Condition: Metastatic Gastro-esophageal Adenocarcinoma
Intervention: Drug: FOLFOX and FOLFIRI
Sponsor: University of Saskatchewan
Not yet recruiting
https://ift.tt/2KA1Djy
Παρασκευή 18 Μαΐου 2018
Cytosponge™ for Post‐Chemoradiation Surveillance of Oesophageal Cancer
Condition: Oesophageal Cancer
Intervention: Device: Cytosponge™
Sponsors: University of Oxford; Centre for Statistics in Medicine; CRUK Population Research Committee; Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology; MRC Cancer Cell Unit Hutchison‐MRC Research Centre, University of Cambridge; Cambridge University Hospitals NHS Foundation Trust
Recruiting
https://ift.tt/2LeoKBA
Intervention: Device: Cytosponge™
Sponsors: University of Oxford; Centre for Statistics in Medicine; CRUK Population Research Committee; Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology; MRC Cancer Cell Unit Hutchison‐MRC Research Centre, University of Cambridge; Cambridge University Hospitals NHS Foundation Trust
Recruiting
https://ift.tt/2LeoKBA
Study of Porcine Fibrin Sealant in Preventing Cervical Anastomotic Leakage After Esophagectomy for Esophageal Carcinoma.
Conditions: Esophageal Cancer; Gastroesophageal Junction Cancer; Anastomotic Leak
Interventions: Biological: Porcine Fibrin Sealant (PFS); Procedure: Surgery
Sponsor: Sun Yat-sen University
Recruiting
https://ift.tt/2Iv4pWI
Interventions: Biological: Porcine Fibrin Sealant (PFS); Procedure: Surgery
Sponsor: Sun Yat-sen University
Recruiting
https://ift.tt/2Iv4pWI
Phase I Durvalumab and Tremelimumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN
Conditions: Larynx; Lip; Oral Cancer; Digestive Organs--Diseases
Interventions: Drug: Durvalumab; Radiation: Intensity Modulated Radiotherapy Treatments; Drug: Tremelimumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; AstraZeneca
Not yet recruiting
https://ift.tt/2L6RvQB
Interventions: Drug: Durvalumab; Radiation: Intensity Modulated Radiotherapy Treatments; Drug: Tremelimumab
Sponsors: UNC Lineberger Comprehensive Cancer Center; AstraZeneca
Not yet recruiting
https://ift.tt/2L6RvQB
Short-term Effect of Chewing Gum in Patients With Mild-moderate Dysphagia After Anterior Cervical Fusion
Condition: Dysphagia
Intervention: Other: chewing gum
Sponsor: Guangdong General Hospital
Recruiting
https://ift.tt/2Iv55eI
Intervention: Other: chewing gum
Sponsor: Guangdong General Hospital
Recruiting
https://ift.tt/2Iv55eI
Scholar : Journal of Clinical and Experimental Neuropsychology, Volume 40, Issue 6, August 2018 is now available online on Taylor & Francis Online
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How do I stop my hair from being dry?
Many people have problems with their hair becoming brittle or dry. Medical conditions may be the cause, but it is often down to lifestyle or personal hygiene habits. Potential remedies are diverse and often simple, and we give 12 here, including oils and plant products that make good conditioners and hair masks.
https://ift.tt/2wUIt66
Scholar : Aging, Neuropsychology, and Cognition, Volume 25, Issue 4, July 2018 is now available online on Taylor & Francis Online
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Scholar : These new articles for American Review of Canadian Studies are available online
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Filtration membranes - Scavengers for leachables?
Publication date: 30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Armin Hauk, Elke Jurkiewicz, Ina Pahl, Thomas Loewe, Roberto Menzel
This publication describes the development of an experimental set-up and testing protocol to test the hypothesis that filters used for sterile filtration can act as scavengers of leachables. The filter materials polyethersulfone (PESU) and cellulose acetate (CA) were tested. These membrane materials are used commonly in downstream operations during biopharmaceutical manufacturing. A solution containing a mixture of eight typical leachables was filtered through the respective filter and the eluate was monitored by HPLC-UV in order to quantify these leachables model compounds (LMC). The results show that substances are efficiently scavenged from an aqueous solution depending on their molecular structure and the filter type used. A mass balance was established by recovering the LMCs from the filters by rinsing the membranes with an organic solvent. Breakthrough curves were determined experimentally and substance specific filter capacities for the individual LMCs are presented. The surface specific filter capacity for the different LMCs range from <0.7 to 45 μg/cm2. An extrapolation of these filter scavenging capacities to process conditions, where the filtration areas can be many square-meters in size, gives indication that the potential removal of expectable process-related leachables during filtration in downstream processing should not be underestimated. The capacity of a filter for the leachable bDtBPP, which is known to inhibit cell growth, was determined in samples after a buffer sterile-filtration using a standardized cell-culture test with CHO cells. The specific filter capacity of bDtBPP obtained with the cell-culture test was nearly identical to the analytically derived result. As outlook, the scavenger effect of a filter is demonstrated for media solutions containing buffer and model proteins.
Graphical abstract
https://ift.tt/2GuIpJU
Metastatic melanoma with balloon/histiocytoid cytomorphology after treatment with immunotherapy: A histologic mimic and diagnostic pitfall
Journal of Cutaneous Pathology, EarlyView.
