Tracking small sensory nerve action potentials in human axonal excitability studies

Publication date: Available online 11 February 2018
Source:Journal of Neuroscience Methods
Author(s): James Howells, Hugh Bostock, Susanna B. Park, Matthew C. Kiernan, David Burke
BackgroundExcitability studies on normal and diseased human axons in vivo have been greatly enhanced by fast non-invasive threshold-tracking techniques, using surface stimulation and recording. Although sensory axons are often more affected in disease, most studies to date have focussed on motor axons, because of technical difficulties in resolving pathologically small nerve volleys in the presence of noise and stimulus artefact.New MethodsThis paper describes techniques for tracking low-amplitude compound action potentials, using a battery-powered, isolated preamplifier of simple construction with high common mode rejection (>125 dB [balanced inputs]) and low noise (<0.4 μV referred to inputs [shorted]).ResultsWe demonstrate the preamplifier's capability by tracking targets as small as 2 μV for a full range of excitability measurements without the usual distortion due to residual stimulus artefact and without the need for clamping, additional filtering or ensemble averaging.Comparison with existing methodsIn practice, threshold-tracking studies have been unable to study sensory axons when the maximal compound sensory action potential was less than about 15 μV. The techniques and amplifier in the present study allow measurements to be made from nerve with maximal responses less than half that size, and we present three recordings in patients with pathologically small nerve action potentials ≤7 μV.ConclusionsBased on measurements of stimulus artefact distortion, noise and the performance in experiments, we conclude that the techniques described here will facilitate the study of diseased axons for which the sensory potentials have high thresholds and may be only a few microvolts in amplitude.



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Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

This article is protected by copyright. All rights reserved.

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The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening

Publication date: Available online 11 February 2018
Source:Pathology - Research and Practice
Author(s): Yibing Fan, Zongji Shen
ObjectiveTo explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions.Methods192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively.Results1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs + ), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ² = 1.05, P> 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively.Conclusions1. The expression of HPV E6/E7 and STAT3 mRNA confirmed using FISH assay is expected to be a new method and molecular marker for cervical lesions screening. Survivin mRNA was excluded due to its poor performance. 2. HPV E6/E7, STAT3, and STAT3 +HR-HPV assays could be new approaches for cervical cancer screening and ASCUS triage, and the efficiency of combined screening program was better than that of a separate one. 3. HPV E6/E7 + STAT3 regimen is expected to be a diagnostic strategy for cervical lesions.



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Colchicine in dermatology: A review

Abstract

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

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Dystrophic calcinosis cutis within burns, successfully treated with excision and secondary intention wound healing

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Strain hardening reduces energy absorption efficiency of austenitic stainless steel foams while porosity does not

Publication date: 5 April 2018
Source:Materials & Design, Volume 143
Author(s): Ali Can Kaya, Paul Zaslansky, Mehmet Ipekoglu, Claudia Fleck
Strain hardening significantly affects the mechanical function of steel foams. We compare hardening and failure of two commercially available austenitic stainless steel foams (316L and 310) spanning strut porosities of 9.4 to 14.4%. Damage is correlated with strut microstructure and geometry, combining in-situ quasi-static compression testing in the SEM, 3D-evaluation by synchrotron μCT and bending simulations. We provide an analytical model for the experimentally observed strain hardening. Upon compression, 316L steel foams exhibit a plateau regime of continuously increasing stress due to the hardening effect, whereas 310 steel foams show almost constant plateau stress. This is explained by the much less ductile behaviour of the 310 steel foam struts as compared to 316L steel foam struts. Finite element modelling suggests that significant stress concentrations develop around microporosities in the 310 struts. Due to its finer and less porous microstructure, the 316L foam exhibits a larger energy absorption capacity than the 310 foams. This results in distinctly different efficiency-strain curves. However, up to about 25% strain, the efficiency values are surprisingly similar. Thus, modification of microstructure and/or pore micro-geometry can be used to optimise the stress-strain response to achieve the desired energy absorption property of steel foams.

Graphical abstract

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Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: Efficacy and foetal outcome a randomised double-blinded trial

BACKGROUND During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN A randomised, double-blind, controlled study. SETTING Single University Hospital. PATIENTS Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 μg kg−1 over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 μg kg−1 h−1 dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION Administration of dexmedetomidine in doses 0.4 and 0.6 μg kg−1 h−1 was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org). Correspondence to Ashraf M. Eskandr, MD, Department of Anesthesia, ICU and Pain Therapy, Faculty of Medicine, Menoufiya University, 3 Yassin Abd-Elghafar Street, Shibin El-koom, Egypt E-mail: ameskandr@yahoo.com © 2018 European Society of Anaesthesiology

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Low anaesthetic waste gas concentrations in postanaesthesia care unit: A prospective observational study

BACKGROUND Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S) The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN A prospective observational study. SETTING Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ± 0.20 ppm in postanaesthesia unit one, 0.82 ± 0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded. Correspondence to Dr. Sebastian Heiderich, MD, Clinic of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany E-mail: heiderich.sebastian@mh-hannover.de © 2018 European Society of Anaesthesiology

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Low perfusion pressure is associated with renal tubular injury in infants undergoing cardiac surgery with cardiopulmonary bypass: A secondary analysis of an observational study

BACKGROUND Earlier work on adults undergoing surgery with cardiopulmonary bypass suggests that there is a close relationship between the lower limit of the cerebral and renal autoregulation pressures. Although cerebral autoregulation during bypass in infants has been extensively investigated, the impact of bypass on kidney function is not well known. It is, nevertheless, acknowledged that the main pathophysiological process involved in cardiac surgery-related kidney damage is tubular injury, and that urine neutrophil gelatinase-associated lipocaline (uNGAL) is a reliable biomarker of injury. OBJECTIVE To identify the most predictive bypass variable for the measurement of renal injury, its threshold value and the most predictive time below that threshold. DESIGN Observational study linking electronically recorded bypass perfusion pressure and oxygen delivery rate with intra-operative uNGAL excretion. Variations in bypass variables were accounted for by their excursions below several thresholds. SETTING French tertiary referral paediatric cardiac centre. PATIENTS A total of 72 infants in whom uNGAL was measured within 1 h of bypass. INTERVENTIONS None. MAIN OUTCOME MEASURE Renal injury, identified by a high creatinine normalised uNGAL concentration (>21.2 μg mmol−1). RESULTS At the end of bypass, 43.75% of infants had high uNGAL. A more than 40% pressure drop below the normal age-standardised mean arterial pressure was associated with high uNGAL. Receiver operating curve [interquartile range] areas were 0.626 [0.501 to 0.752] for a more than 40% drop, and 0.679 [0.555 to 0.804] for a more than 50% drop. A more than 40% pressure drop for 19.5 min provided a 0.65 negative predictive value for high uNGAL, and a more than 50% pressure drop for 5.4 min provided a 0.67 negative predictive value. The link between uNGAL and oxygen delivery rate was negligible. CONCLUSION Maintaining the perfusion pressure above 60% of the normal age-standardised mean arterial pressure may provide an effective renal protective strategy. TRIAL REGISTRATION Registered on October 11, 2010, ClinicalTrials.gov Identifier: NCT01219998. Correspondence to Mirela Bojan, MD, PhD, Department of Anaesthesiology and Critical Care, Necker-Enfants Malades University Hospital, Assistance Publique – Hôpitaux de Paris, 149, rue de Sèvres, 75743 Paris, France Tel: +33 171396663; e-mail: mirela.bojan@nck.aphp.fr © 2018 European Society of Anaesthesiology

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Electromyographic findings in sporadic inclusion body myositis

Publication date: Available online 11 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Monika Nojszewska, Malgorzata Gawel, Biruta Kierdaszuk, Janusz Sierdziński, Elżbieta Szmidt-Sałkowska, Andrzej Seroka, Anna M. Kamińska, Anna Kostera-Pruszczyk
IntroductionClinically oriented diagnostic criteria can be as specific for diagnosis of sporadic inclusion body myositis (sIBM) as pathological criteria, especially at the time of presentation. EMG may provide an convincing proof that a muscle biopsy should be performed.Aimsto compare the EMG results in patients with sIBM divided into subgroups based on the newest ENMC criteria for sIBM and to obtain the utility of EMG in the diagnostic process at the time of presentation.MethodsWe retrospectively analysed 16 patients with sIBM for motor unit action potential (MUAP) morphology as well as occurrence and distribution of abnormal spontaneous activity (SA) in muscles.ResultsAbnormal SA was recorded in 62.5% of sIBM patients. We found statistically significant differences between subgroups in the incidence of polyphasic MUAPs and high amplitude outliers which were more commonly seen in the "clinico-pathologically defined sIBM". Duration of MUAP in the tibialis anterior was significantly shorter in "probable sIBM". Discussion"Pseudo-neurogenic" MUAPs, mainly in lower limb muscles, are more commonly seen in "clinico-pathologically defined sIBM" while myopathic MUAPs with prominent abnormal SA are recorded in patients diagnosed with "probable sIBM". Both EMG patterns may be suggestive of sIBM and be an indication for further diagnosis.



