetlands on the Qinghai-Tibetan Plateau, especially palustrine wetlands. Therefore, targeted strategies should be developed to mitigate the potential impacts of climate warming on the plateau.

Graphical abstract

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The spreaded gracilis flap revisited: Comparing outcomes in lower limb reconstruction

Background

In lower limb reconstruction, the free gracilis muscle flap is usually chosen for coverage of small- to medium-sized defects. Aim of this study was a re-appraisal regarding the reconstructive indications of the gracilis muscle flap with a focus on postoperative complications in order to evaluate if it can also be routinely used to reconstruct large-size lower limb defects.

Methods

A total of 204 patients underwent free gracilis muscle transfers for lower limb reconstruction at our institution. Cases were divided according to the size of the defect into two groups (<150 cm² versus ≥150 cm²). The small- to medium defect size group included 150 patients and the large defect size group included 54 patients. In the large defect size group, the muscle was enlarged as needed by careful dissection of the epimysium and all connective tissue surrounding the intrinsic vessels under loupe magnification to protect the muscle perfusion. Surgical complications were accounted for and the two groups compared accordingly.

Results

Overall, there were no significant differences between the two groups of patients regarding the rate of major (15.72% versus 10.91%; P = .506) and minor surgical complications (6.92% versus 3.64%; P = .522). The total percentage of flap losses in the small to medium defect size group was 5.03%. There were no total flap losses in the large defect size group (P = .117).

Conclusion

The use of the spreaded gracilis flap provides a valuable option for the microsurgeon, especially also to reconstruct large size lower limb defects.

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Reconstruction of severe atherosclerotic and obstructive diabetic feet using thoracodorsal artery perforator flaps with long vascular pedicles

Background

Foot ulcers in diabetic patients often require free flaps. A long vascular pedicle is mandatory so that more proximal vessels can be used as recipient vessels, especially when the flap is used to reconstruct distal foot defects. We evaluated the outcome of diabetic foot defect that were reconstructed using thoracodorsal artery perforator (TDAP) flaps with long vascular pedicles.

Patients and Methods

We reconstructed the foot defects of 22 diabetic patients. Nineteen patients were male, and the mean age was 56.4 years. The defects were located in big toe in 11 patients; fourth and/or fifth toe, including lateral aspect of the foot, in 8 patients; and dorsum of the foot, medial plantar, and first metatarsal medial head in 1 patient each. CT angiography showed that the two main vessels of the lower leg remained intact in 7 patients, only one vessel was intact in the lower leg of 11, and no vessels were visible in 4.

Results

The flap size ranged between 5 × 4 cm² and 18 × 11cm², with a mean pedicle length of 16.5 cm. The anterior tibial artery was used as the recipient vessel in 15 patients, while the posterior tibial artery was used in 7. All the flaps survived. Three wound disruptions and two partial flap losses healed conservatively, without further surgery. Ulcer due to diabetes recurred in three cases. The mean follow-up period was 46.1 months. All wounds healed completely.

Conclusions

TDAP flaps with long vascular pedicles may be a viable choice for reconstructing defects in the feet of diabetic patients.

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Persistent trigeminal artery variant terminating in the posterior inferior cerebellar artery: a case report

Abstract

Persistent trigeminal artery (PTA) is a rare cerebrovascular variation of remnant fetal carotid-vertebrobasilar anastomoses. The PTA variant terminates in the cerebellar artery with no direct connection to the basilar artery. We present a rare case of a PTA variant that terminated directly into the ipsilateral posterior inferior cerebellar artery.

