Πέμπτη 7 Σεπτεμβρίου 2017
Large-Scale Quantitative Proteomics Identifies the Ubiquitin Ligase Nedd4-1 as an Essential Regulator of Liver Regeneration
Publication date: Available online 7 September 2017
Source:Developmental Cell
Author(s): Marc Bachofner, Tobias Speicher, Roman L. Bogorad, Sukalp Muzumdar, Carina P. Derrer, Fabrizio Hürlimann, Friederike Böhm, Paolo Nanni, Tobias Kockmann, Ekaterina Kachaylo, Michael Meyer, Susagna Padrissa-Altés, Rolf Graf, Daniel G. Anderson, Victor Koteliansky, Ulrich auf dem Keller, Sabine Werner
The liver is the only organ in mammals that fully regenerates even after major injury. To identify orchestrators of this regenerative response, we performed quantitative large-scale proteomics analysis of cytoplasmic and nuclear fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly upregulated after two-third hepatectomy, with the ubiquitin ligase Nedd4-1 being a top hit. In vivo knockdown of Nedd4-1 in hepatocytes through nanoparticle-mediated delivery of small interfering RNA caused severe liver damage and inhibition of cell proliferation after hepatectomy, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient internalization of major growth factor receptors involved in liver regeneration and their downstream mitogenic signaling. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process. Finally, they identify an essential function of Nedd4-1 in tissue repair.
Teaser
Using large-scale quantitative proteomics, Bachofner, Speicher et al. identified the ubiquitin ligase Nedd4-1 as an essential regulator of liver regeneration. Nedd4-1 deficiency attenuated growth factor receptor internalization and signaling, demonstrating a crucial role of posttranslational modification of growth factor signaling in liver regeneration.http://ift.tt/2wNldFJ
Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts
Publication date: Available online 7 September 2017
Source:Developmental Cell
Author(s): Bikram Sharma, Lena Ho, Gretchen Hazel Ford, Heidi I. Chen, Andrew B. Goldstone, Y. Joseph Woo, Thomas Quertermous, Bruno Reversade, Kristy Red-Horse
Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function. An upregulation of endocardial SOX17 accompanied compensation in Apj mutants, which was also seen in Ccbe1 knockouts, indicating that the endocardium is activated in multiple cases where sinus venosus angiogenesis is stunted. Our data demonstrate that by diversifying their responsivity to growth cues, distinct coronary progenitor pools are able to compensate for each other during coronary development, thereby providing robustness to organ development.
Graphical abstract
Teaser
Coronary blood vessels of the heart are formed from two progenitor sources: the sinus venosus (SV) and the endocardium. Sharma et al. show that ELA-APJ is only required for growth from the SV and that endocardial-derived CVs can compensate for loss of SV-derived vessels to restore heart function, ensuring developmental robustness.http://ift.tt/2f8ypLj
FPGA implementation of real-time SENSE reconstruction using pre-scan and Emaps sensitivities
Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Muhammad Faisal Siddiqui, Ahmed Wasif Reza, Abubakr Shafique, Hammad Omer, Jeevan Kanesan
Sensitivity Encoding (SENSE) is a widely used technique in Parallel Magnetic Resonance Imaging (MRI) to reduce scan time. Reconfigurable hardware based architecture for SENSE can potentially provide image reconstruction with much less computation time. Application specific hardware platform for SENSE may dramatically increase the power efficiency of the system and can decrease the execution time to obtain MR images. A new implementation of SENSE on Field Programmable Gate Array (FPGA) is presented in this study, which provides real-time SENSE reconstruction right on the receiver coil data acquisition system with no need to transfer the raw data to the MRI server, thereby minimizing the transmission noise and memory usage. The proposed SENSE architecture can reconstruct MR images using receiver coil sensitivity maps obtained using pre-scan and eigenvector (E-maps) methods. The results show that the proposed system consumes remarkably less computation time for SENSE reconstruction, i.e., 0.164ms @ 200MHz, while maintaining the quality of the reconstructed images with good mean SNR (29+ dB), less RMSE (<5×10−2) and comparable artefact power (<9×10−4) to conventional SENSE reconstruction. A comparison of the center line profiles of the reconstructed and reference images also indicates a good quality of the reconstructed images. Furthermore, the results indicate that the proposed architectural design can prove to be a significant tool for SENSE reconstruction in modern MRI scanners and its low power consumption feature can be remarkable for portable MRI scanners.
http://ift.tt/2xgvOK6
Static and dynamic liver stiffness: An ex vivo porcine liver study using MR elastography
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Chun Yang, Meng Yin, Kevin J. Glaser, Xiangyang Zhu, Kai Xu, Richard L. Ehman, Jun Chen
Magnetic resonance elastography (MRE) is an MRI-based noninvasive technique for quantitatively assessing tissue stiffness. The hypothesis of this study is that stiffness increases with portal pressure. We further hypothesized that the rate of stiffness change with pressure would be larger in liver tissue treated to simulate the stiffening effects of fibrosis. In agreement with our hypothesis, the formalin-treated livers were stiffer than the untreated livers, and in both groups the liver stiffness increased with portal venous pressure. The rate of stiffness change with portal pressure was significantly greater after formalin treatment. In this study, we have developed an ex vivo liver model incorporating portal venous pressure variations and observed significant changes in liver stiffness due to portal pressure. This model could be useful for understanding and investigating the changes in the static and dynamic components of liver stiffness.
http://ift.tt/2wNNQjG
MRI protocol optimization for quantitative DCE-MRI of the spine
Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Cristina Lavini, Gem Kramer, Indra Pieters-den Bos, Otto Hoekstra, J. Tim Marcus
PurposeIn this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM).Materials and methodsIn 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2ml/kg body weight) was injected intravenously at a speed of 3ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model.ResultsSagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient–echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5mm and two acquisitions.ConclusionThe proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.
http://ift.tt/2xgy1Fm
The development and optimisation of 3D black-blood R2* mapping of the carotid artery wall
Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Jianmin Yuan, Martin J. Graves, Andrew J. Patterson, Andrew N. Priest, Pascal P.R. Ruetten, Ammara Usman, Jonathan H. Gillard
PurposeTo develop and optimise a 3D black-blood R2* mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering.MethodsTwo different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R2*, and the sternocleidomastoid muscle R2* were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression.ResultsAll sequences resulted in comparable R2* measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression.ConclusionThe use of blood-suppression preparation methods does not affect the measurement of R2*. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R2* measurements of the carotid vessel wall.
http://ift.tt/2wNEepk
COnstrained Data Extrapolation (CODE): A new approach for high definition vascular imaging from low resolution data
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Yang Song, Ehsan Hamtaei, Sean K. Sethi, Guang Yang, Haibin Xie, E. Mark Haacke
PurposeTo introduce a new approach to reconstruct high definition vascular images using COnstrained Data Extrapolation (CODE) and evaluate its capability in estimating vessel area and stenosis.Materials and methodsCODE is based on the constraint that the full width half maximum of a vessel can be accurately estimated and, since it represents the best estimate for the width of the object, higher k-space data can be generated from this information. To demonstrate the potential of extracting high definition vessel edges using low resolution data, both simulated and human data were analyzed to better visualize the vessels and to quantify both area and stenosis measurements. The results from CODE using one-fourth of the fully sampled k-space data were compared with a compressed sensing (CS) reconstruction approach using the same total amount of data but spread out between the center of k-space and the outer portions of the original k-space to accelerate data acquisition by a factor of four.ResultsFor a sufficiently high signal-to-noise ratio (SNR) such as 16 (8), we found that objects as small as 3 voxels in the 25% under-sampled data (6 voxels when zero-filled) could be used for CODE and CS and provide an estimate of area with an error <5% (10%). For estimating up to a 70% stenosis with an SNR of 4, CODE was found to be more robust to noise than CS having a smaller variance albeit a larger bias. Reconstruction times were >200 (30) times faster for CODE compared to CS in the simulated (human) data.ConclusionCODE was capable of producing sharp sub-voxel edges and accurately estimating stenosis to within 5% for clinically relevant studies of vessels with a width of at least 3pixels in the low resolution images.
http://ift.tt/2xgjo50
Reduced distortion artifact whole brain CBF mapping using blip-reversed non-segmented 3D echo planar imaging with pseudo-continuous arterial spin labeling
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Neville D. Gai, Yi Yu Chou, Dzung Pham, John A. Butman
PurposeTo implement and evaluate interleaved blip-up, blip-down, non-segmented 3D echo planar imaging (EPI) with pseudo-continuous arterial spin labeling (pCASL) and post-processing for reduced susceptibility artifact cerebral blood flow (CBF) maps.Materials and methods3D EPI non-segmented acquisition with a pCASL labeling sequence was modified to include alternating k-space coverage along phase encoding direction (referred to as "blip-reversed") for alternating dynamic acquisitions of control and label pairs. Eight volunteers were imaged on a 3T scanner. Images were corrected for distortion using spatial shifting transformation of the underlying field map. CBF maps were calculated and compared with maps obtained without blip reversal using matching gray matter (GM) images from a high resolution 3D scan. Additional benefit of using the correction for alternating blip-up and blip-down acquisitions was assessed by comparing to corrected blip-up only and corrected blip-down only CBF maps. Matched Student t-test of overlapping voxels for the eight volunteers was done to ascertain statistical improvement in distortion.ResultsMean CBF value in GM for the eight volunteers from distortion corrected CBF maps was 50.8±9.9ml/min/100 gm tissue. Corrected CBF maps had 6.3% and 4.1% more voxels in GM when compared with uncorrected blip up (BU) and blip down (BD) images, respectively. Student t-test showed significant reduction in distortion when compared with blip-up images and blip-down images (p<0.001). When compared with corrected BU and corrected BD only CBF maps, BU and BD corrected maps had 2.3% and 1% more voxels (p=0.006 and 0.04, respectively).ConclusionPseudo-continuous arterial spin labeling with non-segmented 3D EPI acquisition using alternating blip-reversed k-space traversal and distortion correction provided significantly better matching GM CBF maps. In addition, employing alternating blip-reversed acquisitions during pCASL acquisition resulted in statistically significant improvement over corrected blip-up and blip-down CBF maps.
