For some people, frequent washing can damage hair and cause a dry, itchy scalp. How often should you wash your hair with shampoo?
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Σάββατο 28 Οκτωβρίου 2017
Should you wash your hair everyday?
Carbon nanotubes physicochemical properties influence the overall cellular behavior and fate
Publication date: Available online 28 October 2017
Source:NanoImpact
Author(s): Reem Eldawud, Alixandra Wagner, Chenbo Dong, Todd Stueckle, Yon Rojanasakul, Cerasela Zoica Dinu
The unique properties of single walled carbon nanotubes (SWCNTs) make them viable candidates for versatile implementation in the next generation of biomedical devices for targeted delivery of chemotherapeutic agents or cellular-sensing probes. Such implementation requires user-tailored changes in SWCNT's physicochemical characteristics to allow for efficient cellular integration while maintaining nanotubes' functionality. However, isolated reports showed that user-tailoring could induce deleterious effects in exposed cells, from decrease in cellular proliferation, to changes in cellular adhesion, generation of reactive oxygen species or phenotypical variations, just to name a few. Before full implementation of SWCNTs is achieved, their toxicological profiles need to be mechanistically correlated with their physicochemical properties to determine how the induced cellular fate is related to the exposure conditions or samples' characteristics. Our study provides a comprehensive analysis of the synergistic cyto- and genotoxic effects resulted from short-term exposure of human lung epithelial cells to pristine (as manufactured) and user-tailored SWCNTs, as a function of their physicochemical properties. Specifically, through a systematic approach we are correlating the nanotube uptake and nanotube-induced cellular changes to the sample's physicochemical characteristics (e.g., metal impurities, length, agglomerate size, surface area, dispersion, and surface functionalization). By identifying changes in active hallmarks involved in cell-cell connections and maintaining epithelial layer integrity, we also determine the role that short-term exposure to SWCNTs plays in the overall cellular fate and cellular transformation. Lastly, we assess cellular structure-function relationships to identify non-apoptotic pathways induced by SWCNTs exposure that could however lead to changes in cellular behavior and cellular transformation. Our results show that the degree of cell transformation is a function of the physicochemical properties of the SWCNT, with the nanotube with higher length, higher metal content and larger agglomerate size reducing cell viability to a larger extent. Such changes in cell viability are also complemented by changes in cell structure, cycle and cell-cell interactions, all responsible for maintaining cell fate.
Graphical abstract
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Editorial Board/Title Page
Publication date: November 2017
Source:Cortex, Volume 96
http://ift.tt/2iHFU0v
The blind mind: No sensory visual imagery in aphantasia
Source:Cortex
Author(s): Rebecca Keogh, Joel Pearson
For most people the use of visual imagery is pervasive in daily life, but for a small group of people the experience of visual imagery is entirely unknown. Research based on subjective phenomenology indicates that otherwise healthy people can completely lack the experience of visual imagery, a condition now referred to as aphantasia. As congenital aphantasia has thus far been based on subjective reports, it remains unclear whether participants are really unable to imagine visually, or if they have very poor metacognition - they have images in their mind, but are blind to them. Here we measured sensory imagery in subjectively self-diagnosed aphantasics, using the binocular rivalry paradigm, as well as measuring their self-rated object and spatial imagery with multiple questionnaires (VVIQ, SUIS and OSIQ). Unlike, the general population, experimentally naive aphantasics showed almost no imagery-based rivalry priming. Aphantasic participants' self-rated visual object imagery was significantly below average, however their spatial imagery scores were above average. These data suggest that aphantasia is a condition involving a lack of sensory and phenomenal imagery, and not a lack of metacognition. The possible underlying neurological cause of aphantasia are discussed as well as future research directions.
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Nonfatal air embolism complicating percutaneous CT-guided lung biopsy and VATS marking: Four cases from a single institution
Publication date: March–April 2018
Source:Clinical Imaging, Volume 48
Author(s): Rika Yoshida, Takeshi Yoshizako, Megumi Nakamura, Shinji Ando, Mitsunari Maruyama, Minako Maruyama, Yoshikazu Takinami, Yukihisa Tamaki, Tomonori Nakamura, Hajime Kitagaki
Systemic air emboli occur as a rare complication of percutaneous needle biopsy of the lung and video-assisted thoracoscopic surgery (VATS) marking.Here we present four cases of systemic air emboli from single institution and the imaging findings and embolism' kinetics using contrast-enhanced media during VATS color marking with indocyanine green. We suggest that early detection using routine whole-lung CT is required for asymptomatic patients with abnormal air. If abnormal air is found, we should keep the patient to the appropriate posture in order to prevent moving the air until it dissipates. Early detection of abnormal air can prevent severe complications.
http://ift.tt/2iHbJXj
Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots
Source:Biomaterials, Volume 153
Author(s): Dandan Zhang, Liewei Wen, Ru Huang, Huanhuan Wang, Xianglong Hu, Da Xing
Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV–vis light under near-infrared light (NIR) excitation, and GQD, which can produce 1O2 efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent 1O2 generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ1O2 burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy.
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Macrophages as a potential tumor-microenvironment target for noninvasive imaging of early response to anticancer therapy
Source:Biomaterials, Volume 152
Author(s): Qizhen Cao, Xinrui Yan, Kai Chen, Qian Huang, Marites P. Melancon, Gabriel Lopez, Zhen Cheng, Chun Li
As a result of therapy-induced apoptosis, peripheral blood monocytes are recruited to tumors, where they become tumor-associated macrophages (TAMs). To date, few studies have investigated noninvasive molecular imaging for assessment of macrophage infiltration in response to therapy-induced apoptosis. Here, noninvasive assessment of changes in tumor accumulation of TAMs was proposed as a new way to measure early tumor response to anticancer therapy. Three different nanoparticles, QD710-Dendron quantum dots (QD710-D), Ferumoxytol, and PG-Gd-NIR813, were used for near-infrared fluorescence imaging, T2-weighted magnetic resonance imaging, and dual optical/T1-weighted MR imaging, respectively, in the MDA-MB-435 tumor model. Treatment with Abraxane induced tumor apoptosis and infiltrating macrophages. In spite of markedly different physicochemical properties among the nanoparticles, in vivo imaging revealed increased uptake of all three nanoparticles in Abraxane-treated tumors compared with untreated tumors. Moreover, imaging visualized increased uptake of QD710-D in MDA-MB-435 tumors but not in drug-resistant MDA-MB-435R tumors grown in the mice treated with Abraxane. Our results suggest that infiltration of macrophages due to chemotherapy-induced apoptosis was partially responsible for increased nanoparticle uptake in treated tumors. Noninvasive imaging techniques in conjunction with systemic administration of imageable nanoparticles that are taken up by macrophages are a potentially useful tool for assessing early treatment response.
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Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection
Source:Biomaterials, Volume 152
Author(s): Guangxue Feng, Jackson Liang Yao Li, Carla Claser, Akhila Balachander, Yingrou Tan, Chi Ching Goh, Immanuel Weng Han Kwok, Laurent Rénia, Ben Zhong Tang, Lai Guan Ng, Bin Liu
The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS). In this report, we demonstrate that AIE-Gd dots enable direct visualization of brain vascular networks under resting condition, and that they form localized punctate aggregates and accumulate in the brain tissue during experimental cerebral malaria, indicative of hemorrhage and BBB malfunction. With its superior detection sensitivity and multimodality, we hereby propose that AIE-Gd dots can serve as a better alternative to Evans blue for visualization and quantification of changes in brain barrier functions.
http://ift.tt/2ydih6M
Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits
Publication date: January 2018
Source:Biomaterials, Volume 153
Author(s): Yuxiao Lai, Huijuan Cao, Xinluan Wang, Shukui Chen, Ming Zhang, Nan Wang, Zhihong Yao, Yi Dai, Xinhui Xie, Peng Zhang, Xinsheng Yao, Ling Qin
Steroid-associated osteonecrosis (SAON) often requires surgical core decompression (CD) in the early stage for removal of necrotic bone to facilitate repair where bone grafts are needed for filling bone defect and avoiding subsequent joint collapse. In this study, we developed a bioactive composite scaffold incorporated with icariin, a unique phytomolecule that can provide structural and mechanical support and facilitate bone regeneration to fill into bone defects after surgical CD in established SAON rabbit model. An innovative low-temperature 3D printing technology was used to fabricate the poly (lactic-co-glycolic acid)/β-calcium phosphate/icariin (PLGA/TCP/Icariin, PTI) scaffold. The cytocompatibility of the PTI scaffold was tested in vitro, and the osteogenesis properties of PTI scaffolds were assessed in vivo in the SAON rabbit models. Our results showed that the fabricated PTI scaffold had a well-designed biomimic structure that was precisely printed to provide increased mechanical support and stable icariin release from the scaffold for bone regeneration. Furthermore, our in vivo study indicated that the PTI scaffold could enhanced the mechanical properties of new bone tissues and improved angiogenesis within the implanted region in SAON rabbit model than those of PLGA/TCP (PT) scaffold. The underlying osteoblastic mechanism was investigated using MC3T3-E1 cells in vitro and revealed that icariin could facilitate MC3T3-E1 cells ingrowth into the PTI scaffold and regulate osteoblastic differentiation. The PTI scaffold exhibited superior biodegradability, biocompatibility, and osteogenic capability compared with those of PT scaffold. In summary, the PTI composite scaffold which incorporated bioactive phyto-compounds is a promising potential strategy for bone tissue engineering and regeneration in patients with challenging SAON.