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Radiation Pneumonitis in Pediatric Hodgkin Lymphoma Patients receiving Radiotherapy to the Chest

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Gary D. Lewis, Jennifer E. Agrusa, Bin S. Teh, Maria M. Gramatges, Viral Kothari, Carl E. Allen, Arnold C. Paulino
PurposeThe purpose of this study is to determine the incidence of radiation pneumonitis (RP) in children receiving radiotherapy (RT) for Hodgkin lymphoma (HL).Patients/MethodsA retrospective chart review was conducted of pediatric HL patients who received multiagent chemotherapy followed by RT to any part of the chest. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to determine the RP grade. Parameters analyzed included gender, age, bleomycin dose, and RT dosimetric variables such as mean lung dose (MLD), mean individual (right versus left) lung dose or iMLD, V5 to V25 and individual (i) lung V5 to V25.ResultsFrom 2008-2016, 54 children with HL received RT to the chest and had follow-up and dosimetry information. All patients received induction chemotherapy; the most common regimen was ABVE-PC based chemotherapy (n = 48). All received a prescribed dose of 21 Gy in 14 fractions. Median follow-up from completion of RT was 39.5 months. Three of 54 patients (5.6%) or 3 of 108 (2.8%) lungs developed RP; two lungs had Grade 1 while one had Grade 2 RP. RP was seen only in patients with MLD > 12.4 Gy (p = 0.009), V5 > 66% (p = 0.033), V10 >55% (p = 0.015), V15 >45% (p = 0.005) and V20 > 32% (p = 0.007). Likewise, RP was only seen in lungs with iMLD > 13.8 Gy, iV5 > 75% (p =0.02), iV10 > 64% (p = 0.02), iV15 > 47% (< 0.005), and iV20 >34% (p = 0.003).ConclusionsRP in pediatric HL patients is an uncommon complication. MLD, iMLD, V5-V20 and iV5-iV20 correlated with RP.



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Design and Evaluation of a Safety-Centered User Interface for Radiation Therapy

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Ashleigh P. Shier, Plinio P. Morita, Colleen Dickie, Mohammad Islam, Catherine Burns, Joseph A Cafazzo
PurposeAs radiotherapy treatment grows more complex over time, treatment delivery has become more susceptible to adverse events and patient safety risks due to use error. The radiotherapy monitoring and treatment delivery user interface explored in this study was redesigned using ecological interface design, a human factors engineering method, and evaluated to improve treatment safety.Methods and MaterialsAn initial design concept was created based on previously completed analysis, and informally evaluated in focus groups with radiation therapists. Sixteen newly graduated radiation therapists used both the redesigned and current system in a usability test to determine if the redesigned system better supported detection of errors.ResultsThe redesigned system successfully improved the error detection rate of two errors, wrong treatment volume and wrong treatment site (p < 0.03 and p < 0.01, respectively). It also improved Level 2 and Level 3 situation awareness, i.e. comprehension of the meaning of the information and the projection of the behavior of the technology (p < 0.01 and p < 0.01 respectively), and achieved a higher user satisfaction.ConclusionsThe ecological interface design approach was found to be effective in redesigning a radiotherapy treatment delivery interface. Radiation therapists were able to deliver simulated radiation therapy with a higher rate of error detection, improved higher-level situation awareness, and participants preferred the redesigned interface to the current interface. Overall, the redesigned interface improved the radiation therapists' system understanding and ability to detect errors that affect patient safety.



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Impact of timing of radiotherapy on outcomes in atypical meningioma: a clinical audit

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): Sidharth Pant, Raees Tonse, Sadhana Kannan, Aliasgar Moiyadi, Prakash Shetty, Sridhar Epari, Ayushi Sahay, Goda Jayant Sastri, Rakesh Jalali, Tejpal Gupta
BackgroundRole of early adjuvant radiotherapy (RT) in patients with atypical meningioma remains controversial.PurposeTo report the impact of timing of RT on outcomes in atypical meningioma.MethodsPatients of atypical meningioma were identified through electronic search of institutional database. Following surgery, RT was delivered either in upfront adjuvant setting (early adjuvant RT) or after recurrence/progression (salvage RT).ResultsThere were 51 patients in early adjuvant RT group and 30 patients in salvage RT group. Six of 51 (12%) patients in early adjuvant RT group recurred/progressed compared to 34 of 35 (97%) patients kept on observation after initial surgery. Thirty of these 34 patients received salvage RT, mostly after re-excision. Twelve of 30 (40%) patients recurred/progressed after salvage RT, compared to 6 of 51 (12%) patients after early adjuvant RT (p=0.003). Post-RT 5-year progression-free survival was significantly better for early adjuvant RT compared to salvage RT (69% vs 28%, log-rank p<0.001).ConclusionsWithin the limitations of any retrospective analysis, upfront early adjuvant RT can significantly reduce the risk of local recurrence/progression in atypical meningiomas compared to initial observation. A sizeable proportion of patients who are observed initially recur/progress over time necessitating salvage therapy. However, re-excision followed by salvage RT may not be as effective as early adjuvant RT.



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Management of Paranasal Sinus Metastasis by Percutaneous CT guided Permanent Seed Brachytherapy: Technical Report

Publication date: Available online 1 February 2018
Source:Practical Radiation Oncology
Author(s): Stephen Doggett, Shigeru Chino, Todd Lempert, Kunal Sidhar




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Pre-Operative Contralateral Radiation Lung Dose is Associated with Post-Operative Pulmonary Toxicity in Patients with Locally-Advanced Non-Small Cell Lung Cancer Treated with Trimodality Therapy

Publication date: Available online 31 January 2018
Source:Practical Radiation Oncology
Author(s): Wenji Guo, Xuan Hui, Salem Alfaifi, Lori Anderson, Scott Robertson, Russell Hales, Chen Hu, Todd McNutt, Stephen Broderick, Jarushka Naidoo, Richard Battafarano, Stephen Yang, K. Ranh Voong
PurposeIn patients with non-small cell lung cancer (NSCLC) who undergo trimodality therapy (chemoradiation followed by surgical resection), it is unknown whether limiting pre-operative radiation dose to the uninvolved lung reduces post-surgical morbidity. This study evaluated whether radiation fall-off dose parameters to the contralateral lung, that is unaffected by NSCLC, are associated with post-operative complications in NSCLC patients treated with trimodality therapy.Methods and materialsWe retrospectively reviewed NSCLC patients who underwent trimodality therapy between March 2008-October 2016, with available restored digital radiation plans. Fischer's exact test was used to assess associations between patient and treatment characteristics and the development of treatment-related toxicity. Spearman's rank correlation was used to measure the strength of association between dosimetric parameters.ResultsForty-six patients were identified who received trimodality therapy with intensity modulated radiation (median 59.4 Gy, range 45-70) and concurrent platinum doublet chemotherapy, followed by surgical resection. The median age was 64.9 years (range 45.6-81.6 years). The median follow-up time was 1.9 years (range 0.3-8.4 years). Twenty-four (52.2%) patients developed any grade pulmonary toxicity and 14 (30.4%) patients developed grade 2+ pulmonary toxicity. There was an increased incidence of any grade pulmonary toxicity in patients with contralateral lung V20≥7% compared to <7% (90%, n=9 versus 41.7%, n=15; p=0.01). Similarly, contralateral lung V10≥20% was associated with an increased rate of any grade pulmonary toxicity compared to V10<20% (80%, n=12 versus 38.7%, n=12; p=0.01). Pneumonectomy/bilobectomy was associated with grade 2+ pulmonary toxicity (p=0.04).ConclusionsPatients who received a higher radiation fall-off dose volume parameter (V20≥7% and V10≥20%) to the contralateral uninvolved lung had a higher incidence of any grade post-operative pulmonary toxicity. Limiting radiation fall-off dose to the uninvolved lung may be an important modifiable radiation parameter in limiting post-operative toxicity in trimodality patients.



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NRG Oncology Medical Physicists’ Manpower Survey Quantifying Support Demands for Multi-Institutional Clinical Trials

Publication date: Available online 4 February 2018
Source:Practical Radiation Oncology
Author(s): James I Monroe, Karan Boparai, Ying Xiao, David Followill, James M Galvin, Eric E Klein, Daniel Low, Jean M Moran, Haoyu Zhong, Jason W Sohn
PurposeA survey was created by XXXX to assess a medical physicists' percent Full Time Equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 ASTRO report, 'Safety Is No Accident', quantified medical physics staffing contributions in FTE Factors for clinical departments. No quantification of FTE effort associated with clinical trials was included.MethodsTo address this lack of information, the XXXX Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of sixteen questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiotherapy institutions included on the membership rosters of the five NCTN clinical trial groups.ResultsOf the 451 institutions who responded; fifty percent (226) of the respondents reported currently participating in radiotherapy trials. On average, the designated physicist at each institution spent 2.4 hours (SD: 5.5 hours) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD: 3.1 hours), 1.8 hours (SD: 3.9 hours), and 0.6 hours (SD: 1.1 hours) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a DICOM server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD: 57.2 hours) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD: 3.4 hours) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD: 1.9 hours) per month.ConclusionOn average, physicist spent a non-trivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiotherapy clinical trials and should be taken into account when staffing radiotherapy institutions.