http://ift.tt/2wMZco1
Toxicity, uptake, and accumulation of nano and bulk cerium oxide particles in Artemia salina
Abstract
Although the toxicological impact of metal oxide nanoparticles has been studied for the last few decades on aquatic organisms, the exact mechanism of action is still unclear. The fate, behavior, and biological activity of nanoparticles are dependent on physicochemical factors like size, shape, surface area, and stability in the medium. This study deals with the effect of nano and bulk CeO2 particles on marine microcrustacean, Artemia salina. The primary size was found to be 15 ± 3.5 and 582 ± 50 nm for nano and bulk CeO2 (TEM), respectively. The colloidal stability and sedimentation assays showed rapid aggregation of bulk particles in seawater. Both the sizes of CeO2 particles inhibited the hatching rate of brine shrimp cyst. Nano CeO2 was found to be more toxic to A. salina (48 h LC50 38.0 mg/L) when compared to bulk CeO2 (48 h LC50 92.2 mg/L). Nano CeO2-treated A. salina showed higher oxidative stress (ROS) than those treated with the bulk form. The reduction in the antioxidant activity indicated an increase in oxidative stress in the cells. Higher acetylcholinesterase activity (AChE) was observed upon exposure to nano and bulk CeO2 particles. The uptake and accumulation of CeO2 particles were increased with respect to the concentration and particle size. Thus, the above results revealed that nano CeO2 was more lethal to A. salina as compared to bulk particles.
http://ift.tt/2gMqqUo
Histiocytoid cardiomyopathy and ventricular noncompaction presenting as sudden death in an adult male
Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): J. Fernando Val-Bernal, Marta Mayorga, Clara Ortega, Emma Linares
Histiocytoid/oncocytic cardiomyopathy (HCM) is a rare, distinctive arrhythmogenic disorder that presents as arrhythmia or sudden death in infants and children. Ventricular noncompaction (VNC) is a rare cardiomyopathy characterized by a thickened endocardial layer of noncompacted myocardium and a thin epicardial layer of compacted myocardium. Only six cases of the association of both cardiomyopathies have been reported previously in the literature. All these cases were in children. To the best of our knowledge, a case of HCM has not been described in the adult. We report the case of a 45-year-old man with an increased heart weight and involvement of both ventricles by HCM and VNC cardiomyopathy. Besides, multiple foci of myocardial disorganization were detected. He died suddenly while hiking. The association of both processes HCM and VNC was an unexpected finding at autopsy. The death was linked to functional abnormalities of the cardiac histiocytoid cells, and it was favored by a state of abnormal development of the heart.
http://ift.tt/2gQNXHC
Upregulation of uc.189 in patients with esophageal squamous cell carcinoma and its clinicopathologic value
Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): Yan Guo, Chenghai Wang, Xin Miao, Siyu Chen, Yu Qian, Guoli Li, Ying Jiang
Ultraconserved elements (UCEs) encoding noncoding RNAs serve as important regulators in cancer biology. Until now, the role of the UCE uc.189 in human cancers remains undefined and the clinical significance of uc.189 in esophageal cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. The correlation of uc.189 with clinicopathological features and prognosis were also analyzed. The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis. High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.
http://ift.tt/2vJSpdJ
AEG-1 mRNA expression in non-small cell lung cancer is associated with increased tumor angiogenesis
Publication date: Available online 7 September 2017
Source:Pathology - Research and Practice
Author(s): Zhihong Ma, Yingrong Chen, Shunli Dong, Xuting Xu, Jin Liu, Pengtao Song, Caihua Yu, Licheng Dai
Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human malignant disease. However, the angiogenesis roles of AEG-1 in non-small cell lung cancer (NSCLC) remain to be further elucidated. In the present study, the expression level of AEG-1 mRNA in seven human lung cell lines and 89 paired tissue samples (tumor tissues (TTs) and pair-matched normal adjacent tissues (PMNATs)) from NSCLC patients was detected by real-time PCR. Staining of vascular endothelial growth factor (VEGF) and intratumoral microvessel density (iMVD, labeled by CD105) were assessed by immunohistochemistry. Furthermore, cell migration and invasion were evaluated by wound healing assay and transwell assays. AEG-1 mRNA level was significantly higher in human lung cancer cells and TTs than that in human normal bronchial epithelial cell line 16HBE and PMNATs, respectively (P<0.001). Higher AEG-1 mRNA level in patients with NSCLC was correlated with clinical stages (P=0.028), differentiation (P=0.042), and lymph node metastasis (P=0.004). Moreover, Upregulated AEG-1 mRNA expression level was associated with higher tumor angiogenesis, reflected by the increase of VEGF expression and iMVD counting (P=0.021, P<0.001). However, 95D cell line transfected with AEG-1 siRNA oligos (siAEG-1) exhibited no significant decrease of cell invasion or migration capacities when compared with the control cells (P>0.05).These results suggested that AEG-1 may play important roles at the transcription level in malignant transformation and tumor angiogenesis in NSCLC, and anti-AEG-1 mRNA expression may be a novel potential strategy for anti-angiogenic therapy of NSCLC.
http://ift.tt/2gPSTMG
The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues
Publication date: Available online 7 September 2017
Source:Cell Reports
Author(s): Ajithkumar Vasanthakumar, Yang Liao, Peggy Teh, Maria F. Pascutti, Anna E. Oja, Alexandra L. Garnham, Renee Gloury, Jessica C. Tempany, Tom Sidwell, Eloy Cuadrado, Paul Tuijnenburg, Taco W. Kuijpers, Najoua Lalaoui, Lisa A. Mielke, Vanessa L. Bryant, Philip D. Hodgkin, John Silke, Gordon K. Smyth, Martijn A. Nolte, Wei Shi, Axel Kallies
After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt+ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including cell survival and proliferation, but was dispensable for IRF4 expression or DNA binding, indicating that both pathways operated independently. Importantly, mutations in the RelA binding partner NF-κB1 compromised eTreg cells in humans, suggesting that the TNFRSF-NF-κB axis was required in a non-redundant manner to maintain eTreg cells in mice and humans.
Graphical abstract
Teaser
Effector regulatory T (eTreg) cells are potent repressors of immune pathology in lymphoid and non-lymphoid tissues. Vasanthakumar et al. have identified a signaling nexus, composed of TNFRSF and NF-κB/RelA, which operates independently of TCR-induced transcription factor IRF4 and is required for the differentiation and maintenance of eTreg cells.http://ift.tt/2wN3ko7
Development of 1,3,4-oxadiazole thione based novel anticancer agents: Design, synthesis and in-vitro studies
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Nalini Yadav, Parveen Kumar, Aruna Chhikara, Madhu Chopra
A series of new 1,3,4-oxadiazole-2(3H)-thione analogues (3a to 3o) have been designed, synthesized and evaluated for their anticancer activity. Four different cancerous cell lines viz. HeLa (cervical), U-87 (glioblastoma), Panc (pancreatic) and MCF-7 (breast) were used to assess the potency of the synthesized compounds as anticancer agents. Among them 3i and 3j showed promising cytotoxicity against HeLa cell line. Further, 3i and 3j successfully inhibited cell cycle progression and displayed cell death in HeLa cells via apoptosis as visualized by Annexin V APC and DNA fragmentation assay. 3i and 3j induced caspase-3 activation, PARP cleavage, increase in expression of proapoptotic protein Bax and decrease in the expression of antiapoptotic protein Bcl-2. Also, 3i and 3j induced overexpression of p21 and decreased expression of cyclin B1 indicating the arrest of cells in G2-M phase of the cell cycle. Therefore, new lead compounds are being suggested having anticancer activity through cell cycle inhibition and apoptosis.