Graphical abstract
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The treatment of a pregnant HIV positive patient with cryptococcal meningitis in Malawi. Case report and review of treatment options
Publication date: Available online 28 October 2017
Source:Medical Mycology Case Reports
Author(s): Philip D. Bright, Duncan Lupiya, Joep J. van Oosterhout, Amy Chen, Thomas S. Harrison, Adrienne K. Chan
This case reports cryptococcal meningitis in an HIV positive woman on antiretroviral therapy, presenting with left middle cerebral artery stroke at 30 weeks gestation. The patient had well-controlled HIV (CD4 count over 200 cells/mL). The immunosuppressive effects of the pregnancy likely contributed to the development of cryptococcal disease. The patient was successfully treated with two weeks of amphotericin B followed by fluconazole, delivered a healthy baby, but remained with a permanent severe neurological deficit.
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Sporotrichosis by Sporothrix schenckii senso stricto with itraconazole resistance and terbinafine sensitivity observed in vitro and in vivo: case report
Publication date: Available online 28 October 2017
Source:Medical Mycology Case Reports
Author(s): Rodrigo Vettorato, Daiane Heidrich, Fernanda Fraga, Amanda Carvalho Ribeiro, Danielle Machado Pagani, Carina Timotheo, Tais Guarienti Amaro, Gerson Vettorato, Maria Lúcia Scroferneker
We report a case of a patient with lymphocutaneous sporotrichosis in the right upper limb. The fungus was identified as Sporothrix schenckii senso stricto by calmodulin gene sequencing. The initial treatment was itraconazole (200mg/day), but in vitro antifungal susceptibility demonstrated high resistant to this and another six antifungals, with exception to terbinafine. The lesions did not regress with itraconazole treatment. Thus, 500mg/day of terbinafine was prescribed and clinical cure was obtained after four months
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Chemical affinity of 10-methacryloyloxydecyl dihydrogen phosphate to dental zirconia: Effects of molecular structure and solvents
Publication date: Available online 14 October 2017
Source:Dental Materials
Author(s): Ying Chen, Zhicen Lu, Mengke Qian, Huaiqin Zhang, Chen Chen, Haifeng Xie, Franklin R. Tay
ObjectivesTo examine whether solvents and changing the molecular structure of 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP) affect its chemical affinity to Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP).MethodsThe present work investigated the chemical affinity between Y-TZP and 10-MDP dissolved in different solvents (acetone/ethanol/water or mixture) using X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and thermodynamic calculations. Shear bond strength (SBS) tests were used to evaluate the influence of different solvents on 10-MDP bonding. In addition, several phosphate ester monomer variants were created by changing the 10-MDP molecular structure. Changes included extending/shortening the spacer chain-length, and installing hydroxyl or carboxyl groups as side chains at different positions along the spacer chain. The thermodynamic parameters of the complexes formed between the 10-MDP variants and tetragonal zirconia were evaluated.ResultsThe acquired data indicated that solvent is necessary for the formation of Zr–O–P bonds between 10-MDP and Y-TZP. Solvents affected the chemical affinity of 10-MDP to Y-TZP; acetone facilitated the best bonding, followed by ethanol. Changing the molecular structure of 10-MDP affected its chemical affinity to Y-TZP. The variants 15-MPDP, 12-MDDP, 6-hydroxyl-10-MDP and 6-carboxy-10-MDP all exhibited higher thermodynamic stability than 10-MDP when coordinated with tetragonal zirconia. In contrast, 2-MEP, 5-MPP, 10-hydroxyl-MDP, 10-carboxy-MDP, 5,6-dihydroxyl-10-MDP and 5,6-dicarboxy-10-MDP exhibited lower thermodynamic stability.Significance10-MDP coordinates with zirconia through dissociating in solvents. Changing the molecular structure of 10-MDP theoretically affects its chemical affinity to Y-TZP.
Graphical abstract
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Editorial Board
Source:Dental Materials, Volume 33, Issue 11
http://ift.tt/2zfo4Jm
Zirconia-incorporated zinc oxide eugenol has improved mechanical properties and cytocompatibility with human dental pulp stem cells
Publication date: Available online 14 October 2017
Source:Dental Materials
Author(s): Soo Kyung Jun, Hae-Won Kim, Hae-Hyoung Lee, Jung-Hwan Lee
ObjectiveZinc oxide eugenol (ZOE) is widely used as a therapeutic dental restorative material. However, ZOE has poor mechanical properties and high cytotoxicity toward human dental pulp stem cells (hDPSCs) due to the release of Zn ions. In this study, zirconia-incorporated ZOE (ZZrOE) was developed to reduce the cytotoxicity and improve the mechanical properties of ZOE with sustained therapeutic effects on inflamed hDPSCs in terms of inflammatory gene expression levels compared with those of the original material.MethodsAfter the setting time and mechanical properties of ZZrOE incorporating varying amounts of zirconia (0, 5, 10, and 20wt% in powder) were characterized, the surface morphology and composition of the resulting ZZrOE materials were investigated. The ions and chemicals released into the cell culture medium from ZOE and ZZrOE (3cm2/mL) were measured by inductively coupled plasma atomic emission spectroscopy and gas chromatography, respectively. After testing cytotoxicity against hDPSCs using the above extracts, the therapeutic effects on lipopolysaccharide-inflamed hDPSCs in terms of compromising the upregulation of inflammatory response-related mRNA expression were tested using real-time PCR.ResultsZZrOE 20% exhibited increased compressive strength (∼45%), 3-point flexural strength (∼150%) and hardness (∼75%), as well as a similar setting time (∼90%), compared with those of ZOE. After the rough surface of ZZrOE was observed, significantly fewer released Zn ions and eugenol (∼40% of that from ZOE) were detected in ZZrOE 20%. ZZrOE showed less cytotoxicity because of the lower amount of Zn ions released from ZOE while showing sustained inhibition of inflammatory marker (e.g., interleukin 1β, 6 and 8) mRNA levels.SignificanceThe improved mechanical properties and cytocompatibility, as well as the sustained therapeutic effects on inflamed hDPSCs, were investigated in ZZrOE compared with those of ZOE. Therefore, ZZrOE has the potential to be used as an alternative to ZOE as a dental restorative material.
Graphical abstract
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3D printed versus conventionally cured provisional crown and bridge dental materials
Source:Dental Materials
Author(s): Anthony Tahayeri, MaryCatherine Morgan, Ana P. Fugolin, Despoina Bompolaki, Avathamsa Athirasala, Carmem S. Pfeifer, Jack L. Ferracane, Luiz E. Bertassoni
ObjectivesTo optimize the 3D printing of a dental material for provisional crown and bridge restorations using a low-cost stereolithography 3D printer; and compare its mechanical properties against conventionally cured provisional dental materials.MethodsSamples were 3D printed (25×2×2mm) using a commercial printable resin (NextDent C&B Vertex Dental) in a FormLabs1+ stereolithography 3D printer. The printing accuracy of printed bars was determined by comparing the width, length and thickness of samples for different printer settings (printing orientation and resin color) versus the set dimensions of CAD designs. The degree of conversion of the resin was measured with FTIR, and both the elastic modulus and peak stress of 3D printed bars was determined using a 3-point being test for different printing layer thicknesses. The results were compared to those for two conventionally cured provisional materials (Integrity®, Dentsply; and Jet®, Lang Dental Inc.).ResultsSamples printed at 90° orientation and in a white resin color setting was chosen as the most optimal combination of printing parameters, due to the comparatively higher printing accuracy (up to 22% error), reproducibility and material usage. There was no direct correlation between printing layer thickness and elastic modulus or peak stress. 3D printed samples had comparable modulus to Jet®, but significantly lower than Integrity®. Peak stress for 3D printed samples was comparable to Integrity®, and significantly higher than Jet®. The degree of conversion of 3D printed samples also appeared higher than that of Integrity® or Jet®.SignificanceOur results suggest that a 3D printable provisional restorative material allows for sufficient mechanical properties for intraoral use, despite the limited 3D printing accuracy of the printing system of choice.
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Incorporation of antibacterial agent derived deep eutectic solvent into an active dental composite
Publication date: Available online 23 October 2017
Source:Dental Materials
Author(s): Jing Wang, Xiaoqing Dong, Qingsong Yu, Sheila N. Baker, Hao Li, Nathaniel E. Larm, Gary A. Baker, Liang Chen, Jingwen Tan, Meng Chen
ObjectiveTo incorporate an antibacterial agent derived deep eutectic solvent (DES) into a dental resin composite, and investigate the resulting mechanical properties and antibacterial effects.MethodThe DES was derived from benzalkonium chloride (BC) and acrylic acid (AA) and was incorporated into the dental resin composite through rapid mixing. A three-point bending test was employed to measure the flexural strength of the composite. An agar diffusion test was used to investigate antibacterial activity. Artificial (accelerated) aging was undertaken by immersing the composites in buffer solutions at an elevated temperature for up to 4 weeks. UV–vis spectrophotometry and NMR analysis were conducted to study BC release from the composite. Finally, the biocompatibility of the composite materials was evaluated using osteoblast cell culture for 7 days. Results were compared to those of a control composite which contained no BC.ResultThe DES-incorporated composite (DES-C) displayed higher flexural strength than a similar BC-incorporated composite BC (BC-C) for the same level of BC. The inclusion of BC conferred antibacterial activity to both BC-containing composites, although BC-C produced larger inhibition halos than DES-C at the same loading of BC. Control composites which contained no BC showed negligible antibacterial activity. After artificial aging, the DES-C composite showed better maintenance of the mechanical properties of the control compared with BC-C, although a decrease was observed during the three-point bending test, particularly upon storage at elevated temperatures. No BC release was detected in the aged solutions of DES-C, whereas the BC-C showed a linear increase in BC release with storage time. Significantly, cell viability results indicated that DES-C has better biocompatibility than BC-C.SignificanceThe incorporation of a BC-based DES into a dental resin composite provides a new strategy to develop antibacterial dental materials with better biocompatibility and longer effective lifetimes without sacrificing the intrinsic mechanical properties of the composite structure.
