Pathogenesis of chronic rhinosinusitis in patients affected by β-thalassemia major and sickle cell anaemia post allogenic bone marrow transplant

Publication date: Available online 6 January 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): F. Martino, R. Di Mauro, K. Paciaroni, J. Gaziev, C. Alfieri, L. Greco, R. Floris, S. Di Girolamo, M. Di Girolamo
ObjectivesSickle cell anemia (SCA) and β -thalassemia major are well-recognized beta-globin gene disorders of red blood cells associated to mortality and morbidity included bone morbidities due to ineffective erythropoiesis and bone marrow expansion, which affect every part of the skeleton. While there are an abundance of described disease manifestations of the head and neck, the manner of paranasal sinuses involvement and its relations to β-thalassemia and SCA process was not studied yet. Therefore, the aim of this study was to investigate a possible increased risk of rhinosinusitis and the real pathogenetic mechanism of it, comparing these two hematological diseases using msCT, gold standard for paranasal sinuses evaluation.MethodsA retrospective analysis of 90 patients affected by β-thalassemia major or SCA (respectively 59 and 31) underwent allogeneic bone marrow transplantation (BMT), and 44 control subjects was performed. Both patient categories and control group have been subjected to hematological and radiological evaluation using 64-multidetector-row CT scanner without contrast injection.ResultsStatistical analysis reveals that patients of the two study groups exhibit a significantly increased risk of sinusitis in comparison with the normal controls (RR: 3.55 for β-thalassemic pediatric subjects; RR: 3.35 for SCA pediatric subjects). A significant difference (p < 0,5) was found between the β -thalassemic patients on the one side, and SCA and control group on the other side, with regard to the evaluation of the typical anatomic alteration of maxillary sinus: β-thalassemic children had significant increase in the bone thickness of anterior and lateral sinus walls and significant reduction in volume and density compared to SCA patients and control group, with normal conditions of these parameters.ConclusionsIn these hematological patients, there is an increased incidence of sinonasal infections due their therapy-induced immunosuppression post transplantation. In β-thalassemic patients, furthermore, the specific anatomical variants play an important confounding factor in radiological interpretation of CT images. Therefore, a cranio-facial CT scan evaluation could be a useful tool in the management of upper airway infections after BMT and should be a routinely exams in order to avoid useless surgical or antibiotic approaches.



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In vivo study of dermal collagen of striae distensae by confocal Raman spectroscopy

Abstract

This research work mainly deals with studying qualitatively the changes in the dermal collagen of two forms of striae distensae (SD) namely striae rubrae (SR) and striae albae (SA) when compared to normal skin (NS) using confocal Raman spectroscopy. The methodology includes an in vivo human skin study for the comparison of confocal Raman spectra of dermis region of SR, SA, and NS by supervised multivariate analysis using partial least squares discriminant analysis (PLS-DA) to determine qualitatively the changes in dermal collagen. These groups are further analyzed for the extent of hydration of dermal collagen by studying the changes in the water content bound to it. PLS-DA score plot showed good separation of the confocal Raman spectra of dermis region into SR, SA, and NS data groups. Further analysis using loading plot and S-plot indicated the participation of various components of dermal collagen in the separation of these groups. Bound water content analysis showed that the extent of hydration of collagen is more in SD when compared to NS. Based on the results obtained, this study confirms the active involvement of dermal collagen in the formation of SD. It also emphasizes the need to study quantitatively the role of these various biochemical changes in the dermal collagen responsible for the variance between SR, SA, and NS.

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Liver PD-1 Immunobiology

Publication date: Available online 6 January 2018
Source:Seminars in Oncology
Author(s): Colleen S. Curran, Elad Sharon
Disruption of liver immune tolerance allows for the development autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC). AIH rarely progresses to HCC but the diseases similarly induce the production of IL-18 and matrix metalloproteinases. These molecules have distinct effects on the immune response, including the Programmed cell-death 1 (PD-1) axis. In this review, differences in PD-1 function and possible cell signals in AIH and HCC are highlighted.



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Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

Abstract

Objective

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban-German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2.

Methods

In this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured.

Results

Analysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volumes and the anteroposterior diameter of the pons, in both manifest SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing patients with nonataxic preclinical SCA2 mutation carriers, we found more pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2. Volumetric data further showed associations with CAG repeat length and predicted age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in patients. Although saccade velocity was associated with reduction in the pontine brainstem in preclinical and manifest SCA2, reduced ability to suppress interfering stimuli measured by the Stroop task was related to cerebellar volume loss in patients.

Interpretation

Preclinical SCA2 mutation carriers exhibit brain abnormalities, which could be targeted as surrogate parameters for disease progression and in future preventive trials.

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Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients?

Abstract

Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (C_min) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 ± 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 ± 623.4 ng/mL, P = 1.75 × 10^-4; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROC_AUC (95%CI) of 0.693 (0.597–0.789) and 207.1 ng/mL with ROC_AUC (95%CI) of 0.646 (0.546–0.745), respectively. Multivariate regression confirmed the correlation of Imatinib C_min with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients.

Since Imatinib is usually administered for a prolonged period, rational management of its side effects is of great importance. Few studies have been conducted to investigate the association between plasma concentration and side effects. In this study, Imatinib-induced myelosuppression was found to be correlated significantly with Imatinib concentration, and the estimated exposure threshold for myelosuppression was 1451.6 ng/mL with ROCAUC (95% CI) of 0.693 (0.597–0.789).

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Presynaptic endocytic factors in autophagy and neurodegeneration

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration. These findings reveal unanticipated connections between the machineries for synaptic neurotransmission and neuronal proteostasis and identify presynaptic endocytic proteins as potential targets to treat neurodegenerative diseases.



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Expansion microscopy: development and neuroscience applications

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Emmanouil D Karagiannis, Edward S Boyden
Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human.



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mGlu5-mediated signalling in developing astrocyte and the pathogenesis of autism spectrum disorders

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Francesco Petrelli, Paola Bezzi
Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear. The aim of this review is to examine what is known about the mGlu5-mediated signalling in the developing astrocytes and its possible contribution to the pathophysiology of autism spectrum disorders.



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Local and long-range circuit elements for cerebellar function

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Le Xiao, Peter Scheiffele
The view of cerebellar functions has been extended from controlling sensorimotor processes to processing 'contextual' information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors: The role for cerebellar granule cells in multimodal integration in the cerebellar cortex and the long-range connectivity between the deep cerebellar nuclei and the basal ganglia. Lastly, we discuss how studies on synapses and circuits of the cerebellum in rodent models of autism-spectrum disorders might contribute to our understanding of the pathophysiology of this class of neurodevelopmental disorders.



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Synapse-to-nucleus communication: from developmental disorders to Alzheimer's disease

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Elena Marcello, Monica Di Luca, Fabrizio Gardoni
In the last decade several synaptonuclear protein messengers including Jacob, CRTC1, AIDA-1, ProSaP2/Shank3 and RNF10 have been identified and characterized as key players for modulation of synaptic transmission and synaptic plasticity. Activation of excitatory glutamatergic synapses leads to their shuttling from the synapse to the nucleus, mostly importin-mediated, and subsequent regulation of gene transcription needed for long lasting modifications of synaptic function. Accordingly, increasing evidences show that alterations of the activity of synaptonuclear messengers are correlated to synaptic failure as observed in different synaptopathies. Specifically, recent studies demonstrate that the modulation of the activity of synaptonuclear messengers could represent a novel molecular target in the pathogenesis of both neurodevelopmental disorders and neurodegenerative diseases such as Alzheimer's disease.



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Application of Statistical Inference for Analysis of Heavy Metal Variability in Roadside Soil

Abstract

Previous studies have found there are a variety of factors that influence heavy metal concentrations and Pb isotope ratios in roadside soil. One issue in assessing these factors is the need to distinguish between the natural sample variability at a single site and the variability between different sites. Data constraint often results in the lack of an adequate number of samples and hence is often a constraint on statistical reliability. Presented herein is a regionalisation approach that can be used to overcome the data constraint. This approach was used to analyse data collected at Miranda Park, Sydney, for assessment of the influence of rainfall, distance, depth and soil types. Application of the regionalisation approach enabled discrimination between natural sample variability and that from changes in the factors being considered. The regionalisation approach mitigates the data constraint and may assist researchers in their analysis of constrained data sets enabling more efficient monitoring of potential environmental issues. Additionally, it was found that the primary factors for heavy metal concentrations were rainfall, distance and soil types while depth was a secondary factor. A similar result was determined for the anthropogenic Pb component but not for the natural Pb component.