https://ift.tt/2IO5Enf
Automated Comprehensive Adolescent Idiopathic Scoliosis Assessment using MVC-Net
Publication date: Available online 18 May 2018
Source:Medical Image Analysis
Author(s): Hongbo Wu, Chris Bailey, Parham Rasoulinejad, Shuo Li
Automated quantitative estimation of spinal curvature is an important task for the ongoing evaluation and treatment planning of Adolescent Idiopathic Scoliosis (AIS). It solves the widely accepted disadvantage of manual Cobb angle measurement (time-consuming and unreliable) which is currently the gold standard for AIS assessment. Attempts have been made to improve the reliability of automated Cobb angle estimation. However, it is very challenging to achieve accurate and robust estimation of Cobb angles due to the need for correctly identifying all the required vertebrae in both Anterior-posterior (AP) and Lateral (LAT) view x-rays. The challenge is especially evident in LAT x-ray where occlusion of vertebrae by the ribcage occurs. We therefore propose a novel Multi-View Correlation Network (MVC-Net) architecture that can provide a fully automated end-to-end framework for spinal curvature estimation in multi-view (both AP and LAT) x-rays. The proposed MVC-Net uses our newly designed multi-view convolution layers to incorporate joint features of multi-view x-rays, which allows the network to mitigate the occlusion problem by utilizing the structural dependencies of the two views. The MVC-Net consists of three closely-linked components: (1) a series of X-modules for joint representation of spinal structure (2) a Spinal Landmark Estimator network for robust spinal landmark estimation, and (3) a Cobb Angle Estimator network for accurate Cobb Angles estimation. By utilizing an iterative multi-task training algorithm to train the Spinal Landmark Estimator and Cobb Angle Estimator in tandem, the MVC-Net leverages the multi-task relationship between landmark and angle estimation to reliably detect all the required vertebrae for accurate Cobb angles estimation. Experimental results on 526 x-ray images from 154 patients show an impressive 4.04° Circular Mean Absolute Error (CMAE) in AP Cobb angle and 4.07° CMAE in LAT Cobb angle estimation, which demonstrates the MVC-Net's capability of robust and accurate estimation of Cobb angles in multi-view x-rays. Our method therefore provides clinicians with a framework for efficient, accurate, and reliable estimation of spinal curvature for comprehensive AIS assessment.
https://ift.tt/2IRXJFw
The challenge of cerebral magnetic resonance imaging in neonates: A new method using mathematical morphology for the segmentation of structures including diffuse excessive high signal intensities.
Publication date: Available online 17 May 2018
Source:Medical Image Analysis
Author(s): Yongchao Xu, Baptiste Morel, Sonia Dahdouh, Élodie Puybareau, Alessio Virzí, Héléne Urien, Thierry Géraud, Catherine Adamsbaum, Isabelle Bloch
Preterm birth is a multifactorial condition associated with increased morbidity and mortality. Diffuse excessive high signal intensity (DEHSI) has been recently described on T2-weighted MR sequences in this population and thought to be associated with neuropathologies. To date, no robust and reproducible method to assess the presence of white matter hyperintensities has been developed, perhaps explaining the current controversy over their prognostic value. The aim of this paper is to propose a new semi-automated framework to detect DEHSI on neonatal brain MR images having a particular pattern due to the physiological lack of complete myelination of the white matter. A novel method for semi- automatic segmentation of neonatal brain structures and DEHSI, based on mathematical morphology and on max-tree representations of the images is thus described. It is a mandatory first step to identify and clinically assess homogeneous cohorts of neonates for DEHSI and/or volume of any other segmented structures. Implemented in a user-friendly interface, the method makes it straightforward to select relevant markers of structures to be segmented, and if needed, apply eventually manual corrections. This method responds to the increasing need for providing medical experts with semi-automatic tools for image analysis, and overcomes the limitations of visual analysis alone, prone to subjectivity and variability. Experimental results demonstrate that the method is accurate, with excellent reproducibility and with very few manual corrections needed. Although the method was intended initially for images acquired at 1.5T, which corresponds to the usual clinical practice, preliminary results on images acquired at 3T suggest that the proposed approach can be generalized.
Graphical abstract
https://ift.tt/2wPhngw
Oncocytic Melanoma: A Study of a Rare Entity
Abstract: The authors report the second case of oncocytic melanoma, one of the rarest known melanoma variants. The diagnosis was established by Fontana stain positivity, expression of S100 protein as well as gp100/HMB45, and demonstration of numerous mitochondria by ultrastructure. Because it is known that some oncocytic tumors of the thyroid gland and kidney contain point mutations and common deletions of mitochondrial DNA, the complete mitochondrial DNA of the reported oncocytic melanoma was also studied. It was normal except for 2 private separate point mutations, predicted to be not pathogenic, which do not seem to play any role in the tumor phenotype. Correspondence: Ludvik R. Donner, MD, PhD, Department of Pathology, Baylor Scott & White Health, Texas A&M College of Medicine, 2401 South 31st Street, Temple, TX 76508 (e-mail: basnikhromobiti70@gmail.com). Supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia—in the framework of project UID/BIM/04293/2013. It was also financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). Further funding was obtained from the project "Advancing cancer research: from basic knowledgment to application" NORTE-01-0145-FEDER-000029: "Projetos Estruturados de I&D&I," funded by Norte 2020—Programa Operacional Regional do Norte. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2KzItKB
https://ift.tt/2KzItKB
Heavily Pigmented Epithelioid Melanoma With Loss of Protein Kinase A Regulatory Subunit-α Expression