Graphical abstract
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Corrosion behavior of titanium in response to sulfides produced by Porphyromonas gingivalis
Publication date: Available online 20 October 2017
Source:Dental Materials
Author(s): Rino Harada, Eitoyo Kokubu, Hideaki Kinoshita, Masao Yoshinari, Kazuyuki Ishihara, Eiji Kawada, Shinji Takemoto
ObjectiveTo investigate the effects of sulfides produced by Porphyromonas gingivalis (P. gingivalis) on the corrosion behavior of titanium.MethodsCommercially pure titanium disks were mirror-polished and immersed in culture medium (BHI), spent medium after culturing P. gingivalis (BHI-S), and culture medium with P. gingivalis (BHI-P), and incubated aerobically at 37°C for 3–14 days. Titanium corrosion was evaluated through surface observation (using scanning electron microscope: SEM), color change (ΔE*ab), glossiness (Gs(20°)), chemical composition and state (using X-ray photoelectron spectroscopy: XPS), and titanium release.ResultsΔE*ab and Gs(20°) did not significantly differ among specimens placed in test mediums for the study duration (p>0.05). SEM images of specimens showed no signs of localized or overall corrosion. XPS analysis indicated showed clear titanium metal state peaks on all specimens in addition to sulfide and sulfate on BHI-S and BHI-P specimens. Valency fraction of titanium decomposed from Ti2p spectrum of BHI-S and BHI-P specimens indicated no progression of oxidation. No significant levels of titanium release were found regardless of the mediums' sulfide content. Results suggested that sulfides produced by P. gingivalis attached on the surface of titanium specimens but did not cause titanium corrosion over the immersion period of 14 days.SignificanceIt is imperative for dental practitioners to be aware of any elements which may influence the clinical success of titanium implants.
Graphical abstract
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Cuspal flexure of composite-restored typodont teeth and correlation with polymerization shrinkage values
Source:Dental Materials
Author(s): Taylor Enochs, Anne E. Hill, Cassandra E. Worley, Crisnicaw Veríssimo, Daranee Tantbirojn, Antheunis Versluis
ObjectiveThe relationship between post-gel shrinkage, total shrinkage, and cuspal flexure was examined. Cuspal flexure was measured on restored typodont teeth, which offered a standardized tooth shape for comparison of shrinkage stress effects among restorative composites.MethodsSix restorative composites were compared (Filtek LS, Venus Flowable, Tetric EvoCeram, Filtek Flowable, Esthet-X, and Filtek Supreme). Total shrinkage was determined from changes in projected surface area before and after polymerization (n=10). Post-gel shrinkage was determined with a biaxial strain gauge that measured strain development during polymerization (n=10). Cuspal flexure was determined using typodont maxillary second premolars with standard MOD slot preparation (n=10). Flexure was determined by comparing the three-dimensionally scanned cuspal surfaces before and after restoration. Restoration bonding to the typodont cavity was achieved by sandblasting and adhesive application. Bond integrity was verified by measuring dye penetration. Results were analyzed using ANOVA and Student–Newman–Keuls post hoc test (significance level 0.05). Pearson was used for correlations.ResultsTotal and post-gel shrinkage were significant different for all composites (t-test; P<0.001). Depending on the composite, only 9–41% of the total shrinkage was recorded as post-gel shrinkage. Bond integrity of restored typodont teeth was 96–99%. Cuspal flexure correlated strongly with post-gel shrinkage, but there was no correlation with total shrinkage.SignificanceCuspal flexure of restored typodont teeth showed the effect of shrinkage stress caused by polymerizing composite restorations, ensuring standardization while maintaining the effects of tooth/cavity geometry. Post-gel shrinkage gave a good indication to screen composites for the stress they may generate; total shrinkage had no direct correlation with stress.
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Collagenous matrix supported by a 3D-printed scaffold for osteogenic differentiation of dental pulp cells
Publication date: Available online 18 October 2017
Source:Dental Materials
Author(s): Farahnaz Fahimipour, Erfan Dashtimoghadam, Morteza Rasoulianboroujeni, Mostafa Yazdimamaghani, Kimia Khoshroo, Mohammadreza Tahriri, Amir Yadegari, Jose A. Gonzalez, Daryoosh Vashaee, Douglas C. Lobner, Tahereh S. Jafarzadeh Kashi, Lobat Tayebi
ObjectiveA systematic characterization of hybrid scaffolds, fabricated based on combinatorial additive manufacturing technique and freeze-drying method, is presented as a new platform for osteoblastic differentiation of dental pulp cells (DPCs).MethodsThe scaffolds were consisted of a collagenous matrix embedded in a 3D-printed beta-tricalcium phosphate (β-TCP) as the mineral phase. The developed construct design was intended to achieve mechanical robustness owing to 3D-printed β-TCP scaffold, and biologically active 3D cell culture matrix pertaining to the Collagen extracellular matrix. The β-TCP precursor formulations were investigated for their flow-ability at various temperatures, which optimized for fabrication of 3D printed scaffolds with interconnected porosity. The hybrid constructs were characterized by 3D laser scanning microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and compressive strength testing.ResultsThe in vitro characterization of scaffolds revealed that the hybrid β-TCP/Collagen constructs offer superior DPCs proliferation and alkaline phosphatase (ALP) activity compared to the 3D-printed β-TCP scaffold over three weeks. Moreover, it was found that the incorporation of TCP into the Collagen matrix improves the ALP activity.SignificanceThe presented results converge to suggest the developed 3D-printed β-TCP/Collagen hybrid constructs as a new platform for osteoblastic differentiation of DPCs for craniomaxillofacial bone regeneration.
Graphical abstract
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Zirconia surface modification by a novel zirconia bonding system and its adhesion mechanism
Source:Dental Materials
Author(s): Takahiro Murakami, Shinji Takemoto, Norihiro Nishiyama, Masahiro Aida
ObjectiveBonding to zirconia has been of great interest over the last 10–15 years. The aim of this study was to develop a zirconia bonding system and clarify its adhesion mechanism.MethodsA zirconia primer was prepared using tetra-n-propoxy zirconium (TPZr) and water. A silane primer was also prepared using γ-methacryloyloxypropyltrimethoxysilane (γ-MPS) and hydrochloric acid. After the zirconia primer was applied to the oxidized zirconia surface, the silane primer was applied to the ZrO2-functionalized layer and the resin cement was applied to the silane-modified layer. Ceramic Primer II was used as a typical MDP-based ceramic primer. Shear bond strengths were measured using a universal testing machine. To clarify the enhancing mechanism of the zirconia bonding system, X-ray photoelectron spectroscopy (XPS) analyses were performed.ResultsThe zirconia bond strength was affected by the surface wettability of zirconia, and the compositions of TPZr and water utilized in the zirconia primer. When the zirconia primer, consisting of 10μL TPZr and 13μL water, was applied to the zirconia surface that had been oxidized by H2O2 above 10%, the maximum bond strength of 8.2MPa was obtained. The mechanism of the zirconia bonding system was established as follows: the hydrolyzed zirconium species formed a more reactive ZrO2-functionalized layer on the oxidized zirconia surface, and the hydrolyzed γ-MPS species adsorbed on that layer introduces a chemical bonding to the resin.SignificanceThe novel zirconia bonding system enhanced the bonding performance of the resin, and showed a greater bond strength than an MDP-based ceramic primer.
http://ift.tt/2zfoxLy
Cytotoxicity and DNA double-strand breaks in human gingival fibroblasts exposed to eluates of dental composites
Source:Dental Materials
Author(s): Yang Yang, Franz-Xaver Reichl, Jianwei Shi, Xiuli He, Reinhard Hickel, Christof Högg
ObjectivePreviously, single composite components were used to study cytotoxicity and induction of DNA double-strand breaks (DNA-DSBs) of dental composite resins. In the present study, cytotoxicity and induction of DNA-DSBs in human gingival fibroblasts (HGFs) were investigated with dental composite eluates consisting of multiple components. The eluates were qualified and quantified.MethodsThe composites Esthet.X® HD, Venus®, X-tra fil®, CLEARFIL™ AP-X, Admira® Fusion and QuiXfil® were polymerized and immersed into Dulbecco's modified Eagle's medium (DMEM) for 72h. Subsequently, HGFs were incubated with the corresponding composite eluates. The cell viability of HGFs was obtained from an XTT assay. DNA-DSBs were determined using a γ-H2AX assay. The qualification and quantification of eluates were performed by gas chromatography/mass spectrometry (GC/MS).ResultsHGFs exposed to the eluates of all investigated composites showed no significant loss of cell viability, compared to negative control. Significant DNA-DSBs induction could be found in HGFs exposed to the eluates of Esthet.X® HD (0.43±0.05 foci/cell) and Venus® (0.39±0.04 foci/cell), compared to control (0.22±0.03 foci/cell). A total of 12 substances were detected from the investigated composite eluates. Five of them were methacrylates: tetraethyleneglycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), ethyleneglycol dimethacrylate (EGDMA) and trimethylolpropane trimethacrylate (TMPTMA). The highest concentration of HEMA (110.5μM), HPMA (86.08μM) and TMPTMA (4.50μM) was detected in the eluates of QuiXfil®. The highest concentration of TEGDMA was 1080μM in Venus® eluates and the highest concentration of EGDMA was 3.18μM in Esthet.X® HD eluates.SignificanceSignificant DNA-DSBs induction can be found in HGFs exposed to the eluates of Esthet.X® HD and Venus®. The interactive effects among released (co)monomers and additives may influence the cytotoxicity and induction of DNA-DSBs, compared to exposure with single composite component.