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Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected non-enhancing tumor for radiotherapy planning of glioblastoma

Publication date: Available online 31 January 2018
Source:Practical Radiation Oncology
Author(s): Aimee R Hayes, Dasantha Jayamanne, Edward Hsiao, Geoffrey P Schembri, Dale L Bailey, Paul J Roach, Mustafa Khasraw, Allison Newey, Helen R Wheeler, Michael Back
AimTo evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiotherapy planning for patients diagnosed with glioblastoma (GBM) and presence of suspected non-enhancing tumors compared with standard magnetic resonance imaging (MRI).MethodsPatients with GBM and contrast-enhancing MRI showing regions suspicious of non-enhancing tumor underwent post-operative FET-PET prior to commencing radiotherapy. Two Clinical Target Volumes (CTVs) were created using pre- and post-operative MRI; MRI-FLAIR sequences (CTVFLAIR) and MRI contrast sequences with an expansion on the surgical cavity (CTVSx). FET-PET was used to create Biological Tumor Volumes (BTVs) by encompassing FET avid regions, forming a BTVFLAIR and BTVSx. Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTVFLAIR and BTVSx. Presence of focal gadolinium contrast enhancement within previously non-enhancing tumor or within the FET avid region was noted on MRI at one and three months after radiotherapy.ResultsTwenty-six patients were identified retrospectively from our database, of which 24 had demonstrable FET uptake. The median CTVFLAIR, CTVSx, BTVFLAIR and BTVSx was 57.1 cc (range 1.1-217.4), 83.6 cc (range 27.2-275.8), 62.8 cc (range 1.1-307.3) and 94.7 cc (range 27.2-285.5) respectively. When FET-PET was utilized, there was a mean increase in volume from CTVFLAIR to BTVFLAIR by 26.8% and CTVSx to BTVSx by 20.6%. A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTVFLAIR and BTVFLAIR (P<0.0001) and CTVSx and BTVSx (p<0.0001). Six out of 24 patients (25%), with FET avidity prior to radiotherapy, showed focal gadolinium enhancement within the radiotherapy portal.ConclusionFET-PET may help improve delineation of GBM in cases with a suspected non-enhancing component. This may result in improved radiotherapy target delineation and reduce the risk of potential geographical miss.SummaryWe investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiotherapy planning for patients diagnosed with glioblastoma (GBM) and a suspected non-enhancing tumor compared with standard magnetic resonance imaging (MRI). We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. In conclusion, FET-PET may help improve delineation of GBM in cases with a suspected non-enhancing component and reduce the risk of potential geographical miss.



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Development of a Virtual Radiation Oncology Clinic for training and simulation of errors in the radiation oncology workflow

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): TR Willoughby, SL Meeks, P Kelly, T Dvorak, K. Muller, T. Dana, F Bova




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An interactive contouring module improves engagement and interest in radiation oncology among pre-clinical medical students: Results of a randomized trial

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): Pushpa Neppala, Michael Sherer, Grant Larson, Alex Bryant, Neil Panjwani, James D. Murphy, Erin F Gillespie
PurposeStudies have shown significant gaps in knowledge of radiation therapy among medical students and primary care providers. The goal of this study was to evaluate the impact of an interactive contouring module on knowledge and interest in radiation oncology among pre-clinical medical students.Methods and MaterialsSecond year medical students at *** were randomized to participate in an interactive contouring exercise or watch a traditional didactic lecture on radiation oncology. Participants completed knowledge tests and surveys at baseline, immediately following the exercise, and 3 months later. Statistical analysis included Wilcoxon signed-rank test for pre- and post-test comparisons and Wilcoxon rank sum test for comparison between groups.ResultsForty-three medical students participated in the trial (21 in the didactic group and 22 in the contouring group). Students completing the contouring module demonstrated similar overall knowledge improvement compared to the traditional didactic group (+8.6% vs. +6.6%, NS) but endorsed greater engagement on a 5-point Likert-type scale (3.10 vs 3.76, p=0.02). At 3-month follow-up, there was a non-significant trend toward improved overall knowledge in the contouring group (43% vs. 51%, p=0.10), with a significance difference in a subset of questions on knowledge of the process of radiation therapy as well as side effects (51% vs. 75%, p=0.002). Students in the contouring group demonstrated more interest in pursuing a clinical radiation oncology rotation (2.52 vs 3.27, p=0.01).ConclusionsUse of an interactive contouring module was an effective method to teach pre-clinical medical students about radiation oncology, with no significant difference in knowledge gained compared to a traditional didactic lecture. However, higher engagement among students completing the contouring module led to improved retention of knowledge of radiation side effects and greater interest in radiation oncology. These data suggest a potential benefit of integrating an interactive radiation oncology module into the pre-clinical medical school curriculum.



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Stereotactic body radiotherapy for high-risk prostate cancer: Not ready

Publication date: Available online 12 January 2018
Source:Practical Radiation Oncology
Author(s): Trevor J. Royce, Ronald C. Chen




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On the origin of epileptic High Frequency Oscillations observed on clinical electrodes

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Mohamad Shamas, Pascal Benquet, Isabelle Merlet, Mohamad Khalil, Wassim El Falou, Anca NICA, Fabrice Wendling
ObjectiveIn this study we aim to identify the key (patho)physiological mechanisms and biophysical factors which impact the observability and spectral features of High Frequency Oscillations (HFOs).MethodsIn order to accurately replicate HFOs we developed virtual-brain / virtual-electrode simulation environment combining novel neurophysiological models of neuronal populations with biophysical models for the source/sensor relationship. Both (patho)physiological mechanisms (synaptic transmission, depolarizing GABAA effect, hyperexcitability) and physical factors (geometry of extended cortical sources, size and position of electrodes) were taken into account. Simulated HFOs were compared to real HFOs extracted from intracerebral recordings of 2 patients.ResultsOur results revealed that HFO pathological activity is being generated by feed-forward activation of cortical interneurons that produce fast depolarizing GABAergic post-synaptic potentials (PSPs) onto pyramidal cells. Out of phase patterns of depolarizing GABAergic PSPs explained the shape, entropy and spatiotemporal features of real human HFOs.ConclusionsThe terminology "high-frequency oscillation" (HFO) might be misleading as the fast ripple component (200-600Hz) is more likely a "high-frequency activity" (HFA), the origin of which is independent from any oscillatory process.SignificanceNew insights regarding the origins and observability of HFOs along depth-EEG electrodes were gained in terms of spatial extent and 3D geometry of neuronal sources.



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10-10 Electrode Placement System

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Marc R. Nuwer




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To warn or not to warn: A reappraisal of brainstem auditory evoked potential warning criteria during surgery

Publication date: Available online 11 February 2018
Source:Clinical Neurophysiology
Author(s): Aatif M. Husain




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A novel antibody-based approach to detect the functional ERCC1-202 isoform

Publication date: Available online 11 February 2018
Source:DNA Repair
Author(s): Mei-Shiue Kuo, Julien Adam, Nicolas Dorvault, Angélique Robin, Luc Friboulet, Jean-Charles Soria, Ken A. Olaussen
ERCC1/XPF endonuclease plays an important role in multiple DNA repair pathways and stands as a potential prognostic and predictive biomarker for cisplatin-based chemotherapy. Four distinct ERCC1 isoforms arising from alternative splicing have been described (201, 202, 203 and 204) but only the 202 isoform is functional in DNA excision repair, when interacting with its obligate partner XPF. Currently, there is no tool to assess specifically the expression of ERCC1-202 due to high sequence homology between the four isoforms. Here, we generated monoclonal antibodies directed against the heterodimer of ERCC1 and its obligate interacting partner XPF by genetic immunization. We obtained three monoclonal antibodies (2C11, 7C3 and 10D10) recognizing specifically the heterodimer ERCC1-202/XPF as well as the ERCC1-204/XPF with no affinity to ERCC1 or XPF monomers. By combining one of these three heterodimer-specific antibodies with a commercial anti-ERCC1 antibody (clone 4F9) unable to recognize the 204 isoform in a proximity ligation assay (PLA), we managed to specifically detect the functional ERCC1-202 isoform. This methodological breakthrough can constitute a basis for the development of clinical tests to evaluate ERCC1 functional proficiency.



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The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation

Publication date: Available online 11 February 2018
Source:DNA Repair
Author(s): Olga Kladova, Milena Bazlekowa-Karaban, Sonia Baconnais, Olivier Pietrement, Alexander A. Ishchenko, Bakhyt T. Matkarimov, Olga S. Fedorova, Eric Le Cam, Barbara Tudek, Nikita A. Kuznetsov, Murat Saparbaev
The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3′-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a.k.a. MED1), and alkyl-N-purine-DNA glycosylase (ANPG, a.k.a. Aag or MPG) excise a variety of damaged bases from DNA. Here we demonstrated that the redox-deficient truncated APE1 protein lacking the first N-terminal 61 amino acid residues (APE1-NΔ61) cannot stimulate DNA glycosylase activities of OGG1, MBD4, and ANPG on duplex DNA substrates. Electron microscopy imaging of APE1–DNA complexes revealed oligomerization of APE1 along the DNA duplex and APE1-mediated DNA bridging followed by DNA aggregation. APE1 polymerizes on both undamaged and damaged DNA in cooperative mode. Association of APE1 with undamaged DNA may enable scanning for damage; however, this event reduces effective concentration of the enzyme and subsequently decreases APE1-catalyzed cleavage rates on long DNA substrates. We propose that APE1 oligomers on DNA induce helix distortions thereby enhancing molecular recognition of DNA lesions by DNA glycosylases via a conformational proofreading/selection mechanism. Thus, APE1-mediated structural deformations of the DNA helix stabilize the enzyme–substrate complex and promote dissociation of human DNA glycosylases from the AP site with a subsequent increase in their turnover rate.Significance StatementThe major human apurinic/apyrimidinic (AP) endonuclease, APE1, stimulates DNA glycosylases by increasing their turnover rate on duplex DNA substrates. At present, the mechanism of the stimulation remains unclear. We report that the redox domain of APE1 is necessary for the active mode of stimulation of DNA glycosylases. Electron microscopy revealed that full-length APE1 oligomerizes on DNA possibly via cooperative binding to DNA. Consequently, APE1 shows DNA length dependence with preferential repair of short DNA duplexes. We propose that APE1-catalyzed oligomerization along DNA induces helix distortions, which in turn enable conformational selection and stimulation of DNA glycosylases. This new biochemical property of APE1 sheds light on the mechanism of redox function and its role in DNA repair.

