Source:Brain Stimulation
Author(s): Greta Vilidaite, Daniel H. Baker
https://ift.tt/2qc9QCS
Σάββατο 7 Απριλίου 2018
Psychophysical measurement of the effects and non-effects of TMS on contrast perception
Source:Brain Stimulation
Author(s): Greta Vilidaite, Daniel H. Baker
https://ift.tt/2qc9QCS
Enriched expression of the ciliopathy gene Ick in cell proliferating regions of adult mice
Source:Gene Expression Patterns
Author(s): Ryotaro Tsutsumi, Taro Chaya, Takahisa Furukawa
Cilia are essential for sensory and motile functions across species. In humans, ciliary dysfunction causes "ciliopathies", which show severe developmental abnormalities in various tissues. Several missense mutations in intestinal cell kinase (ICK) gene lead to endocrine-cerebro-osteodysplasia syndrome or short rib-polydactyly syndrome, lethal recessive developmental ciliopathies. We and others previously reported that Ick-deficient mice exhibit neonatal lethality with developmental defects. Mechanistically, Ick regulates intraflagellar transport and cilia length at ciliary tips. Although Ick plays important roles during mammalian development, roles of Ick at the adult stage are poorly understood. In the current study, we investigated the Ick gene expression in adult mouse tissues. RT-PCR analysis showed that Ick is ubiquitously expressed, with enrichment in the retina, brain, lung, intestine, and reproductive system. In the adult brain, we found that Ick expression is enriched in the walls of the lateral ventricle, in the rostral migratory stream of the olfactory bulb, and in the subgranular zone of the hippocampal dentate gyrus by in situ hybridization analysis. We also observed that Ick staining pattern is similar to pachytene spermatocyte to spermatid markers in the mature testis and to an intestinal stem cell marker in the adult small intestine. These results suggest that Ick is expressed in proliferating regions in the adult mouse brain, testis, and intestine.
https://ift.tt/2JsvoDf
The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart
Source:Peptides
Author(s): Mirali Polshekan, Vahid Khori, Ali Mohammad Alizadeh, Majid Ghayour-Mobarhan, Mohsen Saeidi, Yahya Jand, Maryam Rajaei, Gholamreza Farnoosh, Khadijeh Jamialahmadi
Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model.Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion.Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT.Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase.
https://ift.tt/2GJidQQ
Computational Design and Experimental Characterization of a Novel β-Common Receptor Inhibitory Peptide
Source:Peptides
Author(s): Cody R. Kilar, Sivakumar Sekharan, Larysa Sautina, YanPeng Diao, Shahar Keinan, Yong Shen, Jorg Bungert, Rajesh Mohandas, Mark S. Segal
In short-term animal models of ischemia, erythropoietin (EPO) signaling through the heterodimeric EPO receptor (EPOR)/β-common receptor (βCR) is believed to elicit tissue protective effects. However, large, randomized, controlled trials demonstrate that targeting a higher hemoglobin level by administering higher doses of EPO, which are more likely to activate the heterodimeric EPOR/βCR, is associated with an increase in adverse cardiovascular events. Thus, inhibition of long-term activation of the βCR may have therapeutic implications. This study aimed to design and evaluate the efficacy of novel computationally designed βCR inhibitory peptides (βIP). These novel βIPs were designed based on a truncated portion of Helix-A from EPO, specifically residues 11 to 26 (VLERYLLEAKEAEKIT). Seven novel peptides (P1 to P7) were designed. Peptide 7 (P7), VLERYLHEAKHAEKIT, demonstrated the most robust inhibitory activity. We also report here the ability of P7 to inhibit βCR-induced nitric oxide (NO) production and angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, we found that P7 βIP completely abolished EPO-induced NO production. The inhibitory effect could be overcome with super physiological doses of EPO, suggesting a competitive inhibition. βCR-induced angiogenesis in HUVEC's was also abolished with treatment of P7 βIP, but P7 βIP did not inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis. In addition, we demonstrate that the novel P7 βIP does not inhibit EPO-induced erythropoiesis with use of peripheral blood mononuclear cells (PBMCs). These results, for the first time, describe a novel, potent βCR peptide inhibitor that inhibit the actions of the βCR without affecting erythropoiesis.
https://ift.tt/2qfTxnU
The Superficial Musculoaponeurotic System and Other Considerations in Rejuvenation of the Lower Face and Neck
This article addresses several facelift challenges involving anatomic conditions, including platysma banding, endomorphic facial habitus, and midface hypoplasia. In addition, patient counseling and conveying realistic expectations about limitations of facelift alone, with and without adjunctive procedures, are presented. In addition, a few technical modifications of the facelift procedure contributing to more uniform success and longevity are discussed.