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Bioactivity and fluoride release of strontium and fluoride modified Biodentine
Source:Dental Materials
Author(s): Hazel O. Simila, Natalia Karpukhina, Robert G. Hill
Biodentine™ is a novel tricalcium silicate based material used both as a coronal dentine replacement and in pulp therapy. Its multiple use in sealing perforations, pulp capping and as a temporary restoration arises from its ability to promote dentine formation and to confer an excellent marginal seal. However, there is still room for improvement of this cement as it lacks the anticariogenic effect typically conferred by fluoride ion release as seen in glass ionomer cement based dental materials. Therefore, this study was conducted to investigate the impact of bioactive glass addition to Biodentine™.Objectivewas to compare the apatite formation capacity, specificity of the apatite type formed and fluoride ion release by Biodentine™ cements that have been modified by three different compositions of bioactive glasses.MethodsHigh fluoride, high strontium and high fluoride plus strontium containing bioactive glasses were synthesized, incorporated into Biodentine™ powder and four types of cements prepared. These cements were immersed in phosphate buffered saline solution and incubated for a period of 3 and 24h, 3, 7 and 14 days. Fourier transform infra-red spectroscopy, X-ray diffraction, magic angle spinning nuclear magnetic resonance and fluoride ion release studies were performed.ResultsBioactive glass addition to Biodentine™ led to pronounced formation of apatite. Where the bioactive glass contained fluoride, fluorapatite and fluoride ion release were demonstrated.SignificanceEliciting fluorapatite formation and fluoride ion release from Biodentine™ is an important development as fluoride is known to have antibacterial and anticariogenic effects.
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Instrument-assisted soft tissue mobilization increases myofascial trigger point pain threshold
Publication date: Available online 28 October 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Dawn T. Gulick
BackgroundA myofascial trigger point (MTrP) has been defined as a hyperirritable, palpable nodule in a skeletal muscle. The signs and symptoms of a MTrP include muscle pain, weakness, and dysfunction. MTrPs are common problems associated with soft tissue pathology. Having an intervention to decrease MTrP pain can be clinically valuable.PurposeTo determine if a series of six instrument-assisted soft tissue mobilization (IASTM) treatments rendered over three weeks would influence the pressure pain threshold (PPT) of a myofascial trigger point (MTrP).MethodsRandomized, control trial of healthy individuals (n = 29) with MTrPs in the upper trapezius muscle. The intervention was six IASTM treatments rendered over three weeks. Each treatment included 1 min of sweeping with the GT-1/HG-2 (handle bar), 1 min of swivel with the knob of the GT-1/HG-2 directly over the MTrP, 2 min of fanning with the GT-4/HG-8 (convex single bevel), and concluded with 1 min of sweeping with GT-1/HG-2.The outcome measure used a dolorimeter to compare PPT before and after three weeks in both the treatment and control groups.ResultsPaired t-test for PPT pre-test and post-test of the control and treatment groups were p = 0.42159 and p = 0.00003, respectively. A one-way ANOVA of the control and IASTM groups revealed a statistically significant difference (p < 0.0001). The power calculation was greater than 0.99.ConclusionsA 5-min intervention using three IASTM techniques can effectively increase the PPT of a MTrP in six treatments over a three-week period of time.
http://ift.tt/2z0VLx9
Hyperlipidemia-induced hepassocin in the liver contributes to insulin resistance in skeletal muscle
Publication date: Available online 28 October 2017
Source:Molecular and Cellular Endocrinology
Author(s): Tae Woo Jung, Yoon Hee Chung, Hyoung-Chun Kim, A.M.Abd El-Aty, Ji Hoon Jeong
Hepassocin (HPS) has recently been identified as a novel hepatokine that causes hepatic steatosis. However, the role of HPS in the development of insulin resistance in skeletal muscle under obesity remains unclear. The effect of hyperlipidemia on hepatic HPS expression was evaluated in primary hepatocytes and liver of mice. HPS-mediated signal pathways were explored using small interfering (si) RNAs of specific genes or inhibitors. We found that treatment of primary hepatocytes with palmitate could induce HPS expression through C/EBPβ-mediated transcriptional activation. Furthermore, increased HPS expression was observed in the liver of high fat diet (HFD)-fed or tunicamycin-treated mice. Pretreatment with 4-phenylbutyrate (4-BPA) (an endoplasmic reticulum (ER) stress inhibitor) and suppression of p38 by siRNA abrogated the effect of palmitate on HPS expression in primary hepatocytes. Treatment of differentiated C2C12 cells with recombinant HPS caused c-Jun N-terminal kinase (JNK) phosphorylation and impairment of insulin sensitivity in a dose-dependent manner. siRNA-mediated suppression of JNK reduced the effect of HPS on insulin signaling. Furthermore, the suppression of epidermal growth factor receptor (EGFR) by siRNA mitigated both HPS-induced JNK phosphorylation and insulin resistance. In addition, HPS did not affect inflammation and ER stress in differentiated C2C12 cells. In conclusion, we elucidated that ER stress induced by palmitate could increase the expression of HPS in hepatocytes and further contribute to the development of insulin resistance in skeletal muscle via EGFR/JNK-mediated pathway. Taken together, we suggest that HPS could be a therapeutic target for obesity-linked insulin resistance.
Graphical abstract
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Activin over-expression in the testis of mice lacking the inhibin α-subunit gene is associated with androgen deficiency and regression of the male reproductive tract
Source:Molecular and Cellular Endocrinology
Author(s): Rukmali Wijayarathna, David M. de Kretser, Andreas Meinhardt, Ralf Middendorff, Helen Ludlow, Nigel P. Groome, Kate A. Loveland, Mark P. Hedger
Regionalised interaction of the activins, follistatin and inhibin was investigated in the male reproductive tract of mice lacking the inhibin α-subunit (Inha−/-). Serum and intratesticular activin B, although not activin A and follistatin, were increased in Inha−/- mice at 25 days of age, but all three proteins were elevated at 56 days. None of these proteins were altered within the epididymis and vas deferens at either age. At 25 days, histology of the epididymis and vas deferens was similar to wild-type. At 56 days, the testis contained extensive somatic cell tumours, leading to Leydig cell regression and testosterone deficiency. The epididymis and vas deferens showed epithelial regression and increased prominence of the interstitial stroma. Immunoregulatory and fibrotic gene expression in the epididymis and vas deferens were unchanged. Thus, absence of the inhibin α-subunit has marginal effects on activins in the epididymis and vas deferens, and regression of these tissues is associated with androgen deficiency.
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Morphology and Outcomes of Total Endovascular Treatment of Type B Aortic Dissection with Aberrant Right Subclavian Artery
Publication date: Available online 28 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Min Zhou, Xueqin Bai, Yong Ding, Yonggang Wang, Changpo Lin, Dong Yan, Zhenyu Shi, Weiguo Fu
ObjectivesTo characterize the morphology of type B aortic dissection with aberrant right subclavian artery (ARSA) and present early and midterm outcomes of total endovascular treatment for affected patients.MethodsFrom January 2010 to December 2015, patients with ARSA and type B aortic dissection treated with total endovascular techniques were enrolled. The angle of the aortic arch was measured on pre-operative CTA. Sixty age and gender matched normal aortic arch patients with type B aortic dissection served as controls. Primary outcomes were technical success, 30 day mortality, and late survival. Secondary outcomes included in hospital morbidity, re-intervention rate, and patency of the subclavian artery.ResultsA total of 13 patients (8 men, 5 women; mean age 58 years) were included. The mean angle of the aortic arch in patients with ARSA was significantly smaller than in normal aortic arch patients (117.2° ± 10.8° vs. 124.2° ± 9.4°, respectively; p = .024). Simple thoracic endovascular aortic repair (TEVAR) and TEVAR plus a parallel graft technique were performed in six and seven patients, respectively. Primary technique success was achieved in 11 of the 13 (84.6%) patients. A bird beak configuration occurred significantly more frequently in patients with ARSA than in normal aortic arch patients (91.7% vs. 48.3%, respectively; p = .035). The median follow-up time was 36 months. One patient received a secondary procedure because of a new onset entry tear at the distal end of the stent graft. No posterior circulation stroke, permanent spinal cord ischaemia, or ischaemia of the upper arm was observed.ConclusionsType B aortic dissection with ARSA was associated with a steep aortic arch. Total endovascular treatment for these patients was feasible and safe. Stent grafts with better flexibility and appropriate extension of the proximal landing zone with a parallel graft technique are suggested based on the observed outcomes.
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Determinants of Acute Kidney Injury and Renal Function Decline After Endovascular Abdominal Aortic Aneurysm Repair
Publication date: Available online 27 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Randolph G. Statius van Eps, Banne Nemeth, Ronne T.A. Mairuhu, Jan J. Wever, Hugo T.C. Veger, Hans van Overhagen, Lukas C. van Dijk, Bob Knippenberg
Objective/BackgroundEndovascular aneurysm repair (EVAR) may be associated with renal injury and more insight is needed into potential risk factors. The aim was to identify clinical, anatomical, and peri-procedural parameters as potential risk factors for the occurrence of acute kidney injury (AKI) and to evaluate chronic kidney disease (CKD) after EVAR.MethodsA cohort of 212 consecutive patients who underwent elective EVAR for abdominal aortic aneurysm from January 2009 to October 2016 was included. A subgroup of 149 patients with 2 years follow-up was compared with a set of 135 non-operated aneurysm patients with smaller aneurysms (similar cardiovascular risk profile) to assess CKD. Primary outcomes were AKI (Acute Kidney Injury Network criteria) and CKD measured by estimated glomerular filtration rate (Kidney Disease Improving Global Outcomes guidelines). For AKI, candidate risk factors were identified by univariate and multivariate logistic regression analysis; for chronic renal function decline, risk factors were identified using Cox regression analysis.ResultsAKI occurred in 30 patients (15%). On multivariate analysis, the use of angiotensin II blocker (odds ratio [OR] 4.08, 95% confidence interval [CI] 1.38–12.07) and peri-operative complications (OR 3.12, 95% CI 1.20–8.10) were independent risk factors for AKI, whereas statin use was a protective factor (OR 0.19, 95% CI 0.07–0.52). EVAR resulted in a significant increase (23.5%) in the occurrence of CKD compared with the control group (6.7%; p <.001). On univariate and multivariate Cox regression the risk factors: aortic neck diameter (per mm increase) (hazard ratio [HR] 1.13, 95% CI 1.02–1.25), renal artery stenosis >50% (HR 2.24, 95% CI 1.05–4.79), and the occurrence of AKI (HR 2.19, 95% CI 0.99–4.85) were significant predictors of CKD.ConclusionThis study identified use of angiotensin II blockers and peri-operative complications as risk factors for AKI. In addition, the problem of renal function decline after EVAR is highlighted, which indicates that prolonged protective measures (e.g., in those patients at high risk) over time are needed to improve patient outcomes.