Abstract: Heavily pigmented melanocytic neoplasms are genotypically and phenotypically diverse. Recently, a subset of this histopathologic spectrum was shown to harbor recurrent genetic alterations in the gene-encoding protein kinase A regulatory subunit-α (PRKAR1A). To date, no histopathologic descriptions of melanomas arising from this pathway have been described. We present a case of a darkly pigmented papule arising on the posterior neck of a 28-year-old man. Microscopically, the heavily pigmented compound melanocytic proliferation was centered in the dermis with permeation into the superficial subcutis. Tumor cells were arranged in large confluent nests and fascicles and lacked maturation with descent. The epithelioid melanocytes were characterized by enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, and plentiful gray-brown granular cytoplasm. Mitotic figures were readily identified. By immunohistochemistry, melanocytes were positive for mutant BRAF V600E and showed loss of Prkar1α and p16 expression. A multiplex MART-1/tyrosinase/phosophohistone-H3 immunostain demonstrated an increased mitotic index in melanocytes. The combination of highly atypical cytomorphology and architecture, increased mitoses, and p16 expression loss compelled the diagnosis of melanoma. Overall, we present the first clinicopathologic description of a PRKAR1A-inactivated melanoma to highlight morphological features and discuss mimics that may enter the differential diagnosis. Correspondence: Timothy H. McCalmont, MD (e-mail: Tim.McCalmont@ucsf.edu). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2Lah2bH
https://ift.tt/2Lah2bH
Plexiform Atypical Spitz Tumor With Rosette-Like Giant Cells. A Histologic and Immunohistochemical Study on a Case Suggesting Ganglioneuroblastic Differentiation. Review of the Literature and Considerations on Histogenesis
Abstract: Spitz nevi, atypical Spitz tumors and Spitzoid melanoma, the three clinicopathologic forms that constitute the spectrum of the Spitz-type melanocytic lesions, share a histologic picture characterized by large spindle and/or epithelioid ganglion-like cells, with various admixtures of multinucleate bizarre cells. This remarkable cytology has always been interpreted as an unusual, as well as unexplained form of atypia. We report a case of atypical Spitz tumor with Homer Wright–like rosettes, a feature characteristic of ganglioneuroblastic proliferation. Furthermore, the ganglion-like cells of the tumor showed basophilic punctuation in the cytoplasm, reminiscent of Nissl substance, and a few cells, whether spindled or epithelioid, were positive to neuron-specific enolase and glial fibrillary acid protein. Based on our findings, we hypothesize that the outstanding similarity of the ganglion-like cells of Spitz tumors to the normal parasympathetic ganglion cells and to the cells of ganglioneuroma and ganglioneuroblastoma may not be fortuitous. Instead, it may represent the expression of a specific pattern of melanocytic differentiation, analogous to the neurotization of common and cellular blue nevi, although in this case, it would privilege the parasympathetic lineage over the Schwannian, perineural, or endoneural pathway. Our hypothesis is supported by the literature reports of rosette formation and frank ganglioneuroblastic differentiation in Spitz tumors and melanoma and by the demonstration that parasympathetic neurons take origin from the same tracts of the neural crest as other neural and melanocytic cells. Correspondence: Elena Castelli, MD, Department of Biomedicine, Internal Medicine and Specialized Medicine (DIBIMIS), Section Dermatology, University of Palermo, AOUP Paolo Giaccone, Via del Vespro 131, 90127 Palermo, Italy (e-mail: elena.castelli@unipa.it). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2KzhUVX
https://ift.tt/2KzhUVX
Residue behavior and risk assessment of thifluzamide in the maize field ecosystem
Abstract
In the present work, the dissipation kinetics and final residue levels of thifluzamide in the maize field ecosystem were investigated. Using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction combined with liquid chromatography-tandem mass spectrometric detection (LC-MS/MS), a rapid, sensitive, efficient, and reliable method for extraction and quantitative analysis of thifluzamide residues in maize grain, maize plant, and soil was developed. Satisfactory recoveries of 78.7–97.0% were achieved with relative standard deviations (RSDs) in the range of 1.6 to 8.2%. The limits of detection (LODs) and the limit of quantification (LOQ) were 0.002–0.005 and 0.010 mg kg−1, respectively. The dissipation kinetics of thifluzamide in maize plant was well fitted by the first-order kinetic model with short half-lives of 0.19–0.22 days, while thifluzamide degraded slowly in soil with half-lives of 4.56–15.85 days. The final residues in maize grain, maize plant, and soil samples collected at the milk stage and the physiological maturity stage were no more than 0.010, 0.807, and 0.278 mg kg−1, respectively. Given that no maximum residue limit (MRL) for thifluzamide in maize has been established, the safety of this fungicide application was estimated by a dietary risk assessment. The hazard quotient was 0.03%, which was substantially less than 1, indicating that the long-term risk induced by the thifluzamide application on maize at the recommended dose is negligible. These results help governments to develop regulations for the safe use of thifluzamide.
https://ift.tt/2IskUqv
A 2Ma old baboon-like monkey from Northern Greece and new evidence to support the Paradolichopithecus – Procynocephalus synonymy (Primates: Cercopithecidae)
Publication date: Available online 18 May 2018
Source:Journal of Human Evolution
Author(s): Dimitris S. Kostopoulos, Franck Guy, Zoi Kynigopoulou, George D. Koufos, Xavier Valentin, Gildas Merceron
A new fossil cranium of a large papionin monkey from the Lower Pleistocene site of Dafnero-3 in Western Macedonia, Greece, is described by means of outer and inner morphological and metric traits using high-resolution micro-computed tomography. Comparisons with modern cercopithecids and contemporaneous Eurasian fossil taxa suggest that the new cranium could equally be ascribed to either the Eurasian Paradolichopithecus or to the East Asian Procynocephalus. The combination of the available direct and indirect fossil evidence, including the new cranium from Dafnero, revives an earlier hypothesis that considers these two sparsely documented genera as synonyms. The timing and possible causes of the rise and demise of Paradolichopithecus - Procynocephalus are discussed.