https://ift.tt/2HjcC0u
Controversies in Facial Plastic Surgery
FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA
https://ift.tt/2HhSGLf
Controversies in Facial Plastic Surgery
Over the last 50+ years, the field of facial plastic surgery has evolved into a prominent subspecialty in surgery. This discipline encompasses the care of the entire region of the face, scalp, and neck. With the professional evolution of the field, there has also been an evolution and growth of the knowledge base of facial plastic surgery. The field lends expertise, understanding, and direction in all facets of the regional reconstructive, corrective, and cosmetic concerns.
https://ift.tt/2Hi6B43
Management of the Prominent Ear
This article incorporates the opinions and preferred surgical options in managing patients of 3 prominent facial plastic surgeons who have large otoplasty practices. Six different questions covering the management of prominent ears are answered by the 3 practitioners. Nonsurgical options for the treatment of prominent ears are discussed. The role of cartilage-cutting and cartilage-sparing techniques as well as individual preferred otoplasty techniques are thoroughly covered. Postoperative management of these patients is presented by the individual surgeons.
https://ift.tt/2GN9CbO
Orbital Fractures
Anatomic, rather than volumetric, reconstruction leads to improved outcomes in orbital reconstruction. Endoscopic visualization improves lighting and magnification of the surgical site and allows the entire operative team to understand and participate in the procedure. Mirror-image overlay display with navigation-guided surgery allows in situ fine adjustment of the implant contours to match the contralateral uninjured orbit. Precise exophthalmometry is important before, during, and after surgery to provide optimal surgical results.
https://ift.tt/2Hi6C87
Evaluating New Technology
There are multiple complex issues to consider when evaluating any new technology. First evaluate the efficacy of the device. Then considering your patient population decide whether this technology brings an added benefit to your patients. If it meets these 2 criteria, then proceed to the financial analysis of acquiring this technology. The complete financial analysis has several important components that include but are not limited to cost, value, alternatives, return on investment, and associated marketing expense.
https://ift.tt/2EsKzc1
Injectable Fillers
Injectable products are now being designed to treat specific areas of the face, including the lower lid/cheek region, the midface, and circumoral rhytids. Expert injectors from 3 core disciplines (facial plastic surgery, oculoplastic surgery, and dermatology) were asked to discuss their approaches to the midface, lower lid, and cheek region and their opinions about using cannulas versus needles. The authors describe their techniques for avoiding and managing filler complications. They give insight into how their techniques have changed over the past few years and their use of new products that have been developed.
https://ift.tt/2Hij4VD
Grafting Techniques in Primary and Revision Rhinoplasty
With the adoption of open structure techniques, rhinoplasty has become more reliant on the use of structural grafts to resist change that occurs over time owing to both gravity and the aging process. As surgical procedures have become more technically complex, the type of grafts use for both primary and secondary rhinoplasty have undergone significant evolution. This article provides a case approach focused on the use of structural grafting in rhinoplasty.
https://ift.tt/2GJVi3J
Lip Augmentation
This article examines 6 questions about lip augmentation answered by 3 experts in their field of facial plastic surgery. The topics covered include high-yield areas such as injection, surgical enhancement, rhytid resurfacing, implants, complications, and technique changes over the years. All the authors answered these questions in a "How I do it" manner to provide the reader with a true understanding of their thoughts and techniques. This article provides a practical resource to all physicians and practitioners performing lip augmentation on some of the most common questions and issues.
https://ift.tt/2HlTTl2
Facial Paralysis Discussion and Debate
This article examines 6 questions about facial paralysis answered by 3 experts in their field of facial plastic surgery. The topics covered include routine assessment, neuromuscular training, nonsurgical management, and the future of this field. All the authors answered these questions in a "How I do it" manner to provide the reader with a true understanding of their thoughts and techniques. This article provides a practical resource to all physicians and practitioners treating patients with facial paralysis on some of the most common questions and issues.
https://ift.tt/2EwKzry
Contemporary Laser and Light-Based Rejuvenation Techniques
Laser and light skin rejuvenation have changed dramatically in the last 10 years. CO2 and erbium:YAG remain the main wavelengths, but fractional, nonablative, and combination devices have been added. For those patients with lighter skin types and extensive photodamage and rhytids, full-field ablative laser resurfacing remains the procedure of choice. For those seeking less downtime and risks, fractional devices offer an excellent and growing alternative, although multiple treatments may be required for optimal results. A new generation of hybrid and nonablative devices offers many advantages, yet many of these results may be duplicated with well-proven intense pulsed light.
https://ift.tt/2Hgu9WX
Facial Plastic Surgery Controversies
There are more than 11 million people in the world affected with keloids. Nevertheless, there is a lack of agreement in keloid management. Moreover, keloid research has left gaps in the understanding of its pathogenesis. Six questions are answered by 3 clinical scientists in an attempt to address common keloid controversies.