http://ift.tt/2iJZgSz
A custom-made mouthpiece incorporating tongue depressors and elevators to reduce radiation-induced tongue mucositis during carbon-ion radiotherapy for head and neck cancer
Source:Practical Radiation Oncology
Author(s): Hiroaki Ikawa, Masashi Koto, Daniel K Ebner, Ryo Takagi, Kazuhiko Hayashi, Hiroshi Tsuji, Tadashi Kamada
Here, we introduce a custom-made mouthpiece for carbon-ion radiotherapy for head and neck malignancy. The mouthpiece incorporates either a tongue depressor or elevator depending on tumor location. The risk of tongue mucositis may be reduced without compromising therapeutic efficacy through mouthpiece shaping.
http://ift.tt/2yb7N8d
Inflammation is regulated by the adenosine derivative molecule, IFC-305, during reversion of cirrhosis in a CCl4 rat model
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Rebeca Pérez-Cabeza de Vaca, Mariana Domínguez-López, Nuria Guerrero-Celis, Jesús R. Rodríguez-Aguilera, Victoria Chagoya de Sánchez
Cirrhosis is a liver pathology originated by hepatocytes, Kupffer and hepatic stellate cells interactions and transformations. This pathology is associated with inflammation and fibrosis, originated by molecular signals secreted by immunological and parenchymal cells, such as cytokines and chemokines, like IL-1β, IL-6, TNF-α or MCP-1, driven by Kupffer cells signals. As part of inflammation resolution, the same activated Kupffer cells contribute to anti-inflammatory effects with IL-10 and MMP-9 secretion. In a Wistar rat model, cirrhosis induced with CCl4 is characterized by increased inflammatory cytokines, IL-6, IL-1β, MCP-1, and TNF-α, in plasma and liver tissue. The IFC-305 compound, an adenosine derivative salt, reverses the cirrhosis in this model, suggesting that immune mechanisms related to inflammation should be explored. The IFC-305 reduced inflammatory cytokines, supporting the anti-inflammatory effects induced by the elevation of IL-10, as well as the reduction of M1 inflammatory macrophages (CD11b/c+/CD163+) and the increase of M2 anti-inflammatory macrophages (HIS36+/CD11b+), measured by flow cytometry. Furthermore, the IFC-305 enhances the metabolic activity of arginase and moderates the inducible nitric oxide synthetase, evaluated through biochemical and immunohistochemical methods. These results contribute to understand the function of the IFC-305, which modulates the immune response in the Wistar rat model of CCl4-induced cirrhosis and support the hepatic protective action through an anti-inflammatory effect, mainly mediated by Kupffer cells.
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Disability in activities of daily living among adults with cancer: a systematic review and meta-analysis
Source:Cancer Treatment Reviews
Author(s): Josephine Neo, Lucy Fettes, Wei Gao, Irene J Higginson, Matthew Maddocks
IntroductionPeople with cancer frequently report limitation in Activities of Daily Living (ADLs); essential activities required to live independently within society. Although several studies have assessed ADL related disability, variability in assessment, setting, and population means evidence is difficult to interpret. We aimed to determine the prevalence of ADL related disability, overall and by setting, and the most commonly affected ADLs in people living with cancer.MethodsWe searched twelve databases to June 2016 for observational studies assessing ADL disability in adults with cancer. Data on study design, population, ADL instruments and disability (difficulty with or requiring assistance in ≥1 activity) were extracted, summarised, and pooled to estimate disability prevalence (with 95% confidence intervals, 95% CI) overall and by setting.ResultsForty-three studies comprising 19,246 patients were included. Overall, 36.7% (95% CI 29.8 to 44.3, 18 studies) and 54.6% (95% CI 46.5 to 62.3, 15 studies) of patients respectively reported disability relating to basic instrumental ADLs. Disability was marginally more prevalent in inpatient compared to outpatient settings. The Katz Index (18 studies) and Lawton IADL Scale (11 studies) were the most commonly used instruments. Across the activities studied, the most frequently affected basic ADLs were personal hygiene, walking and transfers, and instrumental ADLs were housework, shopping and transportation.ConclusionsAbout one-third and half of adults with cancer respectively have difficulty or require assistance to perform basic and instrumental ADLs. Our findings highlight the need for rehabilitation focused on functional independence. This underscores the importance of professionals skilled in occupational assessment and therapy in cancer services.
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The clinical development of vaccines for HER2+ breast cancer: current landscape and future perspectives
Source:Cancer Treatment Reviews
Author(s): R.L.B. Costa, H. Soliman, B.J. Czierneicki
Human epidermal growth factor receptor 2 (HER2) is a tumor associated antigen over-expressed in 20-30% of cases of breast cancer. Passive immune therapy with HER2-directed monoclonal antibodies (mabs) has changed the natural history of this subset of breast tumors both in the localized and metastatic settings. The safety and efficacy of HER2 vaccines have been assessed in early phase clinical trials but to date clinically relevant results in late phase trials remain an elusive target. Here, we review the recent translational discoveries related to the interactions between the adaptive immune system and the HER2 antigen in breast cancer, results of published clinical trials, and future directions in the field of HER2 vaccine treatment development.
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Editorial Board
Publication date: November 2017
Source:Clinical Immunology, Volume 184
http://ift.tt/2gK04CU
Reprint of “Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis”
Source:Clinical Immunology
Author(s): Satish Kumar Devarapu, Santhosh Kumar VR, Khader Valli Rupanagudi, Onkar P. Kulkarni, Dirk Eulberg, Sven Klussmann, Hans-Joachim Anders
Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC). We estimated serum levels of CCL2 and CXCL12 in patients with SLE (n=99) and compared the results with healthy individuals (n=21). In order to prove our hypothesis we used l-enantiomeric RNA Spiegelmer® chemokine antagonists, i.e. the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 to treat female MRL/lpr mice from week 12 to 20 of age with either anti-CXCL12 or anti-CCL2 alone or both. SLE patients showed elevated serum levels of CCL2 but not of CXCL12. Female MRL/lpr mice treated with dual blockade showed significantly more effective than either monotherapy in preventing proteinuria, immune complex glomerulonephritis, and renal excretory failure and the results are at par with CYC treatment. Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation.
http://ift.tt/2icvIZW
The influence of continental air masses on the aerosols and nutrients deposition over the western North Pacific
Source:Atmospheric Environment, Volume 172
Author(s): Jiangping Fu, Bo Wang, Ying Chen, Qingwei Ma
The air masses transported from East Asia have a strong impact on the aerosol properties and deposition in the marine boundary layer of the western North Pacific (WNP) during winter and spring. We joined a cruise between 17 Mar. and 22 Apr. 2014 and investigated the changes of aerosol composition and size distribution over the remote WNP and marginal seas. Although the secondary aerosol species (SO42−, NO3− and NH4+) in remote WNP were influenced significantly by the continental transport, NH4+ concentrations were lower than 2.7 μg m−3 in most sampling days and not correlated with non-sea-salt (nss)-SO42- suggesting that the ocean could be a primary source of NH4+. Moderate Cl− depletion (23%) was observed in remote WNP, and the inverse relationship between Cl− depletion percentages and nss-K+ in aerosols suggested that the transport of biomass burning smoke from East Asia might be a vital extra source of Cl−. Both Asian dust and haze events were encountered during the cruise. Asian dust carried large amounts of crustal elements such as Al and Ti to the WNP, and the dusty Fe deposition may double its background concentration in seawater. Differently, a dramatic increase of dry deposition flux of dissolved particulate inorganic nitrogen was observed during the haze event. Our study reveals that the transport of different continental air masses may have distinct biogeochemical impacts on the WNP by increasing the fluxes of different nutrient elements and potentially changing the nutrient stoichiometry.
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Experience of using MOSFET detectors for dose verification measurements in an end-to-end 192Ir brachytherapy quality assurance system
Source:Brachytherapy
Author(s): Maria Persson, Josef Nilsson, Åsa Carlsson Tedgren
PurposeEstablishment of an end-to-end system for the brachytherapy (BT) dosimetric chain could be valuable in clinical quality assurance. Here, the development of such a system using MOSFET (metal oxide semiconductor field effect transistor) detectors and experience gained during 2 years of use are reported with focus on the performance of the MOSFET detectors.Methods and MaterialsA bolus phantom was constructed with two implants, mimicking prostate and head & neck treatments, using steel needles and plastic catheters to guide the 192Ir source and house the MOSFET detectors. The phantom was taken through the BT treatment chain from image acquisition to dose evaluation. During the 2-year evaluation-period, delivered doses were verified a total of 56 times using MOSFET detectors which had been calibrated in an external 60Co beam. An initial experimental investigation on beam quality differences between 192Ir and 60Co is reported.ResultsThe standard deviation in repeated MOSFET measurements was below 3% in the six measurement points with dose levels above 2 Gy. MOSFET measurements overestimated treatment planning system doses by 2–7%. Distance-dependent experimental beam quality correction factors derived in a phantom of similar size as that used for end-to-end tests applied on a time-resolved measurement improved the agreement.ConclusionsMOSFET detectors provide values stable over time and function well for use as detectors for end-to-end quality assurance purposes in 192Ir BT. Beam quality correction factors should address not only distance from source but also phantom dimensions.
http://ift.tt/2yYLTEq
Early outcomes and impact of a hybrid IC/IS applicator for a new MRI-based cervical brachytherapy program
Source:Brachytherapy
Author(s): Matthew M. Harkenrider, Murat Surucu, Grant Harmon, Michael L. Mysz, Steven M. Shea, Joseph Yacoub, Ari Goldberg, Margaret Liotta, Abigail Winder, Ronald Potkul, John C. Roeske, William Small
PurposeThe purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program.MethodsWe accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan–Meier method.ResultsMedian followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis–free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09).ConclusionsThere was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.