Graphical abstract
http://ift.tt/2wdSq9a
Cardioprotective effect of Malva sylvestris L. in myocardial ischemic/reprefused rats
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Hanheng Zuo, Yinping Li, Yinghua Cui, Yi An
PurposeThe present investigation evaluated the cardioprotective effect of Malva sylvestris L. (MS) on myocardial ischemic/reperfusion (MI/R) in rats.MethodsAll animals were divided into four groups: the sham operated group, ischemia/reperfusion group (MI/R), and the MS (250 and 500mg/kg) treated groups, who received MS 250 and 500mg/kg intragastrically for 15 consecutive days, respectively. At the end of the protocol, concentrations of aspartate transaminase (AST), creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH) were estimated in serum and the concentrations of other parameters, such as C-reactive protein, macrophage inflammatory protein 1 alpha (MIP-1α), and nitric oxide (NO) were also estimated in the blood. Tissue homogenate concentrations of inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interlukin-1β (IL-1β), IL-10 and IL-6 as well as oxidative stress parameters, such as lipid peroxidation, catalase, and superoxide dismutase were estimated in MI/R rats.ResultSignificant decreases (p<0.01) in AST, LDH, and CK-MB levels were observed in the MS-treated group compared with those in the MI/R group. C-reactive protein and MIP-1α levels decreased in the MS-treated group compared with those in the MI/R group. Plasma NO level was significantly enhanced in the MS-treated group than in the MI/R group. Moreover, treatment with MS significantly reduced TNF-α, IL-1β, and IL-6 levels and increased IL-10 levels in the MS group compared with the MI/R group. Treatment with MS also attenuated the altered oxidative stress parameters in MI/R rats.ConclusionThe present results indicate the cardioprotective effects of MS of reducing oxidative stress and the inflammatory response in MI/R rats.
http://ift.tt/2wddnkB
N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine as a potential boron delivery agent with respect to glioblastoma
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Łukasz Uram, Joanna Nizioł, Piotr Maj, Justyna Sobich, Wojciech Rode, Tomasz Ruman
Glioblastoma multiforme (GBM) is a central nervous system tumor of grade IV, according to the WHO classification, extremely resistant to all currently used forms of therapy, including resection, radiotherapy, chemotherapy or combined therapy. Therefore, more effective treatment strategies of this tumor are needed, with boron neutron capture therapy (BNCT) being a potential solution, provided a proper cancer cells-targeted 10B delivery agent is found. In search of such an agent, toxicity and capacity to target DNA of a boronated derivative of 2′-deoxycytidine, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine (1), was tested against human tumor vs. normal cells. The present in vitro results revealed 1 to show low toxicity for human U-118 MG glioma cells (in the mM range) and even by 3–4 – fold lower against normal human fibroblasts. In accord, induction of apoptosis dependent on caspase-3 and caspase-7 was detected at high (>20mM) concentration of 1. Although demonstrated to be susceptible to phosphorylation by human deoxycytidine kinase and to undergo incorporation in cellular DNA, the boron analogue did not disturb cell proliferation when applied at non-toxic concentrations and showed low toxicity to a model metazoan organism, Caenorhabditis elegans. Thus, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2′-deoxycytidine appears a promising candidate for a 10B delivery agent to be used in BNCT, with C. elegans indicated as a good model for in vivo studies.
Graphical abstract
http://ift.tt/2wMxfP9
Prophetic medicine as potential functional food elements in the intervention of cancer: A review
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Bassem Y. Sheikh, Md. Moklesur Rahman Sarker, Muhamad Noor Alfarizal Kamarudin, Amin Ismail
Amounting scientific evidences have revealed the antitumor, antimetastatic, antiangiogenic, antiproliferative, chemopreventive and neo-adjuvant efficacy of Prophetic Medicine in various in vitro, in vivo and clinical cancer models. Prophetic Medicine includes plants, dietary materials or spices that were used as remedy recipes and nutrition by the great Prophet Mohammed (peace be upon him) to treat various ailments. Prophetic medicine is the total authentic Hadith narrated by the Prophet (PBUH) in relation to medicine, whether Qur'anic verses or honourable Prophetic Hadith. The ability of functional foods from Prophetic Medicine to modulate various signalling pathways and multidrug resistance conferring proteins with low side-effects exemplify their great potential as neo-adjuvants and/or chemotherapeutics. The present review aims to provide the collective in vitro, in vivo, clinical and epidemiology information of Prophetic Medicines, and their bioactive constituents and molecular mechanisms as potential functional foods for the management of cancer.
Graphical abstract
http://ift.tt/2wM48LH
Perillyl alcohol protects human renal tubular epithelial cells from hypoxia/reoxygenation injury via inhibition of ROS, endoplasmic reticulum stress and activation of PI3K/Akt/eNOS pathway
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Yixiao Xu, Wantie Wang, Keke Jin, Qifan Zhu, Hongzhou Lin, Minye Xie, Dexuan Wang
Ischemia/reperfusion (I/R) injury plays an essential role in renal transplantation, and represents a crucial risk factor for allograft dysfunction and acute renal failure. Modulation of oxidative stress is an effective therapeutic strategy for I/R injury. Perillyl alcohol (POH), a dietary monoterpene with antioxidant activity is found in a variety of plants. The study was carried out to investigate whether treatment of POH could reduce hypoxia/reoxygenation (H/R)-induced injury. H/R induced significant injury in HK-2 cells. H/R caused an increase in ROS level, apoptosis and ER stress. Meanwhile H/R also inhibited the cell viability and PI3K/Akt/eNOS signaling pathway. Pretreatment with POH prior to H/R improved cell viability, reduce ROS level, ER stress and apoptosis. Moreover, POH could also activate the PI3K/Akt/eNOS pathway. Therefore, POH may possess protective effects in H/R-induced cellular damage.
http://ift.tt/2wLI5EL
An increased expression of long non-coding RNA PANDAR promotes cell proliferation and inhibits cell apoptosis in pancreatic ductal adenocarcinoma
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Yuehong Jiang, Enhang Feng, Lifang Sun, Wei Jin, Yuhong You, Yue Yao, Yi Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed. The functional roles of lncRNA PANDAR in PDAC cells were evaluated both in vitro and in vivo. The results indicated that PANDAR was aberrantly overexpressed in PDAC tissues and cell lines, and this overexpression was closely associated with tumor stage and vascular invasion in PDAC patients. Besides, silencing of PANDAR exerted tumor suppressive effect via reducing cell proliferation, colony-forming ability, inducing cell cycle G0/G1 arrest and apoptosis in PANC1 and Capan-2 cells. Further in vivo study confirmed the oncogenesis role of PANDAR in PDAC cells. Overall, our findings may help to develop a potential therapeutic target for the patients with PDAC.
http://ift.tt/2wcUmP8
Glycyrrhizic acid: A promising carrier material for anticancer therapy
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Xitong Su, Lei Wu, Mingming Hu, Wenxiang Dong, Meng Xu, Peng Zhang
Drug delivery systems have become an integral part of anticancer drugs today. Design of novel drug carriers may lead to significant enhancement in antineoplastic therapy. Glycyrrhizic acid (GL), which is the most important active ingredient extracted from the licorice root shows great potential as a carrier material in this field. Recent studies have indicated that the combination of GL and first-line drugs had better therapeutic effects on cancers. GL showed a series of anti-cancer-related pharmacological activities, such as broad-spectrum anti-cancer ability, resistance to the tissue toxicity caused by chemotherapy and radiation, drug absorption enhancing effects and anti-multidrug resistance (MDR) mechanisms, as a carrier material in drug delivery systems. This review introduced the current research progress on pharmacological mechanisms of GL and development of GL-based drug carriers in anti-cancer field to provide basis for the application prospects of GL. The design of novel GL-based drug delivery systems will bring new opportunities and challenges to anti-cancer therapy.
Graphical abstract
http://ift.tt/2wMg3sI
MDR1 polymorphisms affect the outcome of Chinese multiple myeloma patients
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Zhengrui Xiao, Guangli Yin, Ying Ni, Xiaoyan Qu, Hanxin Wu, Hua Lu, Sixuan Qian, Lijuan Chen, Jianyong Li, Hairong Qiu, Kourong Miao
ObjectiveTo illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population.MethodsA total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS.ResultsMDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061–0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264–0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms.ConclusionMDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.
http://ift.tt/2wMjAaG
Peroxisome proliferator-activated receptors as therapeutic targets for heart failure
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Eshak I. Bahbah, Ahmed Elmaraezy, Aya Ashraf Ali, Asmaa Ashraf, Mohamed M. Abdel-Daim
Heart failure (HF) is a common clinical syndrome that affects more than 23 million individuals worldwide. Despite the marked advances in its management, the mortality rates in HF patients have remained unacceptably high. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription regulators, involved in the regulation of fatty acid and glucose metabolism. PPAR agonists are currently used for the treatment of type II diabetes mellitus and hyperlipidemia; however, their role as therapeutic agents for HF remains under investigation. Preclinical studies have shown that pharmacological modulation of PPARs can upregulate the expression of fatty acid oxidation genes in cardiomyocytes. Moreover, PPAR agonists were proven able to improve ventricular contractility and reduce cardiac remodelling in animal models through their anti-inflammatory, anti-oxidant, anti-fibrotic, and anti-apoptotic activities. Whether these effects can be replicated in humans is yet to be proven. This article reviews the interactions of PPARs with the pathophysiological mechanisms of HF and how the pharmacological modulation of these receptors can be of benefit for HF patients.
http://ift.tt/2wddlJv
Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy
Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Zahra Valedkarimi, Hadi Nasiri, Leili Aghebati-Maleki, Jafar Majidi
Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody–cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody–cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody–cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody–cytokine fusion proteins.
http://ift.tt/2wMog07
Secondary Linburg-Comstock syndrome: a case report
Abstract
Linburg-Comstock syndrome is characterized by an inability to flex the interphalangeal joint of the thumb without simultaneous flexion of the distal interphalangeal joint of the index finger due to hereditary interconnections between the flexor pollicis longus (FPL) and the index flexor digitorum profundus (iFDP) resulting in discomfort and symptoms of flexor tenosynovitis. In addition to this anatomic anomaly, our clinical findings suggest that the interconnection can also result secondarily as a consequence of tenosynovial hyperplasia producing adhesions from any cause including previous surgery or trauma using the example of forearm laceration with dissection of the two tendons.