https://ift.tt/2GKAxVu
Vaccine options for influenza: thinking small
Source:Current Opinion in Immunology, Volume 53
Author(s): Bert Schepens, Dorien De Vlieger, Xavier Saelens
Vaccines that direct the immune response towards conserved B cell epitopes of influenza viruses can provide broad protection. In many instances, this requires the design of vaccine antigens that stimulate the immune system to levels that far exceed the natural responses towards such antigens. Here we focus on the matrix protein 2 ectodomain (M2e) as a 'universal' influenza A vaccine candidate. Thanks to its small size and high solubility, M2e can be expressed and delivered in almost any format. Protection against experimental influenza A virus challenge by M2e-based vaccines has been demonstrated in natural host of influenza and clinical studies demonstrated that such vaccines are safe and immunogenic. M2e-specific antibodies protect mainly by Fc receptor-mediated antibody-dependent cellular phagocytosis activity, which is reminiscent to how antibodies directed against the hemagglutinin stalk protect in vivo. Fighting influenza with a broadly protective influenza vaccine will likely require a blend of conserved antigens. M2e deserves its place in such a blend.
https://ift.tt/2GHP3S9
Ion channelopathies of the immune system
Source:Current Opinion in Immunology, Volume 52
Author(s): Martin Vaeth, Stefan Feske
Ion channels and transporters move ions across membrane barriers and are essential for a host of cell functions in many organs. They conduct K+, Na+ and Cl−, which are essential for regulating the membrane potential, H+ to control intracellular and extracellular pH and divalent cations such as Ca2+, Mg2+ and Zn2+, which function as second messengers and cofactors for many proteins. Inherited channelopathies due to mutations in ion channels or their accessory proteins cause a variety of diseases in the nervous, cardiovascular and other tissues, but channelopathies that affect immune function are not as well studied. Mutations in ORAI1 and STIM1 genes that encode the Ca2+ release-activated Ca2+ (CRAC) channel in immune cells, the Mg2+ transporter MAGT1 and the Cl− channel LRRC8A all cause immunodeficiency with increased susceptibility to infection. Mutations in the Zn2+ transporters SLC39A4 (ZIP4) and SLC30A2 (ZnT2) result in nutritional Zn2+ deficiency and immune dysfunction. These channels, however, only represent a fraction of ion channels that regulate immunity as demonstrated by immune dysregulation in channel knockout mice. The immune system itself can cause acquired channelopathies that are associated with a variety of diseases of nervous, cardiovascular and endocrine systems resulting from autoantibodies binding to ion channels. These autoantibodies highlight the therapeutic potential of functional anti-ion channel antibodies that are being developed for the treatment of autoimmune, inflammatory and other diseases.
https://ift.tt/2GHnzfk
Characterization of distinct Arctic aerosol accumulation modes and their sources
Source:Atmospheric Environment, Volume 183
Author(s): R. Lange, M. Dall'Osto, H. Skov, J.K. Nøjgaard, I.E. Nielsen, D.C.S. Beddows, R. Simo, R.M. Harrison, A. Massling
In this work we use cluster analysis of long term particle size distribution data to expand an array of different shorter term atmospheric measurements, thereby gaining insights into longer term patterns and properties of Arctic aerosol. Measurements of aerosol number size distributions (9–915 nm) were conducted at Villum Research Station (VRS), Station Nord in North Greenland during a 5 year record (2012–2016). Alongside this, measurements of aerosol composition, meteorological parameters, gaseous compounds and cloud condensation nuclei (CCN) activity were performed during different shorter occasions. K-means clustering analysis of particle number size distributions on daily basis identified several clusters. Clusters of accumulation mode aerosols (main size modes > 100 nm) accounted for 56% of the total aerosol during the sampling period (89–91% during February–April, 1–3% during June–August). By association to chemical composition, cloud condensation nuclei properties, and meteorological variables, three typical accumulation mode aerosol clusters were identified: Haze (32% of the time), Bimodal (14%) and Aged (6%). In brief: (1) Haze accumulation mode aerosol shows a single mode at 150 nm, peaking in February–April, with highest loadings of sulfate and black carbon concentrations. (2) Accumulation mode Bimodal aerosol shows two modes, at 38 nm and 150 nm, peaking in June–August, with the highest ratio of organics to sulfate concentrations. (3) Aged accumulation mode aerosol shows a single mode at 213 nm, peaking in September–October and is associated with cloudy and humid weather conditions during autumn. The three aerosol clusters were considered alongside CCN concentrations. We suggest that organic compounds, that are likely marine biogenic in nature, greatly influence the Bimodal cluster and contribute significantly to its CCN activity. This stresses the importance of better characterizing the marine ecosystem and the aerosol-mediated climate effects in the Arctic.