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Micro-autologous fat transplantation for rejuvenation of the dorsal surface of the ageing hand

Publication date: Available online 6 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Yun-Nan Lin, Shu-Hung Huang, Tsung-Ying Lin, Chih-Kang Chou, Yu-Hao Huang, Hidenobu Takahashi, Chung-Sheng Lai, Sin-Daw Lin, Tsai-Ming Lin
BackgroundRejuvenation of the dorsal surface of the hand for various conditions, such as cutaneous dyschromia, fine wrinkling, skin laxity, visible extensor tendons, and varicosities appear vital to prevent wrist and digit flexion resulting from hiding of the aged appearance of the hand. Numerous fillers have been applied to re-contour the ageing dorsal surface of the hand; the results were variable. The micro-autologous fat transplantation (MAFT) technique, proposed by Lin et al. in 2006, has demonstrated its feasibility in facial rejuvenation. In this study, we applied the MAFT technique for the rejuvenation of the dorsal portion of the hand.MethodsMAFT was performed in 68 female patients. Fat was harvested by performing liposuction, processed, and refined by centrifugation. Purified fat was micro-transplanted to the dorsal surface of the hand in parcels of small volume.ResultsThe mean age of the patients was 56 years (range, 38-70 years). MAFT was completed in 72 min, on average. The average amount of delivered fat was 13.9 and 13.8 mL for the right and left hands, respectively. The mean follow-up period was 32 months (range, 10-64 months). The 5-point Likert scale revealed that 58.8% of patients were very satisfied and 39.7% were satisfied about their outcome.ConclusionsMAFT has changed the concept of fat grafting, from an operation with unpredictable clinical results to an easy and reliable procedure. MAFT demonstrated high patient satisfaction with long-term results and is an effective approach to rejuvenate the dorsal surface of the hand.



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Pre-culture in endothelial growth medium enhances the angiogenic properties of adipose-derived stem/stromal cells

Abstract

Considerable progress has been made on the development of adipose-derived stem/stromal cells (ASCs) as pro-angiogenic therapeutic tools. However, variable clinical results highlight the need for devising strategies to enhance their therapeutic efficacy. Since ASCs proliferate and stabilize newly formed vessels during the angiogenic phase of adipose tissue formation, we hypothesized that mimicking an angiogenic milieu during culture of ASCs would enhance their capacity to support endothelial cell survival and angiogenesis. To test this, we compared the effect of an endothelial growth medium (EGM-2) and conventional media (αMEM) on the progenitor and angiogenic properties of ASCs. ASCs cultured in EGM-2 (ASC-EGM) displayed the highest clonogenic efficiency, proliferative potential and multilineage potential. After co-culture under growth factor starvation, only ASC-EGM attenuated luciferase-expressing human umbilical vein endothelial cells (HUVEC^luc) apoptosis and supported the formation of endothelial cords in a dose-dependent manner. These effects were recapitulated by the conditioned medium of ASC-EGM, which displayed a 100-fold higher expression of hepatocyte growth factor in comparison with ASC-αMEM. Next, HUVEC^luc and ASCs were co-transplanted subcutaneously into immunodeficient mice, and the survival of HUVEC^luc was monitored by bioluminescent imaging. After 60 days, the survival of HUVEC^luc transplanted alone was equivalent to that of HUVEC^luc co-transplanted with ASC-αMEM (15.0 ± 0.7 vs. 13.0 ± 0.5%). Strikingly, co-transplantation with ASC-EGM increased HUVEC^luc survival to 105.0 ± 3.5%, and the resulting organoids displayed functional vasculature with the highest human-derived vascular area. These findings demonstrate that pre-conditioning of ASCs in endothelial growth medium augment their pro-angiogenic properties and could enhance their therapeutic efficacy against ischemic diseases.

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Chronic spontaneous urticaria and the extrinsic coagulation system

Publication date: Available online 6 October 2017
Source:Allergology International
Author(s): Yuhki Yanase, Shunsuke Takahagi, Michihiro Hide
Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway. Moreover, the expression of TF on endothelial cells is synergistically enhanced by the activation of Toll-like receptors and histamine H1 receptors. The activated coagulation factors may induce plasma extravasation followed by degranulation of skin mast cells and edema formation recognized as wheal in CSU. Molecules involved in this cascade could be a target for new and more effective treatments of urticaria.



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Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data

Abstract

Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90-days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013–2014, with 3343 (13.2%) 30-day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90-day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery.

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Utility of Phox2b Immunohistochemical Stain in Neural Crest Tumors and Non-neural Crest Tumors in Pediatric Patients

Abstract

Background

This study evaluated the utility of Phox2b in pediatric tumors. Previously tyrosine hydroxylase (TH) was the most widely utilized sympathoadrenal marker specific for neural crest tumors with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity.