Graphical abstract

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Functional capacity in adults with cerebral palsy: Lower limb muscle strength matters.

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jarred G. Gillett, Glen A. Lichtwark, Roslyn N. Boyd, Lee A. Barber
ObjectiveTo investigate the relationship between lower limb muscle strength, passive muscle properties and functional capacity outcomes in adults with cerebral palsy (CP).DesignCross-sectional study.SettingTertiary institution biomechanics laboratory.ParticipantsSample of 33 adults with spastic-type CP with a mean age of 25 (range, 15-51) years; mean ± SD body mass 70.15 ± 21.35 kg; Gross Motor Function Classification System (GMFCS) level I n=20, level II n=13.InterventionsNot applicable.Main Outcome MeasuresSix-minute walk test (6MWT) distance (m); lateral step-up (LSU) test performance (total repetitions); timed up-stairs (TUS) performance (s); maximum voluntary isometric strength of plantar flexors (PF) and dorsiflexors (DF) (Nm.kg^-1); and passive ankle joint and muscle stiffness.ResultsMaximum isometric PF strength independently explained 61% of variance in 6MWT performance; 57% of variance in LSU test performance; and 50% of variance in TUS test performance. GMFCS level was significantly and independently related to all three functional capacity outcomes, and age was retained as a significant independent predictor of LSU, and TUS test performance. Passive medial gastrocnemius muscle fascicle stiffness and ankle joint stiffness were not significantly related to functional capacity measures in any of the multiple regression models.ConclusionsLow isometric PF strength was the most important independent variable related to distance walked on the 6MWT, fewer repetitions on the LSU test, and slower TUS test performance. These findings suggest lower isometric muscle strength contributes to the decline in functional capacity in adults with CP.



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What factors are associated with the recovery of autonomy after a hip fracture? A prospective multicentric cohort study

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mattia Morri, Paolo Chiari, Cristiana Forni, Antonella Orlandi Magli, Domenica Gazineo, Natalia Franchini, Lorenzo Marconato, Tiziana Giamboi, Andrea Cotti
Objectiveto identify the factors associated with recovering autonomy in the activities of daily livingDesignA prospective cohort studySettingThe orthopedic and orthogeriatric departments of 2 regional hospitalsParticipantsPatients 65 years of age or older with a diagnosis of fragility hip fracture. There were 840 eligible patients. Forty-three patients were excluded and 55 were lost. Seven hundred and forty-two consecutive patients was enrolled at the time of hospitalization and 727 at follow-up.Main Outcome MeasuresThe level of autonomy at 4 months was assessed using the ADL scale.ResultsThe score of the ADL scale at 4 months had a median equal to 3 (IQR=5). Half of the population was unable to recover their prefracture autonomy levels. The following were found to be risk factors: increasing age (B= 0.02; p<0.001), an elevated number of comorbidities (B=0.044; p=0.005); a lower level of prefracture autonomy (B=0.087; p<0.001); more frequent use of an anti-decubitus mattress (B=0.211; p<0.001), an increased number of days with disorientation (B=0.002; p=0.012); failure to recover deambulation (B=0.199; p<0.001); an increased number of days with diapers (B=0.003; p<0.001), with a urinary catheter (B=0.03; p<0.001) and with bed rails (B=0.001; p=0.014), and a non-intensive care pathway (B=0,199; p=0,014).ConclusionIn the initial phase, treatment of patients with hip fractures is significantly associated with the functional recovery of autonomy and should be activated starting from those factors which have the possibility of being modified in clinical practice: recovery of deambulation, treatment for disorientation and management of incontinence.



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Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities

Publication date: Available online 10 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Weiming Luo, David Tweedie, Shaunna L. Beedie, Neil Vargesson, William D. Figg, Nigel H. Greig, Michael T. Scerba
A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF- α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF- α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF- α. Notable anti-angiogenesis activity was observed for 20, 21 and 22.

Graphical abstract

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Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations

Publication date: Available online 11 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Shinya Yokosaka, Akiko Izawa, Chizuka Sakai, Eri Sakurada, Yasuhiro Morita, Yukihiro Nishio
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs. These novel analogs showed excellent potency in a tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is suitable as versatile payloads in conjugated drugs. Insights into the structure-activity relationships of the analogs are also discussed.

Graphical abstract

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Selenite and methylseleninic acid epigenetically affects distinct gene sets in myeloid leukemia: A genome wide epigenetic analysis

Publication date: Available online 10 February 2018
Source:Free Radical Biology and Medicine
Author(s): Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P. Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq). Both selenite and MSA had major effects on histone marks but the effects of MSA were more pronounced. Gene ontology analysis revealed that selenite affected genes involved in response to oxygen and hypoxia, whereas MSA affected distinct gene sets associated with cell adhesion and glucocorticoid receptors, also apparent by global gene expression analysis using RNA sequencing. The correlation to adhesion was functionally confirmed by a significantly weakened ability of MSA treated cells to attach to fibronectin and linked to decreased expression of integrin beta 1. A striking loss of cellular adhesion was also confirmed in primary patient AML cells. Recent strategies to enhance the cytotoxicity of chemotherapeutic drugs by disrupting the interaction between leukemic and stromal cells in the bone marrow are of increasing interest; and organic selenium compounds like MSA might be promising candidates. In conclusion, these results provide new insight on the mechanism of action of selenium compounds, and will be of value for the understanding, usage, and development of new selenium compounds as anticancer agents.

Graphical abstract

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Accuracy of frozen section in determining meningioma subtype and grade

Publication date: Available online 10 February 2018
Source:Annals of Diagnostic Pathology
Author(s): Richard A. Prayson
Frozen section intraoperative consultation is a well-established means of evaluating brain tumors at the time of surgery. Limitations to the procedure are also well recognized resulting in less than perfect specificity of diagnosis. This study retrospectively reviewed 424 consecutive meningioma cases (N = 310 females; mean age 57.3 years) to examine concordance between frozen section evaluation of meningioma subtype and grade as compared with the final diagnosis subtype and grade. A discrepancy between frozen section diagnosis and final diagnosis was observed in 114 (26.9%) of cases. Of the WHO grade I subtypes, the most common discrepancy involved transitional meningiomas (N = 31) which were most commonly diagnosed at frozen section as either fibrous (N = 18) or meningothelial (N = 13) meningiomas. None of the grade I tumors were diagnosed as higher grade lesions. Of the higher grade meningiomas (WHO grade II and III) (N = 145) reviewed, concordance between tumor type and grade was seen in only 26.2% of cases; most commonly, 73/98 atypical meningiomas were under-graded as some subtype of WHO grade I meningioma (71/73 cases). In conclusion, discrepancies at frozen section with respect to accurately identifying higher grade meningiomas and higher grade meningioma subtypes are common and are generally due to tumor sampling and heterogeneity.



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In situ monitoring of PTHLH secretion in neuroblastoma cells cultured onto nanoporous membranes

Publication date: 1 June 2018
Source:Biosensors and Bioelectronics, Volume 107
Author(s): Alfredo de la Escosura-Muñiz, Marisol Espinoza-Castañeda, Alejandro Chamorro-García, Carlos J. Rodríguez-Hernández, Carmen de Torres, Arben Merkoçi
In this work, we propose for the first time the use of anodic aluminum oxide (AAO) nanoporous membranes for in situ monitoring of parathyroid hormone-like hormone (PTHLH) secretion in cultured human cells. The biosensing system is based on the nanochannels blockage upon immunocomplex formation, which is electrically monitored through the voltammetric oxidation of Prussian blue nanoparticles (PBNPs). Models evaluated include a neuroblastoma cell line (SK-N-AS) and immortalized keratinocytes (HaCaT) as a control of high PTHLH production. The effect of total number of seeded cells and incubation time on the secreted PTHLH levels is assessed, finding that secreted PTHLH levels range from approximately 60 to 400 ng/mL. Moreover, our methodology is also applied to analyse PTHLH production following PTHLH gene knockdown upon transient cell transfection with a specific silencing RNA (siRNA). Given that inhibition of PTHLH secretion reduces cell proliferation, survival and invasiveness in a number of tumors, our system provides a powerful tool for the preclinical evaluation of therapies that regulate PTHLH production. This nanoporous membrane – based sensing technology might be useful to monitor the active secretion of other proteins as well, thus contributing to characterize their regulation and function.

Graphical abstract

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Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes

Abstract

Objective

Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated and the role of high ENO1 expression in keratinocytes was characterized.

Methods

ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyze the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and trans-epithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA).

Results

ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 co-localized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression.

Conclusion

We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

This article is protected by copyright. All rights reserved.

