Wear, strength, modulus and hardness of CAD/CAM restorative materials

Publication date: Available online 14 September 2016
Source:Dental Materials
Author(s): Nathaniel C. Lawson, Ritika Bansal, John O. Burgess
ObjectiveTo measure the mechanical properties of several CAD/CAM materials, including lithium disilicate (e.max CAD), lithium silicate/zirconia (Celtra Duo), 3 resin composites (Cerasmart, Lava Ultimate, Paradigm MZ100), and a polymer infiltrated ceramic (Enamic).MethodsCAD/CAM blocks were sectioned into 2.5mm×2.5mm×16mm bars for flexural strength and elastic modulus testing and 4mm thick blocks for hardness and wear testing. E.max CAD and half the Celtra Duo specimens were treated in a furnace. Flexural strength specimens (n=10) were tested in a three-point bending fixture. Vickers microhardness (n=2, 5 readings per specimen) was measured with a 1kg load and 15s dwell time. The CAD/CAM materials as well as labial surfaces of human incisors were mounted in the UAB wear device. Cusps of human premolars were mounted as antagonists. Specimens were tested for 400,000 cycles at 20N force, 2mm sliding distance, 1Hz frequency, 24°C, and 33% glycerin lubrication. Volumetric wear and opposing enamel wear were measured with non-contact profilometry. Data were analyzed with 1-way ANOVA and Tukey post-hoc analysis (alpha=0.05). Specimens were observed with SEM.ResultsProperties were different for each material (p<0.01). E.max CAD and Celtra Duo were generally stronger, stiffer, and harder than the other materials. E.max CAD, Celtra Duo, Enamic, and enamel demonstrated signs of abrasive wear, whereas Cerasmart, Lava Ultimate, Paradigm MZ100 demonstrated signs of fatigue.SignificanceResin composite and resin infiltrated ceramic materials have demonstrated adequate wear resistance for load bearing restorations, however, they will require at least similar material thickness as lithium disilicate restorations due to their strength.



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Dysphagia

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New Issue Alert 09/14/2016 Dear Reader, We are pleased to deliver your requested table of contents alert for Dysphagia. Volume 31 Number 5 is now available online. Important news In this issue In Memoriam Steven B. Leder, PhD » Abstract   » Full text HTML   » Full text PDF Review Article A Review of Dysphagia Presentation and Intervention Following Traumatic Spinal Injury: An Understudied Population Teresa J. Valenzano, Ashley A. Waito & Catriona M. Steele » Abstract   » Full text HTML   » Full text PDF Review Article Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic Review Dalal Alali, Kirrie Ballard & Hans Bogaardt » Abstract   » Full text HTML   » Full text PDF Original Article An Epidemiologic Study on Ageing and Dysphagia in the Acute Care Geriatric-Hospitalized Population: A Replication and Continuation Study Steven B. Leder, Debra M. Suiter, George O. Agogo & Leo M. Cooney » Abstract   » Full text HTML   » Full text PDF Original Article Cross-Cultural Adaptation and Validation of the Italian Version of SWAL-QOL Daniela Ginocchio, Enrico Alfonsi, Francesco Mozzanica, Anna Rosa Accornero, Antonella Bergonzoni, Giulia Chiarello, Nicoletta De Luca, Daniele Farneti, Simonelli Marilia, Paola Calcagno, Valentina Turroni & Antonio Schindler » Abstract   » Full text HTML   » Full text PDF Original Article Submucosal Elastic Laminae of the Middle and Lower Pharynx: A Histological Study Using Elderly Cadaveric Specimens Ai Kawamoto-Hirano, Yohei Honkura, Masahito Yamamoto, Shin-ichi Abe, Gen Murakami & Yukio Katori » Abstract   » Full text HTML   » Full text PDF Original Article Reliability and Validity of the Turkish Eating Assessment Tool (T-EAT-10) Numan Demir, Selen Serel Arslan, Özgü İnal & A. Ayşe Karaduman » Abstract   » Full text HTML   » Full text PDF Original Article Implications of Variability in Clinical Bedside Swallowing Assessment Practices by Speech Language Pathologists Sue McAllister, Samantha Kruger, Sebastian Doeltgen & Emma Tyler-Boltrek » Abstract   » Full text HTML   » Full text PDF Original Article Clinical Characteristics of Dysphagia in Children with Down Syndrome Arwen Jackson, Jennifer Maybee, Maura K. Moran, Kristine Wolter-Warmerdam & Francis Hickey » Abstract   » Full text HTML   » Full text PDF Original Article Understanding the Viscosity of Liquids used in Infant Dysphagia Management Jacqueline Frazier, Amanda H. Chestnut, Arwen Jackson, Carly E. A. Barbon, Catriona M. Steele & Laura Pickler » Abstract   » Full text HTML   » Full text PDF Original Paper A Pilot Study of the Head Extension Swallowing Exercise: New Method for Strengthening Swallowing-Related Muscle Activity Jong-Chi Oh » Abstract   » Full text HTML   » Full text PDF Original Article Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer Nicole M. Rogus-Pulia, Charles Larson, Bharat B. Mittal, Marge Pierce, Steven Zecker, Korey Kennelty, Amy Kind & Nadine P. Connor » Abstract   » Full text HTML   » Full text PDF Original Article Drugs Related to Oropharyngeal Dysphagia in Older People Marta Miarons, Lluís Campins, Elisabet Palomera, Mateu Serra-Prat, Mateu Cabré & Laia Rofes » Abstract   » Full text HTML   » Full text PDF Original Article A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks Treatment on Older Patients with Oropharyngeal Dysphagia Omar Ortega, Laia Rofes, Alberto Martin, Viridiana Arreola, Irene López & Pere Clavé » Abstract   » Full text HTML   » Full text PDF Clinical Conundrum An Unusual Cause of Dysphagia Stephen Sullivan » Abstract   » Full text HTML   » Full text PDF Erratum Erratum to: Effect of Bolus Viscosity on the Safety and Efficacy of Swallowing and the Kinematics of the Swallow Response in Patients with Oropharyngeal Dysphagia: White Paper by the European Society for Swallowing Disorders (ESSD) Roger Newman, Natàlia Vilardell, Pere Clavé & Renée Speyer » Abstract   » Full text HTML   » Full text PDF

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Outcomes following peripheral nerve decompression with and without associated double crush syndrome: a case control study.