https://ift.tt/2q9TsTt
Four years of highly time resolved measurements of elemental and organic carbon at a rural background site in Central Europe
Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Saliou Mbengue, Michal Fusek, Jaroslav Schwarz, Petr Vodička, Adéla Holubová Šmejkalová, Ivan Holoubek
Elemental carbon (EC) and organic carbon (OC) in fine atmospheric aerosols (PM2.5: aerodynamic diameter smaller than 2.5 μm) have been measured with a semi-automatic instrument during a 4-year survey at the National Atmospheric Observatory Košetice (NAOK), Czech Republic. Ground based measurements were performed from March 2013 to December 2016 with a field Semi-Continuous OCEC Aerosol Analyzer (Sunset Laboratory Inc., USA). The variation of EC and OC concentrations and the OC/EC ratio was characterized for different seasons and days of the week. During our survey, higher concentrations of EC and OC were observed in winter (0.83 ± 0.67 and 3.33 ± 2.28 μg m−3, respectively), and lower concentrations were recorded in summer (0.34 ± 0.18 and 2.30 ± 1.15 μg m−3, respectively). Inversely, the OC/EC ratio with mean value (5.1 ± 2.6) characteristic to rural background area was higher in summer (7.33 ± 3.23) in comparison to the other seasons. Since the data contain values below detection and quantification limits of the measuring device (i.e., censored values), statistical methods for censored data have been used in order to compare mean EC and OC concentrations between various seasons. It was found out that there is a significant difference between summer and the other seasons with the exception of mean OC concentrations at noon. In most cases, there was also a significant difference between winter and the other seasons. Moreover, it was found out that when dealing with OC concentrations, it is possible to replace censored values by a constant and still obtain reasonable results. In case of EC concentrations, the method based on censored distributions should be preferred when the sample size is small and the proportion of censored values is high. The diurnal variation of EC and OC is less pronounced in summer. During working days, the EC diurnal pattern displays a morning (between 6:00 and 10:00) and an afternoon/evening (between 18:00 and 22:00) peaks, while for OC, only the afternoon/evening peak is observed. These seasonal, diurnal and weekly variations of EC and OC concentrations and OC/EC ratio are probably related to variability in terms of emission sources (residential heating, traffic), transport characteristic and meteorological conditions. A weaker correlation between EC and OC in summer (r = 0.56) suggests additional sources and/or transport processes during other seasons. The elevated OC/EC ratio, the higher correlation between OC and O3, and the temperature and solar radiation during summer confirmed an increasing contribution of OC from secondary organic carbon (SOC) estimated as at least 59 ± 11% of total carbon in the PM2.5 using the EC tracer method. Backward trajectories of air masses arriving at 100 m AGL calculated in winter and summer show that higher pollution episodes of EC and OC are predominantly associated with continental air masses confined over Central Europe (about 79%), while lower EC and OC levels are mainly associated with episodes of long-range transport of marine air masses. Interestingly, the results reveal that in winter pollutants emitted during workdays could be accumulated above the region and influence the rural background air quality during some prolonged time of the weekend, especially on Saturday.
https://ift.tt/2GJ9Wbv
Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.
https://ift.tt/2EtMVqN
Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.
https://ift.tt/2Hi0exF
Comparison of Two Music Training Approaches on Music and Speech Perception in Cochlear Implant Users.
| Related Articles |
Comparison of Two Music Training Approaches on Music and Speech Perception in Cochlear Implant Users.
Trends Hear. 2018 Jan-Dec;22:2331216518765379
Authors: Fuller CD, Galvin JJ, Maat B, Başkent D, Free RH
Abstract
In normal-hearing (NH) adults, long-term music training may benefit music and speech perception, even when listening to spectro-temporally degraded signals as experienced by cochlear implant (CI) users. In this study, we compared two different music training approaches in CI users and their effects on speech and music perception, as it remains unclear which approach to music training might be best. The approaches differed in terms of music exercises and social interaction. For the pitch/timbre group, melodic contour identification (MCI) training was performed using computer software. For the music therapy group, training involved face-to-face group exercises (rhythm perception, musical speech perception, music perception, singing, vocal emotion identification, and music improvisation). For the control group, training involved group nonmusic activities (e.g., writing, cooking, and woodworking). Training consisted of weekly 2-hr sessions over a 6-week period. Speech intelligibility in quiet and noise, vocal emotion identification, MCI, and quality of life (QoL) were measured before and after training. The different training approaches appeared to offer different benefits for music and speech perception. Training effects were observed within-domain (better MCI performance for the pitch/timbre group), with little cross-domain transfer of music training (emotion identification significantly improved for the music therapy group). While training had no significant effect on QoL, the music therapy group reported better perceptual skills across training sessions. These results suggest that more extensive and intensive training approaches that combine pitch training with the social aspects of music therapy may further benefit CI users.