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Multitechnique characterization of conventional and experimental Ag-based brazing alloys for orthodontic applications

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Argyro Ntasi, Youssef S. Al Jabbari, Nick Silikas, Theodore Eliades, Spiros Zinelis
ObjectivesTo characterize the microstructure, mechanical properties, ionic release and tarnish resistance of conventional and experimental Ag-based soldering alloys for orthodontic applications.MethodsDisk shaped specimens were prepared from four commercial Ag based soldering alloys [Dentaurum Universal Silver Solder (DEN), Orthodontic Solders (LEO), Ortho Dental Universal Solder (NOB), and Silver Solder (ORT)] and four experimental alloys Ag12Ga, Ag10Ga5Sn, Ag20In and Ag7Sn. The elemental composition and microstructure was determined by SEM/EDX and XRD analysis, while the mechanical properties were determined by Instrumented Indentation Testing. Ionic release of Ag, Cu, Zn, Ga, In and Sn was determined by ICP-EAS in 0.9% NaCl and Ringer's solutions after 28, 49 and 70 days. Tarnish resistance was also tested and colorimetry was applied to quantify the differences in color (DE) before and after immersion in testing media. DSC was used to determine the melting range of the experimental alloys. Mechanical properties, ionic release and DE were statistically compared by ANOVA and Holm-Sidak multiple comparison test (a=0.05).ResultsAll commercially alloys belong to the Ag–Zn–Cu ternary system and consist a Ag rich face centered cubic (FCC) and Cu (FCC) phase. The former is the predominant phase also in experimental alloys. Conventional alloys demonstrated higherhardness, less ductility and lower melting rangers compared to experimental alloys. Immersion testing revealed the release of Cu and Zn ions from the commercially alloys and Ga ions from AgGa and AgGaSn while no ionic release was identified for AgIn and AgSn. All alloys failed tarnish testing according to ISO 10271 showing DE values much higher than the clinical acceptable limit (3.7).SignificanceThe conventional Ag based soldering alloys showed substantial differences in their microstructure, mechanical properties and ionic release, and thus different clinical performance is anticipated. Ga, Sn and In might be employed as alloying addition to modify the properties of Ag brazing alloys.



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Optical properties of composite restorations influenced by dissimilar dentin restoratives

Publication date: Available online 3 February 2018
Source:Dental Materials
Author(s): Jovana Marjanovic, Djordje N. Veljovic, Jovana N. Stasic, Tatjana Savic-Stankovic, Branka Trifkovic, Vesna Miletic
ObjectivesTo evaluate optical properties (color and translucency) of 'sandwich' restorations of resin-based composites and esthetically unfavorable dentin restoratives.MethodsCylindrical 'dentin' specimens (8mm in diameter and 2mm thick, N=5/group) were prepared using EverX Posterior (GC), Biodentine (Septodont), experimental hydroxyapatite (HAP) or conventional composites (Gradia Direct Posterior, GC; Filtek Z250 and Filtek Z500, 3M ESPE). Capping 'enamel' layers were prepared using composites (Gradia Direct Posterior, Filtek Z250 or Z550) of A1 or A3 shade and the following thickness: 0.6, 1 or 2mm. Color (ΔE) and translucency parameter (TP) were determined using a spectrophotometer (VITA Easyshade Advance 4.0, VITA Zahnfabrik). Data were statistically analyzed using analysis of variance with Tukey's post-hoc tests (α=0.05).ResultsTP was greatly affected by layer thickness, whilst ΔE depended on shade and layer thickness of the capping composite. HAP and Biodentine showed significantly lower TP and higher ΔE (deviation from 'ideal white') than composites (p<0.05). Greater TP was seen in EverX_composite groups than in corresponding control groups of the same shade and thickness. TP of composites combined with Biodentine or HAP was below 2, lower than the corresponding control groups (p<0.05). Within-group differences of ΔE were greatest in HAP_composite groups. EverX_Gradia and EverX_FiltekZ250 combinations showed the most comparable ΔE with the control groups.SignificanceA 2mm thick layer of composite covering dentin restoratives with unfavorable esthetics is recommended for a final 'sandwich' restoration that is esthetically comparable to a conventional, mono-composite control restoration.



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Mechanical properties and fracture behavior of flowable fiber reinforced composite restorations

Publication date: Available online 20 January 2018
Source:Dental Materials
Author(s): Lippo Lassila, Filip Keulemans, Eija Säilynoja, Pekka K. Vallittu, Sufyan Garoushi
ObjectiveThe aim was to evaluate the effect of short glass-fiber/filler particles proportion on fracture toughness (FT) and flexural strength (FS) of an experimental flowable fiber-reinforced composite (Exp-SFRC) with two methacrylate resin formulations. In addition, we wanted to investigate how the fracture-behavior of composite restorations affected by FT values of SFRC-substructure.MethodsExp-SFRC was prepared by mixing 50wt% of dimethacrylate based resin matrix (bisGMA or UDMA based) to 50wt% of various weight fractions of glass-fiber/particulate filler (0:50, 10:40, 20:30, 30:20, 40:10, 50:0wt%, respectively). FT and FS were determined for each experimental material following standards. Specimens (n=8) were dry stored (37°C for 2 days) before they were tested. Four groups of posterior composite crowns (n=6) composed of different Exp-SFRCs as substructure and surface layer of commercial particulate filler composite were fabricated. Crowns were statically loaded until fracture. Failure modes were visually examined. The results were statistically analysed using ANOVA followed by post hoc Tukey's test.ResultsANOVA revealed that ratio of glass-fiber/particulate filler had significant effect (p<0.05) on tested mechanical properties of the Exp-SFRC with both monomer systems. Exp-SFRC (50wt%) had significantly higher FT (2.6MPam^1/2) and FS (175.5MPa) (p<0.05) compared to non-reinforced material (1.3MPam^1/2, 123MPa). Failure mode analysis of crown restorations revealed that FT value of the substructure directly influenced the failure mode.SignificanceThis study shows that short glass-fibers can significantly reinforce flowable composite resin and the FT value of SFRC-substructure has prior importance, as it influences the crack arresting mechanism.



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Early responses of human pulp to direct capping with resin adhesive systems and calcium hydroxide

Publication date: Available online 3 February 2018
Source:Dental Materials
Author(s): Anna Poimenova, Efthymia Kitraki, Afroditi Kakaboura, Christos Rahiotis
ObjectiveEarly responses of human pulp to Prime&Bond/phosphoric acid, Clearfil SE Bond, Clearfil S3 Bond and Dycal were investigated ex vivo.Materials and methodsThe three adhesives, Dycal or buffer (DPBS) were applied directly onto the pulp of human teeth slices that were placed in culture for 4 days. Cell viability was monitored by the MTT assay during the culture period. After 4 days, tissue integrity was examined by hematoxylin–eosin staining. Vimentin levels were assessed by Western blotting. TUNEL assay was applied for apoptotic cell detection at specific pulp areas.ResultsProfound reduction of cell viability and tissue integrity was observed in adhesive-treated groups, while the impact of Dycal was found to be less harmful. Extended apoptosis was caused mostly by the Clearfil SE and Prime&Bond. All adhesives reduced Vimentin levels.SignificanceThe study provides evidence that early pulp responses to direct capping with different adhesive systems or calcium hydroxide may vary significantly and underline the need for further studies in relevant ex vivo systems.



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Nano-graphene oxide incorporated into PMMA resin to prevent microbial adhesion

Publication date: Available online 3 February 2018
Source:Dental Materials
Author(s): Jung-Hwan Lee, Jeong-Ki Jo, Dong-Ae Kim, Kapil Dev Patel, Hae-Won Kim, Hae-Hyoung Lee
ObjectiveAlthough polymethyl methacrylate (PMMA) is widely used as a dental material, a major challenge of using this substance is its poor antimicrobial (anti-adhesion) effects, which increase oral infections. Here, graphene-oxide nanosheets (nGO) were incorporated into PMMA to introduce sustained antimicrobial-adhesive effects by increasing the hydrophilicity of PMMA.MethodsAfter characterizing nGO and nGO-incorporated PMMA (up to 2wt%) in terms of morphology and surface characteristics, 3-point flexural strength and hardness were evaluated. The anti-adhesive effects were determined for 4 different microbial species with experimental specimens and the underlying anti-adhesive mechanism was investigated by a non-thermal oxygen plasma treatment. Sustained antimicrobial-adhesive effects were characterized with incubation in artificial saliva for up to 28 days.ResultsThe typical nanosheet morphology was observed for nGO. Incorporating nGO into PMMA roughened its surface and increased its hydrophilicity without compromising flexural strength or surface hardness. An anti-adhesive effect after 1h of exposure to microbial species in artificial saliva was observed in nGO-incorporated specimens, which accelerated with increasing levels of nGO without significant cytotoxicity to oral keratinocytes. Plasma treatment of native PMMA demonstrated that the antimicrobial-adhesive effects of nGO incorporation were at least partially due to increased hydrophilicity, not changes in the surface roughness. A sustained antimicrobial-adhesive property against Candida albicans was observed in 2% nGO for up to 28 days.SignificanceThe presence of sustained anti-adhesion properties in nGO-incorporated PMMA without loading any antimicrobial drugs suggests the potential usefulness of this compound as a promising antimicrobial dental material for dentures, orthodontic devices and provisional restorative materials.