https://ift.tt/2Lbl9UP
Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development
Abstract
The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.https://ift.tt/2rX9Mam
Intrinsic Functional Connectivity Resembles Cortical Architecture at Various Levels of Isoflurane Anesthesia
Abstract
Cortical single neuron activity and local field potential patterns change at different depths of general anesthesia. Here, we investigate the associated network level changes of functional connectivity. We recorded ongoing electrocorticographic (ECoG) activity from temporo-parieto-occipital cortex of 6 ferrets at various levels of isoflurane/nitrous oxide anesthesia and determined functional connectivity by computing amplitude envelope correlations. Through hierarchical clustering, we derived typical connectivity patterns corresponding to light, intermediate and deep anesthesia. Generally, amplitude correlation strength increased strongly with depth of anesthesia across all cortical areas and frequency bands. This was accompanied, at the deepest level, by the emergence of burst-suppression activity in the ECoG signal and a change of the spectrum of the amplitude envelope. Normalization of functional connectivity to the distribution of correlation coefficients showed that the topographical patterns remained similar across depths of anesthesia, reflecting the functional association of the underlying cortical areas. Thus, while strength and temporal properties of amplitude co-modulation vary depending on the activity of local neural circuits, their network-level interaction pattern is presumably most strongly determined by the underlying structural connectivity.https://ift.tt/2k6giI4
Prior Knowledge Guides Speech Segregation in Human Auditory Cortex
Abstract
Segregating concurrent sound streams is a computationally challenging task that requires integrating bottom-up acoustic cues (e.g. pitch) and top-down prior knowledge about sound streams. In a multi-talker environment, the brain can segregate different speakers in about 100 ms in auditory cortex. Here, we used magnetoencephalographic (MEG) recordings to investigate the temporal and spatial signature of how the brain utilizes prior knowledge to segregate 2 speech streams from the same speaker, which can hardly be separated based on bottom-up acoustic cues. In a primed condition, the participants know the target speech stream in advance while in an unprimed condition no such prior knowledge is available. Neural encoding of each speech stream is characterized by the MEG responses tracking the speech envelope. We demonstrate that an effect in bilateral superior temporal gyrus and superior temporal sulcus is much stronger in the primed condition than in the unprimed condition. Priming effects are observed at about 100 ms latency and last more than 600 ms. Interestingly, prior knowledge about the target stream facilitates speech segregation by mainly suppressing the neural tracking of the non-target speech stream. In sum, prior knowledge leads to reliable speech segregation in auditory cortex, even in the absence of reliable bottom-up speech segregation cue.https://ift.tt/2rQWLPq
CdSe/ZnS QD@CNT nanocomposite photocathode for improvement on charge overpotential in photoelectrochemical Li-O2 batteries
Publication date: 1 October 2018
Source:Chemical Engineering Journal, Volume 349
Author(s): Vediyappan Veeramani, Yu-Hsiang Chen, Hung-Chia Wang, Tai-Feng Hung, Wen-Sheng Chang, Da-Hua Wei, Shu-Fen Hu, Ru-Shi Liu
Li-ion batteries play a significant role in portable electronic devices in the running world. However, the limited energy density still needs to be improved for the growing future. Hence, we developed a photocathode nanocomposite material composed of Cadmium Selenide/Zinc Sulfide Quantum Dots with Carbon nanotube (CdSe/ZnS QD@CNT) for an efficient and tunable performance of the photoelectrochemical Li–O2 battery system to overcome the key issue of overpotential. The QD and CNT networks can provide efficient transportation paths of the electron–hole pairs and the O2 gas and lithium ions, respectively. The charging voltage of the photoelectrode is 2.65–4.0 V; therefore, decreased overpotential was due to efficient oxidation of Li2O2 by photoexcited electron–hole pairs by using QDs, resulting in a long-term operational stability over 100 cycles. On the basis of the advantages, the QDs exhibit efficient potential in Li–O2 batteries.
Graphical abstract
https://ift.tt/2k8icry
Metal based triazole compounds: Their synthesis, computational, antioxidant, enzyme inhibition and antimicrobial properties
Publication date: 15 September 2018
Source:Journal of Molecular Structure, Volume 1168
Author(s): Sajjad Hussain Sumrra, Samia Kausar, Muhammad Asam Raza, Muhammad Zubair, Muhammad Nadeem Zafar, Muhammad Arif Nadeem, Ehsan Ullah Mughal, Zahid Hussain Chohan, Fazila Mushtaq, Umer Rashid
The present research work was aimed to synthesize biologically active Schiff base compound, 2-{(E)-[(3-{[(Z)-(2-hydroxyphenyl)methylidene]amino}-1H-1,2,4-triazol-5-yl)imino]methyl}phenol(L) by condensation reaction of 2-hydroxybenzaldehyde with 3,5-diamino-1,2,4-triazole. In order to evaluate the effect of metal ions on the biological properties, ligand (L) was then coordinated to the metal ions such as Fe(II), Co(II), Cu(II), Ni(II) and Zn(II). Characterization of ligand and its metal complexes was done by physical, spectral and analytical data. The synthesized compounds were screened for antioxidant, enzyme inhibition and antibacterial/antifungal activities. The screening results indicated the ligand to possess bioactivity which significantly enhanced upon chelation/coordination with the metal ions. Computational studies were also carried out on the ligand to check orbital involvement and bonding interactions. The optimized frequency, intensity and geometry of the vibrational bands of ligand (L) were obtained through density functional theory (DFT) using 6–311++G (d.p) basis sets. Molecular stability and bond strength were also studied by carrying out the natural bond orbital analysis (NBO). The calculated HOMO and LUMO energies confirmed the charge transfer in the molecule of ligand.
Graphical abstract
https://ift.tt/2rV0wTM
The natural agent 4-vinylphenol targets metastasis and stemness features in breast cancer stem-like cells
Abstract
Background and purpose
Cancer stem-like cells (CSC) are regarded as the source of tumour origins, metastasis and drug resistance, and limits current treatment regimens. Previously, we reported the first study of the anti-angiogenic and anti-tumour activities of 4-vinylphenol. To further examine the therapeutic role of 4-vinylphenol, the inhibitory effects of 4-vinylphenol on cancer stemness, drug resistance and metastasis in breast cancer were investigated in the present study.
Study design and methods
We enriched parental MDA-MB-231 cells with CSCs in serum-free medium to give spheroids. The effects of 4-vinylphenol on cancer stemness, metastasis and drug resistance in CSC-enriched MDA-MB-231 cells were studied in vitro and in vivo.
Results
CSC-enriched MDA-MB-231 cells demonstrated higher tumorigenic and metastatic potential. 4-Vinylphenol reduced spheroid formation and ALDH1 expression in CSC-enriched cultures, revealing its inhibitory effects on the traits of CSCs. 4-Vinylphenol suppressed colony formation and cell proliferation. 4VP also inhibited in vitro invasion and in vivo metastasis in zebrafish model. Our results showed that it reduced vimentin expression, suppressed cell migration, affected the expression and/or activity of MMPs, TIMPs and uPA. In addition, the expressions of caspases 3 and 9 were increased upon its treatment, and surprisingly, prolonged treatment did not confer cancer cells with drug resistance to 4-vinylphenol. 4-Vinylphenol probably exhibited its anti-cancer activities via beta-catenin, EGFR and AKT signaling pathways.