Level of Evidence: Level V, diagnostic study.
http://ift.tt/2wcItsG
Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection
Publication date: Available online 7 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Anne Lejay, Charline Delay, Elie Girsowicz, Bettina Chenesseau, Emilie Bonnin, Mohamed-Zied Ghariani, Fabien Thaveau, Yannick Georg, Bernard Geny, Nabil Chakfe
ObjectiveThe aim of this study was to report outcomes of cryopreserved arterial allografts used as a vascular substitute in the setting of prosthetic material infection.MethodsA retrospective analysis of prospectively collected data was conducted including all consecutive interventions performed with cryopreserved arterial allografts used for vascular reconstruction in the setting of prosthetic material infection between January 2005 and December 2014. Five year outcomes included allograft related re-interventions, survival, primary patency, and limb salvage rates.ResultsFifty-three procedures were performed using cryopreserved allografts for vascular prosthetic infection: 25 procedures (47%) were performed at aorto-iliac level (Group 1) and 28 procedures (53%) at peripheral level (Group 2). The mean follow-up was 52 months. Five year allograft related re-intervention was 55% in Group 1 (6 allograft ruptures and 5 allograft aneurysm degenerations) and 33% in Group 2 (2 allograft ruptures and 7 allograft aneurysm degenerations). Five year survival was 40% and 68%, primary patency was 89% and 59% and limb salvage was 100% and 89% for Group 1 and 2 respectively.ConclusionUse of cryopreserved arterial allografts provides acceptable results but is tempered by suboptimal 5 year outcomes with high re-intervention rates.
http://ift.tt/2eQ0Zob
River biofilm community changes related to pharmaceutical loads emitted by a wastewater treatment plant
Abstract
Wastewater treatment plants (WWTP) are the main sources of a broad spectrum of pharmaceuticals found in freshwater ecosystems. These pollutants raise environmental health concerns because of their highly bioactive nature and their chronic releases. Despite this, pharmaceuticals' effects on aquatic environments are poorly defined. Biofilms represent a major part of the microbial life in rivers and streams. They can drive key metabolic cycles and their organizations reflect exposures to changing chemical, physical, and biological constraints. This study estimated the concentrations, over a 3-year period, of ten pharmaceuticals and five nutrients in a river contaminated by a conventional WWTP fed by urban and hospital wastewaters. Variations in these concentrations were related to biofilm bacterial community dynamics. Rock biofilms had developed over defined periods and were harvested at four locations in the river from the up- and downstream WWTP discharge point. Pharmaceuticals were found in all locations in concentrations ranging from not being detected to 192 ng L−1. Despite the high dilution factor of the WWTP effluents by the receiving river, pharmaceuticals were found more concentrated downstream than upstream the WWTP. Shifts in bacterial community structures linked to the environmental emission of pharmaceuticals were superior to seasonal community changes. A community structure from a site located downstream but close to the WWTP was more strongly associated with high pharmaceutical loads and different from those of biofilm samples from the WWTP upstream or far downstream sites. These latter sites were more strongly associated with high nutrient contents. Low environmental concentrations of pharmaceuticals can thus be transferred from WWTP effluents to a connected stream and induce bacterial aquatic community changes over time.
http://ift.tt/2wMlt74
Introducing nerve-sparing approach during minimally invasive radical hysterectomy for locally-advanced cervical cancer: a multi-institutional experience
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Francesco Raspagliesi, Giorgio Bogani, Arsenio Spinillo, Antonino Ditto, Stefano Bogliolo, Jvan Casarin, Umberto Leone Roberti Maggiore, Fabio Martinelli, Mauro Signorelli, Barbara Gardella, Valentina Chiappa, Cono Scaffa, Simone Ferrero, Antonella Cromi, Domenica Lorusso, Fabio Ghezzi
ObjectiveTo evaluate the impact of nerve-sparing (NS) approach on outcomes of patients undergoing minimally invasive radical hysterectomy (MRH) for locally advanced stage cervical cancer (LACC).MethodsData of consecutive patients undergoing minimally invasive surgery for LACC were retrospectively retrieved in a multi-institutional setting from 2009 to 2016. All patients included had minimally invasive class III radical hysterectomy (MRH or NS-MRH). Propensity matching algorithm was used to decrease possible allocation bias when comparing outcomes between groups.ResultsOverall, 83 patients were included. The prevalence of patients undergoing NS approach increased aver the study period (from 7% in the year 2009-2010 to 97% in the year 2015-2016; p-for-trend<.001). NS-MRH and MRH were performed in 47 (57%) and 36 (43%) patients, respectively. After the application the propensity-matching algorithm, we compared 35 patients' pair (total 70 patients). Postoperative complications rate was similar between groups. Patients undergoing NS-LRH experienced shorter hospital stay than patients undergoing LRH (3.6 vs. 5.0 days). 60-day pelvic floor dysfunction rates, including voiding, fecal and sexual alterations, were lower in the NS group in comparison to control group (p=.02). Five-year disease-free (p=.77) and overall (p=.36) survivals were similar comparing NS-MRH with MRH.ConclusionsThe implementation of NS approach in the setting of LACC improves patients' outcomes, minimizing pelvic dysfunction rates. NS approach has not detrimental effects on survival outcomes.
http://ift.tt/2wLUwl6
Perioperative Therapies – Enhancing the Impact of Cancer Surgery with Repurposed Drugs
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Pan Pantziarka, Gauthier Bouche, Richard Sullivan, André M. Ilbawi, Anna J. Dare, Lydie Meheus
Surgical resection remains the major modality for modern curative treatment for solid tumours. However, post-surgical recurrence, even following clear-margin resection and adjuvant treatment, remains common in many types of cancer. Reducing recurrence rates, therefore, offers the potential to increase cure rates and increase overall survival. Perioperative therapies, simple interventions during the perioperative period, are designed to address some of the factors which influence post-surgical recurrence. A range of perioperative therapies are introduced and the rationale for further clinical investigation outlined.
http://ift.tt/2f83uyX
Frequency and Prognostic Significance of Incidental Prostate Cancer at Radical Cystectomy: Results from an international retrospective study
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Rieken Malte, Luis A. Kluth, Dharam Kaushik, Stephen A. Boorjian, Mohammad Abufaraj, Beat Foerster, Michael Rink, Kilian Gust, Florian Roghmann, Joachim Noldus, Dimitri Vordos, Masayuki Hagiwara, Eiji Kikuchi, Masaomi Ikeda, Kazumasa Matsumoto, Pierre I. Karakiewicz, Morgan Rouprêt, Alberto Briganti, Douglas S. Scherr, Shahrokh F. Shariat, Veronika Seebacher
ObjectivesTo analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort.Patients and MethodsIn this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC.ResultsOverall, incidental PC was found in 513 (24.3%) patients with the lowest frequency in a Japanese center (23/164, 11.2%) and the highest frequency in a North American center (122/325, 37.5%), respectively (p<0.001). Within a median follow up of 27 months (IQR: 50 months), 20 patients (3.9%) were diagnosed with biochemical recurrence (BCR) and none of the patients died of PC. PC pathological tumor stage was more advanced in patients experiencing BCR (p<0.001). In multivariable Cox regression analyses adjusted for standard clinicopathologic features, incidental PC was not associated with cancer-specific (HR: 1.11, 95% CI: 0.91-1.35, p=0.30) or overall mortality (HR: 1.06, 95% CI: 0.83-1.35, p=0.65).ConclusionsIncidental PC at RC for UCB is a frequent event. However, the majority of PC cases are well-differentiated and organ-confined. Presence of incidental PC shows significant geographic differences. The risk of BCR after incidental PC is low and incidental PC is not associated with survival in UCB patients treated with RC.
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Hostility and cognitive control: Evidence of increased cardiovascular reactivity as a function of exposure to affective stress using a dichotic listening paradigm
Source:International Journal of Psychophysiology
Author(s): Alissa K. Holland, Gina A. Mitchell, Angela Steele, Jessica Bunting, David W. Harrison
Indices of cognitive control were examined in men with high and low levels of trait hostility as a function of exposure to affective and cognitive stress. A dual concurrent task paradigm was used whereby participants intentionally directed focus to the left or right ear under dichotic listening conditions before and after exposure to angry infant vocalizations. Analysis of the behavioral data supports the prediction of reduced right frontal regulatory control in men with high levels of hostility as indicated by diminished capacity to suppress report of phonemes presented to the language dominant left hemisphere (right ear) in the Focus Left condition. This diminishment in the capacity to suppress report of phonemes presented to the right ear in the Focus Left condition is suggestive of reduced cognitive control. With respect to the neurophysiological data, heart rate increased for only men with high levels of hostility in the Focus Left condition, and this was especially evident in the post-affective stress condition. This increase in right hemisphere arousal provides additional evidence of reduced cognitive control and support for the capacity model of hostility by implicating poor right frontal regulatory control over right posterior cerebral regions under dual task conditions. The results are discussed in terms of integrating the construct of cognitive control into the capacity model as well as providing implications regarding reductions in the capacity to suppress predominant aggressive responses in domestic settings.
http://ift.tt/2wOcnFy
Three-dimensional printing in contemporary fixed prosthodontics: A technique article
Source:The Journal of Prosthetic Dentistry
Author(s): Sarah Bukhari, Brian J. Goodacre, Abdulaziz AlHelal, Mathew T. Kattadiyil, Paul M. Richardson
Digital dentistry has gained in popularity among clinicians and laboratory technicians because of its versatile applications. Three-dimensional (3D) printing has been applied in many areas of dentistry as it offers efficiency, affordability, accessibility, reproducibility, speed, and accuracy. This article describes a technique where 3D printing is used to fabricate a die-trimmed cast and to replicate gingival tissue and implant analogs. The digital workflow that replaces the conventional laboratory procedure is outlined.