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Evaluation of Weekly Paclitaxel plus Carboplatin Followed by Anthracycline Chemotherapy on the Neoadjuvant Treatment of Patients with Triple-Negative Breast Cancer
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Aurelio B. Castrellon
ObjectiveTo evaluate the effectiveness and tolerability of neoadjuvant chemotherapy with weekly paclitaxel in combination with weekly carboplatin area under curve 2 followed by anthracycline chemotherapy.Patients and methodsThis is a retrospective review of electronic medical records of patients (N = 32) with stage 1c–III triple-negative breast cancer. Patients received neoadjuvant chemotherapy with paclitaxel 80 mg/m2 once per week for 12 weeks in combination with carboplatin area under curve 2 once per week for 12 weeks (wP + wCb), followed by a standard anthracycline regimen including either doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 or 3 weeks, or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for four cycles with myeloid growth factor support.ResultsMost patients (91%) received all 12 cycles of wP + wCb, and 88% received all four planned cycles of anthracycline chemotherapy. Of the patients, 84% completed all planned therapies. The complete pathologic response rate was 60%. In terms of hematologic toxicity, 96% of the patients experienced grade ≥ 3 leucopenia, 40% grade ≥ 3 anemia, and 15% grade ≥ 3 thrombocytopenia, and neutropenic fever was seen in 22% of the patients.ConclusionThe combination of neoadjuvant chemotherapy with wP + wCb before anthracycline chemotherapy can be tolerated by patients with triple-negative breast cancer. Complete pathologic response rates were comparable with those historically seen. Careful selection of patients is fundamental as this regimen is associated with a high incidence of hematologic toxicity.
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Editorial Board
Publication date: November 2017
Source:Journal of Autoimmunity, Volume 84
http://ift.tt/2gQJUvl
Wandering pathways in the regulation of innate immunity and inflammation
Source:Journal of Autoimmunity
Author(s): Alberto Mantovani
Tumor-associated macrophages (TAM) have served as a paradigm of cancer-related inflammation. Moreover, investigations on TAM have led to the dissection of macrophage plasticity and polarization and to the discovery and analysis of molecular pathways of innate immunity, in particular cytokines, chemokines and PTX3 as a prototypic fluid phase pattern recognition molecule. Mechanisms of negative regulation are complex and include decoy receptors, receptor antagonists, anti-inflammatory cytokines and the signalling regulator IL-1R8. In this review, topics and open issues in relation to regulation of innate immunity and inflammation are discussed: 1) how macrophage and neutrophil plasticity and polarization underlie diverse pathological conditions ranging from autoimmunity to cancer and may pave the way to innovative diagnostic and therapeutic approaches; 2) the key role of decoy receptors and negative regulators (e.g. IL-1R2, ACKR2, IL-1R8) in striking a balance between amplification of immunity and resolution versus uncontrolled inflammation and tissue damage; 3) role of humoral innate immunity, illustrated by PTX3, in resistance against selected microbes, regulation of inflammation and immunity and tissue repair, with implications for diagnostic and therapeutic translation.
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Defective regulation of L1 endogenous retroelements in primary Sjogren's syndrome and systemic lupus erythematosus: Role of methylating enzymes
Source:Journal of Autoimmunity
Author(s): Clio P. Mavragani, Adrianos Nezos, Irina Sagalovskiy, Surya Seshan, Kyriakos A. Kirou, Mary K. Crow
ObjectiveTo investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE).MethodsMinor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively. Relative mRNA expression was quantified for full-length L1 transcripts, along with mediators of methylation. In an independent set of 44 MSG samples (11 SS-low risk, 10 SS-high risk, 15 SS-lymphoma and 8 SC), methylation levels of the L1 promoter were determined by bisulphite pyrosequencing.ResultsA strong positive correlation was demonstrated between L1 transcripts and gene products that mediate de novo and constitutive DNA methylation, DNA methyltransferase (DNMT)3B, DNMT1, and methyl CpG binding protein 2 (MeCP2), in both SS MSG and lupus renal tissues. A significant negative correlation was observed between expression of L1 and lymphoid-specific helicase (LSH, encoded by HELLS) in both SS MSG and SLE kidney tissues, as well as between DNMT3A transcripts and L1 expression in SLE kidney tissues and PBMCs. Reduced levels of L1 promoter methylation along with increased DNMT3B, DNMT1, and MeCP2, but reduced LSH levels were detected in SS-low risk patients compared to both SS-lymphoma and SC. The SS-lymphoma group was also characterized by a profound decrease of MeCP2 and DNMT3B compared to SC.ConclusionOur data support a contributory role of altered methylation mechanisms in the pathogenesis of systemic autoimmune disorders and related lymphoproliferative processes and suggest that LSH and DNMT3A should be investigated as candidate upstream mediators of decreased L1 promoter methylation and increased L1 expression.
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Interferon-beta specific T cells are associated with the development of neutralizing antibodies in interferon-beta treated multiple sclerosis patients
Source:Journal of Autoimmunity
Author(s): Sudhakar Reddy Kalluri, Verena Grummel, Zsuzsanna Hracsko, Viola Pongratz, Verena Pernpeintner, Christiane Gasperi, Dorothea Buck, Bernhard Hemmer
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β. T cell responses were determined by split-well and primary proliferation assays against different IFN-β protein preparations and a set of overlapping peptides covering the full sequence of IFN-β. T cell responses to IFN-β were observed in all donors. ADA positive patients showed higher T cell responses to IFN-β protein than ADA negative patients and untreated controls. We identified two immunodominant regions; T cell responses to IFN-β1-40 were observed in all patients independent of ADA status, while T cell responses to IFN-β125-159 were stronger in ADA positive than ADA negative patients. IFN-β specific T cell responses were HLA class II restricted and in ADA positive patients skewed towards a Th2 phenotype. In IFN-β treated patients we observed a correlation between IFN-β specific T cell responses, serum ADA titer and loss of biological activity of IFN-β treatment. Our studies demonstrate the occurrence of an antigen specific HLA class II restricted Th2 T cell response associated with the development of ADA in IFN-β treated patients.
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Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint
Publication date: Available online 21 October 2017
Source:Journal of Autoimmunity
Author(s): Louisa E. Jeffery, Peter Henley, Nefisa Marium, Andrew Filer, David M. Sansom, Martin Hewison, Karim Raza
1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects, including suppression of IL-17 + and IFNγ+ T cells implicated in rheumatoid arthritis (RA), but efficacy at the site of active disease is unclear. To investigate this, T cells from synovial fluid (SF) and paired blood of patients with active RA were studied. 1,25(OH)2D3 had significantly less suppressive effect on Th17 cells (IL-17+IFNγ-) and Th17.1 cells (IL-17+IFNγ+) from SF compared to those from blood, and had no effect on SF CD4+ or CD8+ IFNγ+ T cell frequencies. Memory T cells (CD45RO+) predominate in SF, and 1,25(OH)2D3 had less effect on memory T cells relative to naïve (CD45RA+) T cells. RT-PCR and flow cytometry showed that this was not due to decreased expression of the vitamin D receptor or its transcription partners in memory T cells. Further studies using stimulated CD4+ T cells sorted according to IL-17 and IFNγ expression confirmed the ability of 1,25(OH)2D3 to suppress pre-existing cytokines. However, 1,25(OH)2D3 was most effective at suppressing de novo IL-17 and IFNγ induction. Correspondingly, T cell responses to 1,25(OH)2D3 correlated directly with capacity for phenotype change, which was lower in cells from SF compared to blood. These findings indicate that anti-inflammatory effects of 1,25(OH)2D3 in active RA are impaired because of reduced effects on phenotype-committed, inflammatory memory T cells that are enriched in SF. Restoration of 1,25(OH)2D3 responses in memory T cells may provide a new strategy for treatment of inflammatory diseases such as RA.