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Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more

Publication date: Available online 6 January 2018
Source:Brain Stimulation
Author(s): P. Rebelo, A.L. Green, T.Z. Aziz, A. Kent, D. Schafer, L. Venkatesan, B. Cheeran
BackgroundDirectional Deep Brain Stimulation (D-DBS) allows axially asymmetric electrical field shaping, away from structures causing side-effects. However, concerns regarding the impact on device lifespan and complexity of the monopolar survey have contributed to sparing use of these features.ObjectiveTo investigate whether chronically implanted D-DBS systems can improve the therapeutic window, without a negative impact on device lifespan, in thalamic deep brain stimulation (DBS).MethodsWe evaluated stable outcomes of initial programming sessions (4–6 weeks post-implantation) retrospectively in 8 patients with drug-resistant disabling tremor syndromes. We assessed the impact of directional stimulation on the Therapeutic Window (TW), Therapeutic Current Strength (TCS), tremor scores, disability scores and total electrical energy delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling, based on a range of parameters.ResultsWe report significant gains in TW (91%) and reductions in TCS (31%) with stimulation in the best direction compared to best omnidirectional stimulation alternative. Tremor and ADL scores improvements remained unchanged at six months. There was no increase in averaged IPG power consumption (there is a 6% reduction over the omnidirectional-only alternative). Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation volume at just 69% of the stimulation amplitude of non-directional configuration.Conclusions: D-DBS can improve the therapeutic window over non-directional DBS, leading to significant reduction in disability that may be sustained without additional reprogramming visits. Device lifespan was not negatively impacted by the use of directional stimulation this study due to the programming approach.



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Dr. Martin Citardi Recognized with AAO-HNS Distinguished Service Award

Martin J. Citardi, MD, professor and chair of the Department of Otorhinolaryngology-Head and Neck Surgery at UTHealth's McGovern Medical School,... Read the full article...

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A Comparative Study of Batch and Continuous Bulk Liquid Membranes in the Removal and Recovery of Cu(II) Ions from Wastewater

Abstract

The aim of this work was to compare the performance between a batch bulk liquid membrane (BBLM) and a continuous bulk liquid membrane (CBLM) in the removal and recovery of Cu(II) ions from wastewater. Effects of operating parameters affecting the resistance of Cu(II) ion transfer such as stirring speeds of phases in BBLM, flow rates of phases through CBLM and operating temperature of both BBLM and CBLM on the removal and recovery of Cu(II) ions from aqueous solutions were explored. The variations in Reynolds number and thickness of boundary layer of all phases with stirring speed in BBLM and with flow rate in CBLM, as well as changes in the viscosity of membrane phase with temperature in both BBLM and CBLM were also investigated. A comparison of performance between BBLM and CBLM in the treatment of real industrial wastewater was also conducted and evaluated. It was found that BBLM achieved higher extraction (removal) and stripping (recovery) of Cu(II) ions of up to 16% than CBLM over the range of experimental conditions studied. Both BBLM and CBLM were found to remove and recover Cu(II) ions effectively from real industrial wastewater.

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Improvement of the Gluteal Contour

Publication date: Available online 5 January 2018
Source:Clinics in Plastic Surgery
Author(s): Lázaro Cárdenas-Camarena, Héctor Durán

Teaser

Buttock enlargement with lipoinjection is a procedure that has had a very high demand in the last 5 years. Changes in aesthetics have made more patients request greater volume in their buttocks and hips. The procedure requires not only liposuction, in which the fat is obtained, but also a systematization off the fat injection process in the buttock to obtain the appropriate aesthetic results according to the characteristics of each patient. The procedure achieves very satisfactory results because it can transform the patient's physical appearance significantly.


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Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44^+/high/CD24^−/low/CD117^−/low/CD146^−/low/ALDH1^low profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44^+/high/CD24^+/high/ CD117^−/low/CD146^−/low/ALDH1^low profile in both culture models, although the tumorsphere model showed a significant increase in CD24^+/high subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24^+/high cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

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Spiral enteroscopy-assisted ERCP in bariatric length Roux-en-Y anatomy: a large single-center series and review of the literature (with video)

Deep enteroscopy-assisted ERCP (DEA-ERCP) in post-bariatric Roux-en-Y (RY) anatomy is challenging. Laparoscopy-assisted ERCP (LA-ERCP) or EUS-directed transgastric ERCP (EDGE) are technically easier and faster, but are more invasive and morbid procedures. Therefore, we have used DEA-ERCP as our first-line approach, reserving EDGE and LA-ERCP for cases in which adjunctive techniques that cannot be performed through an enteroscope are required (eg, EUS-FNA, SO manometry), or DEA-ERCP failures. The two main methods for DEA-ERCP are balloon- and spirus-assisted.

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Clinical outcome of endoscopic mucosal resection of sporadic, nonampullary duodenal adenoma: a 10-year retrospective

Sporadic non-ampullary duodenal adenomas (SNADAs), although uncommon, pose clinical challenges. Because SNADAs have malignant potential, endoscopic or surgical resection is generally recommended. Endoscopic mucosal resection (EMR) is increasingly used for resection of SNADAs, but large-scale data on natural history after EMR are scarce. In this study, we aimed to evaluate the clinical outcome of EMR for SNADAs and the natural history after EMR from a large single-operator experience with dedicated follow-up.

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The impact of wire caliber on ERCP outcomes: a multicenter randomized controlled trial of 0.025-inch and 0.035-inch guidewires

Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events using a 0.025-inch and 0.035-inch guidewire.

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Combination of Albumin-Bilrubin Grade and Platelet to Predict Compensated Patient with Hepatocellular Carcinoma Who Do Not Require Endoscopic Screening for Esophageal Varices

s & Aims: There is no consensus for screening high-risk esophageal varices (HRV) in patients with hepatocellular carcinoma (HCC). Here, we aimed to investigate the prevalence and risk factors of HRV in HCC patients and to assess the combination of albumin-bilirubin grade and platelet count (ALBI-PLT score) for predicting compensated patients who do not need unnecessary endoscopic screening for HRV.

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Temporal trends in postcolonoscopy colorectal cancer rates in screen-eligible persons: a population-based study

Colorectal cancers (CRCs) diagnosed between 6 and 36 months after colonoscopy, termed postcolonoscopy CRCs (PCCRCs), arise primarily due to missed or inadequately treated neoplasms during colonoscopy. Quality indicators and technological advances have been introduced to colonoscopy practice that should have reduced the PCCRC rate over time. We assessed temporal trends in the population rate of PCCRC as a measure of changing colonoscopy quality.

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Miniature pig model of human adolescent brain white matter development

Publication date: 15 February 2018
Source:Journal of Neuroscience Methods, Volume 296
Author(s): Meghann C. Ryan, Paul Sherman, Laura M. Rowland, S. Andrea Wijtenburg, Ashley Acheson, Els Fieremans, Jelle Veraart, Dmitry S. Novikov, L. Elliot Hong, John Sladky, P. Dana Peralta, Peter Kochunov, Stephen A. McGuire
BackgroundNeuroscience research in brain development and disorders can benefit from an in vivo animal model that portrays normal white matter (WM) development trajectories and has a sufficiently large cerebrum for imaging with human MRI scanners and protocols.New methodTwelve three-month-old Sinclair™ miniature pigs (Sus scrofa domestica) were longitudinally evaluated during adolescent development using advanced diffusion weighted imaging (DWI) focused on cerebral WM. Animals had three MRI scans every 23.95 ± 3.73 days using a 3-T scanner. The DWI imaging protocol closely modeled advanced human structural protocols and consisted of fifteen b-shells (b = 0–3500 s/mm²) with 32-directions/shell. DWI data were analyzed using diffusion kurtosis and bi-exponential modeling that provided measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axial kurtosis, tortuosity, and permeability-diffusivity index (PDI).ResultsSignificant longitudinal effects of brain development were observed for whole-brain average FA, KA, and PDI (all p < 0.001). There were expected regional differences in trends, with corpus callosum fibers showing the highest rate of change.Comparison with existing method(s)Pigs have a large, gyrencephalic brain that can be studied using clinical MRI scanners/protocols. Pigs are less complex than non-human primates thus satisfying the "replacement" principle of animal research.ConclusionsLongitudinal effects were observed for whole-brain and regional diffusion measurements. The changes in diffusion measurements were interepreted as evidence for ongoing myelination and maturation of cerebral WM. Corpus callosum and superficial cortical WM showed the expected higher rates of change, mirroring results in humans.



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Effect of transcranial direct current stimulation on short-term and long-term treatment of chronic tinnitus

This study was conducted to investigate the effectiveness of anodal and cathodal methods in reducing the intensity of tinnitus and to compare them with the control.

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Juvenile idiopathic arthritis: magnetic resonance imaging of the clinically unaffected knee

Abstract

Background

Synovial thickening detected on magnetic resonance imaging (MRI) is present in a significant number of children with clinically inactive juvenile idiopathic arthritis (JIA).

Objective

To evaluate patient characteristics and disease activity parameters in a cohort of children with clinically inactive JIA, both with and without synovial thickening, in order to clarify the observed discrepancy between clinical and MRI assessments.