http://ift.tt/2gLBRf2
A chairside technique to add customized anterior acrylic resin teeth to a surgical obturator
Source:The Journal of Prosthetic Dentistry
Author(s): Kamarul Hisham Kamarudin, Mariko Hattori, Yuka I. Sumita, Hisashi Taniguchi
A surgical obturator may need to be modified during the healing process after tissue resection. Apart from relining the fitting surfaces to accommodate the healing wound and changes in the surrounding tissues, other modifications such as adding teeth are sometimes required to improve esthetics and speech. This article describes a chairside technique to add customized acrylic resin teeth to an existing surgical obturator.
http://ift.tt/2eQp0vb
Maxillofacial prosthetic treatment factors affecting oral health-related quality of life after surgery for patients with oral cancer
Source:The Journal of Prosthetic Dentistry
Author(s): Miki Hagio, Ken Ishizaki, Masahiro Ryu, Takeshi Nomura, Nobuo Takano, Kaoru Sakurai
Statement of problemAfter oral cancer surgery, tissue defects can cause deformity and limited mobility, complicating many essential functions. For patients with mandibular, tongue, and oral floor defects, evidence regarding the effects of maxillofacial prosthetics on their oral health-related quality of life (OHRQoL) is lacking. Therefore, maxillofacial prosthetic reconstruction has been implemented with no clear treatment goals.PurposeThe purpose of this study was to identify factors affecting the improvement of OHRQoL by using maxillofacial prosthetic treatment after surgery to repair maxillary, mandibular, tongue, and oral floor defects.Material and methodsAll individuals who agreed to maxillofacial prosthetics after surgery for oral cancer were enrolled. Oral function and OHRQoL were evaluated before maxillofacial prosthesis placement and 1 month after final adjustments. The oral functions evaluated included masticatory function, swallowing function, and articulatory function. The Oral Health Impact Profile (OHIP-J54) was used to evaluate OHRQoL. Factors affecting changes in the OHIP-J54 score for participants' background and oral functions before and after treatment were analyzed through logistic regression analysis (stepwise method).ResultsParticipants included 34 men and 16 women with an average age of 72.4 ±8.7 years. "Psychological discomfort" was correlated with the patient's sex and masticatory function. "Physical disability" was related to articulatory function. "Handicap" was related to the swallowing function. "Additional Japanese questions" were related to the patient's sex.ConclusionsParticipants' sex and their oral functions, including masticatory, swallowing, and articulatory functions, were associated with improved OHRQoL because of maxillofacial prosthetics after surgery for oral cancer.
http://ift.tt/2gLuHY1
A risk-based decision making tree for managing fractured abutment and prosthetic screws: A systematic review
Source:The Journal of Prosthetic Dentistry
Author(s): Ryan M. Mizumoto, Faris Z. Jamjoom, Burak Yilmaz
Statement of problemIn implant dentistry, a variety of techniques are used to manage fractured abutment and prosthetic screws. All of them pose various degrees of difficulty to both the clinician and patient and risk involving damage to the implants and prostheses.PurposeThe purpose of this systematic review was to classify and organize the various reported techniques for managing fractured abutment and or prosthetic screws into a risk-based, decision making tree that could be used to guide the clinician through this difficult and time-consuming clinical procedure.Material and methodsA systematic search of the PubMed/MEDLINE database for articles published before June 2016 was performed by 2 independent reviewers. Studies published in English that described a clinical technique to retrieve or manage a fractured abutment or prosthetic screws were included. Techniques were classified according to risk of irreversible damage to the implant. Low-risk techniques were defined as those involving the use of basic hand instruments and instrument modification; moderate-risk techniques were defined as those involving the use of screw retrieval kits, rotary instruments, and screw modification; and high-risk techniques were defined as those involving modification of the implant. Published techniques were then organized into a decision-making tree.ResultsA total of 35 articles were included. The reported techniques ranged from straightforward instrumentation and instrument modification to screw or implant modifications. Seven techniques were considered low risk, 17 moderate risk, and 11 high risk.ConclusionsThe proposed risk-based decision tree is a useful tool in helping clinicians choose the most appropriate strategy or sequence of strategies that offers maximum benefit to the patient while minimizing associated risks.
http://ift.tt/2ePmQMg
3D-printed cone-beam computed tomography scans: A tool for patient education
Source:The Journal of Prosthetic Dentistry
Author(s): A. Brian Urtula, João Malta Barbosa, Gonçalo Bártolo Caramês, Ali Alper Çomut
http://ift.tt/2gLCuW0
Use of silver diamine fluoride for the maintenance of dental prostheses in a high caries-risk patient: A medical management approach
Source:The Journal of Prosthetic Dentistry
Author(s): Lola Giusti, Cathrine Steinborn, Maya Steinborn
A technique for using silver diamine fluoride (SDF) as part of a regimen to help maintain dental prostheses in a patient with scleroderma and at high risk of caries is presented. Medically compromised, xerostomic, or elderly patients generally face greater risk of caries and specifically with prosthetic retainer teeth. SDF is a minimally invasive solution to this problem. A technique is described for using SDF to arrest and prevent new caries with the goal of maintaining fixed and removable prostheses and supporting teeth in a cost-effective manner.
http://ift.tt/2eQ6rHg
Evaluation of the multi-slice computed tomography outcomes in diaphragmatic injuries related to penetrating and blunt trauma
Publication date: Available online 6 September 2017
Source:Clinical Imaging
Author(s): Mehmet Turmak, Muhammed Akif Deniz, Cihan Akgül Özmen, Aydın Aslan
PurposeTraumatic diaphragmatic rupture is a diagnostic challenge for both surgeons and radiologists and generally occurs secondary to blunt and penetrating trauma of thoracoabdominal region.Material and methods56 patients who underwent surgical procedure due to blunt or penetrating trauma were included to the study.ResultsThere were 37 diaphragmatic ruptures in the left side and 19 patients in the right side. The most common radiological finding was "the direct monitoring of defect" (54,3%).ConclusionFindings suggestive of diaphragmatic rupture must be carefully evaluated in patients with blunt or penetrating thoracoabdominal trauma.
http://ift.tt/2wN67Oc
Altered expression of the FMR1 splicing variants landscape in premutation carriers
Publication date: Available online 7 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Elizabeth Tseng, Hiu-Tung Tang, Reem Rafik AlOlaby, Luke Hickey, Flora Tassone
FMR1 premutation carriers (55–200 CGG repeats) are at risk for developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), an adult onset neurodegenerative disorder. In addition, 20% of female carriers will develop Fragile X-associated Primary Ovarian Insufficiency (FXPOI), in addition to a number of clinical problems affecting premutation carriers throughout their life span. Marked elevation in FMR1 mRNA levels have been observed with premutation alleles resulting in RNA toxicity, the leading molecular mechanism proposed for the FMR1 associated disorders observed in premutation carriers.The FMR1 gene undergoes alternative splicing and we have recently reported that the relative abundance of all FMR1 mRNA isoforms is significantly increased in premutation carriers.In this study, we further investigated the transcriptional FMR1 isoforms distribution pattern in different tissues and identified a total of 49 isoforms, some of which observed only in premutation carriers and which might play a role in the pathogenesis of FXTAS.Further, we investigated the distribution pattern and expression levels of the FMR1 isoforms in asymptomatic premutation carriers and in those with FXTAS and found no significant difference between the two groups.Our findings suggest that the characterization of the expression levels of the different FMR1 isoforms is fundamental for understanding the regulation of the FMR1 gene as imbalance in their expression could lead to an altered functional diversity with neurotoxic consequences. Their characterization will also help to elucidating the mechanism(s) by which "toxic gain of function" of the FMR1 mRNA may play a role in FXTAS and/or in the other FMR1-associated conditions.
http://ift.tt/2xf8exf
Resveratrol, piceatannol and analogs inhibit activation of both wild-type and T877A mutant androgen receptor
Publication date: Available online 6 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Johan Lundqvist, Corrado Tringali, Agneta Oskarsson
Prostate cancer growth and progression is mainly dependent on androgens and many current prostate cancer treatment options target the synthesis or function of androgens. We have previously reported that resveratrol and synthetic analogs of resveratrol with a higher bioavailability inhibit the synthesis of androgens in human adrenocortical H295R cells. Now we have studied the antiandrogenic properties of resveratrol, piceatannol and analogs in two different prostate cell lines; LNCaP and RWPE. LNCaP carry a T877A mutation in the androgen receptor while RWPE has a wild-type androgen receptor. We found that resveratrol, piceatannol and all studied analogs were able to inhibit a dihydrotestosterone-induced activation of the androgen receptor, showing that they act as antiandrogens. In LNCaP cells, all studied compounds were able to statistically significantly decrease the androgenic signaling in concentrations ≥1μM and the synthetic analogs trimethylresveratrol (RSVTM) and tetramethylpiceatannol (PICTM) were the most potent compounds. RWPE cells were not as responsive to the studied compounds as the LNCaP cells. A statistically significant decrease in the androgenic signaling was observed at concentrations ≤5μM for most compounds and RSVTM was found to be the most potent compound. Further, we studied the effects of resveratrol, piceatannol and analogs on the levels of prostate-specific antigen (PSA) in LNCaP cells and found that all studied compounds decreased the level of PSA and that the synthetic analogs diacetylresveratrol (RSVDA), triacetylresveratrol (RSVTA) and RSVTM were the most potent compounds, decreasing the PSA level by approx. 50% at concentrations ≥10μM. In a cell-free receptor binding assay we were unable to show binding of resveratrol or analogs to the ligand binding domain of the androgen receptor, indicating that the observed effects are mediated via other mechanisms than direct ligand competition. We conclude that the resveratrol, piceatannol and analogs are highly interesting for chemoprevention of prostate cancer, since they have a high potency both as inhibitors of androgen synthesis and androgen receptor activation.
http://ift.tt/2eJFGAA
Context for Practice: Prevention of Pressure Injury and Incontinence-Associated Dermatitis.