Graphical abstract
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CD4+CD28+KIR+CD11ahi T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients
Source:Journal of Autoimmunity
Author(s): Elizabeth Gensterblum, Paul Renauer, Patrick Coit, Faith M. Strickland, Nathan C. Kilian, Shaylynn Miller, Mikhail Ognenovski, Jonathan D. Wren, Pei-Suen Tsou, Emily E. Lewis, Kathleen Maksimowicz-McKinnon, W. Joseph McCune, Bruce C. Richardson, Amr H. Sawalha
ObjectiveThe goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus.MethodsThe size of the CD4+CD28+KIR+CD11ahi T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11ahi T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine. Genome-wide DNA methylation was analyzed using an array-based approach, and the transcriptome was assessed by RNA sequencing. Transcripts in the CDR3 region were used to assess the TCR repertoire. Chromatin accessibility was determined using ATAC-seq.ResultsA total of 31,019 differentially methylated sites were identified in induced KIR+CD11ahi T cells with >99% being hypomethylated. RNA sequencing revealed a clear pro-inflammatory transcriptional profile. TCR repertoire analysis suggests less clonotype diversity in KIR+CD11ahi compared to autologous KIR-CD11alow T cells. Similarly, primary KIR+CD11ahi T cells isolated from lupus patients were hypomethylated and characterized by a pro-inflammatory chromatin structure. We show that the genetic risk for lupus was significantly higher in African-American compared to European-American lupus patients. The demethylated CD4+CD28+KIR+CD11ahi T cell subset size was a better predictor of disease activity in young (age ≤ 40) European-American patients independent of genetic risk.ConclusionCD4+CD28+KIR+CD11ahi T cells are demethylated and characterized by pro-inflammatory epigenetic and transcriptional profiles in lupus. Eliminating these cells or blocking their pro-inflammatory characteristics might present a novel therapeutic approach for lupus.
http://ift.tt/2gQ22Fv
NEPHRUTIX: A randomized, double-blind, placebo vs Rituximab-controlled trial assessing T-cell subset changes in Minimal Change Nephrotic Syndrome
Publication date: Available online 19 October 2017
Source:Journal of Autoimmunity
Author(s): Ahmed Boumediene, Pauline Vachin, Kelhia Sendeyo, Julie Oniszczuk, Shao-yu Zhang, Carole Henique-Greciet, Andre Pawlak, Vincent Audard, Mario Ollero, Vincent Guigonis, Djillali Sahali
Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular disease. We have analyzed the modifications on T-cell subsets in twenty-three patients who were highly steroid/calcineurin inhibitor and/or mycophenolate mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab-controlled trial. Patients with FRNS entered the trial at remission and were randomly assigned to receive either Rituximab or placebo. In both groups, patient blood samples were analyzed at inclusion and then monthly until six months post-perfusion. Disclosure of patient's allocation code occurred in relapse or at the end of the trial. All patients under placebo displaying relapse were subsequently treated with Rituximab.Despite the significant decrease of immunosuppressive drugs, remission was maintained in all patients included in the Rituximab group, except one (n = 9/10). On the other hand, relapses occurred within a few weeks (means ≈ 7.3 weeks) in all patients receiving placebo (n = 13).At inclusion, before rituximab therapy, the frequency of different T-cell subsets were highly similar in both groups, except for CD8+ and invariant TCRVα24 T-cell subsets, which were significantly increased in patients of the Placebo group ((p = 0,0414 and p = 0.0428, respectively). Despite the significant decrease of immunosuppressive drugs, remission was maintained in all patients included in the Rituximab group (n = 10), except one. Relapses were associated with a significant decrease in CD4+CD25highFoxP3high Tregulatory cells (p = 0.0005) and IL2 expression (p = 0.0032), while CMIP abundance was significantly increased (p = 0.03). Remissions after Rituximab therapy were associated in both groups with significant decrease in the frequency of CD4+CD45RO+CXCR5+, invariant natural killer T-cells (INKT) and CD4−CD8− (double-negative, DN) T-cells expressing the invariant Vα24 chain (DN-TCR Vα24) T-cells, suggesting that MCNS involves a disorder of innate and adaptive immune response, which can be stabilized by Rituximab treatment.
http://ift.tt/2yS3Wwp
An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8+ T cells involved in multiple sclerosis
Publication date: Available online 18 October 2017
Source:Journal of Autoimmunity
Author(s): Bryan Nicol, Marion Salou, Isabel Vogel, Alexandra Garcia, Emilie Dugast, Jeremy Morille, Stéphanie Kilens, Eric Charpentier, Audrey Donnart, Steven Nedellec, Marylène Jacq-Foucher, Fabienne Le Frère, Sandrine Wiertlewski, Arnaud Bourreille, Sophie Brouard, Laure Michel, Laurent David, Pierre-Antoine Gourraud, Nicolas Degauque, Arnaud B. Nicot, Laureline Berthelot, David-Axel Laplaud
Several lines of evidence support a key role for CD8+ T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8+ T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date. The frequency, phenotype, and function of CD8+ T cells with an intermediate CD161 expression level were characterized ex-vivo, in vitro, and in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing, and immunohistofluorescence of cells derived from healthy volunteers (n = 61), MS subjects (n = 90), as well as inflammatory (n = 15) and non-inflammatory controls (n = 6). We report here that CD8+CD161int T cells present characteristics of effector cells, up-regulate cell-adhesion molecules and have an increased ability to cross the blood-brain barrier and to secrete IL-17, IFNγ, GM-CSF, and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the peripheral blood, RNAseq, RT-PCR, high-throughput TCR repertoire analyses, and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients, with the presence of supernumerary clones compared to healthy controls. Our data demonstrate that intermediate levels of CD161 expression identifies activated and effector CD8+ T cells with pathogenic properties that are recruited to MS lesions. This suggests that CD161 may represent a biomarker and a valid target for the treatment of neuroinflammation.
http://ift.tt/2gQSDgZ
How available to European children and young people with cerebral palsy are features of their environment that they need?
Source:Research in Developmental Disabilities, Volume 71
Author(s): Sandra Martina Espín-Tello, Allan Colver
BackgroundThe UN Convention on the Rights of Persons with Disabilities requires accessibility to the physical and social environments. However, individuals with cerebral palsy (CP) have many difficulties in accessing the environment they need for functional independence and social inclusion.AimsTo examine the availability of environmental features which children with CP need for optimal participation, and whether availability changed for them between ages 8–12 and 13–17 years.MethodsThe sample is the 594 children with CP, born 31/07/1991–01/04/1997, who took part in the SPARCLE study at age 8–12 (SPARCLE 1) and again at 13–17 years (SPARCLE 2). Participants were randomly sampled from population registers of children with CP in eight European regions; one further region recruited from multiple sources. Data about environment were captured with the European Child Environment Questionnaire (60 items). Differences in availability of environmental features between childhood and adolescence were assessed using McNemar's test; differences between regions were assessed by ranking regions. Differences in availability between regions were assessed by ranking regions.ResultsFor seven environmental features significantly (p<0.01) fewer individuals needed the feature in SPARCLE 2 than in SPARCLE 1, whilst for two features more individuals needed the feature. Nine features in SPARCLE 1 and six features in SPARCLE 2 were available to less than half the participants who needed them. Eight features showed significantly (p<0.01) higher availability in SPARCLE 2 than in SPARCLE 1 (enlarged rooms, adapted toilet, modified kitchen and hoists at home, adapted toilets and lifts at school, an adequate vehicle, grants for home modifications) while none showed significantly lower availability. The relative rankings of the better and less good regions persisted from the age 8–12year age group to the 13–17year age group.ConclusionsNeeded environmental features are unavailable to many children at ages 8–12 and 13–17 years. This lack of availability is more pronounced in some regions than others, which probably results from their policy, legislative and statutory frameworks.
http://ift.tt/2ibLwfA
The bouba-kiki effect and its relation to the Autism Quotient (AQ) in autistic adolescents
Source:Research in Developmental Disabilities, Volume 71
Author(s): Rinat Gold, Osnat Segal
The bouba-kiki effect refers to the correspondence between arbitrary visual and auditory stimuli. Previous studies indicate ASD persons' reduced bouba-kiki effect compared to controls.This study examines the relation between ASD symptomology and performance on the bouba-kiki task. Twenty ASD participants and 20 matched controls were presented the bouba-kiki task. Autism-Quotient (AQ) scores and several cognitive measures were obtained for all participants. Results demonstrate that among all measures, only AQ scores were significantly correlated to the performance on the bouba-kiki task in the ASD group.Results thus support the existence of a relation between autism symptoms and performance on the bouba-kiki task, and are discussed in light of current theories.
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The effect of asymmetrical limited hip flexion on seating posture, scoliosis and windswept hip distortion
Source:Research in Developmental Disabilities, Volume 71
Author(s): Atli Ágústsson, Þórarinn Sveinsson, Elisabet Rodby-Bousquet
BackgroundPostural asymmetries with seating problems are common in adults with cerebral palsy.AimsTo analyse the prevalence of asymmetrical limited hip flexion (<90°) in adults with CP, and to evaluate the association between asymmetrical limited hip flexion and postural asymmetries in the sitting position.Methods and proceduresCross-sectional data of 714 adults with CP, 16–73 years, GMFCS level I–V, reported to CPUP, the Swedish cerebral palsy national surveillance program and quality registry, from 2013 to 2015. Hip range of motion was analysed in relation to pelvic obliquity, trunk asymmetry, weight distribution, scoliosis and windswept hip distortion.Outcomes and resultsThe prevalence of asymmetrical limited hip flexion increased as GMFCS level decreased. Of adults at GMFCS level V, 22% had asymmetrical limited hip flexion (<90°). The odds of having an oblique pelvis (OR 2.6, 95% CI:1.6–2.1), an asymmetrical trunk (OR 2.1, 95% CI:1.1–4.2), scoliosis (OR 3.7, 95% CI:1.3–9.7), and windswept hip distortion (OR 2.6, 95% CI:1.2–5.4) were higher for adults with asymmetrical limited hip flexion compared with those with bilateral hip flexion>90°.Conclusions and implicationsAsymmetrical limited hip flexion affects the seating posture and is associated with scoliosis and windswept hip distortion.
http://ift.tt/2ibuhv0
Effectiveness of cognitive orientation to (daily) occupational performance (CO-OP) on children with cerebral palsy: A mixed design
Source:Research in Developmental Disabilities, Volume 71
Author(s): Neda Ghorbani, Mehdi Rassafiani, Sara Izadi-Najafabadi, Farzaneh Yazdani, Nazila Akbarfahimi, Naser Havaei, Soraya Gharebaghy
BackgroundCerebral palsy (CP) is the most common cause of physical disabilities during childhood. Therapeutic interventions mainly focus on impairment reduction to address motor-based difficulties. In contrast, Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive approach, providing intervention at the level of activity and participation.AimsThis study aims to determine whether the CO-OP approach improves motor skills and achievement in motor-based occupational performance goals in children with CP.Methods and proceduresIn this mixed design research (i.e., a multiple baseline single case experimental design and a one-group pretest-posttest design), five children with CP participated in 12 CO-OP intervention sessions. Repeated measures of motor skills for the multiple baseline single case experimental design were taken using the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP); pre- and post-measures of parent/child perception of performance and satisfaction were identified using the Canadian Occupational Performance Measure (COPM); level of achievement was identified using Goal Attainment Scaling (GAS).Outcomes and resultsAccording to the BOTMP results, all children were able to engage in the CO-OP intervention to improve motor performance. Significant differences after treatment were found in both performance and performance satisfaction ratings using the COPM as rated by parents and children. The GAS results showed progress in achievement levels for all children; all goals were achieved or exceeded.Conclusions and implicationsCO-OP intervention can be helpful in improving motor skills and achieving self-identified, motor-based goals in children with CP.