Methods

Phox2b IHC was performed on 159 pediatric tumors including (1) 65 neural crest tumors with neuronal differentiation [peripheral neuroblastic tumors (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn), and 10 ganglioneuroma (GN); (2) 23 neural crest tumors with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (3) 27 other neural crest tumors including one composite rhabdomyosarcoma/neuroblastoma; and (4) 44 non-neural crest tumors. TH IHC was performed on group (1), (2) and (3).

Results

Phox2b was diffusely expressed in pNT (n=65/65): strongly in NB-UD and NB-PD, and in NB-D, GNB and GN with less intensity. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but 9/15 NB-UD and a nodule in GNBn didn't express TH (n=55/65). PCC/PG expressed diffuse Phox2b (n=23/23) and diffuse TH except for one tumor (n=22/23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumors were negative for Phox2b (n=0/44).

Conclusion

Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacked TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural-crest origin.

This article is protected by copyright. All rights reserved.

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Alveolar herniation in transbronchial lung biopsy: a newly recognized diagnostic pitfall

Abstract

Artifacts in transbronchial lung biopsy (TBLB) related to the procedure or subsequent handling are well described in the literature, and some may lead to a misdiagnosis of non-small cell lung cancer (NSCLC). ^1,2,3 We report a series of 8 cases with another, yet undescribed artifact consisting of displacement of alveolar pneumocytes and macrophages into the bronchial mucosa posing a diagnostic challenge to distinguish it from lung cancer. The 5 men and 3 women aged between 36 and 82 years had a suspected clinical diagnosis of ILD (4x), diffuse ground glass opacities (2x) or bilateral pulmonary nodules (2x), respectively, with no clinical suspicion of lung cancer.

This article is protected by copyright. All rights reserved.

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Abstract: Facelift Technique for the Management of Soft Tissue Drooping after Facial Bone Contouring Surgery in Asian Patients

No abstract available

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Diagnostic flaws in oral lichen planus and related lesions

Publication date: Available online 6 October 2017
Source:Oral Oncology
Author(s): A. Thirumal Raj, Shankargouda Patil




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CRD and beyond: multivariable regression models to predict severity of hazelnut allergy

Abstract

Background

Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity.

Aim

To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy.

Methods

Patients reporting hazelnut allergy (n=423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during DBPCFC) were categorized in mild, moderate and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (OR) and areas under receiver operating characteristic (ROC) curves (AUC) were used to evaluate their predictive value.

Results

Cor a 9 and 14 were positively (OR 10.5 and 10.1 respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk), increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3% and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker.

Conclusion

A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

This article is protected by copyright. All rights reserved.

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Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack

Abstract

We studied the kinetics of C1-inhibitor (C1-INH) and other complement parameters in a self-limited edematous attack (EA) in a patient with hereditary angioedema due to C1-INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1-INH concentration and functional activity (C1-INH_c+f), C1(q,r,s), C3, C4, C3a, C4a, C5a and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period. The highest C1-INH_c+f, C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1-INH did not increase after resolution of the attack suggesting that factors other than C1-INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs.

This article is protected by copyright. All rights reserved.

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Microvasculature dropout detected by the optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy

Objective

To investigate microcirculation characteristics of peripapillary superficial retina and optic disc in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA).

Methods

Forty-one eyes of 30 NAION patients and 30 eyes of 30 normal subjects were evaluated with OCTA (AngioVue, Optovue). The whole vessel density, inside disc vessel density, peripapillary vessel density, and vessel densities based on the sectorial division in the nerve head mode peripapillary superficial retina and RPC mode optic disc were measured respectively.

Results

In the NAION group, vessel densities in both the peripapillary superficial retina and optic disc were significant reduced (P < 0.01), as compared with the control group. The whole vessel density of the optic disc in chronic NAION group were significantly lower than that in acute NAION group (P < 0.01). The whole and temporal vessel density of the peripapillary superficial retina was significantly correlated with log MAR VA (r = −0.381 and r = −0.337, both P < 0.05). Vessel densities in both the peripapillary superficial retina and optic disc were reduced (P < 0.05) in unilateral involved eyes, as compared to the unaffected fellow eyes, except for the inside disc (P = 0.270) and SN (P = 0.054) vessel density in the optic disc, while there was no difference in the fellow eyes compared to the normal eyes.