Background: Double crush syndrome, the association between proximal and distal nerve lesions, has been established. This investigation compares the outcomes of nerve surgery in patients with isolated peripheral compression versus those with double crush syndrome treated with peripheral nerve and cervical spine surgeries. Methods: This case controlled study enrolled 80 patients; 40 underwent carpal or cubital tunnel surgery and cervical spine surgery (double crush group) and 40 controls, matched by age and sex, underwent only peripheral nerve decompression (peripheral nerve group). A minimum of 18 months was required following peripheral nerve and cervical spine surgery for office assessment (mean 4.9 years and 6.0 years, respectively). Statistical analysis compared post-operative function and symptom severity questionnaires, physical examination, and patient-reported satisfaction between groups. Results: Patients in the double crush group reported significantly more disability and persistent symptoms on the QuickDASH questionnaire (29 versus 13) and Levine Katz symptom severity (2.0 versus 1.4) and functional status scales (1.9 versus 1.4). Double crush patients reported significantly lower satisfaction. The double crush group exhibited a greater frequency of persistent signs of nerve irritability and muscle weakness compared the control group. Conclusion: At a minimum of 18 months following peripheral nerve surgery, patients with a history of cervical spine surgery are likely to have inferior patient-reported outcomes, persistent nerve dysfunction, and lower satisfaction after peripheral nerve release as compared to patients following isolated peripheral nerve surgery. Double crush syndrome was associated with poorer outcome after peripheral nerve surgery despite treatment of cervical spine nerve compression. (C)2016American Society of Plastic Surgeons

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Mechanical micronization of lipoaspirates: squeeze and emulsification techniques.

Introduction: Condensation of grafted fat has been considered a key for achieving better outcomes after fat grafting. The purpose of this study was to investigate the therapeutic potentials of two mechanical tissue micronizing procedures: squeeze and emulsification. Materials and Methods: Human aspirated fat was centrifuged (centrifuged fat: CF) and fragmented with an automated slicer (squeezed fat: SF). Alternatively, CF was emulsified by repeated transfer between two syringes through a small-hole connecter, then separated by mesh filtration into two portions: residual tissue of emulsified fat (REF) and filtrated fluid of emulsified fat (FEF). The four products were examined for cellular components. Results: Histological and electron microscopic analyses revealed that SF and REF contained broken adipocytes and fragmented capillaries. Compared to CF, the SF and REF products exhibited increased specific gravity and increased numbers of adipose-derived stem/stromal cells (ASCs) and endothelial cells (ECs) per volume, suggesting successful cell/tissue condensation in both SF and REF. Although cell number and viability in the stromal vascular fraction (SVF) were well maintained in both SF and REF, SVF culture assay showed that ASCs were relatively damaged in REF but not in SF. By contrast, no ASCs were cultured from FEF. Conclusion: Our results demonstrated that mechanical micronization is easily conducted as a minimal manipulation procedure, which can condense the tissue by selectively removing adipocytes without damaging key components, such as ASCs and ECs. Depending on the extent of adipocyte removal, the product may be a useful therapeutic tool for efficient tissue volumization or therapeutic revitalization/fertilization. (C)2016American Society of Plastic Surgeons

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Platysma Bands: Is a Change Needed in the Surgical Paradigm?.

Background: Platysma bands are one of the first signs of aging of the neck. Current theories suggest that these bands develop due to skin sagging followed by loss of muscle tone. Treatment strategies, therefore, aim to tighten skin and muscle. The aim of the present study was to demonstrate that platysma bands are due to muscular activity during the aging process and not secondary to skin sagging. This suggests a new approach to managing platysma bands. Methods: A descriptive, prospective clinical study of 25 patients who presented with definitive, unilateral, facial palsy following otoneurosurgical treatment. We targeted our observations on anterior neck bands. Patients were followed for up to 10 years. Results: Of the 25 patients, 76% had visible platysma bands on the healthy side, but not on the paralyzed side, of their face. Platysma bands were present on both sides in the 12% of patients who had a spastic form of facial paralysis. There was no worsening of the platysma band appearance in any patient. No ptosis of the neck skin on the paralyzed side was observed. Conclusions: This study demonstrated that platysma bands are not related to relaxation of the platysma and skin laxity, but are due to activity of the platysma muscle. The skin follows the muscle. These observations support a change in surgical management of the aging neck, moving from tightening the skin to denervating the platysma muscle. Further studies need to fully characterise the efficacy and safety of platysma muscle denervation in this indication. Clinical question/level of evidence: to be assigned by journal (C)2016American Society of Plastic Surgeons

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Mechanical micronization of lipoaspirates: squeeze and emulsification techniques.

No abstract available

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Risk Factor Analysis for Capsular Contracture, Malposition, and Late Seroma in Subjects Receiving Natrelle 410 Form-Stable Silicone Breast Implants.

Background: Natrelle(R) 410 silicone breast implants are approved in the US for breast augmentation, reconstruction, and revision. Methods: In two ongoing, prospective, multicenter 10-year studies, 17,656 subjects received Natrelle 410 implants for augmentation (n=5059), revision-augmentation (n=2632), reconstruction (n=7502), or revision-reconstruction (n=2463). Capsular contracture, implant malposition, and late seroma were documented. Cox proportional hazards regression analyses evaluated potential associations between subject-, implant-, and surgery-related factors and these complications. Results: Median follow-up was 4.1, 2.6, 2.1, and 2.3 years in the augmentation, revision-augmentation, reconstruction, and revision-reconstruction cohorts, respectively. Incidence of capsular contracture across cohorts ranged from 2.3% to 4.1%, malposition from 1.5% to 2.7%, and late seroma from 0.1% to 0.2%. Significant risk factors for capsular contracture were subglandular implant placement, periareolar incision site, and older device age in the augmentation cohort (p

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In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor HIF-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

Publication date: Available online 14 September 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Azusa Maeda, Yonghong Chen, Jiachuan Bu, Hilda Mujcic, Bradly G. Wouters, Ralph S. DaCosta
PurposeTo investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques.Methods and MaterialsA BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber (DSWC) model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12 or 24 Gy. The DSWC model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24 Gy-irradiation. The hind leg model was used to monitor tumor size, hypoxia and vascularity for up to 65 days after 24 Gy-irradiation. Tumors were assessed histologically to validate in vivo observations.ResultsIn vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4-24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with non-irradiated controls 14 days after irradiation. This observation corresponded with increased expression of Hypoxia-Inducible Factor-1α (HIF-1α) in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth.ConclusionsIrradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of HIF-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy (SBRT).