PMID: 29621947 [PubMed - in process]
https://ift.tt/2EsKkxo
In situ formation of interpenetrating polymer network using sequential thermal and click crosslinking for enhanced retention of transplanted cells
Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Hamid Sadeghi Abandansari, Mohammad Hossein Ghanian, Fahimeh Varzideh, Elena Mahmoudi, Sarah Rajabi, Payam Taheri, Mohammad Reza Nabid, Hossein Baharvand
Injectable hydrogels, which are used as scaffolds in cell therapy, provide a minimally invasive strategy to enhance cell retention and survival at injection site. However, till now, slow in situ gelation, undesired mechanical properties, and weak cell adhesion characteristics of reported hydrogels, have led to improper results. Here, we developed an injectable fully-interpenetrated polymer network (f-IPN) by integration of Diels-Alder (DA) crosslinked network and thermosensitive injectable hydrogel. The proposed DA hydrogels were formed in a slow manner showing robust mechanical properties. Interpenetration of thermosensitive network into DA hydrogel accelerated in situ gel-formation and masked the slow reaction rate of DA crosslinking while keeping its unique features. Two networks were formed by simple syringe injection without the need of any initiator, catalyst, or double barrel syringe. The DA and f-IPN hydrogels showed comparable viscoelastic properties along with outstanding load-bearing and shape-recovery even under high levels of compression. The subcutaneous administration of cardiomyocytes-laden f-IPN hydrogel into nude mice revealed high cell retention and survival after two weeks. Additionally, the cardiomyocyte's identity of retained cells was confirmed by detection of human and cardiac-related markers. Our results indicate that the thermosensitive-covalent networks can open a new horizon within the injection-based cell therapy applications.
Graphical abstract
https://ift.tt/2GJNEq2
Programmed ‘triple-mode’ anti-tumor therapy: Improving peritoneal retention, tumor penetration and activatable drug release properties for effective inhibition of peritoneal carcinomatosis
Source:Biomaterials, Volume 169
Author(s): Kondareddy Cherukula, Woo Kyun Bae, Jae Hyuk Lee, In-Kyu Park
Peritoneal carcinomatosis (PC) is a fatal condition arising in the gastrointestinal tract. PC patients administered drugs locally in the tumor region, such as in intraperitoneal chemotherapy (IPCh), suffer from low drug retention time and tumor penetration. Herein, we synthesized a lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle (LAPMi) nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming positive charged nanomicellar structures loaded with paclitaxel (PTX) (LAPMi-PTX) for IPCh. The incorporation of a positive surface charge aided in prolonging the peritoneal retention time, presumably via ascites-induced protein corona formation, and the subsequent size expansion caused resistance against undesired clearance through lymphatic openings. Furthermore, preferential tumor penetration by LAPMi-PTX is attributable to the permeation-enhancing properties of LCA, and the subsequent tumor activatable drug release was induced by the presence of disulfide linkages. By integrating these properties, LAPMi exhibited prolonged peritoneal residence time, enhanced tumor permeation and chemotherapeutic effect evidenced by in vitro, tumor spheroid and in vivo studies. Importantly, our strategy enabled significant PC inhibition and increased the overall survival rate of tumor-bearing mice. In conclusion, we provided a new paradigm of intractable PC treatment by enabling the prolonged residence time of the nanoconstruct, thereby enhancing tumor penetration and anti-tumor therapy.
https://ift.tt/2HgoJv8
Cytokine induced killer cells-assisted delivery of chlorin e6 mediated self-assembled gold nanoclusters to tumors for imaging and immuno-photodynamic therapy
Source:Biomaterials, Volume 170
Author(s): Fangfang Xia, Wenxiu Hou, Yanlei Liu, Wentao Wang, Yu Han, Meng Yang, Xiao Zhi, Chenlu Li, Daizong Qi, Tianliang Li, Jesus Martinez de la Fuente, Chunlei Zhang, Jie Song, Daxiang Cui
The cytotoxicity and unique tumor-tropic properties of cytokine-induced killer (CIK) cells render them promising in the field of cancer immunotherapy and delivery systems. Here, we report a novel and facile approach to assemble gold nanoclusters (GNCs) into stable and monodispersed nanoparticles (NPs) using Chlorin e6 (Ce6) molecules. Notably, the fluorescence intensity of the GNCs-Ce6 NPs was about 4.5 folds stronger than the GNCs counterparts. The as-prepared GNCs-Ce6 NPs were conjugated with CD3 antibody (Ab) and further employed to label CIK cells to create a CIK cell-based drug delivery system (Ce6-GNCs-Ab-CIK). The Ce6-GNCs-Ab-CIK exhibited high tumor-targeting efficiency and excellent therapeutic efficacy toward MGC-803 tumor-bearing mice. Benefiting from the synergistic therapeutic effect between GNCs-Ce6-Ab NPs and CIK cells, the GNCs-Ce6-Ab-CIK strategy may present an ideal cancer theranostic platform for tumor targeted imaging and combination therapy.