Materials and methods

We prospectively enrolled 52 clinically inactive JIA patients (median age 13.3 years, 63.5% girls) who underwent MRI of the knee as major target joint in JIA. Children were divided into two groups based on MRI outcome: group 1, with synovial thickening on MRI; and group 2, with no synovial thickening on MRI. We used the Juvenile Arthritis MRI Scoring system to evaluate synovial thickness. We compared patient characteristics and disease activity parameters between the groups.

Results

Synovial thickening on MRI was present in 18 clinically inactive patients (group 1, 34.6%). The age was significantly lower for the patients in group 1 (median 10.7 versus 14.4, P=0.008). No significant differences were observed in any of the other patient characteristics nor the disease activity parameters tested.

Conclusion

Synovial thickening on MRI was present in nearly 35% of the children with clinically inactive JIA. Children with synovial thickening on MRI were significantly younger than those without. This might indicate that younger patients are at risk of subclinical disease activity and under-treatment, although the exact clinical relevance of synovial thickening on MRI has not been determined.

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The role of tryptophan metabolism in postpartum depression

Abstract

The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%–20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD. Importantly, an increase in stress hormones and immune-inflammatory activity drives tryptophan to the production of neuroregulatory kynurenine pathway products and away from the serotonin and melatonin pathways. This links the PPD to other disorders of depressed mood, which are classically associated with decreased serotonin and melatonin, coupled to increases in kynurenine pathway products. Several kynurenine pathway products, such as kynurenic acid and quinolinic acid, can have neuroregulatory effects, with consequences pathological underpinnings of the PPD. The current article reviews the role of alterations in tryptophan metabolism in the PPD.

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Defining the Key Competencies in Radiation Protection for Endovascular Procedures: A Multispecialty Delphi Consensus Study

Publication date: Available online 5 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Bart Doyen, Blandine Maurel, Jonathan Cole, Heidi Maertens, Tara Mastracci, Isabelle Van Herzeele
ObjectivesRadiation protection training courses currently focus on broad knowledge topics which may not always be relevant in daily practice. The goal of this study was to determine the key competencies in radiation protection that every endovascular team member should possess and apply routinely, through multispecialty clinical content expert consensus.MethodsConsensus was obtained through a two round modified Delphi methodology. The expert panel consisted of European vascular surgeons, interventional radiologists, and interventional cardiologists/angiologists experienced in endovascular procedures. An initial list of statements, covering knowledge skills, technical skills and attitudes was created, based on a literature search. Additional statements could be suggested by the experts in the first Delphi round. Each of the statements had to be rated on a 5- point Likert scale. A statement was considered to be a key competency when the internal consistency was greater than alpha = 0.80 and at least 80% of the experts agreed (rating 4/5) or strongly agreed (rating 5/5) with the statement. Questionnaires were emailed to panel members using the Surveymonkey service.ResultsForty-one of 65 (63.1%) invited experts agreed to participate in the study. The response rates were 36 out of 41 (87.8%): overall 38 out of 41(92.6%) in the first round and 36 out of 38 (94.7%) in the second round. The 71 primary statements were supplemented with nine items suggested by the panel. The results showed excellent consensus among responders (Cronbach's alpha = 0.937 first round; 0.958 s round). Experts achieved a consensus that 30 of 33 knowledge skills (90.9%), 23 of 27 technical skills (82.1%), and 15 of 20 attitudes (75.0%) should be considered as key competencies.ConclusionsA multispecialty European endovascular expert panel reached consensus about the key competencies in radiation protection. These results may serve to create practical and relevant radiation protection training courses in the future, enhancing radiation safety for both patients and the entire endovascular team.



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Commentary on “Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in vitro”

Publication date: Available online 6 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Sandro Lepidi




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Combination of MPPa-PDT and HSV1-TK/GCV gene therapy on prostate cancer

Abstract

We combined pyropheophorbide-a methyl ester, photodynamic therapy (MPPa-PDT), 670 ± 10 nm, 4 mW/cm², with herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) to improve the therapeutic effect. We built HSV1-TK expression vector GV230-TK and we observed a bright green fluorescence under fluorescence microscope. It indicated the recombinant plasmid was transfected into PC-3M prostate cancer cells successfully. As the abundant glucose-regulated protein 78 (GRP78) promoter in PC-3M cells can cause active expression of HSV1-TK, cell protein was collected for western blot to determine the expression of HSV1-TK. In CCK-8 assay (n = 6), the cell survival rate of combined treatment group was about 10%, less than that of pure MPPa-PDT group (23%) and pure HSV1-TK/GCV group (35%) (t test, P < 0.05). Flow cytometry was used to measure the cytotoxicity; the apoptosis rate of combined treatment group was about 38%, higher than that of pure MPPa-PDT group (about 22%) and pure HSV1-TK/GCV group (about 19%). The results showed that the combination of the two treatments can effectively improve the cytocidal effect in PC-3M cells.

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Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1

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


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Emergence of insulin resistance following empirical glibenclamide therapy: a case report of neonatal diabetes with a recessive INS gene mutation

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


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Patterns of Involved-Field Radiation Therapy (IFRT) Protocol Deviations in Pediatric versus Adolescent and Young Adults with Hodgkin Lymphoma: A Report from the Children’s Oncology Group (COG) AHOD0031

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): A. Parzuchowski, Rizvan Bush, Qinglin Pei, D.L. Friedman, T.J. FitzGerald, S.L. Wolden, K.V. Dharmarajan, L.S. Constine, F. Laurie, S.K. Kessel, B. Appel, K. Fernandez, A. Punnett, C.L. Schwartz, J. Cox, S.A. Terezakis
BackgroundThis protocol for pediatric intermediate-risk Hodgkin Lymphoma (IRHL) evaluated the use of a dose-intensive chemotherapy regimen (ABVE-PC) with response-based therapy augmentation (addition of DECA) or therapy reduction (elimination of radiation). Central review of radiotherapy data for quality assurance (QA) was performed, and the association between radiation protocol deviation (RPD) and relapse was assessed in pediatric (<15) and AYA (≥15-21) groups.ProcedureIFRT treatment planning was reviewed prior to the start of treatment and at the completion of treatment. Records were reviewed through the Quality Assurance Review Center's (QARC) central review to identify RPD, classified according to dose (DD), volume (VD), under-treatment (UT), and over-treatment (OT). DD and VD were further classified as major or minor.ResultsOf the 1,712 patients enrolled, 1,155 received IFRT and 216 (18.7%) had RPD. DD and VD patterns were similar between pediatric and AYA groups. Minor VD was most common. UT RPD accounted for 69% in the pediatric group and 75% in the AYA group. Of 35 relapses and RPD, 29 had an under-treatment RPD. Among the patients who received IFRT, there was a significant difference in the cumulative incidence rates of relapse between pediatric and AYA groups (p=0.03) but no significant difference between patients with and without RPD (p=0.2).ConclusionsThe majority of RPD were minor and under-treatments in both the AYA and pediatrics population. There was no observed difference in RPD between the pediatric and AYA patients. Thus, in a well-defined and standardized protocol, RPD distributions for AYA patients are similar to the pediatrics population. However, the increased cumulative incidence of relapse in the AYA population who received IFRT compared to the pediatrics population needs to be further explored given the potential differences in clinical outcomes in the AYA population.

Teaser

As ******** is the largest phase III study to date on intermediate-risk Hodgkin Lymphoma in pediatric patients, we investigated the patterns of radiation protocol deviation and relapse between the pediatric and adolescent and young adult patient cohorts. We demonstrate that there were no statistically significant differences in deviation patterns between the two cohorts, though of those that received IFRT, there was a significant difference in cumulative incidence rates of relapse between the two groups.


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Phase II Study of Bortezomib in Combination with Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients with Newly-Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Xiao-Tang Kong, Nhung T. Nguyen, Yoon J. Choi, Guicheng Zhang, HuyTram N. Nguyen, Emese Filka, Stacey Green, William H. Yong, Linda M. Liau, Richard M. Green, Tania Kaprealian, Whitney B. Pope, P. Leia Nghiemphu, Tim Cloughesy, Andrew Lassman, Albert Lai
Purpose/ObjectiveTo assess the safety and efficacy of upfront treatment using bortezomib in combination with standard radiation therapy (RT) and temozolomide, followed by adjuvant bortezomib and temozolomide for up to 24 cycles in patients with newly-diagnosed glioblastoma multiforme (GBM).Patients and MethodsTwenty-four newly-diagnosed GBM patients were enrolled. Patients received standard external beam regional RT with concurrent temozolomide commencing 3-6 weeks after surgery, followed by adjuvant temozolomide and bortezomib for up to 24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, 11, 29, 32, 36, and 39. Post RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, and 11 every 4 weeks.ResultsNo unexpected adverse events occurred from the addition of bortezomib. Efficacy analysis showed median progression free survival (PFS) of 6.2 months (95% CI, 3.7-8.8) with promising PFS rates at 18 months and beyond compared to historical norms (25.0% at 18 and 24 months, 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI, 6.7-31.4) with improved OS rates at 12 months and beyond (87.5% at 12, 50.0% at 24, 34.1% at 36 throughout 60 months) compared to historical norms. Median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be reached) and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients.ConclusionAddition of bortezomib to current standard radio-chemotherapy in newly-diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Teaser

We conducted a phase II study of bortezomib in combination with temozolomide and regional radiotherapy (RT) in 24 newly-diagnosed GBM patients. Addition of bortezomib to current standard care was well-tolerated, and observed toxicities were acceptable. Overall survival rates were improved compared to historical norms, especially in MGMT methylated patients. Further clinical investigation is warranted in larger cohort of patients.