Teaser

In vivo imaging methods were used to investigate the effects of high-dose irradiation on tumor vasculature and microenvironment using a BxPC3 pancreatic tumor model. A single dose of 24 Gy caused transient vascular dysfunction associated with adhesion of platelets and leukocytes to vascular endothelium, increased vascular permeability, and HIF-1 expression. Furthermore, tumor recurrence was evident by 65 days after irradiation. These data demonstrate the extent of radiation-induced vascular damage and its potential influence on tumor response.


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Verification of dose distribution in carbon ion radiotherapy for stage I lung cancer

Publication date: Available online 14 September 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Daisuke Irie, Jun-ichi Saitoh, Katsuyuki Shirai, Takanori Abe, Yoshiki Kubota, Makoto Sakai, Shin-ei Noda, Tatsuya Ohno, Takashi Nakano
PurposeTo evaluate robustness of dose distribution of carbon-ion radiotherapy (C-ion RT) in non-small-cell lung cancer (NSCLC) and to identify factors affecting the dose distribution by simulated dose distribution (SimDD).Methods and MaterialsEighty irradiation fields for delivery of C-ion RT were analyzed in 20 patients with stage I NSCLC. Computed tomography (CT) images were obtained twice before treatment initiation. SimDD was reconstructed on CT for confirmation under the same settings as actual treatment with respiratory gating and bony structure matching. Dose–volume histogram (DVH) parameters, such as %D95 (percentage of D95 relative to the prescribed dose) were calculated. Patients with any field for which the %D95 of gross tumor volume (GTV) was below 90% were classified as unacceptable for treatment, and the optimal target margin for such cases was examined.ResultsFive patients with a total of eight fields (10% of total number of fields analyzed) were classified as unacceptable according to %D95 of GTV, although most patients showed no remarkable change in the DVH parameters. Receiver operating characteristic (ROC) curve analysis showed that tumor displacement and change in water-equivalent pathlength (WEL) were significant predictive factors of unacceptable cases (p < 0.001 and p = 0.002, respectively). The main cause of degradation of the dose distribution was tumor displacement in seven of the eight unacceptable fields. A 6-mm planning target volume margin ensured a GTV %D95 of >90% except in one extremely unacceptable field.ConclusionsAccording to this simulation analysis of C-ion RT for stage I NSCLC, a few fields were reported as unacceptable and required resetting of body position and reconfirmation. In addition, tumor displacement and change in WEL (bone shift and/or chest wall thickness) were identified as factors influencing the robustness of dose distribution. Such uncertainties should be regarded in planning.

Teaser

Dose distribution of carbon ion radiotherapy for stage I lung cancer under the bony structure-matching method was simulated, and its robustness for interfractional changes was evaluated. Eight of 80 field irradiations showed unacceptable degradation of D95 of gross tumor volume, although most field irradiations were robust. The degradation resulted from tumor displacement without correlation with respiration and change in water-equivalent pathlength on the beam pathway. Such uncertainty factors should be regarded in planning.


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Effect of dried nut fortification on functional, physicochemical, textural, and microbiological properties of yogurt

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): S. Ozturkoglu-Budak, C. Akal, A. Yetisemiyen
In this study, walnut, hazelnut, almond, and pistachio were incorporated to produce functional yogurt. The effects on physicochemical and instrumental textural characteristics, syneresis, folic acid, selenium, tocopherols, omega fatty acid contents, and viable counts of Streptococcus thermophilus and Lactobacillus bulgaricus were evaluated during storage. Fortified yogurts demonstrated higher protein and total solid contents and lower syneresis compared with control yogurt on d 21. Addition of nuts also increased S. thermophilus and L. bulgaricus counts except for walnut. The concentrations of folic acid, α-tocopherol, selenium, and omega fatty acids were determined to be higher in fortified yogurts compared with the levels found in nut types. However, a decreasing trend was observed in all components during storage. As a consequence, each nut could be incorporated into yogurt because of a specific functional property. For instance, walnut could be preferred for omega acid enrichment.



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Prediction of fat globule particle size in homogenized milk using Fourier transform mid-infrared spectra

Publication date: Available online 13 September 2016
Source:Journal of Dairy Science
Author(s): Larissa Di Marzo, Patrick Cree, David M. Barbano
Our objective was to develop partial least square models using data from Fourier Transform mid-infrared (MIR) spectra to predict the particle size distributions d(0.5) and d(0.9), surface volume mean diameter D[3,2], and volume moment mean diameter D[4,3] of milk fat globules and validate the models. The goal of the study was to produce a method built into the MIR milk analyzer that could be used to warn the instrument operator that the homogenizer is near failure and needs to be replaced to ensure quality of results. Five homogenizers with different homogenization efficiency were used to homogenize pasteurized modified unhomogenized milks and farm raw bulk milks. Homogenized milks were collected from the homogenizer outlet and then run through an MIR milk analyzer without an in-line homogenizer to collect a MIR spectrum. A separate portion of each homogenized milk was analyzed with a laser light-scattering particle size analyzer to obtain reference values. The study was replicated 3 times with 3 independent sets of modified milks and bulk tank farm milks. Validation of the models was done with a set of 34 milks that were not used in the model development. Partial least square regression models were developed and validated for predicting the following milk fat globule particle size distribution parameters from MIR spectra: d(0.5) and d(0.9), surface volume mean diameter D[3,2], and volume moment mean diameter D[4,3]. The basis for the ability to model particle size distribution of milk fat emulsions was hypothesized to be the result of the partial least square modeling detecting absorbance shifts in MIR spectra of milk fat due to the Christiansen effect. The independent sample validation of particle size prediction methods found more variation in d(0.9) and D[4,3] predictions than the d(0.5) and D[3,2] predictions relative to laser light-scattering reference values, and this may be due to variation in particle size among different pump strokes. The accuracy of the d(0.9) prediction for routine quality assurance, to determine if a homogenizer within an MIR milk analyzer was near the failure level [i.e., d(0.9) >1.7 μm] and needed to be replaced, is fit-for-purpose. The daily average particle size performance [i.e., d(0.9)] of a homogenizer based on the mean for the day could be used for monitoring homogenizer performance.