Graphical abstract

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Zirconia toughened mica glass ceramics for dental restorations

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Sivaranjani Gali, Ravikumar K., B.V.S. Murthy, Bikramjit Basu
ObjectiveThe objective of the present study is to understand the role of yttria stabilized zirconia (YSZ) in achieving the desired spectrum of clinically relevant mechanical properties (hardness, elastic modulus, fracture toughness and brittleness index) and chemical solubility of mica glass ceramics.MethodsThe glass–zirconia mixtures with varying amounts of YSZ (0, 5, 10, 15 and 20wt.%) were ball milled, compacted and sintered to obtain pellets of glass ceramic-YSZ composites. Phase analysis was carried out using X-ray diffraction and microstructural characterization with SEM revealed the crystal morphology of the composites. Mechanical properties such as Vickers hardness, elastic modulus, indentation fracture toughness and chemical solubility were assessed.ResultsPhase analysis of sintered pellets of glass ceramic-YSZ composites revealed the characteristic peaks of fluorophlogopite (FPP) and tetragonal zirconia. Microstructural investigation showed plate and lath-like interlocking mica crystals with embedded zirconia. Vickers hardness of 9.2GPa, elastic modulus of 125GPa, indentation toughness of 3.6MPa·m^1/2, and chemical solubility of 30μg/cm² (well below the permissible limit) were recorded with mica glass ceramics containing 20wt.% YSZ.SignificanceAn increase in hardness and toughness of the glass ceramic-YSZ composites with no compromise on their brittleness index and chemical solubility has been observed. Such spectrum of properties can be utilised for developing a machinable ceramic for low stress bearing inlays, onlays and veneers.



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Long-term dentin remineralization by poly(amido amine) and rechargeable calcium phosphate nanocomposite after fluid challenges

Publication date: Available online 3 February 2018
Source:Dental Materials
Author(s): Kunneng Liang, Shimeng Xiao, Junling Wu, Jiyao Li, Michael D. Weir, Lei Cheng, Mark A. Reynolds, Xuedong Zhou, Hockin H.K. Xu
ObjectivePrevious studies investigated short-term dentin remineralization; studies on long-term dentin remineralization after fluid challenges mimicking fluids in oral environment are lacking. The objective of this study was to develop a long-term remineralization method to via poly(amido amine) (PAMAM) and rechargeable composite containing nanoparticles of amorphous calcium phosphate (NACP) after fluid challenges for the first time.MethodsNACP composite was immersed at pH 4 to exhaust its calcium (Ca) and phosphate (P) ions, and then recharged with Ca and P ions, to test the remineralization of the exhausted and recharged NACP composite. Dentin was acid-etched with 37% phosphoric acid. Four groups were prepared: (1) dentin control, (2) dentin with PAMAM, (3) dentin with the recharged NACP composite, and (4) dentin with PAMAM plus recharged NACP composite. PAMAM-coated dentin was immersed in phosphate-buffered saline with shaking for 72 days, because there is fluid flow in the mouth which could potentially detach the PAMAM from dentin. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 35 days.ResultsAfter 72days of immersion plus shaking, the PAMAM still successfully fulfilled its mineralization nucleation. The recharged NACP composite still provided acid-neutralization and ion re-release, which did not decrease with increasing the number of recharge cycles. The immersed-PAMAM plus NACP achieved complete dentin remineralization and restored the hardness to that of healthy dentin.SignifianceIn conclusion, superior long-term remineralization of the PAMAM plus NACP method was demonstrated for the first time. The immersed-PAMAM plus recharged NACP completely remineralized the pre-demineralized dentin, even after prolonged fluid-challenge similar to that in oral environment. The novel PAMAM plus NACP composite method is promising to provide long-term tooth protection and caries inhibition.



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The two sides of the C-factor

Publication date: Available online 2 February 2018
Source:Dental Materials
Author(s): Alex S.L. Fok, Wondwosen A. Aregawi
ObjectiveThe aim of this paper is to investigate the effects on shrinkage strain/stress development of the lateral constraints at the bonded surfaces of resin composite specimens used in laboratory measurement.MethodsUsing three-dimensional (3D) Hooke's law, a recently developed shrinkage stress theory is extended to 3D to include the additional out-of-plane strain/stress induced by the lateral constraints at the bonded surfaces through the Poisson's ratio effect. The model contains a parameter that defines the relative thickness of the boundary layers, adjacent to the bonded surfaces, that are under such multiaxial stresses. The resulting differential equation is solved for the shrinkage stress under different boundary conditions. The accuracy of the model is assessed by comparing the numerical solutions with a wide range of experimental data, which include those from both shrinkage strain and shrinkage stress measurements.ResultsThere is good agreement between theory and experiments. The model correctly predicts the different instrument-dependent effects that a specimen's configuration factor (C-factor) has on shrinkage stress. That is, for noncompliant stress-measuring instruments, shrinkage stress increases with the C-factor of the cylindrical specimen; while the opposite is true for compliant instruments. The model also provides a correction factor, which is a function of the C-factor, Poisson's ratio and boundary layer thickness of the specimen, for shrinkage strain measured using the bonded-disc method. For the resin composite examined, the boundary layers have a combined thickness that is ∼11.5% of the specimen's diameter.SignificanceThe theory provides a physical and mechanical basis for the C-factor using principles of engineering mechanics. The correction factor it provides allows the linear shrinkage strain of a resin composite to be obtained more accurately from the bonded-disc method.



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Profiling cytokine levels in chlorhexidine and EGCG-treated odontoblast-like cells

Publication date: Available online 7 February 2018
Source:Dental Materials
Author(s): Alexander Terry Stavroullakis, Marcela Rocha Carrilho, Celine Marie Levesque, Anuradha Prakki
ObjectiveTo screen the effect of two compounds, chlorhexidine diacetate (CHX) and epigallocatechin-gallate (EGCG), on the levels of cytokines produced by odontoblast-like cells (MDPC-23).MethodsCells were seeded at 24h and 48h with serial dilution of the compounds to determine cell metabolic activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (n=3). Cells with no compound treatment were used as control (Ctr). For the highest equal non-cytotoxic compound dilution tested at 48h cell treatment, total protein concentration was measured using a Pierce bicinchoninic acid (BCA) assay (n=3), and expression of 23 cytokines was analyzed using the Bio-Plex cytokine assay (n=2). Data were analyzed by one-way ANOVA and Tukey's test (α=5%).ResultsThe MTT assay revealed that at 24h and 48h, CHX and EGCG did not reduce cell metabolic activity at concentrations of 2.5–20μM (CHX) and 2.5–160μM (EGCG), respectively (p>0.05). At 48h, total protein levels were consistent across all groups for 20μM compound dilution (Ctr: 1.04mg/mL; CHX: 0.98mg/mL; and EGCG: 1.06mg/mL). At 20μM dilution, both CHX and EGCG significantly increased the secretion of IL-1β, IL-10, IL-12, KC, MIP-1α, IFN-γ and IL-6 (p<0.05). Treatment with CHX significantly increased secretion of IL-4 and RANTES (p<0.05). Treatment: with EGCG significantly increased Eotaxin secretion (p<0.05). Both CHX and EGCG significantly decreased secretion of IL-17 (p<0.05). GM-CSF and TNF-α did not present significant change in secretion after treatment with either CHX or EGCG (p>0.05).SignificanceBoth CHX and EGCG modulate secretion of various inflammatory and anti-inflammatory mediators in odontoblastic cells.



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Editorial Board

Publication date: February 2018
Source:Dental Materials, Volume 34, Issue 2





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Influence of thread shape and inclination on the biomechanical behaviour of plateau implant systems

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Michele Calì, Elisabetta Maria Zanetti, Salvatore Massimo Oliveri, Riccardo Asero, Stefano Ciaramella, Massimo Martorelli, Cristina Bignardi
ObjectiveTo assess the influence of implant thread shape and inclination on the mechanical behaviour of bone-implant systems. The study assesses which factors influence the initial and full osseointegration stages.MethodsPoint clouds of the original implant were created using a non-contact reverse engineering technique. A 3D tessellated surface was created using Geomagic Studio^® software. From cross-section curves, generated by intersecting the tessellated model and cutting-planes, a 3D parametric CAD model was created using SolidWorks^® 2017. By the permutation of three thread shapes (rectangular, 30° trapezoidal, 45° trapezoidal) and three thread inclinations (0°, 3° or 6°), nine geometric configurations were obtained. Two different osseointegration stages were analysed: the initial osseointegration and a full osseointegration. In total, 18 different FE models were analysed and two load conditions were applied to each model. The mechanical behaviour of the models was analysed by Finite Element (FE) Analysis using ANSYS^® v. 17.0. Static linear analyses were also carried out.ResultsANOVA was used to assess the influence of each factor. Models with a rectangular thread and 6° inclination provided the best results and reduced displacement in the initial osseointegration stages up to 4.58%. This configuration also reduced equivalent VM stress peaks up to 54%. The same effect was confirmed for the full osseointegration stage, where 6° inclination reduced stress peaks by up to 62%.SignificanceThe FE analysis confirmed the beneficial effect of thread inclination, reducing the displacement in immediate post-operative conditions and equivalent VM stress peaks. Thread shape does not significantly influence the mechanical behaviour of bone-implant systems but contributes to reducing stress peaks in the trabecular bone in both the initial and full osseointegration stages.