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Local Control following Stereotactic Body Radiation Therapy for Liver Tumors

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nitin Ohri, Wolfgang A. Tomé, Alejandra Méndez Romero, Moyed Mifften, Randall K. Ten Haken, Laura A. Dawson, Jimm Grimm, Ellen Yorke, Andrew Jackson
PurposeNumerous dosing and fractionation schedules have been used to treat hepatic tumors with stereotactic body radiation therapy (SBRT). In this report, we have quantitatively evaluated published experiences with hepatic SBRT to determine local control rates following treatment of primary and metastatic liver tumors and to examine if outcomes are affected by SBRT dosing regimen.MethodsWe identified published articles that reported local control rates following SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the Linear Quadratic Equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 v. >100 Gy10). Comparisons were made using logrank testing.ResultsThirteen papers met all inclusion criteria and formed the dataset for this analysis. One, two, and three-year actuarial local control rates following SBRT for primary liver tumors (n=431) were 93%, 89%, and 86%, respectively. Lower one (90%), two (79%), and three-year (76%) actuarial local control rates were observed for liver metastases (n=290, logrank p=0.011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs less than or equal to 100 Gy10 (3-year local control 65%, p<0.001).ConclusionSBRT for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly-utilized schedules. Excellent local control rates are also seen following SBRT for liver metastases when biologically effective doses above 100 Gy10 are utilized.

Teaser

We have quantitatively evaluated published experiences with hepatic SBRT to determine local control rates for primary and metastatic liver tumors and have examined if outcomes are affected by SBRT dosing regimen. We found that for primary liver tumors SBRT provides high rates of durable local control, with no clear evidence of a dose-response relationship for commonly-utilized schedules. While for liver metastases following SBRT excellent local control rates are seen when utilizing biologically effective doses above 100 Gy10.


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Radiation Dose-Volume Effects for Liver SBRT

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Moyed Miften, Yevgeniy Vinogradskiy, Vitali Moiseenko, Jimm Grimm, Ellen Yorke, Andrew Jackson, Wolfgang A. Tomé, Randall Ten Haken, Nitin Ohri, Alejandra Méndez Romero, Karyn A. Goodman, Lawrence B. Marks, Brian Kavanagh, Laura A. Dawson
Stereotactic Body Radiation Therapy (SBRT) has emerged as an effective, non-invasive treatment option for primary liver cancer and metastatic disease occurring in the liver. While SBRT can be highly effective for establishing local control in hepatic malignancies, there is a tradeoff between tumor control and normal tissue complications. The objective of this work was to review the normal tissue dose-volume effects for SBRT-induced liver and gastrointestinal (GI) toxicities, and derive normal tissue complication probability models.



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Early Tissue Effects of Stereotactic Body Radiotherapy in Spinal Metastases

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jasper G. Steverink, Stefan M. Willems, Marielle E.P. Philippens, Nicolien Kasperts, Wietse S.C. Eppinga, Anne L. Versteeg, Joanne M. van der Velden, Salman Faruqi, Arjun Sahgal, Jorrit-Jan Verlaan
IntroductionStereotactic body radiotherapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent literature suggests radio-biologic effects of SBRT expanding beyond the traditional concept of DNA-damage. Anti-tumor immunity, vascular damage leading to tumor necrosis and increased rates of tumor apoptosis are implied, yet in-human evidence remains scarce. This study reports unique pathologic confirmation of SBRT-induced biologic effects within spinal metastases treated with pre-operative SBRT.Materials and MethodsTen patients with spinal metastases secondary to various solid tumors were treated with pre-operative single-fraction SBRT (18 Gy) to the MRI-defined macroscopic metastasis followed by spinal stabilization within 24 hours. Perioperative samples of spinal metastases were obtained, and 6 patients also had a pre-SBRT biopsy for matched comparison. Samples were stained for tumor necrosis on routine HE slices and subsequently underwent immunohistochemical staining for T-cells (CD3+, CD4+, CD8+), NK-cells (CD56+), endothelium (CD31+) and apoptotic activity (Caspase-3).ResultsPerioperative biopsies were obtained approximately 6 hours (range 4.5-7.5h) or 21 hours (range 18.5-22.5h) post-SBRT. Necrosis was observed in 83% of 21h post-SBRT samples (5/6), as compared to 0% in pre-SBRT biopsies (0/6) and 6h post-SBRT biopsies (0/4). Tumor cell apoptosis increased greatly in 21h post-SBRT samples compared to pre- and 6h post-SBRT. CD31+ vessel counts decreased post-SBRT as did mitotic activity. Notably, both of the renal cell metastases displayed major decreases in vessel density. Desmoplastic reaction was visible in 67% (4/6) with pre-SBRT samples compared to 100% (10/10) post-SBRT samples. T- and NK-cell counts were relatively unaffected.ConclusionHigh-dose single-fraction SBRT induced tumor necrosis, desmoplasia and tumor apoptosis and decreased tumor vessel density within 24 hours, even in renal cell metastases. The role of immune cells seems limited in this early phase. These first-in-man results imply direct vascular- and DNA-damage mechanisms important in the clinical efficacy specific to spine SBRT.



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Radiation as an Effective Salvage Therapy for Secondary CNS Lymphoma

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sarah A. Milgrom, Chelsea C. Pinnix, T Linda Chi, Thinh H. Vu, Jillian R. Gunther, Tommy Sheu, Nathan Fowler, Jason R. Westin, Loretta J. Nastoupil, Yasuhiro Oki, Luis E. Fayad, Sattva Neelapu, Maria Alma Rodriguez, Frederick B. Hagemeister, Michelle A. Fanale, Hun J. Lee, Chitra Hosing, Sairah Ahmed, Yago Nieto, Elizabeth J. Shpall, Bouthaina S. Dabaja
We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma. The cohort comprised 44 patients with systemic diffuse large-B cell lymphoma (DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse, who received RT. Twenty-nine patients (66%) were in systemic remission when diagnosed with CNS disease. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% CI: 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation (SCT) after RT, and had brain parenchymal (vs. leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: one involved the brain parenchyma and 7 involved the spine and/or CSF/meninges. We conclude that RT is associated with high response rates and may contribute to long-term OS. Additionally, RT may provide CNS disease control that facilitates successful salvage with SCT in patients with chemorefractory disease.

Teaser

We reviewed the outcomes of patients with secondary central nervous system involvement by diffuse large-B cell lymphoma, who were treated with radiation therapy (RT) at a single institution. RT was associated with high rates of radiographic disease response and local control. Overall survival was superior in patients who achieved a complete or partial response to RT, who underwent autologous stem cell transplantation after RT, and who had brain parenchymal (vs. leptomeningeal) disease.


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Making Contact: The Key to Dental Inclusion

Publication date: Available online 6 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Thomas B. Dodson




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Effects of different peracetic acid formulations on post space radicular dentin

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Lauriê Garcia Belizário, Milton Carlos Kuga, Gabriela Mariana Castro-Núñez, Wilfredo Gustavo Escalante-Otárola, Marcus Vinicius Reis Só, Jefferson Ricardo Pereira
Statement of problemThe optimal irrigating solution with antimicrobial and dentin cleansing properties for post space preparation for fiber posts is unclear. Peracetic acid is one option but is available in various chemical formulations that require evaluation.PurposeThe purpose of this in vitro study was to evaluate dentin surface cleanliness based on the presence of a smear layer and the number of open dentin tubules. It also investigates the chemical composition of residues after canal irrigation with a 1% peracetic acid solution (PA) at low or high concentration of hydrogen peroxide during the preparation of intracanal fiber posts.Material and methodsAfter filling the root canals of 40 mandibular incisors, a rotary instrument was used for intracanal preparation to place fiber posts. The teeth were divided into 4 groups (n=10) according to the post space irrigation protocol as follows: CG (control): distilled water; NA (NaOCl): 2.5% sodium hypochlorite; LH: PA with low concentration of hydrogen peroxide; and HH: PA with high concentrations of hydrogen peroxide. After irrigation, the teeth were sectioned, and the intracanal dentin surface was subjected to analysis using energy dispersive spectroscopy to evaluate chemical composition and to scanning electron microscopy (×500) to evaluate the presence of the smear layer. The number of open dentin tubules was measured by scanning electron microscopy analysis (×2000) using photo-editing software. ANOVA and the Tukey test (α=.05) were used to evaluate the data, except for the presence of a smear layer, for which the Kruskal-Wallis and Dunn tests were used (α=.05).ResultsThe highest concentrations of oxygen in the dentin residues were detected in LH and HH (P<.05); CG and NA showed similar oxygen concentrations (P>.05). NA had a higher concentration of chlorine (P<.05), whereas LH had a lower amount of smear layer and a larger number of open dentin tubules than the other groups (P<.05). These were equivalent to each other (P>.05), except for HH, which also had a larger number of open dentin tubules than CG and NA (P<.05).ConclusionsPA 1% with a low concentration of hydrogen peroxide yielded a lower amount of smear layer and a larger number of open dentin tubules in the dentin of the post space when compared with PA 1% with a high concentration of hydrogen peroxide, despite maintaining a similar oxygen concentration in these dentin residues.