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Ten years results of the Canadian breast intensity modulated radiation therapy (IMRT) randomized controlled trial

Publication date: Available online 13 September 2016
Source:Radiotherapy and Oncology
Author(s): Jean-Philippe Pignol, Pauline Truong, Eileen Rakovitch, Margriet G. Sattler, Timothy J. Whelan, Ivo A. Olivotto
Background and purposeWe report the long-term outcomes in patients enrolled in a multicenter randomized controlled trial comparing Intensity Modulated Radiation Therapy (IMRT) with standard wedge radiotherapy.Materials and methodsTrial participants were assessed to compare long-term side effects between treatment arms. The primary endpoint was chronic breast pain assessed by trained observers blinded to treatment allocation. Secondary endpoints included cosmesis and quality of life measures.ResultsMedian follow-up time was 9.8years and 241 patients were available for assessment. There was no significant difference in chronic pain between treatment arms (OR=0.74, range 0.432–1.271). There were also no differences for the secondary endpoints. Univariate and multivariate analyses identified young age (p=0.013) and pain during RT (p<0.001) to be associated with chronic pain. Acute moist desquamation was associated with late subcutaneous fibrosis (p=0.003) and telangiectasia (p=0.039). Pain during RT was associated with a long-term poorer self-assessed cosmetic outcome (p<0.001) and quality of life (p<0.001).ConclusionsBreast IMRT cannot be recommended for all patients to reduce long-term side effects. However, late toxicities were significantly correlated with acute side effects, which are increased in patients having poor dose distribution. Breast IMRT may hence be useful for selected patients.



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Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial

Publication date: Available online 14 September 2016
Source:Radiotherapy and Oncology
Author(s): Daniëlle B.P. Eekers, Erik Roelofs, Urszula Jelen, Maura Kirk, Marlies Granzier, Filippo Ammazzalorso, Peter H. Ahn, Geert O.R.J. Janssens, Frank J.P. Hoebers, Tobias Friedmann, Timothy Solberg, Sean Walsh, Esther G.C. Troost, Johannes H.A.M. Kaanders, Philippe Lambin
Background and PurposeIn this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs).Material and MethodsTwenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT).ResultsWhen comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D2) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on http://ift.tt/2cUTYB5 this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation.



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Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Zhentao Man, Xiaoqing Hu, Zhenlong Liu, Hongjie Huang, Qingyang Meng, Xin Zhang, Linghui Dai, Jiying Zhang, Xin Fu, Xiaoning Duan, Chunyan Zhou, Yingfang Ao
Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering.



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Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model

Publication date: November 2016
Source:Biomaterials, Volume 108
Author(s): Alyssa L. Siefert, Allison Ehrlich, María Jesús Corral, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Tarek M. Fahmy
Leishmania (Viannia) panamensis (L. (V.) panamensis) is a species of protozoan parasites that causes New World leishmaniasis, which is characterized by a hyper-inflammatory response. Current treatment strategies, mainly chemotherapeutic, are suboptimal due to adverse effects, long treatment regimens, and increasing drug resistance. Recently, immunotherapeutic approaches have shown promise in preclinical studies of leishmaniasis. As NPs may enable broad cellular immunomodulation through internalization in phagocytic and antigen-presenting cells, we tested the therapeutic efficacy of biodegradable NPs encapsulating a pathogen-associated molecular pattern (PAMP), CpG-rich oligonucleotide (CpG; NP-CpG), in mice infected with L. (V.) panamensis. NP-CpG treatment reduced lesion size and parasite burden, while neither free CpG nor empty NP showed therapeutic effects. NP-encapsulation led to CpG persistence at the site of infection along with an unexpected preferential cellular uptake by myeloid derived suppressor cells (MDSCs; CD11b⁺Ly6G⁺Ly6C⁻) as well as CD19⁺ dendritic cells. This corresponded with the suppression of the ongoing immune response measured by the reduction of pathogenic cytokines IL-10 and IL-13, as well as IL-17 and IFNγ, in comparison to other treatment groups. As chronic inflammation is generally associated with the accumulation of MDSCs, this study may enable the rational design of cost-effective, safe, and scalable delivery systems for the treatment of inflammation-mediated diseases.



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Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models

Publication date: October 2016
Source:Molecular Immunology, Volume 78
Author(s): Hee-Yun Kim, Sun-Young Nam, Sung-Yeoun Hwang, Hyung-Min Kim, Hyun-Ja Jeong
KMP6 (Pyeongwee-San) is a Korean Medicine used to treat gastrointestinal disorders. Recently, we reported KMP6 had beneficial effects on allergic inflammatory diseases. The aim of this study was to evaluate the effects of atractylone (Atr), a constituent of KMP6, on allergic rhinitis (AR) and to identify the mechanism responsible for these effects. The anti-allergic inflammatory effects of Atr were evaluated on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells and in an ovalbumin (OVA)-induced AR animal model using Western blotting, quantitative real-time PCR, ELISA, and immunohistochemistry methods. In HMC-1 cells, Atr and KMP6 attenuated PMACI-caused proinflammatory cytokine production and mRNA expression. We found that PMACI induced caspase-1/nuclear factor (NF)-κB/mitogen activated protein kinases (MAPKs) activation. PMACI-caused caspase-1/NF-κB/MAPKs activations were attenuated by Atr and KMP6. In AR animal model, Atr and KMP6 reduced AR clinical symptoms and biomarkers including rub scores, total IgE, histamine, prostaglandin D2, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor-α, cyclooxygenase-2, intercellular adhesion molecule-1, and macrophage inflammatory protein-2. In addition, Atr and KMP6 attenuated eosinophils and mast cells invasions into nasal mucosa tissues and diminished mast cell-derived caspase-1 activation. These results indicate that Atr is an active constituent of KMP6 and a potential therapeutic agent for AR.



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Patient Experiences of Life Years After Severe Civilian Lower Extremity Trauma With Vascular Injury

Publication date: Available online 13 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K. Bernhoff, M. Björck, J. Larsson, E. Jangland
ObjectiveSevere lower limb trauma with arterial injury is often devastating for the individual. Many studies describe how to manage these injuries when they occur. Short-term functional outcome is quite well described, but the patients are often young, and their suffering is physical, mental, and social from a lifelong perspective. The aim of this study was to report patient experiences of their lives several years after their accidents, and to explore mechanisms of how to improve management.MethodThe Swedvasc registry was searched for participants from 1987 to 2011, living in the region of Uppsala, Sweden. Some amputated participants were added from the Walking Rehabilitation Center. There were five reconstructed patients with an intact limb, and three with amputations. In depth interviews were conducted and systematically analyzed, using A Giorgi's descriptive phenomenological method.ResultsEight patients participated, five with reconstructed and three with amputated limbs. Life affecting functional impairments were described by all patients. The patients undergoing amputation had received more structured follow up and support through the Walking Rehabilitation Center. The satisfaction with the cosmetic result was poorer than expected. All patients had developed strategies of how to cope with their impairments and stated they now lived "normal lives."ConclusionsDespite substantial physical, psychological, and cosmetic impairments years after severe lower limb trauma, the participants described life as "normal" and mainly satisfactory. Transition to the new situation could have been facilitated by more frequent and continuous follow up after discharge from hospital, in particular among the non-amputated patients who tend to be lost to follow up. Findings also indicate that family members have to be acknowledged, strengthened, and supported.