Conclusion
4-Vinylphenol was shown to inhibit metastasis and cancer stemness in CSC-enriched breast cancer cells. Since conventional therapies not targeting CSCs possibly lead to failure to eliminate cancer, 4-vinylphenol is a highly potential therapeutic agent for breast cancer patients.
https://ift.tt/2ISk1Ho
Traitement chirurgical des cancers bronchiques non à petites cellules (CBNPC) de stade précoce par segmentectomie à thorax fermé : résultats préliminaires
Publication date: Available online 18 May 2018
Source:Revue des Maladies Respiratoires
Author(s): A. Seguin-Givelet, J. Lutz, E. Brian, M. Grigoroiu, D. Gossot
Le taux de résections infra-lobaires anatomiques (RILA) pour cancer bronchique non à petites cellules (CBNPC) de stade précoce est en progression. Cependant les indications restent controversées. Le but de cette étude est d'analyser les résultats préliminaires des RILA à thorax fermé dans le traitement des CBNPC de stade précoce, en termes de complications, de validité carcinologique et de survie. Nous rapportons les résultats préliminaires d'une série consécutive de 226 segmentectomies à thorax fermé pour suspicion de CBNPC de stade précoce.Patients et méthodesEntre 2007 et 2016, nous avons réalisé 322 RILA par thoracoscopie, dont 226 pour une suspicion de CBNPC de stade précoce chez 222 patients. Les données, entrées prospectivement, ont été analysées de façon rétrospective en intention de traiter. La survie globale et sans récidive a été estimée par une courbe de Kaplan-Meier et les différences calculées par un test de log-rank.RésultatsVingt-deux patients avaient un stade p supérieur à leur stade c (10,4 %) : 10 patients pour une atteinte T3 ou T4, 6 patients pour une atteinte N1 et 6 autres pour une atteinte N2. Sur les six atteintes N1, trois ont été découvertes en peropératoire sur l'examen extemporané des ganglions intersegmentaires et ont amené à convertir la segmentectomie en lobectomie. Dix conversions en thoracotomie ont été réalisées (3,9 %). Dix-sept patients ont eu une résection plus étendue que prévue (7,5 %), le plus souvent pour raison carcinologique : ganglion intersegmentaire envahi (n=3) ou marge de résection insuffisante sur le plan intersegmentaire (n=7) en examen extemporané. La morbidité et la mortalité ont été respectivement de 25,7 % et de 1,3 %. Pour les cancers pT1aN0, les survies globales et sans récidive à 3 ans ont été respectivement de 87,1 % et 80,6 %. Pour les cancers pT1bN0, ces survies ont été respectivement de 88,8 % et 75,3 %.ConclusionDans les CBNPC de stade précoce, les RILA par thoracoscopie permettent de réduire la morbidité peropératoire tout en offrant une survie satisfaisante. Toutefois, une technique rigoureuse doit être appliquée pour diminuer le taux de conversion en thoracotomie et le taux de résection étendue (transformation en lobectomie) lorsque cela s'avère nécessaire sur le plan carcinologique.The rate of segmental resection for early stage non-small cell lung carcinoma (NSCLC) is increasing. However, the indications remain controversial. The aim of this study is to analyze the preliminary results of thoracoscopic segmental resection in early stage NSCLC in terms of morbidity, oncological validity and survival. We report the preliminary results of a consecutive series of 226 thoracoscopic segmentectomies for suspicion of early stage NSCLC.Patients and methodsBetween 2007 and 2016, we performed 322 thoracoscopic anatomical sublobar resections (ASLR). Two hundred and twenty six of these were for suspicion of early stage NSCLC in 222 patients. Data were recorded prospectively and analysed retrospectively on an intent-to-treat basis. Overall and disease-free survivals were estimated on a Kaplan-Meier curve and differences were calculated by a log-rank test.ResultsTwenty-two patients were upstaged (10.4%), in 10 cases to T3 or T4, in 6 cases to N1 and in 6 others to N2 for metastasis. Out of the 6 N1 cases, 3 were discovered at frozen section and resulted in a switch from segmentectomy to lobectomy. There were 10 conversions to thoracotomy (3.9%). Seventeen patients had a more extensive resection than initially planned (7.5%), most often for oncological reasons: invasion of intersegmental lymph nodes (n=3) or insufficient resection margin at frozen section (n=7). Morbidity and mortality were 25.7% and 1.3 % respectively. For pT1aN0 carcinomas, overall and disease-free survivals were 87.1% and 80.6%, respectively. For pT1bN0 carcinomas, overall and disease-free survivals were 88.8 %, and 75.3% respectively.ConclusionFor early stage NSCLC, thoracoscopic ASLR allows reduced perioperative morbidity while offering satisfactory survival. However, a rigorous technique must be applied to reduce the rates of conversion to thoracotomy and extension to lobectomy when required for oncological reasons.
https://ift.tt/2IM46KH
Une complication inhabituelle d'une crise d’asthme sévère
Publication date: Available online 18 May 2018
Source:Revue des Maladies Respiratoires
Author(s): S. Niang, M. Diedhiou, A. Ndichout
https://ift.tt/2IyF3Yg
Πέμπτη 17 Μαΐου 2018
NonScarring Diffuse Hair Loss in Women: a Clinico‐Etiological Study from tertiary care center in North‐West India
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2IPhltR
Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years
Clinical Endocrinology, EarlyView.
https://ift.tt/2rRxWUh
Identification of tumor margins using diffuse reflectance spectroscopy with an extended‐wavelength spectrum in a porcine model
Skin Research and Technology, EarlyView.
https://ift.tt/2INRB1g
Violaceous papules on the hands
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2wR9MOv
A simple and cost‐efficient adherent culture platform for human gastric primary cells, as an in vitro model for Helicobacter pylori infection
Helicobacter, EarlyView.
https://ift.tt/2L5DXot
Glucocorticoid withdrawal affects stress‐induced changes in urocortin 2 gene expression in the rat adrenal medulla and brain
Journal of Neuroendocrinology, Volume 30, Issue 5, May 2018.
https://ift.tt/2k66IVz
Oxytocin levels in saliva correlate better than plasma levels with concentrations in the cerebrospinal fluid of patients in neurocritical care
Journal of Neuroendocrinology, Volume 30, Issue 5, May 2018.
https://ift.tt/2rSU1kq
The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase
Publication date: Available online 17 May 2018
Source:Cell Metabolism
Author(s): Phillip J. White, Robert W. McGarrah, Paul A. Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M. Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L. Lapworth, Inna Astapova, Sarah A. Hannou, Tabitha George, Michelle Arlotto, Lyra B. Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A. Herman, R. Max Wynn, David T. Chuang, Christopher B. Newgard
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Hepatic overexpression of BDK increased ACL phosphorylation and activated de novo lipogenesis. BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding or expression of the ChREBP-β transcription factor. These studies identify BDK and PPM1K as a ChREBP-regulated node that integrates BCAA and lipid metabolism. Moreover, manipulation of the BDK:PPM1K ratio relieves key metabolic disease phenotypes in a genetic model of severe obesity.