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Application of radiopaque micro-particle fillers for 3-D imaging of periodontal pocket analogues using cone beam CT

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): M. Elashiry, M.M. Meghil, S. Kalathingal, A. Buchanan, R. Elrefai, S. Looney, M. Rajendran, M. Ochieng, N. Young, A. Elawady, R.M. Arce, K.H. Sandhage, C.W Cutler
BackgroundPeriodontitis is an infectious/inflammatory disease most often diagnosed by deepening of the gingival sulcus, which leads to periodontal pockets (PPs) conventional manual periodontal probing does not provide detailed information on the three-dimensional (3-D) nature of PPs.ObjectivesTo determine whether accurate 3-D analyses of the depths and volumes of calibrated PP analogues (PPAs) can be obtained by conventional cone beam computed tomography (CBCT) coupled with novel radiopaque micro-particle fillers (described in the companion paper) injected into the PPAs.MethodsTwo PPA models were employed: (1) a human skull model with artificial gingiva applied to teeth with alveolar bone loss and calibrated PPAs, and (2) a pig jaw model with alveolar bone loss and surgically-induced PPAs The PPAs were filled with controlled amounts of radiopaque micro-particle filler using volumetric pipetting Inter-method and intra-method agreement tests were then used to compare the PPA depths and volumes obtained from CBCT images with values obtained by masked examiners using calibrated manual methods.ResultsSignificant inter-method agreement (0.938–0.991) and intra-method agreement (0.94–0.99) were obtained when comparing analog manual data to digital CBCT measurements enabled by the radiopaque filler.SignificanceCBCT imaging with radiopaque micro-particle fillers is a plausible means of visualizing and digitally assessing the depths, volumes, and 3-D shapes of PPs This approach could transform the diagnosis and treatment planning of periodontal disease, with particular initial utility in complex cases Efforts to confirm the clinical practicality of these fillers are currently in progress.



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The effect of hydrofluoric acid concentration on the fatigue failure load of adhesively cemented feldspathic ceramic discs

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Andressa B. Venturini, Catina Prochnow, Gabriel K.R. Pereira, Arie Werner, Cornelis J. Kleverlaan, Luiz Felipe Valandro
ObjectiveThis study investigated the influence of hydrofluoric acid (HF) etching at different concentrations on the fatigue failure load of adhesively cemented feldspathic ceramic discs (Vita Mark II). Besides, their effect on the micromorphology of ceramic surface was investigated.MethodsEighty ceramic discs (ϕ=10 mm; thickness=1.5 mm) were cemented to epoxy supporting discs (ϕ=10 mm; thickness=2.0mm) using different surface conditioning methods (n=20): nonetched control (CTRL), or etched for 60s with different HF concentrations: 1% (HF1), 5% (HF5), or 10% (HF10). All the ceramic discs received a silane application (Monobond Plus). The epoxy discs were etched with 10% HF for 60s and received a primer coating (Multilink Primer A+B). Adhesively cementation was performed (Multilink Automix), and the assemblies (ceramic discs/epoxy discs) were subjected to cyclic loads in water by a staircase approach (500,000 cycles; 20Hz; initial load=290N; step size=30N). Fatigue failure load data were analyzed using 1-way ANOVA and post-hoc Tukey's tests (α=.05).ResultsMean failure load of the HF5 group (255.0±23.0N) was significantly lower; HF1 group (301.7±71.0N) presented intermediate values, and the highest values were achieved in CTRL (351.7±13.4N) and HF10 (341.7±20.6N) groups. All the failures were radial cracks starting from the bonding surface.SignificanceIn terms of fatigue failure load, etching with 1% and 5% HF had a deleterious effect on the fatigue behavior of an adhesively cemented feldspathic ceramic, while 10% HF had no negative influence.



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Genotoxic and mutagenic potential of camphorquinone in L5178/TK+/− mouse lymphoma cells

Publication date: Available online 17 January 2018
Source:Dental Materials
Author(s): J. Volk, C. Ziemann, G. Leyhausen, W. Geurtsen
ObjectivesCamphorquinone (CQ) is the most important photoinitiator used in dental composite resins. Sparse data indicate a mutagenic potential of CQ. Therefore, it was aim of this study to evaluate the cytotoxicity, genotoxicity, and mutagenicity of CQ in L5178Y TK^+/− mouse lymphoma cells.MethodsL5178Y/TK^+/− cells were exposed to different concentrations of non-irradiated CQ (0.25–2.5mM). Cytotoxicity was evaluated by propidium iodide assay, determination of suspension growth rate, relative total growth and the mitotic index. Intracellular levels of reactive oxygen/nitrogen species (ROS/RNS) were quantified by 2′,7′-dichlorofluoresceine diacetate (DCFH-DA). Early induction of DNA strand breaks and oxidative DNA base lesions was assessed using the 8-hydroxyguanine DNA-glycosylase 1 (hOGG1)-modified alkaline comet assay, whereas mutagenicity of CQ was determined in the mouse lymphoma TK assay (MLA), according to OECD Guideline No. 490.ResultsCQ (0.5–2.5mM) induced concentration- and time-dependent inhibition of cell growth associated with increased ROS/RNS production, amounting to 2342%±1108% of controls after 90min at 2.5mM. Additionally, CQ concentration-dependently caused direct DNA-damage, i.e. formation of DNA strand breaks and 8-hydroxy-2′-deoxyguanosine. Whereas the MLA indicated lack of mutagenicity of CQ after a 4h of treatment, CQ concentration-dependently increased total mutant frequency (MF) after 24h (about 2-fold at 2.5mM). But, based on the global evaluation factor concept, increase in MF did not reach biologically relevance.SignificanceCQ induced concentration-dependent, cytotoxic and genotoxic effects in L5178Y/TK^+/− cells, most likely due to oxidative stress, but without mediating obvious biological relevant mutagenicity.



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In memoriam of Professor David B. Mahler (1923–2017)

Publication date: Available online 1 February 2018
Source:Dental Materials





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In-vitro wear of natural tooth surface opposed with zirconia reinforced lithium silicate glass ceramic after accelerated ageing

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Salma M. Fathy, Michael V. Swain
ObjectiveTo evaluate the effect of different pH media on zirconia-reinforced lithium silicate glass ceramic and how they interact with opposing dentition after being aged in different pH cycling and high temperature conditions.MethodsTwenty-five rectangular shaped specimens were prepared from lithium silicate reinforced with zirconia blanks (Suprinity, Vita Zahnfabrick) and stored in different pH media (3 & 7.2) for different periods (24h & 7 days) at temperature (55°C). After their surface roughness (Ra) evaluation, aged ceramic specimens were subjected to cyclic abrasive wear with opposing natural teeth enamel for 150,000 cycles using a chewing simulator. Weight loss and Scanning Electron Microscope (SEM) images were used to evaluate the cyclic wear results.ResultsAfter different pH storage, ceramic group stored at 3 pH for 1-W (1 week) gave significantly higher mean Ra value (0.618μm±0.117) than control lowest mean value (0.357μm±0.054) before cyclic wear. On the other hand, it caused the least significant weight loss value (0.004gm±0.001) to opposing tooth enamel. There was significant tooth enamel weight loss (0.043gm±0.004) when opposed with ceramic group stored in 3 pH media for 24h (24-H). Their SEM images showed a prominent wear scar on enamel cusp tip. There was a significant increase in surface roughness Ra of ceramic material after abrasive cyclic wear.SignificanceGreat attention should be paid to Ra of this type of glass ceramic even if it is considered as minimal values. It can induce a significant amount of enamel tooth wear after a period equivalent to one year of intra-oral function rather than the significantly higher surface Ra of such ceramic type can do.



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Strength and fracture toughness of zirconia dental ceramics

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Miquel Turon-Vinas, Marc Anglada
ObjectiveThe aim of the paper is to determine and discuss the correlation between the fracture toughness and the fracture stress in zirconia transforming ceramics with a small artificial crack. As an R-curve behaviour is usually present in transforming ceramics for both small and long cracks, predictions of the fracture stress can only be done with an accurate knowledge of the R-curve and crack dimensions.MethodsFirst, basic concepts of fracture mechanics, strength and testing of ceramic materials are introduced. This is followed by a very brief introduction to zirconia dental ceramics and to strength degradation by hydrothermal ageing of 3Y-TZP. Fracture toughness of 3Y-TZP and 12Ce-TZP are then determined for a short (∼50μm) sharp edge crack produced by ultra short pulsed laser ablation on prismatic bending bars in four point bending. The crack size is small but large enough for controlling fracture and for applying elastic fracture mechanics.ResultsIn both materials the determined fracture toughness is similar, in spite of their difference R-curves. The results of fracture toughness and fracture stress are analysed by using a simple function to represent the R-curve, but which contains the main ingredients of experimental R-curves extracted from the literature either for short or long cracks in 12Ce-TZP.SignificanceIt is concluded that the high R-curves reported in the literature for long and short cracks in 12Ce-TZP and 3Y-TZP might have only a marginal influence on the fracture resistance with cracks of the size studied. This effect is of more significance in 12Ce-TZP. The use of an ideal and simple model of R-curve is presented as a useful guide to predict whether the fracture stress will be enhanced by an existent R-curve.



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8DSS peptide induced effective dentinal tubule occlusion in vitro

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Kunneng Liang, Shimeng Xiao, Hongling Liu, Wenyuan Shi, Jianshu Li, Yuan Gao, Libang He, Xuedong Zhou, Jiyao Li
ObjectiveEight repetitive nucleotide sequences of aspartate–serine–serine (8DSS) derived from dentin phosphoprotein (DPP) has been proved to be a good remineralization agency. In this study, 8DSS peptide was employed to induce dentinal tubule occlusion.MethodsDentin samples were acid-etched, and then the samples were coated with 8DSS solution. The binding capacity of 8DSS to acid-etched dentin was tested by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Subsequently, the 8DSS-treated dentin samples were immersed in artificial saliva for 1, 2 and 4 weeks. After 4 weeks, the remineralized dentin was treated with 6wt% citric acid (pH 1.5) solution for 1min. Dentin permeability measurement and scanning electron microscopy (SEM) were carried out after different periods. Energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD) were used to identify the mineral phase of the regenerated minerals.ResultsThe results showed that 8DSS had a good binding capacity to the acid-etched dentin, and significantly reduced the dentin permeability by inducing minerals deposited within the dentinal tubules. After 4 weeks, all the dentinal tubules were occluded by large bulk of regenerated minerals, which largely decreased the diameters of the tubules. The regenerated minerals deposited with a deep depth within the dentinal tubules, ensuring an effective occlusion even after an acid challenge. The results of XRD and EDS confirmed that the regenerated minerals were mainly hydroxyapatite (HA).Significance8DSS peptide induced strong dentinal tubule occlusion. 8DSS have a great potential to be used in the treatment of dentin hypersensitivity in the future.