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Deep Rtms for Neuropsychiatric Symptoms of Huntington's Disease: Case Report

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Molly Davis, Angela Phillips, Aron Tendler, Angela Oberdeck




http://ift.tt/2cdUcjK

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum Reproducibly Improves Symptoms of Body Dysmorphic Disorder

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Juan Carlos Baldermann, Sina Kohl, Veerle Visser-Vandewalle, Martin Klehr, Daniel Huys, Jens Kuhn




http://ift.tt/2cvWiZB

The Difficult Journey from Genome-wide Association Studies to Pathophysiology: The Melatonin Receptor 1B (MT2) Paradigm

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Amélie Bonnefond, Angeliki Karamitri, Ralf Jockers, Philippe Froguel




http://ift.tt/2cMzPIB

Never Waste a Good Crisis: Confronting Reproducibility in Translational Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Daniel J. Drucker
The lack of reproducibility of preclinical experimentation has implications for sustaining trust in and ensuring the viability and funding of the academic research enterprise. Here I identify problematic behaviors and practices and suggest solutions to enhance reproducibility in translational research.

Teaser

Reproducibility challenges in preclinical research threaten the integrity and viability of our research enterprise. Here Drucker discusses the complexity of methodological, technical, and ethical issues contributing to lack of reproducibility and suggests options for discussion that may enhance the reproducibility and translational relevance of preclinical studies.


http://ift.tt/2cDNTas

Physiological Regulation: How It Really Works

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Douglas S. Ramsay, Stephen C. Woods
Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.

Teaser

Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.


http://ift.tt/2cMyxgS

Pharma and Academia: What We Have Here Is a Failure to Communicate

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Morris J. Birnbaum
In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, I discuss obstacles to these relationships being optimally productive.

Teaser

In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, Birnbaum discusses obstacles to these relationships being optimally productive.


http://ift.tt/2cDNbK0

The Irony of Tumor-Induced Inflammation

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Florian R. Greten
Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. (2016) have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.

Teaser

Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.


http://ift.tt/2cMywJQ

Weeding Out the Bad Apples

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Nikla Emambokus, Anne Granger




http://ift.tt/2cDN3dN

Beige Communication through Gap Junctions and Adaption by Autophagy

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Sven Enerbäck
How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 43 (Cx43) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.

Teaser

How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 45 (Cx45) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.


http://ift.tt/2cMzQMJ

Specialized Hub Beta Cells Trade Maximal Insulin Production for Perfect Timing

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Jelena Kolic, James D. Johnson
The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized hubs, identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.

Teaser

The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized "hubs," identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.


http://ift.tt/2cDNDYY

Fueling Performance: Ketones Enter the Mix

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Brendan Egan, Dominic P. D'Agostino
Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. (2016) demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.

Teaser

Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.


http://ift.tt/2cMyQbI

Mitochondrial Transfer from Astrocytes to Neurons following Ischemic Insult: Guilt by Association?

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Michael V. Berridge, Remy T. Schneider, Melanie J. McConnell
Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.

Teaser

Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.


http://ift.tt/2cDNXH7

Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Harding H. Luan, Ruslan Medzhitov
Itaconate is a newly discovered mammalian metabolite bearing significant implications for our understanding of cellular immunometabolism and antimicrobial defense. Here, we explore recent findings regarding the role of itaconate in the innate immune response and highlight the emerging principle that metabolites can have distinct immunological functions independent of bioenergetics.

Teaser

In this Minireview, Luan and Medzhitov discuss the newly discovered mammalian metabolite itaconate as both a regulator and effector of immunity. More generally, they explore the emerging concept that metabolites have distinct immunological functions that could be employed as antimicrobial therapeutics.


http://ift.tt/2cMBn5k

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Yi Zhu, Yong Gao, Caroline Tao, Mengle Shao, Shangang Zhao, Wei Huang, Ting Yao, Joshua A. Johnson, Tiemin Liu, Aaron M. Cypess, Olga Gupta, William L. Holland, Rana K. Gupta, David C. Spray, Herbert B. Tanowitz, Lei Cao, Matthew D. Lynes, Yu-Hua Tseng, Joel K. Elmquist, Kevin W. Williams, Hua V. Lin, Philipp E. Scherer
"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.

Graphical abstract

Teaser

Cold activates the "beiging" of white adipocytes through a sympathetic neuronal signal. White adipose tissue, however, is sparsely innervated. Here, Zhu et al. (2016) show that connexin 43 (Cx43) cell-to-cell gap junction channels are necessary for the propagation of sympathetic signals leading to the beiging of white adipocyte clusters.


http://ift.tt/2cDNbtu

Sex and Gender: Critical Variables in Pre-Clinical and Clinical Medical Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Eugenia Morselli, Aaron P. Frank, Roberta S. Santos, Luciana A. Fátima, Biff F. Palmer, Deborah J. Clegg




http://ift.tt/2cDOGIq

MATERNAL EXPOSURE TO BISPHENOL-A DURING PREGNANCY INCREASES PANCREATIC Β-CELL GROWTH DURING EARLY LIFE IN MALE MICE OFFSPRING

Endocrinology, Early Release.


http://ift.tt/2cYRYGG

Ghrelin octanoylation is completely stabilized in biological samples by alkyl fluorophosphonates

Endocrinology, Early Release.


http://ift.tt/2cIkutK

Caregivers’ perception of factors associated with a healthy diet among people with intellectual disability living in community residences: A Concept mapping method

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Marte Pilskog Ruud, Ruth Kjærsti Raanaas, Mona Bjelland
BackgroundMany people with intellectual disabilities (ID) living in community-based residences have been found to have unhealthy diet and weight disturbances. In Norway, a majority of people with ID live in such residences.AimsThe aim of the study was to examine factors affecting the caregivers' opportunity to promote a healthy diet among the residents.Methods and proceduresA concept mapping methodology was adopted, including group-based brainstorming, idea synthesising, sorting, rating and analysis of the results. Informants were caregivers in four different community residences for people with mild to moderate ID in the southeast of Norway. A total of 13 informants were recruited (12 females and 1 male), and 10 informants completed two sessions.ResultsEight clusters were identified as affecting the caregivers' ability to promote a healthy diet: "Availability and accessibility", "Guidance and autonomy", "Competence among staff", "Planning and involvement", "Customization", "External conditions affecting staff", "Legislation, rules and structure" and "Everyday challenges", each including both barriers and facilitators.Conclusions and implicationsMultiple factors affect the caregivers' ability to promote a healthy diet. Caregivers' opportunity to promote a healthy diet is complex. Availability and accessibility of healthy food is crucial, but a healthy diet also requires time and competence among the caregivers.