https://ift.tt/2EtKAMx
Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds
Source:Biomaterials, Volume 169
Author(s): Aaron H. Morris, Danielle K. Stamer, Britta Kunkemoeller, Julie Chang, Hao Xing, Themis R. Kyriakides
Decellularized biologic scaffolds are gaining popularity over synthetic biomaterials as naturally derived materials capable of promoting improved healing. Nevertheless, the most widely used biologic material – acellular dermal matrix (ADM) – exhibits slow repopulation and remodeling, which prevents integration. Additionally, engineering control of these materials is limited because they require a natural source for their production. In the current report, we demonstrate the feasibility of using genetically engineered animals to create decellularized biologic scaffolds with favorable extracellular matrix (ECM) properties. Specifically, we utilized skin from thrombospondin (TSP)-2 KO mice to derive various decellularized products. Scanning electron microscopy and mechanical testing showed that TSP-2 KO ADM exhibited an altered structure and a reduction in elastic modulus and ultimate tensile strength, respectively. When a powdered form of KO ADM was implanted subcutaneously, it was able to promote enhanced vascularization over WT. Additionally, when implanted subcutaneously, intact slabs of KO ADM were populated by higher number of host cells when compared to WT. In vitro studies confirmed the promigratory properties of KO ADM. Specifically, degradation products released by pepsin digestion of KO ADM induced greater cell migration than WT. Moreover, cell-derived ECM from TSP-2 null fibroblasts was more permissive to fibroblast migration. Finally, ADMs were implanted in a diabetic wound model to examine their ability to accelerate wound healing. KO ADM exhibited enhanced remodeling and vascular maturation, indicative of efficient integration. Overall, we demonstrate that genetic manipulation enables engineered ECM-based materials with increased regenerative potential.
https://ift.tt/2Hj6PIq
Statistical analysis of bank deposits dataset
Source:Data in Brief, Volume 18
Author(s): Pelumi E. Oguntunde, Hilary I. Okagbue, Patience I. Adamu, Omoleye A. Oguntunde, Sola J. Oluwatunde, Abiodun A. Opanuga
This article presents the statistical analysis of the deposit activities in each of the account types of a leading bank in Nigeria. The mean effect of these account types on the bank was determined using analysis of variance (ANOVA). Further test which include the Tukey's simultaneous test for differences of means was also conducted.
https://ift.tt/2HgrRY0
Data of chemical analysis and electrical properties of SnO2-TiO2 composite nanofibers
Source:Data in Brief, Volume 18
Author(s): Zinab H. Bakr, Qamar Wali, Jamil Ismail, Naveen Kumar Elumalai, Ashraf Uddin, Rajan Jose
In this data article, we provide energy dispersive X-ray spectroscopy (EDX) spectra of the electrospun composite (SnO2-TiO2) nanowires with the elemental values measured in atomic and weight%. The linear sweep voltammetry data of composite and its component nanofibers are provided. The data collected in this article is directly related to our research article "Synergistic combination of electronic and electrical properties of SnO2 and TiO2 in a single SnO2-TiO2 composite nanowire for dye-sensitized solar cells" [1].
https://ift.tt/2EtavEc
A two-step approach for mining patient treatment pathways in administrative healthcare databases
Source:Artificial Intelligence in Medicine
Author(s): Ahmed Najjar, Daniel Reinharz, Catherine Girouard, Christian Gagné
Clustering electronic medical records allows the discovery of information on healthcare practices. Entries in such medical records are usually composed of a succession of diagnostics or therapeutic steps. The corresponding processes are complex and heterogeneous since they depend on medical knowledge integrating clinical guidelines, the physician's individual experience, and patient data and conditions. To analyze such data, we are first proposing to cluster medical visits, consultations, and hospital stays into homogeneous groups, and then to construct higher-level patient treatment pathways over these different groups. These pathways are then also clustered to distill typical pathways, enabling interpretation of clusters by experts. This approach is evaluated on a real-world administrative database of elderly people in Québec suffering from heart failures.
https://ift.tt/2qg76DA
Glioblastoma Metastatic to the Ovary, a Very Different Krukenberg Tumor?
Source:Practical Radiation Oncology
Author(s): Robin E. Bonomi, Josh Kovoor, Mark Zaki, Mark Szlaczky, Michael Christensen, William Kupsky, Geoffrey Barger, Steven Miller, Michael M. Dominello
https://ift.tt/2Hiswbg
Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction
Source:Biomaterials, Volume 169
Author(s): Long V. Le, Priya Mohindra, Qizhi Fang, Richard E. Sievers, Michael A. Mkrtschjan, Christopher Solis, Conrad W. Safranek, Brenda Russell, Randall J. Lee, Tejal A. Desai
Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.
https://ift.tt/2GE1U7H
Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models
Source:Biomaterials, Volume 169
Author(s): Maofan Zhang, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi, Kin Man Au, Yusra Medik, Kyle Roche, Kyle Wagner, Zachary Rodgers, Andrew Z. Wang
Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic.