Conclusion

In NAION patients, a dropout of microvasculature in peripapillary superficial retina and optic disc could be detected by OCTA directly. OCTA might become a useful tool for detection and monitoring of NAION. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.

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Pilocytic Astrocytoma of Fornix Mimicking a Colloid Cyst: Report of 2 Cases and Review of the Literature

Publication date: January 2018
Source:World Neurosurgery, Volume 109
Author(s): Guive Sharifi, Reza Rahmanzadeh, Mahmoud Lotfinia, Ramin Rahmanzade
BackgroundColloid cyst is a gelatin-containing cyst in the brain almost always found in the third ventricle. The specific shape and location of these cysts, a round well-delineated mass in the rostral part of the third ventricle adjacent to the foramen of Monro, on imaging are the main findings for diagnosis. Several masses of the third ventricle masquerading colloid cysts on images have been reported. Based on different surgical approaches, preoperative misdiagnosis of colloid cyst may have great impact on prognosis.MethodsWe report 2 cases that presented with severe headache and hydrocephalus, and their preoperative images were highly indicative of colloid cyst.ResultsHistopathologic investigations after tumor resection showed pilocytic astrocytoma of fornix in both cases.ConclusionsFifteen cases of colloid cyst misdiagnosis with other masses have been reported thus far; among them, 2 cases were pilocytic astrocytoma. In this study we report 2 other cases. Furthermore, we discuss additional clues helping to differentiate pilocytic astrocytoma from colloid cyst on images.



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Persistent trigeminal artery variant terminating in the posterior inferior cerebellar artery: a case report

Abstract

Persistent trigeminal artery (PTA) is a rare cerebrovascular variation of remnant fetal carotid-vertebrobasilar anastomoses. The PTA variant terminates in the cerebellar artery with no direct connection to the basilar artery. We present a rare case of a PTA variant that terminated directly into the ipsilateral posterior inferior cerebellar artery.

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Concept, Importance and Practice of Lateral Tucking in Tympanoplasty

Abstract

The current study aims at observing the technique and results of doing lateral tucking during tympanoplasty surgery. It is intended to provide additional support to the graft and prevent displacement as well. 98 cases included in the study and the graft uptake rate of 97.96% noted. Average pre operative air bone gap (ABG) was 31.12 db and average post operative ABG observed to be 14.01 db. Gain of 17.11 ± 7 db achieved by the procedure. Lateral tucking is a concept that requires to be inculcated in routine tympanoplasty surgeries, especially where canal skin incisions are used. It is easy to practice and the results are good and complications are minimal.

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Premonitory urges and tics in Tourette syndrome: computational mechanisms and neural correlates

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Vasco A Conceição, Ângelo Dias, Ana C Farinha, Tiago V Maia
Tourette syndrome is characterized by open motor behaviors — tics — but another crucial aspect of the disorder is the presence of premonitory urges: uncomfortable sensations that typically precede tics and are temporarily alleviated by tics. We review the evidence implicating the somatosensory cortices and the insula in premonitory urges and the motor cortico-basal ganglia-thalamo-cortical loop in tics. We consider how these regions interact during tic execution, suggesting that the insula plays an important role as a nexus linking the sensory and emotional character of premonitory urges with their translation into tics. We also consider how these regions interact during tic learning, integrating the neural evidence with a computational perspective on how premonitory-urge alleviation reinforces tics.



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Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma

Abstract

Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18–80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14–38) versus 17% (95% CI 2–32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20–38) in the AXI-arm and 27.4 weeks (95% CI 18.4–36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls. There is no indication that upfront combination of axitinib with LOM improves results (European Clinical Trials Database (EudraCT) Study Number: 2011-000900-16).

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"Anticancer Res"[jour]; +91 new citations

91 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Anticancer Res"[jour]

These pubmed results were generated on 2017/10/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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TREM2 EXPRESSION IN THE HUMAN BRAIN: A MARKER OF MONOCYTE RECRUITMENT?