Graphical abstract

http://ift.tt/2c7ZXfM

Psychometric properties of the Arabic self-report version of the strengths and difficulties questionnaire

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Mahmoud Mohamed Emam, Maher M. Abu Hilal, Ali Mahdi Kazem, Suad Juma Alkharousi
Students in middle school tend to display emotional and behavioural difficulties (EBDs) compared to other forms of psychopathology. Early identification of EBDs is therefore a priority in order to prevent the chronic co-morbidity with other forms of psychopathology which may affect students' academic achievement. Assessment of EBDs has been traditionally undertaken via proxy reporting; but psychometrically rigorous instruments are needed so that children and adolescents can report on their own emotions and behaviours. Such need increases in the Omani context given the lack of EBDs adequate assessment instruments. In the current study the factor structure of the Arabic self-report version of the Strengths and Difficulties Questionnaire (A-SDQ) was examined in a sample of 815 middle school students (mean age=14 years). The study tested the SDQ original five-factor model which received considerable empirical support. Responses on the A-SDQ were compared to responses obtained via proxy reports from teachers and parents through confirmatory factor analyses (CFAs). Results showed a reasonable fit for the three informant forms. Nevertheless, there were differences in item loadings across the three informant forms. Additionally, participants' self-report responses were tested for invariance across gender. CFAs provided support to the invariance hypothesis for item loadings, indicating that the items were similarly valid indices of the five factors for males and females. Factor correlations, factor variances and item residuals were not invariant across gender.What this paper addsThis paper, to our knowledge, is the first research paper that provides empirical evidence on the Arabic self report version of the Strengths and Difficulties Questionnaire (A-SDQ) within a school-based sample. Though the focus was on the self-report version we collected data from the proxy versions for parents and teachers to provide additional evidence on the construct validity of the (A-SDQ) through cross informant data.



http://ift.tt/2c82ZQQ

Age- and Gender-Specific Risk of Thyroid Cancer in Patients with Familial Adenomatous Polyposis

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cIaEIC

Age-dependent increases in adrenal cytochrome b5 and serum 5-androstenediol-3-sulfate

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cYMf3K

Exploring Inpatient Hospitalizations and Morbidity in Patients with Adrenal Insufficiency

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cI9IUz

Most cleaved anti-Müllerian hormone binds its receptor in human follicular fluid but little is competent in serum

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cYKHXr

Diagnostic roles of MUC1 and GLUT1 in differentiating thymic carcinoma from type B3 thymoma

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Jun Du, Qin Shen, Honglin Yin, Qiu Rao, Xiaojun Zhou
MUC1 is a transmembrane mucin that has been related to tumor progression and outcome in various malignancies. GLUT1 is a member of the mammalian facilitative glucose transporter (GLUT) family of passive carriers that functions as an energy-independent system for transporting glucose. Both of them are useful markers for the diagnosis, progression, and prognosis of various tumors, especially those that are cancerous. However, the clinical significance of MUC1 and GLUT1 in thymic epithelial tumors remains uncertain due to a lack of quality specimen and studies at sufficient scale, both owing, in part, to the rarity of the tumors. The aim of this article is to study the expression patterns of MUC1 and GLUT1 in thymic carcinoma and type B3 thymoma, and to evaluate their diagnostic value for these two types of tumors via immunohistochemistry. Forty-three patients were included in the study, including twenty-two with thymic carcinoma and twenty-one with type B3 thymoma. Tumor issue sections were immunohistochemically stained for MUC1 and GLUT1; meanwhile, some tumors were also stained with CKpan, TDT, CD5, and CD117. MUC1 was expressed in a total of 17 cases, with a positive rate of 77.27% (17/22) in thymic carcinoma and 9.52% (2/21) in type B3 thymoma, revealing a significant difference (p<0.0001). A significant difference (p<0.0001) was also shown for GLUT1, where the positive rates for thymic carcinoma and type B3 thymoma were 100% (22/22) and 42.86% (9/21), respectively. The expression of MUC1 was significantly correlated with GLUT1 (p<0.0001). Furthermore, GLUT1 staining sensitivity and specificity for thymic carcinoma were 100% (22/22) and 70.97% (22/31), respectively, while MUC1 staining sensitivity and specificity were 77.27% (17/22) and 89.47% (17/19), respectively.In conclusion, our study shows that MUC1 and GLUT1 staining may play a useful role in differentiating thymic carcinoma from type B3 thymoma, with high sensitivity and specificity.



http://ift.tt/2cWLWn7

Salivary gland-like breast carcinomas: an infrequent disease

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Santiago Sherwell-Cabello, Antonio Maffuz-Aziz, Nina Paola Ríos-Luna, Verónica Bautista-Piña, Sergio Rodríguez-Cuevas
ObjectiveTo show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution.Materials and MethodsA retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included.ResultsIn this period, 6,384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1–108 months). No patient developed local or distant recurrence.ConclusionsSalivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected.