Author: Gray, Mikel
Page: 406-408
http://ift.tt/2gLqYKg
Letter to the Editor.
Author: Siegel, Tracey J. EdD, MSN, RN, CNE, CWCN; Garrigues, Layla J. PhD, RN
Page: 410-411
http://ift.tt/2wM1wgZ
Effectiveness and Value of Prophylactic 5-Layer Foam Sacral Dressings to Prevent Hospital-Acquired Pressure Injuries in Acute Care Hospitals: An Observational Cohort Study.
Author: Padula, William V.
Page: 413-419
http://ift.tt/2gLUbEK
Midrange Braden Subscale Scores Are Associated With Increased Risk for Pressure Injury Development Among Critical Care Patients.
Author: Alderden, Jenny; Cummins, Mollie Rebecca; Pepper, Ginette Alyce; Whitney, JoAnne D.; Zhang, Yingying; Butcher, Ryan; Thomas, Donna
Page: 420-428
http://ift.tt/2wLVRr1
Midrange Braden Subscale Scores Are Associated With Increased Risk for Pressure Injury Development Among Critical Care Patients.
Author:
Page: E1-E2
http://ift.tt/2gLSIyc
Prevention of Heel Pressure Injuries and Plantar Flexion Contractures With Use of a Heel Protector in High-Risk Neurotrauma, Medical, and Surgical Intensive Care Units: A Randomized Controlled Trial.
Author: Meyers, Tina
Page: 429-433
http://ift.tt/2wLYkC5
High-Frequency Ultrasound: Description of Sacral Tissue Characteristics in Healthy Adults.
Author: Burk, Ruth S.; Schubert, Christine M.; Pepperl, Anathea; Grap, Mary Jo
Page: 434-439
http://ift.tt/2gMgWbw
The Efficacy of a Viscoelastic Foam Overlay on Prevention of Pressure Injury in Acutely Ill Patients: A Prospective Randomized Controlled Trial.
Author: Park, Kyung Hee; Park, Joohee
Page: 440-444
http://ift.tt/2wLprgo
Predictors of Intraoperative Pressure Injury in Patients Undergoing Major Hepatobiliary Surgery.
Author: Chen, Yan; He, Li; Qu, Wei; Zhang, Chen
Page: 445-449
http://ift.tt/2gLmAuw
Effects of Curvilinear Supine Position on Tissue Interface Pressure: A Prospective Before-and-After Study.
Author: Guo, Yue; Li, Yan; Zhao, Kuaile; Yue, Xiao; Yu, Yunhong; Kuang, Wan; Liu, Jing; Li, Xiangyan; Zhao, Tiyu
Page: 450-454
http://ift.tt/2wM1mGp
Pressure Injury Knowledge in Critical Care Nurses.
Author: Miller, Donna M.; Neelon, Lisa; Kish-Smith, Kathleen; Whitney, Laura; Burant, Christopher J.
Page: 455-457
http://ift.tt/2gLoVpj
WOCN Society Position Paper: Avoidable Versus Unavoidable Pressure Ulcers/Injuries.
Author: Schmitt, Shawneen; Andries, Marti K.; Ashmore, Patti M.; Brunette, Glenda; Judge, Kathleen; Bonham, Phyllis A.
Page: 458-468
http://ift.tt/2wLSTmw
Sexual Experiences of Chinese Patients Living With an Ostomy.
Author: Zhu, Xiaomei; Chen*, Yongyi; Tang, Xinhui; Chen, Yupan; Liu, Yangyu; Guo, Wei; Liu, Aizhong
Page: 469-474
http://ift.tt/2gLm2EY
Incontinence Briefs Containing Spiral-Shaped Fiber Acidify Skin pH of Older Nursing Home Residents at Risk for Incontinence-Associated Dermatitis.
Author: Bliss, Donna Z.; Bland, Peggy; Wiltzen, Kjerstie; Gannon, Alexandra; Wilhems, Anna; Mathiason, Michelle A.; Turnbaugh, Robert
Page: 475-480
http://ift.tt/2wLNtHW
Effects of a Skin Barrier Cream on Management of Incontinence-Associated Dermatitis in Older Women: A Cluster Randomized Controlled Trial.
Author: Kon, Yuka; Ichikawa-Shigeta, Yoshie; Iuchi, Terumi; Nakajima, Yukari; Nakagami, Gojiro; Tabata, Keiko; Sanada, Hiromi; Sugama, Junko
Page: 481-486
http://ift.tt/2gLon2J
Quantitation of 24-Hour Moisturization by Electrical Measurements of Skin Hydration.
Author: Wickett, R. Randall; Damjanovic, Bronson
Page: 487-491
http://ift.tt/2wLSOiI
Improvised Skin Graft for a Large Superficial Hematoma: A Case Study.
Author: Kindel, Nicole
Page: 492-494
http://ift.tt/2gM6L78
Similarities in smell and taste preferences in couples increase with relationship duration
Source:Appetite, Volume 120
Author(s): Agata Groyecka, Agnieszka Sorokowska, Anna Oleszkiewicz, Thomas Hummel, Krystyna Łysenko, Piotr Sorokowski
Numerous studies point to partners' congruence in various domains and note an increase in their compatibility over time. However, none have explored a shift in chemosensory perception related to relationship duration. Here, we examined the relationship between the time heterosexual couples have spent together and the degree to which they share their gustatory and olfactory preferences. Additionally, we investigated whether these preferences are associated with relationship satisfaction. One-hundred couples aged from 18 to 68 years being together for a period between 3 and 540 months rated the pleasantness of a wide variety of olfactory and gustatory stimuli. We showed that both taste and smell preferences are more similar the longer couples have been in a relationship. We also observed a very interesting trend in terms of smell preferences, with relationship satisfaction being negatively related to congruence in smell preferences between partners. We discuss these results from the perspective of evolutionary psychology.
http://ift.tt/2vQNwn1
Pica is prevalent and strongly associated with iron deficiency among Hispanic pregnant women living in the United States
Source:Appetite, Volume 120
Author(s): Aditi Roy, Elena Fuentes-Afflick, Lia C.H. Fernald, Sera L. Young
IntroductionAnecdotal evidence suggests that pica occurs among Hispanic women in the United States, especially during pregnancy. However, the prevalence and socio-demographic and biological factors associated with pica in this population have not been adequately identified.MethodsTrained, bilingual study personnel conducted structured interviews at public health clinics in Salinas Valley, California with 187 pregnant Hispanic women in their 2nd or 3rd trimesters of pregnancy. Hemoglobin was measured using Hemocue; concentrations of transferrin receptor (TfR) and alpha-1 acid glycoprotein (AGP) were measured in dried blood spots. Multivariable stepwise regression analyses were conducted with pica during pregnancy as the dependent variable and individual- and family-level factors as independent variables to identify significant associations. Additionally, multivariable models were built to explore the associations between pica and iron status (iron deficiency and anemia).ResultsHalf of all participants (51.3%) had ever engaged in pica, and 37.6% had done so during the current pregnancy. Pica substances included large quantities of ice, frost, raw starches, and various earthen items. Pica during the current pregnancy was significantly associated with higher TfR concentrations [OR: 1.29; 95% CI: 1.11, 1.51] indicative of low iron stores and greater food insecurity [OR: 1.20, 95% CI: 1.03, 1.40]. Women who engaged in pica during the current pregnancy were more likely to be iron deficient [adjusted OR: 2.58; 95% CI: 1.19, 5.60], but not anemic [adjusted OR: 1.40; 0.60, 3.23].ConclusionsAmong pregnant Hispanic women, pica was prevalent and strongly associated with iron deficiency and food insecurity. Clinicians should screen for pica during pregnancy in Hispanic populations, and future studies should elucidate the underlying etiology and consequences of engaging in pica during pregnancy.
http://ift.tt/2xSpWDK
Lasers and intense pulsed light (IPL) association with cancerous lesions
Abstract
The development and use of light and lasers for medical and cosmetic procedures has increased exponentially over the past decade. This review article focuses on the incidence of reported cases of skin cancer post laser or IPL treatment. The existing evidence base of over 25 years of laser and IPL use to date has not raised any concerns regarding its long-term safety with only a few anecdotal cases of melanoma post treatment over two decades of use; therefore, there is no evidence to suggest that there is a credible cancer risk. Although laser and IPL technology has not been known to cause skin cancer, this does not mean that laser and IPL therapies are without long-term risks. Light therapies and lasers to treat existing lesions and CO2 laser resurfacing can be a preventative measure against BCC and SCC tumour formation by removing photo-damaged keratinocytes and encouraged re-epithelisation from stem cells located deeper in the epidermis. A review of the relevant literature has been performed to address the issue of long-term IPL safety, focussing on DNA damage, oxidative stress induction and the impact of adverse events.