Abstract

Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labelled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68-positive but TREM2 negative. Our observations, using the HPA010917 anti-TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer's disease. This article is protected by copyright. All rights reserved.

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Redefining “Learning” in Statistical Learning: What Does an Online Measure Reveal About the Assimilation of Visual Regularities?

Abstract

From a theoretical perspective, most discussions of statistical learning (SL) have focused on the possible "statistical" properties that are the object of learning. Much less attention has been given to defining what "learning" is in the context of "statistical learning." One major difficulty is that SL research has been monitoring participants' performance in laboratory settings with a strikingly narrow set of tasks, where learning is typically assessed offline, through a set of two-alternative-forced-choice questions, which follow a brief visual or auditory familiarization stream. Is that all there is to characterizing SL abilities? Here we adopt a novel perspective for investigating the processing of regularities in the visual modality. By tracking online performance in a self-paced SL paradigm, we focus on the trajectory of learning. In a set of three experiments we show that this paradigm provides a reliable and valid signature of SL performance, and it offers important insights for understanding how statistical regularities are perceived and assimilated in the visual modality. This demonstrates the promise of integrating different operational measures to our theory of SL.

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Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy

Abstract

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3⁺ cells and CD8⁺ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16⁺ and CD68⁺ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

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Write right, quite right: Orthography in Latin anatomical terms

Abstract

Spelling variants are common in Latin anatomical terms. Some of these variants cause confusion with respect to the meaning of the word by altering the base of the word to resemble a different word base. Thus these variants should be considered errors, comparable to errors in declension of nouns and adjectives, and errors in the formation of neologisms. Use of correct Latin words in Latin anatomical terms should increase the rigor, stability and universality of the nomenclature. This article is protected by copyright. All rights reserved.

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The new frontier of studying human anatomy - introducing evidence-based anatomy

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Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy

Abstract

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3⁺ cells and CD8⁺ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16⁺ and CD68⁺ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

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Emerging techniques in assessment and treatment of muscle tension dysphonia.

Emerging techniques in assessment and treatment of muscle tension dysphonia.

Curr Opin Otolaryngol Head Neck Surg. 2017 Oct 03;:

Authors: Andreassen ML, Litts JK, Randall DR

Abstract
PURPOSE OF REVIEW: The purpose of this review is to summarize current evidence regarding treatment for muscle tension dysphonia (MTD) and to present recent advances in evaluation and management.
RECENT FINDINGS: It is generally accepted that voice therapy for MTD is effective, but current systematic reviews report limited evaluation specific to MTD patients with moderate evidence, at best, available to support voice therapy techniques. Individual studies are difficult to compare because of heterogeneity. Considerable work is underway to identify most important metrics to include in assessment, and to advance and define direct voice therapy approaches.
SUMMARY: Further standardization of assessment and treatment protocols for MTD will improve future research. Novel therapeutic techniques are under investigation. In small studies, these have found value in improving voice outcomes and measures compared with pretreatment values but have not met success greater than existing therapeutic methods.

PMID: 28984699 [PubMed - as supplied by publisher]

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Speech-Language Pathology Evaluation and Management of Hyperkinetic Disorders Affecting Speech and Swallowing Function.

Speech-Language Pathology Evaluation and Management of Hyperkinetic Disorders Affecting Speech and Swallowing Function.