Graphical abstract

http://ift.tt/2cvuvMn

Selective Staining of Gastric Biopsies for H. Pylori Does Not Affect Detection Rates or Turnaround Time and Improves Cost Compared to Reflexive Staining

Publication date: Available online 13 September 2016
Source:Pathology - Research and Practice
Author(s): Lauren Decker, Joshua Keith Routh, Jessica Sara Snider, Joshua Anspach Hanson
AimsTo evaluate how reflexive versus selective H. pylori stains affect detection rates, turnaround time (TAT), and cost savings in a real life practice environment following an institutional policy change.MethodsThe aforementioned parameters were evaluated in all cases in the year preceding and the year following an institutional policy change from reflexive to selective staining.Results1,497 patients comprised the reflexive stain (RS) group of which 228 (15.2%) were H. pylori positive. 1,629 patients comprised the selective stain (SS) group of which 237 (14.5%) were H. pylori positive. There was no significant difference in H. pylori detection rates between the RS and SS groups (OR=0.95, 95% CI=0.78-1.15, p=0.59). TATs were similarly equivalent with a mean of 52.4hours for the RS cohort and 53.7hours for the SS cohort (p=0.344), both of which included a resident preview day. We calculated an average laboratory cost savings of $11.68 per case, which saved our department over $15,000 (37%) in the year following the policy change.ConclusionsOur results support a policy of selective staining for H. pylori as opposed to reflexive staining and go on to show that laboratories that change their policy can expect to generate cost savings without compromising detection rates or TAT.



http://ift.tt/2cMoqZE

NCI embraces scientific road map to achieve Cancer Moonshot goals

National Cancer Institute Acting Director Douglas Lowy, M.D., today accepted, with revisions that reflect NCAB's discussion, the recommendations of a Blue Ribbon Panel (BRP) on 10 approaches most likely to make a decade's worth of progress against cancer in five years, a key goal of the White House Cancer Moonshot.

http://ift.tt/2cmw7VL

Oxygen can impair cancer immunotherapy in mice

Researchers have identified a mechanism in mice by which anticancer immune responses are inhibited within the lungs, a common site of metastasis for many cancers.

http://ift.tt/2cUFfWK

Uncovering a new principle in chemotherapy resistance in breast cancer

A laboratory study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.

http://ift.tt/2cUFbGx

International collaboration to create new cancer models to accelerate research

An international project to develop a large, globally accessible bank of new cancer cell culture models for the research community launched today.

http://ift.tt/2cmwOhB

NCI launches largest-ever study of breast cancer genetics in black women

The Breast Cancer Genetic Study in African-Ancestry Populations initiative is a collaborative research project that will identify genetic factors that may underlie breast cancer disparities. It is the largest study ever to investigate how genetic and biological factors contribute to breast cancer risk among black women.

http://ift.tt/2cUGipm

Significant expansion of data available in the Genomic Data Commons

The recently launched Genomic Data Commons will get a dramatic increase in the power and utility of its resources with the signing today of a data sharing agreement between the NCI and Foundation Medicine, Inc. (FMI), a molecular information company.

http://ift.tt/2cmw1gP

Newly launched Genomic Data Commons to facilitate data and clinical information sharing

The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

http://ift.tt/2cUFiBQ

NIH study visualizes proteins involved in cancer cell metabolism

Scientists using cryo-electron microscopy have broken through a technological barrier in visualizing proteins with an approach that may have an impact on drug discovery and development, capturing images of an enzyme found in cells at a resolution of 1.8 angstroms.

http://ift.tt/2cmvuLC

Increased Physical Activity Associated with Lower Risk of 13 Types of Cancer

A new study of the relationship between physical activity and cancer has shown that greater levels of leisure-time physical activity were associated with a lower risk of developing 13 different types of cancer; the risk of developing seven cancer types was 20 percent lower among the most active participants as compared with the least active participants.

http://ift.tt/2cUGg0I

Analysis of rare endocrine cancer reveals novel genetic alterations

A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

http://ift.tt/2cmwvDy

Clustered structural and functional plasticity of dendritic spines

Publication date: Available online 13 September 2016
Source:Brain Research Bulletin
Author(s): Ju Lu, Yi Zuo
The configuration of synaptic circuits underlies their ability to process and store information. Research on dendritic spines has revealed that their structural and functional alterations are clustered along the parent dendrite. Here we review the evidence supporting such notion of clustered synaptic plasticity, discuss its functional implications and possible contributing factors, and suggest potential strategies to deal with open challenges.



http://ift.tt/2cllAzm

Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death

Publication date: Available online 12 September 2016
Source:Free Radical Biology and Medicine
Author(s): Zheng Li, Ji-Wei Wang, Wei-Zhi Wang, Xiao-Fei Zhi, Qun Zhang, Bo-Wen Li, Lin-Jun Wang, Kun-Ling Xie, Jin-Qiu Tao, Jie Tang, Song Wei, Yi Zhu, Hao Xu, Dian-Cai Zhang, Li Yang, Ze-Kuan Xu
Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer.

Graphical abstract

http://ift.tt/2cFIBMA

Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis

Publication date: Available online 12 September 2016
Source:Free Radical Biology and Medicine
Author(s): Da Hyun Lee, Dai Hoon Han, Ki Taek Nam, Jeong Su Park, Soo Hyun Kim, Milim Lee, Gyuri Kim, Byung Soh Min, Bong-Soo Cha, Yu Seol Lee, Su Haeng Sung, Haengdueng Jeong, Hye Won Ji, Moon Joo Lee, Jae Sung Lee, Hui-Young Lee, Yoomi Chun, Joungmok Kim, Masaaki Komatsu, Yong-ho Lee, Soo Han Bae
Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2–Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis. In addition, we identified that the hepatic mRNA levels of Nrf2 target genes such as Nqo-1 and GSTA-1 were significantly increased in NASH patients. Ezetimibe, a drug approved by the Food and Drug Administration for the treatment of hypercholesterolemia, improves NAFLD and alleviates oxidative stress. However, the precise mechanism of its antioxidant function remains largely unknown. We now demonstrate that ezetimibe activates Nrf2-Keap1 pathway which was dependent of autophagy adaptor protein p62, without causing cytotoxicity. Ezetimibe activates AMP-activated protein kinase (AMPK), which in turn phosphorylates p62 (p-S351) via their direct interaction. Correspondingly, Ezetimibe protected liver cells from saturated fatty acid-induced apoptotic cell death through p62-dependent Nrf2 activation. Furthermore, its role as an Nrf2 activator was supported by methione- and choline- deficient (MCD) diet-induced NASH mouse model, showing that ezetimibe decreased the susceptibility of the liver to oxidative injury. These data demonstrate that the molecular mechanisms underlying ezetimibe's antioxidant role in the pathogenesis of NASH.