http://ift.tt/2wLszc1
Increased expression of importin-β, exportin-5 and nuclear transportable proteins in Alzheimer's disease aids anatomic pathologists in its diagnosis
Publication date: February 2018
Source:Annals of Diagnostic Pathology, Volume 32
Author(s): Gerard Nuovo, Vicky Amann, James Williams, Paige Vandiver, Maria Quinonez, Paolo Fadda, Bernard Paniccia, Louisa Mezache, Adel Mikhail
Understanding the metabolic profile of neurons with the hyperphosphorylated tau protein characteristic of Alzheimer's disease is essential to unraveling new potential therapies and diagnostics for the surgical pathologist. We stratified 75 brain tissues from Alzheimer's disease into hyperphosphorylated tau positive or negative and did co-expression analyses and qRTPCR for importin-β and exportin-5 plus several bcl2 family members and compared the data to controls, Down's dementia and Parkinson's disease. There was a significant increase in the expression of importin-β and exportin-5 in Alzheimer's disease relative to the three other categories (each p value<0.0001) where each protein co-localized with hyperphosphorylated tau. Both apoptotic and anti-apoptotic proteins were each significantly increased in Alzheimer's disease relative to the three other groups. Neurons with hyperphosphorylated tau in Alzheimer's disease have the profile of metabolically active cells including increased exportin-5 and importin-β mRNA and proteins which indicates that immunohistochemistry testing of these proteins may aid the surgical pathologist in making a definitive diagnosis.
http://ift.tt/2wMps3L
Hamartia in hippocampal sclerosis-associated mesial temporal lobe epilepsy
Publication date: Available online 6 September 2017
Source:Annals of Diagnostic Pathology
Author(s): K.L. Gawelek, J.M. Gales, R.A. Prayson
Hamartia are small collections of rounded glioneuronal cells that are thought to be due to aberrant cell migration. Their presence has been recognized in association with mesial temporal lobe epilepsy; their prevalence among cases of hippocampal sclerosis (HS) and any potential association with patient demographics and outcomes is unknown. This study examines hamartia in a series of 292 patients with pathologically confirmed HS. Medical records were reviewed for pertinent patient clinical information (follow-up mean 5years). Hamartia were identified in 96 cases (33%) and were seen primarily in the amygdala (n=88) and less commonly in the hippocampus (n=10) and temporal lobe (n=4). A statistically significant relationship was found between the presence of hamartia and male gender, younger age of seizure onset, and history of childhood febrile seizures and developmental delay. It is unclear if these associations represent a real association or are a result of the underlying pathologies related to chronic epilepsy. At follow-up, there were no significant differences between patients who had hamartia and those who lacked this finding. Hamartia were observed in all subtypes of HS and there was a significant difference found in subtype distribution as well as proportion of cases between subtypes, but no association with any specific subtype overall. The presence of hamartia was not associated with the coexistence of focal cortical dysplasia or any specific histologic pattern of dysplasia. Hamartia are a common concomitant finding in HS and indicates evidence of aberrant cell migration in the hippocampal and parahippocampal regions in these patients.
http://ift.tt/2gLRKlQ
Erratum to: “Immunohistochemistry staining for mismatch repair proteins: the endoscopic biopsy material provides useful and coherent results” [Hum Pathol 2015;46:1705-1711]
Publication date: Available online 7 September 2017
Source:Human Pathology
Author(s): Alex Vilkin, Ya'ara Leibovici-Weissman, Marisa Halpern, Sara Morgenstern, Eli Brazovski, Rachel Gingold-Belfer, Nir Wasserberg, Baruch Brenner, Yaron Niv, Orly Sneh-Arbib, Zohar Levi
http://ift.tt/2xT54wv
The TREX1 Dinosaur Bites the Brain through the LINE
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): José Luis García Pérez, Marta E. Alarcón-Riquelme
In this issue of Cell Stem Cell, Thomas et al. (2017) define the nature of accumulated ssDNA present in the neuron and astrocyte cytoplasm of TREX1 mutated stem cell-derived organoids. Accumulated ssDNAs are derived from LINE-1 endogenous retroelements, providing new clues as to the development of Aicardi-Goutières syndrome in the neural system.
Teaser
In this issue of Cell Stem Cell, Thomas et al. (2017) define the nature of accumulated ssDNA present in the neuron and astrocyte cytoplasm of TREX1 mutated stem cell-derived organoids. Accumulated ssDNAs are derived from LINE-1 endogenous retroelements, providing new clues as to the development of Aicardi-Goutières syndrome in the neural system.http://ift.tt/2ePVfut
Putting Two Heads Together to Build a Better Brain
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): John K. Mich, Jennie L. Close, Boaz P. Levi
3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which can now achieve functional circuit integration.
Teaser
3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which can now achieve functional circuit integration.http://ift.tt/2j80TcA
Survival of the Fittest: Darwinian Selection Underpins Chemotherapy Resistance in AML
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Laura MacPherson, Mark A. Dawson
Intratumor heterogeneity driving therapeutic resistance is a major challenge in cancer management. Recently in Nature, Shlush et al. (2017) provide a tour de force of genomics coupled to functional assays to demonstrate that resistance emerges from a pre-existing subpopulation of acute myeloid leukemia (AML) cells with a stem cell transcription program.
Teaser
Intratumor heterogeneity driving therapeutic resistance is a major challenge in cancer management. Recently in Nature, Shlush et al. (2017) provide a tour de force of genomics coupled to functional assays to demonstrate that resistance emerges from a pre-existing subpopulation of acute myeloid leukemia (AML) cells with a stem cell transcription program.http://ift.tt/2ePV1n7
Hypothalamic Neurons Take Center Stage in the Neural Stem Cell Niche
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Julia P. Andreotti, Luiza Lousado, Luiz Alexandre V. Magno, Alexander Birbrair
Neural stem cells (NSCs) are a heterogeneous population of cells that generate new neurons in adult animals. Recently in Science, Paul et al. (2017) show that hypothalamic neurons control activation of a subset of NSCs in response to feeding, providing insights into how physiological cues may influence stem cell activation.
Teaser
Neural stem cells (NSCs) are a heterogeneous population of cells that generate new neurons in adult animals. Recently in Science, Paul et al. (2017) show that hypothalamic neurons control activation of a subset of NSCs in response to feeding, providing insights into how physiological cues may influence stem cell activation.http://ift.tt/2j8ohXB
CRISPR: Established Editor of Human Embryos?
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Xiao-Jiang Li, Zhuchi Tu, Weili Yang, Shihua Li
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.
Teaser
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.http://ift.tt/2ePK1WE
Open Sesame: Open Chromatin Regions Shed Light onto Non-coding Risk Variants
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Kun Yang, Akira Sawa
Human genetics and stem cell biology have advanced neurobiology for neurodevelopmental psychiatric disorders. In this issue of Cell Stem Cell, Forrest et al. (2017) demonstrate that studying the landscape of open chromatin regions in stem cell-derived neurons helps functional interpretation of non-coding genetic variants associated with these diseases.
Teaser
Human genetics and stem cell biology have advanced neurobiology for neurodevelopmental psychiatric disorders. In this issue of Cell Stem Cell, Forrest et al. (2017) demonstrate that studying the landscape of open chromatin regions in stem cell-derived neurons helps functional interpretation of non-coding genetic variants associated with these diseases.http://ift.tt/2j80A1q
Synergistic Engineering: Organoids Meet Organs-on-a-Chip
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Takanori Takebe, Boyang Zhang, Milica Radisic
Organoid technology and organ-on-a-chip engineering have emerged as two distinct approaches for stem cell-derived 3D tissue preparation. Their strategic integration can address each approach's limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine.
Teaser
Organoid technology and organ-on-a-chip engineering have emerged as two distinct approaches for stem cell-derived 3D tissue preparation. Their strategic integration can address each approach's limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine.http://ift.tt/2ePotK0
Mitochondrial Replacement Techniques: Remaining Ethical Challenges
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Annelien L. Bredenoord, John B. Appleby
Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.
Teaser
Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.http://ift.tt/2j824J3
MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Daniel G. Abernathy, Woo Kyung Kim, Matthew J. McCoy, Allison M. Lake, Rebecca Ouwenga, Seong Won Lee, Xiaoyun Xing, Daofeng Li, Hyung Joo Lee, Robert O. Heuckeroth, Joseph D. Dougherty, Ting Wang, Andrew S. Yoo
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9∗ and miR-124 (miR-9/9∗-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9∗-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show that ISL1 and LHX3 selectively drive conversion to a highly homogeneous population of human spinal cord motor neurons. This study shows that modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, providing a general platform for high-efficiency generation of distinct subtypes of human neurons.
Graphical abstract
Teaser
Abernathy et al. show that widespread epigenetic changes underlie miRNA-mediated direct reprogramming of primary adult human fibroblasts into neurons, revealing modular synergism between miRNAs and transcription factors to allow lineage-specific neuronal reprogramming. This work provides a platform for generating distinct subtypes of human neurons from patients.http://ift.tt/2ePZu9f
A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Jason Tchieu, Bastian Zimmer, Faranak Fattahi, Sadaf Amin, Nadja Zeltner, Shuibing Chen, Lorenz Studer
Directing the fate of human pluripotent stem cells (hPSCs) into different lineages requires variable starting conditions and components with undefined activities, introducing inconsistencies that confound reproducibility and assessment of specific perturbations. Here we introduce a simple, modular protocol for deriving the four main ectodermal lineages from hPSCs. By precisely varying FGF, BMP, WNT, and TGFβ pathway activity in a minimal, chemically defined medium, we show parallel, robust, and reproducible derivation of neuroectoderm, neural crest (NC), cranial placode (CP), and non-neural ectoderm in multiple hPSC lines, on different substrates independently of cell density. We highlight the utility of this system by interrogating the role of TFAP2 transcription factors in ectodermal differentiation, revealing the importance of TFAP2A in NC and CP specification, and performing a small-molecule screen that identified compounds that further enhance CP differentiation. This platform provides a simple stage for systematic derivation of the entire range of ectodermal cell types.