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Comparison of the mechanical properties of translucent zirconia and lithium disilicate

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Sung Joon Kwon, Nathaniel C. Lawson, Edward E. McLaren, Amir H. Nejat, John O. Burgess
Statement of problemThree mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) possesses excellent mechanical properties but is relatively opaque. Five mol% yttria-stabilized zirconia polycrystal (5Y-ZP) offers improved translucency, but many of its clinical properties have not been compared with those of 3Y-TZP and lithium disilicate.PurposeThe purpose of this in vitro study was to compare the flexural strength, translucency parameter, bond strength, and enamel and material wear of 5Y-ZP (Katana UTML) with 3Y-TZP (Katana HT) and lithium disilicate (e.max CAD).Material and methodsFlexural strength bars were sectioned (n=10, 25×4×2 mm), sintered or crystallized, polished, and fractured at 1 mm/min. Translucency specimens (1 mm thick) were fabricated (n=10). Their L*a*b* values were measured against a black-and-white background with a spectrophotometer, and ΔE00 was calculated. Zirconia bond strength specimens were airborne-particle abraded with 50 μm alumina followed by the application of a 10-methacryloxydecyl dihydrogen phosphate–containing primer (Clearfil Ceramic Primer). Lithium disilicate bond strength specimens were etched with 5% hydrofluoric acid followed by application of a silane-containing primer (Clearfil Ceramic Primer). A Tygon tube filled with resin cement (Panavia SA) was fixed to the surface of the ceramics and light-polymerized. After 1 day or 150 days of water storage, the resin cement was debonded in a macroshear test (n=10). The cusps of extracted human molars were isolated and mounted into the University of Alabama at Birmingham wear-testing device. Wear testing was performed with a 20-N load for 300000 cycles in 33% glycerin. The volumetric wear of polished zirconia, lithium disilicate, and enamel were measured along with the wear of the opposing enamel cusps using a noncontact profilometer (n=8). The data were compared by ANOVA and Tukey-Kramer analysis (α=.05).ResultsNo statistical difference was seen between the bond strengths (P=.155) or the opposing enamel wear (P=.533) of different ceramics. A statistically significant difference was seen between the flexural strength (P<.001), translucency parameter (P<.001), and wear (P<0.01) of the materials. The flexural strength values (MPa) were 1194 ±111 (Katana HT), 688 ±159 (Katana UTML), and 450 ±53 (e.max LT). The translucency parameter values were 6.96 ±0.53 (Katana HT), 8.30 ±0.24 (Katana UTML), 9.28 ±0.36 (e.max LT), and 12.64 ±0.48 (e.max HT). Bond strength values (MPa) at 1 and 150 days were 34.22 ±5.14 and 28.37 ±6.03 (Katana HT), 35.04 ±5.69 and 25.03 ±6.44 (Katana UTML), and 35.50 ±3.45 and 22.32 ±3.45 (e.max LT). Material and enamel wear (mm³) were 0 and 0.24 ±0.19 (Katana HT), 0 and 0.23 ±0.09 (Katana UTML), 0.28 ±0.13 and 0.31 ±0.10 (e.max CAD), and 0.09 ±0.03 and 0.31 ±0.14 (enamel).Conclusions5Y-TZP has a flexural strength and translucency parameter between those of 3Y-TZP and lithium disilicate. Both the short-term and long-term bond strength of 5Y-ZP and 3Y-TZP was shown to be similar to lithium disilicate. 5Y-ZP demonstrated no measurable material wear and opposing enamel wear similar to that of all the other materials tested.



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Comparison between masticatory index and mixing index among complete denture wearers and associated factors: A multivariate analysis

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hala A. Elmoula, Nadia Khalifa, Mohammed Nasser Alhajj
Statement of problemMasticatory performance is an important and complex multifactorial process in clinical practice. An exploration of the relationships and effects of the associated factors is lacking.PurposeThis clinical survey compared masticatory efficiency (mixing index) with perceived masticatory ability (masticatory index) among complete denture wearers and sought to clarify the relationship between these indices and other factors.Materials and methodsThe study consisted of 58 complete denture wearers (37 men, 21 women) ranging between 37 and 80 years of age. Participants were interviewed and examined clinically. The perceived masticatory ability of participants regarding 15 types of Sudanese food was evaluated. The degree of mixing of a 2-colored chewing gum was used to measure masticatory efficiency. Multiple regression and structural equation modeling analyses were used to assess the association between both indices and other related factors.ResultsMost of the complete denture wearers could eat soft foods easily but found it difficult to eat hard foods and avoided them. No significant differences in masticatory efficiency could be observed regarding sex or age. Values of the mixing index ranged from 13 (well-mixed colors) to 34 (poorly mixed). Perceived masticatory ability was significantly associated with previous denture experience and the duration of denture wearing (P=.01). Masticatory efficiency was significantly associated with denture quality (P=.001) and with perceived masticatory ability (P=.004).ConclusionsA significant association was noted between denture quality and masticatory performance. A significant association was also observed between perceived masticatory ability and masticatory efficiency, and both can be used to evaluate masticatory performance among complete denture wearers.



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Disinfection of polyvinyl siloxane impression material by gaseous ozone

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hakki Celebi, Emine Begüm Büyükerkmen, Emrah Torlak
Statement of problemImpression materials must be disinfected to avoid cross-contamination before they are sent to the dental laboratory. However, whether aqueous state disinfectants affect material wettability is unclear.PurposeThe purpose of this in vitro study was to compare the efficacy of gaseous ozone and sodium hypochlorite (NaOCl) in disinfecting light-body consistency hydrophilized polyvinyl siloxane (PVS) impression specimens inoculated with a cocktail of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. The effect of both disinfectants on the wettability of the material was also evaluated on uninoculated specimens.Material and methodsDisk-shaped specimens (N=140) were subjected to the either gaseous ozone or NaOCl for up to 30 minutes at room temperature. In the ozone group, the specimens were ozonated under a continuous stream of gaseous ozone at a concentration of 12.8 mg/L, while the specimens in the NaOCl group were immersed into 0.5% NaOCl solution. Reductions in the size of the bacterial population at the end of the exposure times were determined by the plate count technique. The contact angle measurements on the impression surface were used to determine the wettability of the specimens. Results were analyzed with 1-way ANOVA followed by the Tukey post hoc test (α=.05).ResultsThe material exposed to both disinfectants for 30 minutes demonstrated a reduction in the number of bacteria of up to more than 3 log. The contact angle of water on the material increased significantly (P<.001) after only 5 minutes of contact with the NaOCl solution. However, the treatment with gaseous ozone for 30 minutes resulted in a reduced contact angle (P<.001).ConclusionsGaseous ozone treatment was identified as a promising method of disinfecting polymerized PVS impression materials because of its positive effect on the wettability of the material.



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Fracture analysis of CAD-CAM high-density polymers used for interim implant-supported fixed, cantilevered prostheses