Graphical abstract

http://ift.tt/2cFJ6X8

An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy

Publication date: Available online 12 September 2016
Source:Free Radical Biology and Medicine
Author(s): Jiayu Zhu, Huihui Wang, Feng Chen, Jingqi Fu, Yuanyuan Xu, Yongyong Hou, Henry H. Kou, Cheng Zhai, M. Bud Nelson, Qiang Zhang, Melvin E. Andersen, Jingbo Pi
The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes in response to oxidative and xenobiotic stress. A large number of Nrf2-antioxidant response element (ARE) activators have been screened for use as chemopreventive agents in oxidative stress-related diseases and even cancer. However, constitutive activation of Nrf2 occurs in a variety of cancers. Aberrant activation of Nrf2 is correlated with cancer progression, chemoresistance, and radioresistance. In this review, we examine recent studies of Nrf2-ARE inhibitors in the context of cancer therapy. We enumerate the possible Nrf2-inhibiting mechanisms of these compounds, their effects sensitizing cancer cells to chemotherapeutic agents, and the prospect of applying them in clinical cancer therapy.

Graphical abstract

http://ift.tt/2cMnbtq

Copeptin in obese children and adolescents: Relationships to body mass index, cortisol and gender

Abstract

Objective

Copeptin has been reported to be associated with stress, obesity and the Metabolic Syndrome (MetS) in adults. However, data in childhood are scarce. Therefore, we studied the relationships between copeptin, cortisol, puberty, and parameters of the MetS in children.

Design

Cross-sectional study.

Patients

51 obese children (10.8±3.2years, 39% male, 45% prepubertal, body mass index standard deviation score (BMI-SDS) 2.77±0.56) and 24 lean children of similar age, gender, and pubertal stage.

Measurements

Copeptin, serum cortisol, 24h urinary free cortisol, BMI-SDS and, as parameters of the MetS, insulin resistance index (HOMA), HbA1c, uric acids, blood pressure and lipids.

Results

Copeptin levels were significantly (p=0.047) higher in obese children (5.8±2.8pmol/l) compared to lean children (4.6±2.2pmol/l). BMI-SDS (coefficient 0.38 ±0.35, p=0.033), but not any parameter of the MetS, was significantly related to copeptin in multiple linear regression analyses adjusted for age, gender and pubertal stage. 24h urinary free cortisol (coefficient 0.13±0.06,p<0.001), but not serum cortisol, was significantly related to copeptin in multiple linear regression analyses adjusted for age, gender, pubertal stage and BMI-SDS. Pubertal boys (6.6±2.8pmol/l) demonstrated significantly (p=0.042) higher copeptin levels compared to pubertal girls (4.8±2.6pmol/l), while coeptin concentrations did not differ between prepubertal girls and boys.

Conclusions

Copeptin levels are related to 24h urinary free cortisol in obese children. Pubertal boys, but not prepubertal boys demonstrated higher copeptin levels than girls, suggesting that sex hormones are involved in the regulation of copeptin levels. Further studies are necessary to understand the relationship between obesity, cortisol, gender, pubertal stage and copeptin levels.

This article is protected by copyright. All rights reserved.

http://ift.tt/2cvIEWe

Constitutively active Stat5b signaling confers tolerogenic functions to dendritic cells of NOD mice and halts diabetes progression

Publication date: Available online 12 September 2016
Source:Journal of Autoimmunity
Author(s): Echarki Zerif, Aida Maalem, Simon Gaudreau, Chantal Guindi, Muhammad Ramzan, Steeve Véroneau, Denis Gris, Jana Stankova, Marek Rola-Pleszczynski, Walid Mourad, Gilles Dupuis, Abdelaziz Amrani
Defects in dendritic cells (DCs) development and function lead to autoimmune disorders. Autoimmune diabetes in humans and NOD mice results from a breakdown of self-tolerance, ending in T cell-mediated β-cell destruction. DCs dysfunction in NOD mice results in part from a defect in the JAK-STAT5 signaling pathway associated with the idd4 susceptibility locus. The involvement of Stat5b in DCs tolerogenic functions remains unknown. We have generated transgenic mice (NOD.CD11c^Stat5b−CA) expressing a constitutively active form of the Stat5b gene (Stat5b-CA) under control of CD11c promoter. All NOD.CD11c^Stat5b−CA mice were protected against diabetes. Protection was associated with an increased in the pool and suppressive function of Tregs, a promotion of Th2 and Tc2 immune response and a decreased percentage of CD8⁺ T cells. Splenic DCs of NOD.CD11c^Stat5b−CA mice acquired a mature phenotype, promoted and induced better conversion of CD4⁺CD25^-Foxp3^- T cells into Tregs (CD4⁺CD25⁺Foxp3⁺ T cells) than DCs of NOD mice. Stat5b-CA.DC-educated CD4⁺CD25⁻ T cells delayed diabetes onset whereas Stat5b-CA.DC-educated Tregs blocked ongoing diabetes in 8–10 weeks old NOD recipient mice. Importantly, injection of Stat5b.CA.DC to 8–10-week old NOD mice halted diabetes progression and educated their splenocytes to loose their diabetogenic potential when transferred to NOD.SCID mice. Our work is the first to report that an active form of Stat5b restored DCs tolerogenic functions that re-educated Tregs to re-establish and to sustain long-term protective immune response against diabetes in NOD mice.



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First Successful Eye Surgeries Performed on the Preceyes System

Preceyes, a Dutch spinout company from Eindhoven University of Technology that was incorporated in 2011, has announced the successful use of the company's surgical robotic system in the first of 12 patients undergoing treatment, led by professor Robert MacLaren at the University of Oxford.

The robotic technology is intended to improve clinical outcomes in the 1.3 million surgical procedures performed annually worldwide to treat vitreoretinal disease. Utilizing the Preceyes platform the system's creators also hope to open-up innovative drug and gene therapy treatment options for the estimated 50-75 million people suffering with retinal disease induced visual impairment.

Conventional vitreoretinal surgical procedures require ultra-precise manual movements of surgical equipment within the eye at the sub-millimeter scale, often risking hemorrhage or retinal damage. The Preceyes system integrates robotic control of these surgical instruments at the operating table, while keeping the surgeon in constant contact with the patient throughout the procedure.

The surgical system improves performance by downscaling hand movements and filtering-out any operator unsteadiness or tremor. This gives the surgeon a unique level of precision, down to the scale of a human hair, and allows for the possibility of performing procedures that were previously impossible.

The Preceyes system also allows for an instrument's position to be fixed while the interventionist alters their grip or prepares the patient for targeted drug delivery. This position "freezing" function is particularly important for the emerging field of retinal gene therapy, which has hopes of reversing blindness, as stem cells may be precisely injected over a number of minutes.

The Preceyes team plans to launch the surgical system with a targeted market entrance in late 2018.

Here's a company video explaining the workings of the Preceyes surgical system:

Link: Preceyes homepage…

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