Graphical abstract
Teaser
Tchieu et al. develop a chemically defined culture platform that allows parallel derivation of human PSCs into all major ectodermal lineages. The utility of this platform is shown through genetic dissection of the roles of TFAP transcription factors in ectoderm and a chemical screen that identified compounds promoting cranial placode differentiation.http://ift.tt/2ePJqnS
ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Nicole I. Park, Paul Guilhamon, Kinjal Desai, Rochelle F. McAdam, Ellen Langille, Madlen O'Connor, Xiaoyang Lan, Heather Whetstone, Fiona J. Coutinho, Robert J. Vanner, Erick Ling, Panagiotis Prinos, Lilian Lee, Hayden Selvadurai, Gurnit Atwal, Michelle Kushida, Ian D. Clarke, Veronique Voisin, Michael D. Cusimano, Mark Bernstein, Sunit Das, Gary Bader, Cheryl H. Arrowsmith, Stephane Angers, Xi Huang, Mathieu Lupien, Peter B. Dirks
http://ift.tt/2ePFu6y
The TREX1 Dinosaur Bites the Brain through the LINE
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): José Luis García Pérez, Marta E. Alarcón-Riquelme
In this issue of Cell Stem Cell, Thomas et al. (2017) define the nature of accumulated ssDNA present in the neuron and astrocyte cytoplasm of TREX1 mutated stem cell-derived organoids. Accumulated ssDNAs are derived from LINE-1 endogenous retroelements, providing new clues as to the development of Aicardi-Goutières syndrome in the neural system.
Teaser
In this issue of Cell Stem Cell, Thomas et al. (2017) define the nature of accumulated ssDNA present in the neuron and astrocyte cytoplasm of TREX1 mutated stem cell-derived organoids. Accumulated ssDNAs are derived from LINE-1 endogenous retroelements, providing new clues as to the development of Aicardi-Goutières syndrome in the neural system.http://ift.tt/2ePVfut
Putting Two Heads Together to Build a Better Brain
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): John K. Mich, Jennie L. Close, Boaz P. Levi
3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which can now achieve functional circuit integration.
Teaser
3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which can now achieve functional circuit integration.http://ift.tt/2j80TcA
Survival of the Fittest: Darwinian Selection Underpins Chemotherapy Resistance in AML
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Laura MacPherson, Mark A. Dawson
Intratumor heterogeneity driving therapeutic resistance is a major challenge in cancer management. Recently in Nature, Shlush et al. (2017) provide a tour de force of genomics coupled to functional assays to demonstrate that resistance emerges from a pre-existing subpopulation of acute myeloid leukemia (AML) cells with a stem cell transcription program.
Teaser
Intratumor heterogeneity driving therapeutic resistance is a major challenge in cancer management. Recently in Nature, Shlush et al. (2017) provide a tour de force of genomics coupled to functional assays to demonstrate that resistance emerges from a pre-existing subpopulation of acute myeloid leukemia (AML) cells with a stem cell transcription program.http://ift.tt/2ePV1n7
Hypothalamic Neurons Take Center Stage in the Neural Stem Cell Niche
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Julia P. Andreotti, Luiza Lousado, Luiz Alexandre V. Magno, Alexander Birbrair
Neural stem cells (NSCs) are a heterogeneous population of cells that generate new neurons in adult animals. Recently in Science, Paul et al. (2017) show that hypothalamic neurons control activation of a subset of NSCs in response to feeding, providing insights into how physiological cues may influence stem cell activation.
Teaser
Neural stem cells (NSCs) are a heterogeneous population of cells that generate new neurons in adult animals. Recently in Science, Paul et al. (2017) show that hypothalamic neurons control activation of a subset of NSCs in response to feeding, providing insights into how physiological cues may influence stem cell activation.http://ift.tt/2j8ohXB
CRISPR: Established Editor of Human Embryos?
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Xiao-Jiang Li, Zhuchi Tu, Weili Yang, Shihua Li
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.
Teaser
Off-target effects and mosaicism are major concerns for applying CRISPR-Cas9 to correct genetic mutations. A recent article in Nature by Ma et al. (2017) uses an elegant CRISPR-Cas9 approach that repairs a genetic mutation in human embryos with negligible mosaicism and no off-target effects, bringing this editing tool closer to clinical application.http://ift.tt/2ePK1WE
Open Sesame: Open Chromatin Regions Shed Light onto Non-coding Risk Variants
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Kun Yang, Akira Sawa
Human genetics and stem cell biology have advanced neurobiology for neurodevelopmental psychiatric disorders. In this issue of Cell Stem Cell, Forrest et al. (2017) demonstrate that studying the landscape of open chromatin regions in stem cell-derived neurons helps functional interpretation of non-coding genetic variants associated with these diseases.
Teaser
Human genetics and stem cell biology have advanced neurobiology for neurodevelopmental psychiatric disorders. In this issue of Cell Stem Cell, Forrest et al. (2017) demonstrate that studying the landscape of open chromatin regions in stem cell-derived neurons helps functional interpretation of non-coding genetic variants associated with these diseases.http://ift.tt/2j80A1q
Synergistic Engineering: Organoids Meet Organs-on-a-Chip
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Takanori Takebe, Boyang Zhang, Milica Radisic
Organoid technology and organ-on-a-chip engineering have emerged as two distinct approaches for stem cell-derived 3D tissue preparation. Their strategic integration can address each approach's limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine.
Teaser
Organoid technology and organ-on-a-chip engineering have emerged as two distinct approaches for stem cell-derived 3D tissue preparation. Their strategic integration can address each approach's limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine.http://ift.tt/2ePotK0
Mitochondrial Replacement Techniques: Remaining Ethical Challenges
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Annelien L. Bredenoord, John B. Appleby
Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.
Teaser
Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.http://ift.tt/2j824J3
MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Daniel G. Abernathy, Woo Kyung Kim, Matthew J. McCoy, Allison M. Lake, Rebecca Ouwenga, Seong Won Lee, Xiaoyun Xing, Daofeng Li, Hyung Joo Lee, Robert O. Heuckeroth, Joseph D. Dougherty, Ting Wang, Andrew S. Yoo
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9∗ and miR-124 (miR-9/9∗-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9∗-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show that ISL1 and LHX3 selectively drive conversion to a highly homogeneous population of human spinal cord motor neurons. This study shows that modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, providing a general platform for high-efficiency generation of distinct subtypes of human neurons.
Graphical abstract
Teaser
Abernathy et al. show that widespread epigenetic changes underlie miRNA-mediated direct reprogramming of primary adult human fibroblasts into neurons, revealing modular synergism between miRNAs and transcription factors to allow lineage-specific neuronal reprogramming. This work provides a platform for generating distinct subtypes of human neurons from patients.http://ift.tt/2ePZu9f
A Modular Platform for Differentiation of Human PSCs into All Major Ectodermal Lineages
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Jason Tchieu, Bastian Zimmer, Faranak Fattahi, Sadaf Amin, Nadja Zeltner, Shuibing Chen, Lorenz Studer
Directing the fate of human pluripotent stem cells (hPSCs) into different lineages requires variable starting conditions and components with undefined activities, introducing inconsistencies that confound reproducibility and assessment of specific perturbations. Here we introduce a simple, modular protocol for deriving the four main ectodermal lineages from hPSCs. By precisely varying FGF, BMP, WNT, and TGFβ pathway activity in a minimal, chemically defined medium, we show parallel, robust, and reproducible derivation of neuroectoderm, neural crest (NC), cranial placode (CP), and non-neural ectoderm in multiple hPSC lines, on different substrates independently of cell density. We highlight the utility of this system by interrogating the role of TFAP2 transcription factors in ectodermal differentiation, revealing the importance of TFAP2A in NC and CP specification, and performing a small-molecule screen that identified compounds that further enhance CP differentiation. This platform provides a simple stage for systematic derivation of the entire range of ectodermal cell types.
Graphical abstract
Teaser
Tchieu et al. develop a chemically defined culture platform that allows parallel derivation of human PSCs into all major ectodermal lineages. The utility of this platform is shown through genetic dissection of the roles of TFAP transcription factors in ectoderm and a chemical screen that identified compounds promoting cranial placode differentiation.http://ift.tt/2ePJqnS
ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells
Publication date: 7 September 2017
Source:Cell Stem Cell, Volume 21, Issue 3
Author(s): Nicole I. Park, Paul Guilhamon, Kinjal Desai, Rochelle F. McAdam, Ellen Langille, Madlen O'Connor, Xiaoyang Lan, Heather Whetstone, Fiona J. Coutinho, Robert J. Vanner, Erick Ling, Panagiotis Prinos, Lilian Lee, Hayden Selvadurai, Gurnit Atwal, Michelle Kushida, Ian D. Clarke, Veronique Voisin, Michael D. Cusimano, Mark Bernstein, Sunit Das, Gary Bader, Cheryl H. Arrowsmith, Stephane Angers, Xi Huang, Mathieu Lupien, Peter B. Dirks
http://ift.tt/2ePFu6y
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