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Burak Yilmaz, Gülce Alp, Jeremy Seidt, William M. Johnston, Roger Vitter, Edwin A. McGlumphy
Statement of problemThe load-to-fracture performance of computer-assisted design and computer-assisted manufacturing (CAD-CAM) high-density polymer (HDP) materials in cantilevers is unknown.PurposeThe purposes of this in vitro study were to evaluate the load-to-fracture performance of CAD-CAM–fabricated HDPs and to compare that with performance of autopolymerized and injection-molded acrylic resins.Material and methodsSpecimens from 8 different brands of CAD-CAM HDPs, including Brylic Solid (BS); Brylic Gradient (BG); AnaxCAD Temp EZ (AE); AnaxCAD Temp Plus (AP); Zirkonzahn Temp Basic (Z); GDS Tempo-CAD (GD); Polident (Po); Merz M-PM-Disc (MAT); an autopolymerized acrylic resin, Imident (Conv) and an injection-molded acrylic resin, SR-IvoBase High Impact (Inj) were evaluated for load-to-fracture analysis (n=5). CAD-CAM specimens were milled from poly(methyl methacrylate) (PMMA) blocks measuring 7 mm in buccolingual width, 8 mm in occlusocervical thickness, and 30 mm in length. A wax pattern was prepared in the same dimensions used for CAD-CAM specimens, flasked, and boiled out. Autopolymerizing acrylic resin was packed and polymerized in a pressure container for 30 minutes. An identical wax pattern was flasked and boiled out, and premeasured capsules were injected (SR-IvoBase) and polymerized under hydraulic pressure for 35 minutes for the injection-molded PMMA. Specimens were thermocycled 5000 times (5°C to 55°C) and fixed to a universal testing machine to receive static loads on the 10-mm cantilever, vertically at a 1 mm/min crosshead speed until fracture occurred. Maximum load-to-fracture values were recorded. ANOVA was used to analyze the maximum force values. Significant differences among materials were analyzed by using the Ryan-Einot-Gabriel-Welsch multiple range test (α=.05).ResultsStatistically significant differences were found among load-to-fracture values of different HDPs (P<.001). GD and Po materials had significantly higher load-to-fracture values than other materials (P<.001), and no statistically significant differences were found between GD and Po. The lowest load-to-fracture values were observed for autopolymerized and BG materials, which were significantly lower than those of GD, Po, AE, AP, Z, MAT, Inj, and BS. The load-to-fracture value of autopolymerized acrylic resin was not significantly different from that of BG CAD-CAM polymer.ConclusionsGD and Po CAD-CAM materials had the highest load-to-fracture values. AE, AP, Z, MAT, and BS CAD-CAM polymers and injection-molded acrylic resin had similar load-to-fracture values, which were higher than those of BG and autopolymerized acrylic resin. Autopolymerized acrylic resin load-to-fracture value was similar to that of BG CAD-CAM polymer, which is colored in a gradient pattern.



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Optical behaviors of esthetic CAD-CAM restorations after different surface finishing and polishing procedures and UV aging: An in vitro study

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hamiyet Kilinc, Sedanur Turgut
Statement of problemEsthetic computer-aided design and computer-aided manufacturing (CAD-CAM) materials have various chemical compositions and can be prepared by using different finishing and polishing procedures. Their optical properties may change over time, depending on these factors. However, information about their stain resistance is still scarce.PurposeThe purpose of this in vitro study was to evaluate the optical properties of esthetic CAD-CAM materials after different finishing and polishing procedures and ultraviolet (UV) aging.Material and methodsLava Ultimate, Cerasmart, Vita Enamic, Vita Suprinity, and Vita Mark II materials were used. A total of 150 specimens (14×12×1 mm) were prepared (n=10). A spectrophotometer was used to measure color parameters after different finishing and polishing procedures (control, manual polishing, glazing) and ultraviolet (UV) aging. Lightness (L*), green-red (a*), blue-yellow (b*), chroma (Ch), and hue (h) parameters were recorded, and change in lightness (ΔE*) values were calculated. Statistical analyses were performed with 2-way ANOVA, the Fisher least significant difference test, and the paired samples t test (α=.05).ResultsSignificant interactions were noted between the aging conditions, material type, and finishing and polishing procedures for all evaluated parameters (P<.001). Vita Suprinity and Vita Mark II glazing groups resulted in significantly higher L1* values (P<.05) after the first color measurements. The b1* and C1 values of Vita Suprinity were higher than for other materials (P<.05). The highest ΔE* value was observed in the Lava Ultimate-glazing group (ΔE*=22.7) and the lowest in the Vita Mark II-control group (ΔE*=0.86).ConclusionsThe optical properties of CAD-CAM materials can be affected by the material type and the applied surface finishing and polishing procedure. Manual polishing seems to be a better choice for Lava Ultimate and Cerasmart and glazing for Vita Enamic. For ceramic materials, manual polishing or glazing can be recommended in terms of color stability.



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Effect of ceramic material and resin cement systems on the color stability of laminate veneers after accelerated aging

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Seong-Min Lee, Yu-Sung Choi
Statement of problemLaminate veneers are susceptible to color change during clinical service. Studies that compare the effects of different ceramic and resin cement systems on color stability are lacking.PurposeThe purpose of this in vitro study was to evaluate the color stability of laminate veneers after accelerated aging using different ceramic and resin cement systems.Material and methodsCeramic specimens (N=168; shade A1; thickness, 0.50 ±0.05 mm; diameter, 10.00 ±0.10 mm) were prepared using nanofluorapatite and lithium disilicate (high translucency [HT] to low translucency [LT]) ceramics. Light-polymerizing (LP) cements were classified by brightness (high or low). Dual-polymerizing cements were classified by composition (base-only [DB] or base-catalyst [DC]) for comparison of color stability on the basis of polymerization type. DB cement was light-polymerizing, whereas DC cement was dual-polymerizing. They were further classified by shade (transparent, white, or yellow [n=7, each]). Color difference (ΔE) values were obtained by spectrophotometric quantification of L* (lightness), a* (green-red), and b* (blue-yellow) values before and after aging. The Kruskal-Wallis, Mann-Whitney U, Wilcoxon signed rank, and Bonferroni post hoc tests were used for statistical analysis.ResultsAfter specimens were subjected to accelerated aging, HT ceramic specimens luted with yellow-shade DC cement exhibited the greatest color change (ΔE=2.11), whereas HT and LT ceramic specimens luted with low-brightness LP cement exhibited the least color change (ΔE=1.37). In HT ceramic specimens, which exhibited the greatest color change of the 3 ceramic types, transparent shade cement exhibited significantly lower ΔE values than the other shades with DB (P<.001) and DC cements (P=.010). High-brightness cement exhibited significantly higher ΔE values than low-brightness cement when used with NF (P=.017), HT (P<.001), and LT (P<.001) ceramics. The ΔE values of DB cement were not always lower than those of DC cement. For all specimens, the aging of laminate veneers decreased the L* values and increased the a* and b* values.ConclusionsCeramic and resin-cement systems affected the color stability of laminate veneers. Relative to other ceramics, HT lithium disilicate ceramics exhibited greater color changes upon aging. For HT ceramics, the use of transparent shade resin cement is recommended. The lower the brightness of resin cement, the higher the color stability of veneers. For luting of 0.5-mm-thick laminate veneers with dual-polymerizing cement, light polymerization did not yield better color stability than dual polymerization over time.



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The hemi-engaging fixed dental implant prosthesis: A technique for improved stability and handling

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Todd R. Schoenbaum, Richard G. Stevenson, Eric Balinghasay
Clinicians commonly contend that the screw-retained, implant-supported fixed dental prosthesis (FDP) should be fabricated with all nonengaging abutments to allow for the inherent nonparallelism of the implants and the inability of the abutment connections to draw together during insertion and removal. The problem with a fully nonengaging FDP is difficulty in handling and more strain on the abutment screws, ultimately leading to increased rates of breakage and loosening. The hemi-engaging FDP design regains much of the advantage afforded by the internal connection and improves prosthetic handing both clinically and in the laboratory. The benefits of this technique are best seen for short-span (fewer than 5 units), screw-retained, implant-supported FDPs.



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C-Cbl and Cbl-b expression in skull base chordomas is associated with tumor progression and poor prognosis

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): Peng Luo, Xin Wang, Jinpeng Zhou, Long Li, Zhitao Jing
Chordomas are rare, locally aggressive malignancies that are often difficult to eradicate. Surgery and radiotherapy are the first-line treatments, but the probability of local recurrence is high. According to our previous research, c-Cbl and Cbl-b have been linked to tumor progression and poor prognosis of glioma. However, their role in skull base chordomas is unclear. To clarify this issue, in the present study we analyzed the expression of c-Cbl and Cbl-b in relation to the clinicopathological features and clinical outcome of skull base chordomas patients (n=70). C-Cbl and Cbl-b expression was evaluated by immunohistochemistry and a survival analysis was performed based on clinical data. We found that c-Cbl and Cbl-b were upregulated in 30/70 (42.9%) and 32/70 (45.7%) patient with skull base chordomas, respectively. A Kaplan-Meier analysis and log-rank test indicated that high c-Cbl and Cbl-b levels were significantly associated with overall survival (P=0.003 and P=0.008, respectively) and progression-free survival (P<0.001 and P=0.022, respectively). These data indicated that c-Cbl and Cbl-b expression in skull base chordomas can predict tumor invasion and poor prognosis and are therefore potential therapeutic targets for chordomas treatment.