http://ift.tt/2gLf9E2
An evaluation of the production effects of video self-modeling
Source:Research in Developmental Disabilities, Volume 71
Author(s): Roderick D. O'Handley, Keith D. Allen
A multiple baseline across tasks design was used to evaluate the production effects of video self-modeling on three activities of daily living tasks of an adult male with Autism Spectrum Disorder and Intellectual Disability. Results indicated large increases in task accuracy after the production of a self-modeling video for each task, but before the video was viewed by the participant. Results also indicated small increases when the participant was directed to view the same video self-models before being prompted to complete each task.
http://ift.tt/2iaYQRt
IFC-EDITORIAL BOARD
Source:Research in Developmental Disabilities, Volume 71
http://ift.tt/2gRlu4S
Best seating condition in children with spastic cerebral palsy: One type does not fit all
Source:Research in Developmental Disabilities, Volume 71
Author(s): Mattana Angsupaisal, Linze-Jaap Dijkstra, Sacha la Bastide-van Gemert, Jessika F. van Hoorn, Karine Burger, Carel G.B. Maathuis, Mijna Hadders-Algra
BackgroundThe effect of forward-tilting of the seat surface and foot-support in children with spastic cerebral palsy (CP) is debated.AimTo assess the effect of forward-tilting of the seat surface and foot-support in children with CP on kinematic head stability and reaching.MethodsNineteen children functioning at Gross Motor Function Classification System levels I–III participated [range 6–12y; ten unilateral spastic CP (US-CP) and nine bilateral spastic CP (BS-CP)]. Kinematic data were recorded of head sway and reaching with the dominant arm in four sitting conditions: a horizontal and a 15° forward (FW) tilted seat surface, each with and without foot-support.ResultsSeating condition did not affect head stability during reaching, but did affect kinematic reaching quality. The major reaching parameters, i.e., the proportion of reaches with one movement unit (MU) and the size of the transport MU, were not affected by foot-support. Forward-tilting had a positive effect on these parameters in children with US-CP, whereas the horizontal condition had this effect in children with BS-CP.ImplicationsA 15° forward-tilted seating and foot-support do not affect head stability. Reaching in children with US-CP profits from forward-tilting; in children with BS-CP forward-tilting worsens reaching − effects that are independent of foot-support.
http://ift.tt/2yU3zkE
Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base
Publication date: November–December 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): Whitney A. Sumner, Arya Amini, Todd C. Hankinson, Nicholas K. Foreman, Laurie E. Gaspar, Brian D. Kavanagh, Sana D. Karam, Chad G. Rusthoven, Arthur K. Liu
Aim/BackgroundPapillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation.Materials and methodsThe NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan–Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed.ResultsIn total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27–0.85; p=0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22–0.76; p=0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n=13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01–0.80; p=0.032) and for patients >18 years (n=184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31–1.00; p=0.049), respectively.ConclusionsIn this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.
http://ift.tt/2xuOmCF
Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy
Publication date: Available online 28 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Luisa Calvanese, Annalia Focà, Annamaria Sandomenico, Giuseppina Focà, Andrea Caporale, Nunzianna Doti, Emanuela Iaccarino, Antonio Leonardi, Gabriella D'Auria, Menotti Ruvo, Lucia Falcigno
Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1).By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface.Data indicate with high accuracy the antibody-antigen contact atoms and confirm the information previously obtained by immune-enzymatic methods. Main residues contacted by 3D1 are P46, V47, E49 and E50, which belong to the Nodal loop involved in the interaction with the co-receptor.
Graphical abstract
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Bioactive natural products
Publication date: 15 November 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 22
Author(s): Mathias Christmann
http://ift.tt/2iJtgOr
Natural products and morphogenic activity of γ-Proteobacteria associated with the marine hydroid polyp Hydractinia echinata
Publication date: 15 November 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 22
Author(s): Huijuan Guo, Maja Rischer, Martin Sperfeld, Christiane Weigel, Klaus Dieter Menzel, Jon Clardy, Christine Beemelmanns
Illumina 16S rRNA gene sequencing was used to profile the associated bacterial community of the marine hydroid Hydractinia echinata, a long-standing model system in developmental biology. 56 associated bacteria were isolated and evaluated for their antimicrobial activity. Three strains were selected for further in-depth chemical analysis leading to the identification of 17 natural products. Several γ-Proteobacteria were found to induce settlement of the motile larvae, but only six isolates induced the metamorphosis to the primary polyp stage within 24h. Our study paves the way to better understand how bacterial partners contribute to protection, homeostasis and propagation of the hydroid polyp.
Graphical abstract
http://ift.tt/2zdKeeS
Editorial board
Publication date: 15 November 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 22
http://ift.tt/2zdKcUi
Anti-tuberculosis activity and structure–activity relationships of oxygenated tricyclic carbazole alkaloids and synthetic derivatives
Publication date: 15 November 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 22
Author(s): Carsten Börger, Christian Brütting, Konstanze K. Julich-Gruner, Ronny Hesse, V. Pavan Kumar, Sebastian K. Kutz, Marika Rönnefahrt, Claudia Thomas, Baojie Wan, Scott G. Franzblau, Hans-Joachim Knölker
A series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of Mycobacterium tuberculosis and a mammalian cell line (vero cells). From this series, twelve carbazoles showed a significant anti-TB activity. The four most active compounds were the naturally occurring carbazole alkaloids clauszoline-M (45), murrayaline-C (41), carbalexin-C (27), and the synthetic carbazole derivative 22 with MIC90 values ranging from 1.5 to 3.7μM. The active compounds were virtually nontoxic for the mammalian cell line in the concentration range up to 50μM.
Graphical abstract
http://ift.tt/2iHNkB1
Heterocycles: versatile control elements in bioactive macrocycles
Publication date: Available online 27 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Harjeet S. Soor, Solomon D. Appavoo, Andrei K. Yudin
The potential of macrocyclic peptides as therapeutics has garnered much attention over the last several years. Unlike their linear counterparts, macrocycles have higher resistance to enzymatic degradation and often display improved bioavailability. However, macrocycles are typically not lipophilic enough for cellular membrane penetration, which prevents them from interacting with intracellular targets. Methods to increase cellular permeability have involved the incorporation of bicyclic scaffolds, D-amino acids and N-methylation of amides. These modifications exert their effect through conformational control of macrocycles and have been well studied in the literature. In contrast, the structural consequences of heterocycle incorporation into macrocyclic rings has not been as exhaustively investigated. In this mini-review we discuss key examples in which heterocycles influence the conformational stability and other properties of macrocycles.
Graphical abstract
http://ift.tt/2iJtd5d
Tumour Lateralization in Cushing's disease by Inferior Petrosal Sinus Sampling with desmopressin
Abstract
Background
Bilateral inferior petrosal sinus sampling (IPSS) with corticotropin-releasing hormone (CRH) is currently the gold standard in the diagnosis of Cushing's disease (CD) and has also been used in tumour lateralization. Our objective was to determine the diagnostic value and lateralization accuracy of IPSS with desmopressin.
Methods
We retrospectively analyzed 91 patients with Cushing's syndrome who had either negative findings on pituitary dynamic enhanced magnetic resonance imaging (MRI) or non-suppressed high dose dexamethasone suppression tests (HDDST). Thin-slice thoracoabdominal computed tomography (CT) and octreotide receptor imaging of whole body were also negative to rule out ectopic adrenocorticotropin hormone (ACTH) syndrome. All patients went through IPSS with desmopressin. Afterwards, transsphenoidal pituitary surgery, light microscope pathology and immunohistological staining for ACTH were performed in all patients.
Results
1. Diagnosis of CD. Among the 91 patients included, 90 were confirmed with CD, of whom 89 had positive IPSS findings, therefore the sensitivity was 98.9%. The one patient who was negative for CD also had negative IPSS findings, therefore the specificity was 100%. 2. Tumour lateralization. Among the 51 patients who were ultimately diagnosed with CD and whose lateralization by IPSS and surgery was either left or right, 37 had IPSS lateralization in concordance with surgery, therefore the concordance rate was 72.5%. Patients in the concordant group had a higher frequency of right lateralization by surgery.
Conclusions
IPSS with desmopressin is a sensitive approach in the diagnosis of CD and has moderate accuracy in tumour lateralization, making it an alternative choice to IPSS with CRH.
This article is protected by copyright. All rights reserved.
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Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6)
Abstract
Purpose
To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy.
Methods
Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity.
Results
A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1–6.0 months) and 17.4 months (95% CI 9.9–21.9 months), respectively, while the 1-year survival rate was 58.6%.
Conclusions
Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.
http://ift.tt/2yUrDSd
Apoptosis during arenavirus infection: mechanisms and evasion strategies
Source:Microbes and Infection
Author(s): Bjoern Meyer, Allison Groseth
In recent years there has been a greatly increased interest in the interactions of arenaviruses with the apoptotic machinery, and particularly the extent to which these interactions may be an important contributor to pathogenesis. Here we summarize the current state of our knowledge on this subject and address the potential for interplay with other immunological mechanisms known to be regulated by these viruses. We also compare and contrast what is known for arenavirus-induced apoptosis with observations from other segmented hemorrhagic fever viruses.
http://ift.tt/2gUOSHb
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