Graphical abstract
Teaser
Branched-chain amino acids (BCAA) are strongly associated with metabolic diseases. White et al. demonstrate that the kinase (BDK) and phosphatase (PPM1K) that regulate a rate-limiting BCAA metabolic enzyme, BCKDH, also regulate ATP-citrate lyase, a key lipogenic enzyme, thus identifying a new regulatory node that integrates BCAA and lipid metabolism.https://ift.tt/2wXrDmW
Testosterone induced downregulation of migration and proliferation in human Umbilical Vein Endothelial Cells by Androgen Receptor dependent and independent mechanisms
Publication date: Available online 17 May 2018
Source:Molecular and Cellular Endocrinology
Author(s): Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova
Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools. At a concentration of 1 μM, T downregulated the proliferation of HUVEC by inducing arrest in the G1 cell cycle phase in an Androgen Receptor (AR)-independent manner. We show that upon treatment with 1 μM T also induced downregulation of HUVEC migration. This process was AR-dependent and was associated with persistent phosphorylation of ezrin, radixin and moesin. Regardless of the mechanism of action, the treatment of HUVEC with both supra- and physiological doses of T was associated with posttranscriptional stabilization of the AR upon ligand binding.
https://ift.tt/2rQiPKU
Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Longwang Chen, Yang Lu, Linjun Zhao, Lili Hu, Qiaomeng Qiu, Zhuoling Zhang, Mengfang Li, Guangliang Hong, Bing Wu, Guangju Zhao, Zhongqiu Lu
Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4+CD25+regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis.
https://ift.tt/2Gtvsjx
Molecular analysis in liquid biopsies for diagnostics of primary central nervous system lymphoma: review of literature and future opportunities
Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Laura S. Hiemcke-Jiwa, Roos J. Leguit, Tom J. Snijders, N. Mehdi Jiwa, Jonas. J.W. Kuiper, Roel A. de Weger, Monique C. Minnema, Manon M.H. Huibers
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with a poor prognosis, for which accurate and timely diagnosis is of utmost importance. Unfortunately, diagnosis of PCNSL can be challenging and a brain biopsy (gold standard for diagnosis) is an invasive procedure with the risk of major complications. Thus, there is an urgent need for an alternative strategy to diagnose and monitor these lymphomas.Currently, liquid biopsies from cerebrospinal fluid (CSF) are used for cytomorphologic and flow cytometric analysis. Recently, new biomarkers such as genetic mutations and interleukins have been identified in these liquid biopsies, further expanding the diagnostic armamentarium.In this review we present an overview of genetic aberrations (>70) reported in this unique lymphoma. Of these genes, we have selected those that are reported in ≥3 studies. Half of the selected genes are implicated in the NFκB pathway (CARD11, CD79B, MYD88, TBL1XR1 and TNFAIP3), while the other half are not related to this pathway (CDKN2A, ETV6, PIM1, PRDM1 and TOX). Although this underlines the crucial role of the NFκB pathway in PCNSL, CD79B and MYD88 are at present the only genes mentioned in liquid biopsy analysis.Finally, a stepwise approach is proposed for minimally invasive liquid biopsy analysis and work-up of PCNSL, incorporating molecular analysis. Prioritization and refinements of this approach can be constructed based upon multidisciplinary collaboration as well as novel scientific insights.
https://ift.tt/2IN5yfD
A network meta-analysis of the treatments for esophageal squamous cell carcinoma in terms of survival
Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Amin Doosti-Irani, Kourosh Holakouie-Naieni, Abbas Rahimi-Foroushani, Mohammad Ali Mansournia, Peiman Haddad
We aimed to compare treatments for patients with esophageal squamous cell carcinoma (SCC) in terms of survival.Medline, Web of Science, Scopus, the Cochrane Library and Embase were searched. Randomized controlled trials (RCT) that had compared esophageal SCC treatments were included. The hazard ratio (HR) with 95% credible interval (CrI) was used to summarize the effect measures in the Bayesian network meta-analysis.Out of 23256 references, 43 RCTs with 34 treatments were included. Carboplatin and paclitaxel plus radiotherapy plus surgery (carbo-pacli + RT + S) compared with surgery alone decreased risk of death (HR = 0.49; 95% CrI: 0.26, 0.90). The HRs for carbo-pacli + RT + S versus surgery plus cisplatin and fluorouracil and surgery plus cisplatin and vindesine were 0.44 (0.22, 0.86) and 0.41 (0.20, 0.83), respectively. Among all treatments in network, carbo-pacli + RT + S ranked as first treatment.It seems carbo-pacli + RT + S was a better treatment among available treatments in network in terms of survival in patients with esophageal SCC.
https://ift.tt/2x08DEL
Long-term survival after liver metastasectomy in gastric cancer: Systematic review and meta-analysis of prognostic factors.