https://ift.tt/2q90WVU
Ultra-thin, aligned, free-standing nanofiber membranes to recapitulate multi-layered blood vessel/tissue interface for leukocyte infiltration study
Source:Biomaterials, Volume 169
Author(s): Sang Min Park, HyeMi Kim, Kwang Hoon Song, Seongsu Eom, HyoungJun Park, Junsang Doh, Dong Sung Kim
Leukocyte infiltration plays critical roles in tissue inflammation for pathogen clearance and tumor eradication. This process is regulated by complex microenvironments in blood vessels, including inflamed endothelium, blood flow, and perivascular components. The role of perivascular components in leukocyte infiltration has not been systematically investigated until recently mostly due to lack of technology. In this work, we developed a three-dimensional multi-layered blood vessel/tissue model with a nanofiber membrane, enabling real-time visualization of dynamic leukocyte infiltration and subsequent interaction with perivascular macrophages. We directly fabricated a highly aligned, free-standing nanofiber membrane with an ultra-thin thickness of ∼1 μm in microfluidic systems. Coating the nanofiber membrane with matrigel showed synergetic topographical and biochemical effects on the reconstitution of a well-aligned endothelial monolayer on the membrane. Our 3D multi-layered blood vessel/tissue model will offer a powerful and versatile tool for investigating the mechanism of leukocyte tissue infiltration and subsequent immune responses.
https://ift.tt/2qdF8sp
Clinical evaluation of the bulk fill composite QuiXfil in molar class I and II cavities: 10-year results of a RCT
Source:Dental Materials
Author(s): Katrin Heck, Juergen Manhart, Reinhard Hickel, Christian Diegritz
ObjectiveThe objective of this RCT was to compare the 10-year clinical performance of QuiXfil with that of Tetric Ceram in posterior single- or multi-surface cavities.Methods46 QuiXfil (Xeno III) and 50 Tetric Ceram (Syntac classic) composite restorations were placed in 14 stress bearing class I and 82 class II cavities in first or second molars. Clinical evaluation was performed at baseline and after up to 10 years by using modified US Public Health Service criteria. At the last recall period, 26 QuiXfil and 30 Tetric Ceram restorations in 11 stress bearing class I and 45 class II cavities, were assessed.ResultsTen failed restorations were observed during the follow-up period, four Tetric Ceram restorations failed due to secondary caries (2), tooth fracture (1) and bulk fracture combined with secondary caries (1) whereas six QuiXfil restorations failed due to secondary caries (1), tooth fracture (2), secondary caries combined with restoration fracture (1), restoration fracture (1) and postoperative sensitivity (1). Fisher's exact test yielded no significant difference between both materials (p=0.487).SignificanceBoth materials, bulk fill QuiXfil restorations and Tetric Ceram restorations, showed highly clinical effectiveness during the 10-year follow-up.
https://ift.tt/2Et5g7E
Geometrical accuracy of metallic objects produced with additive or subtractive manufacturing: A comparative in vitro study
Source:Dental Materials
Author(s): Michael Braian, David Jönsson, Mir Kevci, Ann Wennerberg
ObjectiveTo evaluate the accuracy and precision of objects produced by additive manufacturing systems (AM) for use in dentistry and to compare with subtractive manufacturing systems (SM).MethodsTen specimens of two geometrical objects were produced by five different AM machines and one SM machine. Object A mimics an inlay-shaped object, while object B imitates a four-unit bridge model. All the objects were sorted into different measurement dimensions (x, y, z), linear distances, angles and corner radius.ResultsNone of the additive manufacturing or subtractive manufacturing groups presented a perfect match to the CAD file with regard to all parameters included in the present study. Considering linear measurements, the precision for subtractive manufacturing group was consistent in all axes for object A, presenting results of <0.050mm. The additive manufacturing groups had consistent precision in the x-axis and y-axis but not in the z-axis. With regard to corner radius measurements, the SM group had the best overall accuracy and precision for both objects A and B when compared to the AM groups.SignificanceWithin the limitations of this in vitro study, the conclusion can be made that subtractive manufacturing presented overall precision on all measurements below 0.050mm. The AM machines also presented fairly good precision, <0.150mm, on all axes except for the z-axis. Knowledge regarding accuracy and precision for different production techniques utilized in dentistry is of great clinical importance. The dental community has moved from casting to milling and additive techniques are now being implemented. Thus all these production techniques need to be tested, compared and validated.
https://ift.tt/2JrkfT8
Towards circuit optogenetics
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): I-Wen Chen, Eirini Papagiakoumou, Valentina Emiliani
Optogenetics neuronal targeting combined with single-photon wide-field illumination has already proved its enormous potential in neuroscience, enabling the optical control of entire neuronal networks and disentangling their role in the control of specific behaviors. However, establishing how a single or a sub-set of neurons controls a specific behavior, or how functionally identical neurons are connected in a particular task, or yet how behaviors can be modified in real-time by the complex wiring diagram of neuronal connections requires more sophisticated approaches enabling to drive neuronal circuits activity with single-cell precision and millisecond temporal resolution. This has motivated on one side the development of flexible optical methods for two-photon (2P) optogenetic activation using either, or a hybrid of two approaches: scanning and parallel illumination. On the other side, it has stimulated the engineering of new opsins with modified spectral characteristics, channel kinetics and spatial distribution of expression, offering the necessary flexibility of choosing the appropriate opsin for each application. The need for optical manipulation of multiple targets with millisecond temporal resolution has imposed three-dimension (3D) parallel holographic illumination as the technique of choice for optical control of neuronal circuits organized in 3D. Today 3D parallel illumination exists in several complementary variants, each with a different degree of simplicity, light uniformity, temporal precision and axial resolution. In parallel, the possibility to reach hundreds of targets in 3D volumes has prompted the development of low-repetition rate amplified laser sources enabling high peak power, while keeping low average power for stimulating each cell.All together those progresses open the way for a precise optical manipulation of neuronal circuits with unprecedented precision and flexibility.