Tremor Other Hyperkinet Mov (N Y). 2017;7:489

Authors: Barkmeier-Kraemer JM, Clark HM

Abstract
BACKGROUND: Hyperkinetic dysarthria is characterized by abnormal involuntary movements affecting respiratory, phonatory, and articulatory structures impacting speech and deglutition. Speech-language pathologists (SLPs) play an important role in the evaluation and management of dysarthria and dysphagia. This review describes the standard clinical evaluation and treatment approaches by SLPs for addressing impaired speech and deglutition in specific hyperkinetic dysarthria populations.
METHODS: A literature review was conducted using the data sources of PubMed, Cochrane Library, and Google Scholar. Search terms included 1) hyperkinetic dysarthria, essential voice tremor, voice tremor, vocal tremor, spasmodic dysphonia, spastic dysphonia, oromandibular dystonia, Meige syndrome, orofacial, cervical dystonia, dystonia, dyskinesia, chorea, Huntington's Disease, myoclonus; and evaluation/treatment terms: 2) Speech-Language Pathology, Speech Pathology, Evaluation, Assessment, Dysphagia, Swallowing, Treatment, Management, and diagnosis.
RESULTS: The standard SLP clinical speech and swallowing evaluation of chorea/Huntington's disease, myoclonus, focal and segmental dystonia, and essential vocal tremor typically includes 1) case history; 2) examination of the tone, symmetry, and sensorimotor function of the speech structures during non-speech, speech and swallowing relevant activities (i.e., cranial nerve assessment); 3) evaluation of speech characteristics; and 4) patient self-report of the impact of their disorder on activities of daily living. SLP management of individuals with hyperkinetic dysarthria includes behavioral and compensatory strategies for addressing compromised speech and intelligibility. Swallowing disorders are managed based on individual symptoms and the underlying pathophysiology determined during evaluation.
DISCUSSION: SLPs play an important role in contributing to the differential diagnosis and management of impaired speech and deglutition associated with hyperkinetic disorders.

PMID: 28983422 [PubMed - in process]

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Velopharyngeal Dystonia: An Unusual Focal Task-specific Dystonia?

Velopharyngeal Dystonia: An Unusual Focal Task-specific Dystonia?

Tremor Other Hyperkinet Mov (N Y). 2017;7:365

Authors: Patel AS, Sulica L, Frucht SJ

Abstract
BACKGROUND: Velopharyngeal dysfunction produces a nasal speech pattern because of the inability to close the nasal airway during speech, most often associated with anatomical abnormalities of the palate.
CASE REPORT: We describe two cases of possible velopharyngeal dystonia, a task-specific movement disorder causing a speech pattern similar to velopharyngeal dysfunction. Both patients experienced treatment response with anticholinergic medication.
DISCUSSION: Dystonia affecting speech via involvement of the pharyngeal musculature may be an unrecognized etiology of voice disorders.

PMID: 28983420 [PubMed - in process]

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Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs

Abstract

Lower limbs represent the second most common site of all melanomas and the first one in females (1,2). Few studies have explored the diagnostic clues helping in the early diagnosis for melanoma on lower limbs (3).

This article is protected by copyright. All rights reserved.

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Development of an international core outcome set for peripheral vascular malformations (OVAMA project)

Summary

Background

An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome.

Objective

The Outcome measures for VAscular MAlformations (OVAMA) project aimed to reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS.

Methods

Thirty-six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a 3-round e-Delphi process using online surveys, participants repeatedly rated the importance of these domains on a 5-point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was pre-defined as 80% agreement on the importance of a domain amongst both the physician group and the patient/parent group. Outcomes were then reevaluated in an online consensus meeting.

Results

167 physicians and 134 patients and parents of patients with LM (n=50), VM (n=71) and AVM (n=29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician-reported location-specific signs, patient-reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type-specific signs and symptoms were included for LM, VM and AVM, separately.

Conclusion

It is recommended to measure at least these core outcome domains in therapeutic-efficacy studies on peripheral vascular malformations.

This article is protected by copyright. All rights reserved.

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Prevalence of Goitre in Raichur District (Karnataka): A Descriptive Study

Abstract

This prevalence study was exclusively for the goitre detection in individuals who has no prior awareness of thyroid disorder and also those patients giving history of signs and symptoms of such conditions. Subjects underwent investigations for (T3, T4, TSH and FNAC) to analyze status and type of Goitre. Of the first 30 cases, only 8 cases were investigated and later on personal  interest  for confirmation of goitre disorder prevalence additional 70 cases were assessed of which 51 cases were investigated. On basis of investigation and epidemiology, we concluded that probably soil and water sources contain less iodine. Sample shown are comparatively less, but in our area number of goitre  cases are more and it needs further extensive survey.