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Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): David Creytens, Thomas Mentzel, Liesbeth Ferdinande, Joost van Gorp, Jo Van Dorpe, Uta Flucke




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Differentiating Breast Carcinoma with Signet-Ring Features from Gastrointestinal Signet-Ring Carcinoma: Assessment of Immunohistochemical Markers

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): Yiang Hui, Yihong Wang, Gahie Nam, Jacqueline Fanion, Ashlee Sturtevant, Kara A. Lombardo, Murray B. Resnick
Signet-ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with signet-ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing signet-ring features were reviewed. Non-mammary and non-gastrointestinal tumors with this morphology were included for comparison. Estrogen receptor (ER), progesterone receptor (PR), e-cadherin, CK7, CK20, GCDFP-15, mammaglobin, CDX2, GATA-3, and HepPar-1 immunohistochemistry was performed. Expression patterns were compared between breast and gastrointestinal tumors as well as lobular breast and gastric tumors. Ninety-three cases were identified: 33 breast carcinomas including 13 lobular, 50 gastrointestinal tumors including 23 gastric, and 10 from other sites. ER (Sensitivity=81.8%, Specificity=100%, Positive predictive value (PPV)=100%, Negative predictive value (NPV)=89.3%) and GATA-3 (Sensitivity=100%, Specificity=98%, PPV=96.8%, NPV=100%) expression were associated with breast origin. CK20 (Sensitivity=66.7%, Specificity=93.3%, PPV=94.1%, NPV=63.6%) and CDX2 (Sensitivity=72%, Specificity=100%, PPV=100%, NPV=68.9%) demonstrated the strongest discriminatory value for gastrointestinal origin. These markers exhibited similar discriminatory characteristics when comparing lobular and gastric signet ring carcinomas. In a limited trial on metastatic breast and gastric cases, these markers successfully discriminated between breast and gastric primary sites in 15 of 16 cases. ER and GATA-3 are most supportive of mammary origin and constitute an effective panel for distinguishing primary breast from primary gastrointestinal signet-ring tumors when combined with CK20 and CDX2 immunohistochemistry.



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Balance and fear of falling in subjects with Parkinson’s disease is improved after exercises with motor complexity

Publication date: March 2018
Source:Gait & Posture, Volume 61
Author(s): Carla Silva-Batista, Daniel M. Corcos, Hélcio Kanegusuku, Maria Elisa Pimentel Piemonte, Lilian Teresa Bucken Gobbi, Andrea C. de Lima-Pardini, Marco Túlio de Mello, Claudia L.M. Forjaz, Carlos Ugrinowitsch
Resistance training with instability (RTI) uses exercises with high motor complexity that impose high postural control and cognitive demands that may be important for improving postural instability and fear of falling in subjects with Parkinson's disease (PD). Here, we hypothesized that: 1) RTI will be more effective than resistance training (RT) in improving balance (Balance Evaluation Systems Test [BESTest] and overall stability index [Biodex Balance System^®]) and fear of falling (Falls Efficacy Scale-International [FES-I] score) of subjects with Parkinson's disease (PD); and 2) changes in BESTest and FES-I after RTI will be associated with changes in cognitive function (Montreal Cognitive Assessment [MoCA] score – previously published) induced by RTI. Thirty-nine subjects with moderate PD were randomly assigned to a nonexercising control, RT, and RTI groups. While RT and RTI groups performed progressive RT twice a week for 12 weeks, the RTI group added progressive unstable devices to increase motor complexity of the resistance exercises. There were significant group × time interactions for BESTest, overall stability index, and FES-I scores (P < 0.05). Only RTI improved BESTest, overall stability index and FES-I scores, and RTI was more effective than RT in improving biomechanical constraints and stability in gait (BESTest sections) at post-training (P < 0.05). There were strong correlations between relative changes in BESTest and MoCA (r = 0.72, P = 0.005), and FES-I and MoCA (r = −0.75, P = 0.003) after RTI. Due to the increased motor complexity in RTI, RTI is recommended for improving balance and fear of falling, which are associated with improvement in cognitive function of PD.



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Minimally invasive skin tape strip RNA-seq identifies novel characteristics of type 2-high atopic dermatitis disease endotype

Publication date: Available online 6 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Nathan Dyjack, Elena Goleva, Cydney Rios, Byung Eui Kim, Lianghua Bin, Patricia Taylor, Caroline Bronchick, Clifton F. Hall, Brittany N. Richers, Max A. Seibold, Donald Y. Leung
BackgroundExpression profiling of skin biopsies has established molecular features of the skin in atopic dermatitis (AD). Invasiveness of biopsies has prevented their use in defining individual level AD pathobiological mechanisms (endotypes) in large research studies.ObjectiveTo determine if minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes.MethodsWe sampled non-lesional and lesional skin tape strips and biopsies from adult Caucasian subjects AD patients (18 males, 12 females; age (Mean±SE) 36.3±2.2 yrs) and healthy controls (9 males, 16 females; age (Mean±SE) 34.8±2.2 yrs). Ampliseq whole transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsies, and clinical trait correlations were performed.ResultsSkin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (FDR<5%) separated AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of AD subjects exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes including overexpression of IL13, IL4R, CCL22, CCR4 (log2FC=5.5, 2.0, 4.0, and 4.1, respectively), and at a pathway level by T-helper 2/dendritic cell activation. Both expression and immunostaining of skin biopsies indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing the high affinity IgE receptor (FcεRI). The type 2-high endotype group exhibited more severe disease by both EASI score and body surface area covered by lesions.ConclusionMinimally invasive expression profiling of non-lesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.



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Do performance measures of strength, balance and mobility predict quality of life and community reintegration after stroke?

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Joshua W. Cohen, Tanya D. Ivanova, Brenda Brouwer, Kimberly J. Miller, Dianne Bryant, S. Jayne Garland
ObjectiveTo investigate the extent to which physical performance measures of strength, balance and mobility taken at discharge from inpatient stroke rehabilitation can predict health-related quality of life (HRQoL) and community reintegration after 6 months.DesignLongitudinal StudySettingUniversity LaboratoryParticipantsSeventy-five adults recruited within one month following discharge home from inpatient stroke rehabilitation. Inclusion criteria were: major unilateral hemispheric stroke, English speaking, able to communicate, discharged home. Serious comorbidities and a prior stroke affecting the opposite side were exclusion criteria.InterventionsNot applicable.Main Outcome Measure(s)Short Form 36-Item Health Survey (SF-36) for HRQoL and the Subjective Index of Physical and Social Outcome (SIPSO) for community reintegration. Physical performance measures were the 6-minute walk test (6MWT), Timed up and Go (TUG), Berg Balance Scale, Community Balance and Mobility scale, and isokinetic torque and power of hip, knee and ankle on the paretic and non-paretic sides. Other prognostic variables included age, sex, stroke type and location, comorbidities, and motor Functional Independence Measure.ResultsSeparate stepwise linear regressions were performed with the SF-36 and SIPSO as dependent variables. The total paretic lower limb torque and 6MWT predicted the SF-36 Physical Component Summary (Adjusted R²=0.30). Total paretic lower limb torque, and TUG predicted the SIPSO Physical component (Adjusted R²=0.47). Total paretic lower limb torque significantly predicted the SF-36 Mental Component Score, but the adjusted R² was very low (0.06). Similarly, the TUG significantly predicted the SIPSO social component, but again, the adjusted R² was low (0.09).ConclusionsMeasures of physical performance including muscle strength and mobility at discharge can partially predict HRQoL and community reintegration 6 months later. Further research is necessary for more accurate predictions.



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A comparison of cell survival and heat shock protein expression after radiation in normal dermal fibroblasts, microvascular endothelial cells, and different head and neck squamous carcinoma cell lines

Abstract

Objectives

Head and neck squamous cell carcinoma (HNSCC) shows increased radioresistance due to the manipulation of homeostatic mechanisms like the heat shock response. This study intended to comparatively analyze effects of ionizing radiation on different HNSCC cell lines (PCI) and normal human dermal fibroblasts (NHFs) and human dermal microvascular endothelial cells (HDMECs) to uncover differences in radiation coping strategies.

Materials and methods

Proliferation (BrdU assay), apoptosis (caspase 3/7) and intracellular protein expression of heat shock protein (HSP)-70, and phosphorylated and total HSP27, determined by enzyme-linked immunosorbent assay (ELISA), were analyzed after exposure to increasing doses of ionizing radiation (2, 6, and 12 Gray, Gy).

Results

Cell count decreased dose-dependently, but PCI cell lines consistently showed higher numbers compared to NHF and HDMEC. Likewise, high doses reduced cell proliferation, but low-dose radiation (2 Gy) instead increased proliferation in PCI 9 and 52. Apoptosis was not detectable in PCI cell lines. Basic HSP70 expression was high in PCI cells with little additional increase by irradiation. PCI cells yielded high basic total HSP27 concentrations but irradiation dose-dependently increased HSP27 in HDMEC, NHF, and PCI cells. Phosphorylated HSP27 concentrations were highest in NHF.

Conclusion

PCI cell lines showed higher resistance to dose-dependent reduction in cell number, proliferation, and protection from apoptosis compared to NHF and HDMEC. In parallel, we observed a high basic and radiation-induced expression of intracellular HSP70 leading to the assumption that the radioresistance of PCI cells is conferred by HSP70.

Clinical relevance

HNSCC use HSP to escape radiation-induced apoptosis and certain subtypes might increase proliferation after low-dose irradiation.