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Development of a novel dental resin cement incorporating FGF-2-loaded polymer particles with the ability to promote tissue regeneration

Publication date: Available online 1 February 2018
Source:Dental Materials
Author(s): Ririko Tsuboi, Jun-Ichi Sasaki, Haruaki Kitagawa, Itsumi Yoshimoto, Fumio Takeshige, Satoshi Imazato
ObjectiveAiming to achieve bioactive dental resins that promote healing of surrounding tissues, we developed novel poly(2-hydroxyethyl methacrylate/trimethylolpropane trimethacrylate) (polyHEMA/TMPT) particles. These particles have been reported to be useful as a non-biodegradable carrier for fibroblast growth factor-2 (FGF-2) in vitro. The aim of this study was to evaluate the ability of an adhesive resin incorporating FGF-2-loaded polymer particles to promote tissue regeneration in vitro and in vivo.MethodsExperimental adhesive resins were prepared by incorporating FGF-2-loaded polyHEMA/TMPT particles into a 4-META/MMA-based adhesive resin, and the release profiles of FGF-2 were evaluated. The proliferation of osteoblast-like cells in the eluate from cured experimental resin was assessed. When the experimental resin was implanted into rat calvaria defects, bone regeneration was evaluated by microcomputed tomography and histological observations.ResultsSustained release of FGF-2 from the experimental resin was observed for 14 days. Eluate from the cured experimental resin significantly promoted the proliferation of osteoblast-like cells. Significantly greater bone regeneration was observed using the experimental resin compared with the control resin without FGF-2.Significance4-META/MMA-based adhesive resin incorporating FGF-2-loaded polymer particles is useful to promote tissue regeneration, suggesting that its application would be beneficial for root-end filling or the repair of fractured roots in cases with severely damaged periodontal tissue.



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Optimization of large MOD restorations: Composite resin inlays vs. short fiber-reinforced direct restorations

Publication date: Available online 20 January 2018
Source:Dental Materials
Author(s): Luciana Mara Soares, Mehrdad Razaghy, Pascal Magne
ObjectiveTo compare mechanical performance and enamel-crack propensity of direct, semi-direct, and CAD/CAM approaches for large MOD composite-resin restorations.Methods45 extracted maxillary molars underwent standardized slot-type preparation (5-mm depth and bucco-palatal width) including immediate dentin sealing (Optibond FL) for the inlays (30 teeth). Short-fiber reinforced composite-resin (EverX Posterior covered by Gradia Direct Posterior) was used for the direct approach, Gradia Direct Posterior for the semi-direct, and Cerasmart composite resin blocks for CAD/CAM inlays. All inlays were adhesively luted with light-curing composite-resin (preheated Gradia Direct Posterior). Shrinkage-induced enamel cracks were tracked by transillumination photography. Cyclic axial isometric chewing (5-Hz) was simulated, starting with a load of 200N (5000 cycles), followed by stages of 400, 600, 800, 1000, 1200, and 1400N (maximum 30,000 cycles each) until fracture or to a maximum of 185,000 cycles. Survived specimens were subjected to cyclic-load-to-failure test at 30-degree angle on the palatal cusp.ResultsOnly small shrinkage-induced cracks were found in 47% of the direct restorations compared to 7% and 13% of semi-direct and CAD/CAM inlays, respectively. Survival to accelerated fatigue was similar for all three groups (Kaplan–Meier p>.05) and ranged between 87% (direct) and 93% (semi-direct and CAD/CAM). Cyclic-load-to-failure tests did not yield significant differences either (Life Table analysis, p>.05) with median values of 1675N for CAD/CAM inlays, 1775N for fiber-reinforced direct restorations and 1900N for semi-direct inlays.SignificanceAll three restorative techniques yielded excellent mechanical performance above physiological masticatory loads. Direct restorations performed as good as inlays when a short-fiber reinforced composite-resin base was used.



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The positive effects of secreting cytokines IL-17 and IFN-γ on the early-stage differentiation and negative effects on the calcification of primary osteoblasts in vitro

Publication date: April 2018
Source:International Immunopharmacology, Volume 57
Author(s): Zhongxiu Wang, Jingyi Tan, Lihong Lei, Weilian Sun, Yanmin Wu, Peihui Ding, Lili Chen
ObjectiveInterleukin-17 (IL-17) and interferon-gamma (IFN-γ) are all pro-inflammatory cytokines produced by specific subsets of T-cells and are also considered crucial regulators in bone remodeling, but their effects on osteogenesis have not been carefully studied. So, this study aimed to investigate the effects of secreting cytokines IL-17 and IFN-γ on the osteogenesis of primary osteoblasts and to clarify the potential roles of the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway in bone remodeling.MethodsThe proliferation of osteoblasts was evaluated by MTT assay. Osteogenic activity was tested by alkaline phosphatase (ALP) activity assay and alizarin red staining. The mRNA levels of ALP, osteocalcin, osteoprotegerin (OPG), Runt-related transcription factor 2 (Runx2) and receptor activator of nuclear factor-kappa B ligand (RANKL) were also measured by real-time quantitative PCR. The JAK2-STAT3 pathway was evaluated by Western blot.ResultsOsteoblasts showed no obvious proliferation when treated with IL-17 and/or IFN-γ, but higher ALP activities were observed in primary osteoblasts treated with IL-17 or IL-17 + IFN-γ in induction medium. We also found that IL-17 could promote the gene expression of Alp, Runx2, Osteocalcin, Opg, and Rankl, while IFN-γ might attenuate this effect. Nevertheless, IL-17 and IFN-γ exhibited an inhibitory effect on the calcification of primary osteoblasts. We also found that IL-17 could directly facilitate RANKL expressions by JAK2-STAT3 pathway.ConclusionThe positive effects of IL-17 and IFN-γ on the early-stage differentiation and the negative effects on the calcification of murine calvarial osteoblasts contribute to our understanding of the role and interaction of inflammatory factors in the bone remodeling and as fundamental mechanisms involved in the destruction of alveolar bone.



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GC-EI-MS identification data of neutral sugars of polysaccharides extracted from Zizyphus lotus fruit

Publication date: Available online 10 February 2018
Source:Data in Brief
Author(s): Khaoula Mkadmini Hammi, Majdi Hammami, Christophe Rihouey, Didier Le Cerf, Riadh Ksouri, Hatem Majdoub
Gas chromatography coupled to mass spectrometer (GC-MS) was used to identify and to quantify neutral sugars that constitute the water soluble polysaccharides from Zizyphus lotus fruit. The trimethylsilyl (TMS) method was successfully used for derivatization of the monosaccharides units of extracted polysaccharides that were released by hydrolysis method. Sugars were identified based on their retention times compared with those of standards and the NIST MS Spectral Library. All sugars were quantified in TIC (Total Ion Current) mode using calibration curves. Data is related to "Optimization extraction of polysaccharide from Tunisian Zizyphus lotus fruit by response surface methodology: Composition and antioxidant activity" [1].



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Antioxidant activities of traditional plants in Sri Lanka by DPPH free radical-scavenging assay

Publication date: Available online 10 February 2018
Source:Data in Brief
Author(s): Kotaro Hara, Takao Someya, Katsura Sano, Yoshimasa Sagane, Toshihiro Watanabe, R.G.S. Wijesekara
This article describes free radical-scavenging activities of extracts of several plants harvested in Sri Lanka through the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. These plants have traditionally been used in the indigenous systems of medicine in Sri Lanka, such as Ayurveda, as described below. (English name, "local name in Sri Lanka," (scientific name)).bougainvillea plant, "bouganvilla," (Bougainvillea grabla), purple fruited pea eggplant,"welthibbatu," (Solanum trilobatum) [1], country borage plant, "kapparawalliya," (Plectranthus amboinicus) [2], malabar nut plant, "adhatoda," (Justicia adhatoda) [3], long pepper plant,"thippili," (Piper longum) [4], holy basil plant, "maduruthala," (Ocimum tenuiflorum) [5], air plant, "akkapana," (Kalanchoe pinnata) [6], plumed cockscomb plant, "kiri-henda," (Celosia argentea) [7], neem plant,"kohomba," (Azadirachta indica) [8], balipoovu plant, "polpala," (Aerva lanata) [9], balloon-vine plant, "wel penera," (Cardiospermum halicacabum) [10], emblic myrobalan plant, "nelli," (Phyllanthus emblica) [11], indian copperleaf plant, "kuppameniya," (Acalypha indica) [12], spreading hogweed plant, "pita sudu sarana," (Boerhavia diffusa) [13], curry leaf plant, "karapincha," (Murraya koenigii) [14], indian pennywort plant, "gotukola," (Centera asiatica) [15], jewish plum plant, "ambarella,"(Spondias dulcis) [16].



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