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The Association Between Habitual Walking Speed and Medial Femoral Cartilage Deformation Following 30-Minutes Of Walking

Publication date: Available online 7 October 2017
Source:Gait & Posture
Author(s): Matthew S. Harkey, J. Troy Blackburn, Hope Davis, Leslie Sierra-Arévalo, Daniel Nissman, Brian Pietrosimone
Habitual walking speed is a key functional outcome that has implications for knee biomechanics that occur during gait. Lower extremity biomechanics during walking affects the loading of the femoral cartilage. Ultrasonography (US) can be used to assess resting femoral cartilage thickness and acute cartilage deformation in response to walking. The purpose of this study was to determine the association between habitual walking speed and both resting femoral cartilage thickness and deformation. Twenty-four healthy participants with no history of knee injury volunteered for this study. Habitual walking speed was assessed with a 20-meter walk test. Femoral cartilage thickness was assessed with US in the medial condyle, lateral condyle, and intercondylar regions prior to and immediately following 30minutes of walking. Femoral cartilage deformation was calculated as the percent change in cartilage thickness acutely following the walking protocol. Separate Pearson product moment correlations were used to assess the association between habitual walking speed and each US cartilage variable. Slower habitual walking speed was significantly associated with greater medial femoral cartilage deformation (r=0.48, P=0.018), but not with lateral and intercondylar deformation. Habitual walking speed was not significantly associated with the resting cartilage thickness in any cartilage region. These findings highlight the in vivo association between walking speed and medial femoral cartilage deformation. When controlling for body mass index, the association between walking speed and medial cartilage deformation was weakened (Δr=−0.12). Future studies are needed to determine the extent to which BMI influences the association between walking speed and cartilage deformation.



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Accuracy of three methods in gait event detection during overground running

Publication date: Available online 6 October 2017
Source:Gait & Posture
Author(s): Shiwei Mo, Daniel H.K. Chow
Inertial measurement units (IMUs) have been extensively used to detect gait events. Various methods have been proposed for detecting initial contact (IC) and toe-off (TO) using IMUs affixed at various anatomical locations. However, the accuracy of such methods has yet to be compared. This study evaluated the accuracy of three common methods used for detecting gait events during jogging and running: (1) S-method, in which IC is identified as the instant of peak foot-resultant acceleration and TO is identified when the acceleration exceeds a threshold of 2g in the region of interest; (2) M-method, in which IC and TO are defined as the minimum before the positive peak shank vertical acceleration and the minimum in the region of interest, respectively; and (3) L-method, in which IC is indicated by the instant of peak pelvis anteroposterior acceleration and TO is identified by the maximum in the region of interest. The performance of the IMU-based methods in detecting IC and TO and estimating stance time (ST) were tested on 11 participants at jogging and running speeds against a reference provided by a force-platform method. The S-method was the most accurate for IC detection (overall mean absolute difference (MAD): 4.7±4.1ms). The M-method was the most accurate for TO detection (overall MAD: 7.0±3.5ms). A combination of M- and S-methods, called the MS-method, was the most accurate for ST estimation (overall MAD: 9.0±3.9ms). Thus, the MS-method is recommended for ST estimation; however, this method requires four IMUs for bilateral estimation.



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ADAM8 expression in breast cancer derived metastases: Functional implications on MMP-9 expression and transendothelial migration in breast cancer cells

Abstract

Metastatic breast cancer affects long-term survival and is a major cause of cancer death for women worldwide. The Metalloprotease-Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB-231 breast cancer cells with ADAM8 knockdown (MB-231_shA8) and scramble control cells (MB-231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB-231_shA8 in contrast to MB-231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood-brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP-9 gene was affected by ADAM8 knockdown in MB-231_shA8 cells. Following re-expression of wild-type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB-231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP-9 transcription. Application of ADAM8 and MMP-9 antibodies reduced transmigration of MB-231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP-9 regulation. ADAM8-dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB-231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P-selectin glycoprotein ligand (PSGL-1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP-9 and shedding of PSGL-1 from breast cancer cells. This article is protected by copyright. All rights reserved.

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Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy

Abstract

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3⁺ cells and CD8⁺ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16⁺ and CD68⁺ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

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Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02

Abstract

Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination.

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Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli

Abstract

During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information.

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