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A comparison of cell survival and heat shock protein expression after radiation in normal dermal fibroblasts, microvascular endothelial cells, and different head and neck squamous carcinoma cell lines

Abstract

Objectives

Head and neck squamous cell carcinoma (HNSCC) shows increased radioresistance due to the manipulation of homeostatic mechanisms like the heat shock response. This study intended to comparatively analyze effects of ionizing radiation on different HNSCC cell lines (PCI) and normal human dermal fibroblasts (NHFs) and human dermal microvascular endothelial cells (HDMECs) to uncover differences in radiation coping strategies.

Materials and methods

Proliferation (BrdU assay), apoptosis (caspase 3/7) and intracellular protein expression of heat shock protein (HSP)-70, and phosphorylated and total HSP27, determined by enzyme-linked immunosorbent assay (ELISA), were analyzed after exposure to increasing doses of ionizing radiation (2, 6, and 12 Gray, Gy).

Results

Cell count decreased dose-dependently, but PCI cell lines consistently showed higher numbers compared to NHF and HDMEC. Likewise, high doses reduced cell proliferation, but low-dose radiation (2 Gy) instead increased proliferation in PCI 9 and 52. Apoptosis was not detectable in PCI cell lines. Basic HSP70 expression was high in PCI cells with little additional increase by irradiation. PCI cells yielded high basic total HSP27 concentrations but irradiation dose-dependently increased HSP27 in HDMEC, NHF, and PCI cells. Phosphorylated HSP27 concentrations were highest in NHF.

Conclusion

PCI cell lines showed higher resistance to dose-dependent reduction in cell number, proliferation, and protection from apoptosis compared to NHF and HDMEC. In parallel, we observed a high basic and radiation-induced expression of intracellular HSP70 leading to the assumption that the radioresistance of PCI cells is conferred by HSP70.

Clinical relevance

HNSCC use HSP to escape radiation-induced apoptosis and certain subtypes might increase proliferation after low-dose irradiation.

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Retraction notice to “The effect of prednisolone and/or acyclovir in relation to severity of Bell's palsy at presentation” [Egypt. J. Ear Nose Throat Allied Sci. 14(3) (2013) 155–159]

Publication date: November 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences, Volume 18, Issue 3
Author(s): Ahmed Mohammed Abdelghany, Samer Badee Kamel




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Editorial Board

Publication date: November 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences, Volume 18, Issue 3





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Text neck and neck pain in 18–21-year-old young adults

Abstract

Purpose

The aim of this study was to investigate whether there is an association between text neck and neck pain in young adults.

Methods

Observational cross-sectional study with 150 18–21-year-old young adults from a public high school in the state of Rio de Janeiro was performed. In the self-report questionnaire, the participants answered questions on sociodemographic factors, anthropometric factors, time spent texting or playing on a mobile phone, visual impairments, and concern with the body posture. The neck posture was assessed by participants' self-perception and physiotherapists' judgment during a mobile phone texting message task. The Young Spine Questionnaire was used to evaluate the neck pain. Four multivariate logistic regression models were fitted to investigate the association between neck posture during mobile phone texting and neck pain, considering potential confounding factors.

Results

There is no association between neck posture, assessed by self-perception, and neck pain (OR = 1.66, p = 0.29), nor between neck posture, assessed by physiotherapists' judgment, and neck pain (OR = 1.23, p = 0.61). There was also no association between neck posture, assessed by self-perception, and frequency of neck pain (OR = 2.19, p = 0.09), nor between neck posture, assessed by physiotherapists' judgment, and frequency of neck pain (OR = 1.17, p = 0.68).

Conclusion

This study did not show an association between text neck and neck pain in 18–21-year-old young adults. The findings challenge the belief that neck posture during mobile phone texting is associated to the growing prevalence of neck pain.

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Chemotherapy-induced metastasis: mechanisms and translational opportunities

Abstract

Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy. However, these repair responses are exploited by tumor cells at every step of the metastatic cascade, ranging from tumor cell invasion, intravasation and hematogenous dissemination to extravasation and effective colonization at the metastatic site. A better understanding of the mechanistic underpinnings of chemotherapy-induced metastasis will allow us to better predict which patients are more likely to exhibit pro-metastatic responses to chemotherapy and will help develop new therapeutic strategies to neutralize chemotherapy-driven prometastatic changes.

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The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival

Publication date: March 2018
Source:European Journal of Cancer, Volume 91
Author(s): Anja Ulmer, Klaus Dietz, Melanie Werner-Klein, Hans-Martin Häfner, Claudia Schulz, Philipp Renner, Florian Weber, Helmut Breuninger, Martin Röcken, Claus Garbe, Gerhard Fierlbeck, Christoph A. Klein
IntroductionComplete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes.Patients and methodsWe quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 10⁶ lymph node cells, i.e. the disseminated cancer cell density (DCCD).ResultsWe uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCDNSN = DCCDSN^c/10^1−c (c = 0.69; 95% confidence interval [CI]: 0.62–0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCDSN (p = 0.02; HR 1.34, 95% CI: 1.05–1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07–2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCDSN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs.ConclusionThe assessment of DCCDSN renders CLND for staging purposes unnecessary.



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Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography

Abstract

Background

Respiratory impedance comprises the resistance and reactance of the respiratory system, and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown.

Objective

We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma.

Methods

Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA).

Results

Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percent predicted forced expiratory volume in 1 second, and percent predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance.

Conclusions & Clinical Relevance

Respiratory resistance is associated with airway narrowing.

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IL-6 pathway upregulation in subgroup of severe asthma is associated with neutrophilia and poor lung function

Summary

We have investigated the IL-6 pathway in the severe asthma phenotypes using U-BIOPRED database. A subset of severe asthma patients has increased IL6R mRNA levels and IL-6 protein levels in the sputum. This sub-population is highly neutrophilic and has poorer lung function. These neutrophilic patients have a high unmet medical need and they could potentially benefit from therapy targeting IL-6.

This article is protected by copyright. All rights reserved.

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A single-incision thoracoscopic and robotic hybrid procedure via the axillary approach in a patient with thyroid, lung, and mediastinal tumors

Abstract

A 66-year-old woman was referred to our institute for an enlarging tumor of the thyroid, and neck and chest computed tomography scan showed not only a thyroid tumor, but also an anterior mediastinal tumor and ground-glass nodules in the lung. Because of persisting symptoms, an enlarging thyroid mass, and the possibility of cancer, excision of the tumors was proposed. A 6-cm-long vertical skin incision was made in the right axilla, a mini-thoracotomy was made in the third intercostal space, and an additional port was placed in the fifth intercostal space. Thoracoscopic partial resection of the right upper lobe of the lung was performed first. Then, the da Vinci surgical system (da Vinci, Intuitive Surgical Inc., Sunnyvale, CA, USA) was introduced through the mini-thoracotomy. The mediastinal tumor was then excised circumferentially robotically. After resection of the lung and mediastinal tumors, the da Vinci was undocked, and a subcutaneous tunnel from the axillary incision to the thyroid was created using the flap dissection technique. The da Vinci was re-introduced through the axillary incision. A long camera port was used, and the skin and muscle flap was elevated to maintain adequate working space during the robot-assisted thyroidectomy. Total operating time was 277 min, and the patient's postoperative course was uneventful. The histopathological examinations of the lung, mediastinal, and thyroid tumors were adenocarcinoma, thymolipoma, and adenomatous goiter, respectively. In conclusion, single-incision robotic surgery for three lesions was achieved safely with good clinical results and excellent cosmetic results.

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Loss of Eed leads to lineage instability and increased CD8 expression of mouse CD4+ T cells upon TGFβ signaling

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Taku Naito, Sawako Muroi, Ichiro Taniuchi, Motonari Kondo
Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a repressive epigenetic modification catalyzed by polycomb repressive complex 2 (PRC2) that is required for proper cell fate determination as well as cellular function. Numerous studies have been performed to elucidate the role of PRC2 in T-cell differentiation and function; however, its role in the regulation of T-helper (Th) subset differentiation and identity has not been fully explored. Here, we report that Eed, an essential subunit of PRC2, is crucial to maintain the identity of CD4⁺ T cells under TGFβ-induced regulatory T cell (Treg)-polarizing conditions. Mouse CD4⁺ T cells lacking Eed exhibited unstable CD4 expression upon TCR stimulation in vitro. Helper lineage instability was further augmented by Treg-polarizing conditions, leading to the immense up-regulation of CD8α as well as other molecules, resembling CD4⁺ CD8αα⁺ intraepithelial lymphocyte (DP-IEL) differentiation. Genetic studies suggested that the altered balance between transcription factors T-bet, Runx3, and Th-POK underlies the induction of the DP-IEL-like phenotype in Eed-deficient CD4⁺ cells. Furthermore, comparison to Th1- and Th17-polarizing conditions indicated that cooperation between Smad3 and the T-bet-Runx3 axis facilitated by the loss of H3K27me3 is crucial for phenotype induction. Collectively, our results provide insight into the molecular mechanism that maintains and regulates the proper cellular response upon TGFβ signaling in CD4⁺ T cells.



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