Publication date: Available online 17 May 2018
Source:Cancer Treatment Reviews
Author(s): Francesco Montagnani, Francesca Crivelli, Giuseppe Aprile, Caterina Vivaldi, Irene Pecora, Rocco De Vivo, Mario Alberto Clerico, Lorenzo Fornaro
BackgroundDespite the amelioration of systemic therapy, overall survival (OS) of metastatic gastric cancer (GC) patients remains poor. Liver is a common metastatic site and retrospective series suggest a potential OS benefit from hepatectomy, with interesting 5-year (5y) and 10-year (10y) OS rates in selected patients. We aim to evaluate the impact of liver resection and related prognostic factors on long-term outcome in this setting.MethodsWe searched Pubmed, EMBASE, and Abstracts/posters from international meetings since 1990. Data were extracted from publish papers. Random effects models meta-analyses and meta-regression models were built to assess 5yOS and the impact of different prognostic factor. Heterogeneity was assessed using between study variance, I2 and Cochran's Q. Funnel plot were used to assess small study bias.ResultsThirty-three observational studies (for a total of 1304 patients) were included. Our analysis demonstrates a 5yOS rate of 22% (95%CI: 18%-26%) and 10yOS rate of 11% (95%CI: 7%-18%) among patients undergoing radical hepatectomy. A favorable effect on OS was shown by several factors linked to primary cancer (lower T and N stage, no lympho-vascular or serosal invasion) and burden of hepatic disease (≤3 metastases, unilobar involvement, greatest lesion <5 cm, negative resection margins). Moreover, lower CEA and CA19.9 levels and post-resection chemotherapy were associated with improved OS.ConclusionsSurgical resection of liver metastases from GC seems associated with a significant chance of 5yOS and 10yOS and compares favourably with results of medical treatment alone. Prospective evaluation of this approach and validation of adequate selection criteria are needed.
https://ift.tt/2L9fvmd
Extracellular matrix expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Majed Felemban, Birthe Dorgau, Nicola Claire Hunt, Dean Hallam, Darin Zerti, Roman Bauer, Yuchun Ding, Joseph Collin, David Steel, Natalio Krasnogor, Jumana Al-Aama, Susan Lindsay, Carla Mellough, Majlinda Lako
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch's membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis.Statement of SignificanceThe expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin were expressed in Bruch's membrane; whereas Brevican, Versican, IMPG1 & IMPG2 in the developing interphotoreceptor matrix (IPM). Retinal organoids were successfully generated from pluripotent stem cells. The expression of ECM components was examined in the retinal organoids found to recapitulate human retinal development in vivo. Using functional blocking experiments, this study also highlight an important role of IMPG1 and CD44 in the development of photoreceptors and IPM formation.
Graphical abstract
https://ift.tt/2GunwOK
Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Linhua Zhang, Yu Qin, Zhiming Zhang, Fan Fan, Chenlu Huang, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Deling Kong, Chun Wang, Hongfan Sun, Xigang Leng, Dunwan Zhu
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy.Statement of SignificanceThe combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.
Graphical abstract
https://ift.tt/2rQbpr2
ssSupramolecular poly(acrylic acid)/F127 hydrogel with hydration-controlled nitric oxide release for enhancing wound healing
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Mathilde Champeau, Valéria Póvoa, Lucas Militão, Flávia Cabrini, Guilherme F. Picheth, Florian Meneau, Carlos P. Jara, Eliana P. de Araujo, Marcelo G. de Oliveira
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200 min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40 nmol/g h to 1.5 μmol/g h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5 days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5 to 3.4 days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing.Statement of SignificanceThe topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor Snitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel.
Graphical abstract
https://ift.tt/2rR6R3v
Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer
Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): T. Aparicio, O. Bouché, E. Francois, F. Retornaz, E. Barbier, J. Taieb, S. Kirscher, P.-L. Etienne, R. Faroux, F. Khemissa Akouz, F. El Hajbi, C. Locher, Y. Rinaldi, T. Lecomte, S. Lavau-Denes, M. Baconnier, A. Oden-Gangloff, D. Genet, L. Bedenne, E. Paillaud
BackgroundOlder patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older.Patients and methodsPatients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS).Results102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75–91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status.ConclusionNormal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.
https://ift.tt/2wNzbc5
Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis
Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): Carmen Criscitiello, Mehra Golshan, William T. Barry, Giulia Viale, Stephanie Wong, Michele Santangelo, Giuseppe Curigliano
PurposeWe conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC).Patients and methodsThe primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant.ResultsThirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5–76% across arms with an average BCT of 57% (95% CI 52–62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I2 = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3–60% across studies. The average pCR across all study arms was 24% (95% CI 19–29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27).ConclusionspCR does not increase BCT in patients receiving NST for EBC.
https://ift.tt/2IviVSE
International Organization of Psychophysiology
Publication date: June 2018
Source:International Journal of Psychophysiology, Volume 128
https://ift.tt/2Iq2wyB
Editorial Board
Publication date: June 2018
Source:International Journal of Psychophysiology, Volume 128
https://ift.tt/2KBL1b5
Kasuistik: Metamizol-induzierte Agranulozytose
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 388-394
DOI: 10.1055/s-0043-115329
Metamizol hat insgesamt ein günstiges Nebenwirkungsprofil – aber es birgt ein höheres Risiko einer medikamenteninduzierten Agranulozytose als andere Schmerzmittel und darf daher nicht unkritisch eingesetzt werden. Dieser Beitrag berichtet von einem Patienten, der nach prothetischem Hüftersatz eine medikamenteninduzierte Agranulozytose – mutmaßlich durch Metamizol – entwickelt und trotz maximaler Therapie im septischen Schock verstirbt.
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Georg Thieme Verlag KG Stuttgart · New York
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Kardioanästhesie: Monitoring der Gerinnung und Gerinnungstherapie
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 364-379
DOI: 10.1055/s-0043-112099
Die Transfusion von allogenen Blutprodukten ist mit einer Erhöhung der perioperativen Morbidität und Letalität assoziiert. Störungen der Hämostase sind insbesondere bei kardiochirurgischen Patienten häufig anzutreffen und können zu transfusionspflichtigen Blutungen führen. Eine zielgerichtete Therapie der häufig komplexen Gerinnungsstörungen erfordert eine differenzierte Diagnostik.
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Georg Thieme Verlag KG Stuttgart · New York
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Kolloide zur Volumentherapie nach Verbrennung geeignet?
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 324-324
DOI: 10.1055/a-0607-6170
Georg Thieme Verlag KG Stuttgart · New York
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Hypertone Lösungen bei hämorrhagischem Schock ohne gesicherten Vorteil
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 327-328
DOI: 10.1055/a-0607-6183
Georg Thieme Verlag KG Stuttgart · New York
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Kardioanästhesie: anästhesiologisches Management
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 346-362
DOI: 10.1055/s-0043-106337
Das anästhesiologische Management herzchirurgischer Patienten hat sich in den letzten Jahren deutlich weiterentwickelt. Diese Übersicht widmet sich vor allem folgenden Bereichen: pharmakologische Kardioprotektion bei herzchirurgischen Eingriffen, Narkosemanagement an der Herz-Lungen-Maschine, Protokolle der „Enhanced Recovery After Cardiac Surgery" sowie innovative minimalinvasive Operationsverfahren wie die kathetergestützte Aortenklappenimplantation.
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Georg Thieme Verlag KG Stuttgart · New York
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Hypotonie nach Spinalanästhesie zur Sectio: Noradrenalin oder Phenylephrin?
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 328-328
DOI: 10.1055/a-0607-6144
Georg Thieme Verlag KG Stuttgart · New York
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Obere Altersgrenze bei ambulanter Anästhesie: Möglichkeiten und Risiken
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 380-386
DOI: 10.1055/s-0042-124408
Zahlreiche Operationen werden heute auch noch in höherem Lebensalter ambulant durchgeführt. Dieser Übersichtsartikel stellt die Vorteile der ambulanten Anästhesie bei älteren Patienten dar, zeigt aber auch die Risiken einer zu frühen Entlassung auf. Für den klinischen Alltag werden praktische Hilfestellungen für die Patientenauswahl gegeben und Risikofaktoren für eine ungeplante stationäre Aufnahme identifiziert.
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Georg Thieme Verlag KG Stuttgart · New York
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Pssst … AINS-Secrets: heute aus der Urologie – TUR-Syndrom
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 395-398
DOI: 10.1055/s-0042-101662
Georg Thieme Verlag KG Stuttgart · New York
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Erratum: Atemwegsmanagement – der schwierige Atemweg beim thoraxchirurgischen Patienten
Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0613-2898
Georg Thieme Verlag KG Stuttgart · New York
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Sauerstoffgabe für die Mutter bei Kaiserschnitt und oxidativer Stress des Kindes
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 322-322
DOI: 10.1055/a-0607-6131
Georg Thieme Verlag KG Stuttgart · New York
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Preface
Publication date: June 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 3
Author(s): Matti Poutanen, Manuel Tena-Sempere
https://ift.tt/2rOLaRx
Editorial Board
Publication date: June 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 3
https://ift.tt/2Gr1L2l
Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Anna M. Nicholson, Cora Olpe, Alice Hoyle, Ann-Sofie Thorsen, Teja Rus, Mathilde Colombé, Roxanne Brunton-Sim, Richard Kemp, Kate Marks, Phil Quirke, Shalini Malhotra, Rogier ten Hoopen, Ashraf Ibrahim, Cecilia Lindskog, Meagan B. Myers, Barbara Parsons, Simon Tavaré, Mark Wilkinson, Edward Morrissey, Douglas J. Winton
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
Graphical abstract
Teaser
Winton and colleagues describe stem cell dynamics in normal human colon to identify the efficiency of clone fixation within the epithelium and the rate of subsequent lateral expansion. Against these benchmarks biased stem cell behaviors advantaged in both fixation and expansion can be quantified to predict the age-related burden of pro-oncogenic mutation.https://ift.tt/2wS4Mtf
High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Stefan M. Czerniecki, Nelly M. Cruz, Jennifer L. Harder, Rajasree Menon, James Annis, Edgar A. Otto, Ramila E. Gulieva, Laura V. Islas, Yong Kyun Kim, Linh M. Tran, Timothy J. Martins, Jeffrey W. Pippin, Hongxia Fu, Matthias Kretzler, Stuart J. Shankland, Jonathan Himmelfarb, Randall T. Moon, Neal Paragas, Benjamin S. Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening.
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Teaser
Organoids derived from human iPSCs have great potential for drug screening, but their complexity poses a challenge for miniaturization and automation. Freedman and colleagues establish a robotic pipeline to manufacture and analyze kidney organoids in microwell arrays. They apply this system to improve differentiation, measure toxicity, and comprehend disease.https://ift.tt/2IPmx0M
Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): David Petrik, Michael H. Myoga, Sofia Grade, Niklas J. Gerkau, Melanie Pusch, Christine R. Rose, Benedikt Grothe, Magdalena Götz
One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.
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Teaser
Stem cells need to adapt to signals from the environment to regulate their output. Here, we show the key role of a flow-sensitive ion channel in regulating the activation of adult neural stem cells and their output.https://ift.tt/2Kxs9Ks
Non-viral delivery of an optogenetic tool into cells with self-healing hydrogel
Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Fu-Yu Hsieh, Hao-Wei Han, Xiao-Ru Chen, Chii-Shen Yang, Yen Wei, Shan-hui Hsu
Optogenetics offers unique, temporally precise control of neural activity in genetically targeted specific neurons that express light-sensitive opsin molecules. Three-dimensional (3D) delivery of optogenetics can be realized by co-injection of bacteriorhodopsin (HEBR) plasmid with a chitosan-based self-healing hydrogel with strong shear-thinning properties. The HEBR protein shows photoelectrical properties and can be used as an optical switch for cell activation. We optimize the shear force generated during the process of injection (∼100 Pa), which is transient because of the self-healing nature of the hydrogel. This transient force exerted by the self-healing hydrogel may allow the cytosolic delivery of HEBR plasmid with excellent cell viability and a high efficiency approaching 80%. When excited with green light, HEBR-delivered neural stem cells (NSCs) can proliferate and specifically differentiate into neurons in vitro and rescue the function of nerve impaired zebrafish in vivo. This novel optogenetic method combining 3D injectable self-healing hydrogel offers potential temporal-spatial approaches to treat neurodegenerative diseases in the future.
https://ift.tt/2KzfGWJ
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