Graphical abstract
https://ift.tt/2H3XQNy
Importance of the subcellular location of protein deposits in neurodegenerative diseases
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Anne Bertolotti
Alzheimer's disease, Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS) and prion disorders are devastating neurodegenerative diseases of increasing prevalence in aging populations. Although clinically different, they share similar molecular features: the accumulation of one or two proteins in abnormal conformations inside or outside neurons. Enhancing protein quality control systems could be a useful strategy to neutralize the abnormal proteins causing neurodegenerative diseases. This review emphasizes the subcellular location of protein deposits in neurodegenerative diseases and the need to tailor strategies aimed at boosting protein quality control systems to the affected subcellular compartment. Inhibition of a protein phosphatase terminating the unfolded protein response will be discussed as a strategy to protect from diseases associated with misfolded proteins in the endoplasmic reticulum.
https://ift.tt/2uWyTyE
The cysteine residue of glial fibrillary acidic protein is a critical target for lipoxidation and required for efficient network organization
Publication date: Available online 7 April 2018
Source:Free Radical Biology and Medicine
Author(s): Álvaro Viedma-Poyatos, Yolanda de Pablo, Milos Pekny, Dolores Pérez-Sala
The type III intermediate filament protein glial fibrillary acidic protein (GFAP) contributes to the homeostasis of astrocytes, where it co-polymerizes with vimentin. Conversely, alterations in GFAP assembly or degradation cause intracellular aggregates linked to astrocyte dysfunction and neurological disease. Moreover, injury and inflammation elicit extensive GFAP organization and expression changes, which underline reactive gliosis. Here we have studied GFAP as a target for modification by electrophilic inflammatory mediators. We show that the GFAP cysteine, C294, is targeted by lipoxidation by cyclopentenone prostaglandins (cyPG) in vitro and in cells. Electrophilic modification of GFAP in cells leads to a striking filament rearrangement, with retraction from the cell periphery and juxtanuclear condensation in thick bundles. Importantly, the C294S mutant is resistant to cyPG addition and filament disruption, thus highlighting the critical role of this residue as a sensor of oxidative damage. However, GFAP C294S shows defective or delayed network formation in GFAP-deficient cells, including SW13/cl.2 cells and GFAP- and vimentin-deficient primary astrocytes. Moreover, GFAP C294S does not effectively integrate with and even disrupts vimentin filaments in the short-term. Interestingly, short-spacer bifunctional cysteine crosslinking produces GFAP-vimentin heterodimers, suggesting that a certain proportion of cysteine residues from both proteins are spatially close. Collectively, these results support that the conserved cysteine residue in type III intermediate filament proteins serves as an electrophilic stress sensor and structural element. Therefore, oxidative modifications of this cysteine could contribute to GFAP disruption or aggregation in pathological situations associated with oxidative or electrophilic stress.
Graphical abstract
https://ift.tt/2GJb3rA
The role of ophthalmic imaging in central nervous system degeneration in systemic lupus erythematosus
Source:Autoimmunity Reviews
Author(s): Arnaldo Dias-Santos, Rita Pinto Proença, Joana Tavares Ferreira, Sofia Pinheiro, João Paulo Cunha, Rui Proença, Maria Francisca Moraes-Fontes
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder that can involve any organ system. Central nervous system involvement can be a severe life threatening complication, ultimately resulting in severe neurodegenerative changes. Magnetic resonance imaging suggests that neurodegeneration, which may have deleterious effects on brain function, may occur early in SLE and experimental models suggest that neuroprotection may be feasible and beneficial.The retina is an extension of the brain. Recent ophthalmic imaging technologies are capable of identifying early changes in retinal and choroidal morphology and circulation that may reflect CNS degeneration. However, their utility in monitoring CNS involvement in SLE has been poorly studied as these have only been performed in small cohorts, in a cross-sectional design, non-quantitatively and without correlation to disease activity.The authors aim to review the current understanding of neurodegeneration associated with SLE, with particular focus on the visual pathway. We describe the neuropathology of the visual system in SLE and the evidence for retinal and choroidal neurodegenerative and microvascular changes using optical coherence tomography technology. We aim to describe the potential role of optical imaging modalities in NPSLE diagnosis and their likely impact on the study of neuronal function.
https://ift.tt/2EqYrn2
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
Source:Autoimmunity Reviews
Author(s): Franziska Sotzny, Julià Blanco, Enrica Capelli, Jesús Castro-Marrero, Sophie Steiner, Modra Murovska, Carmen Scheibenbogen
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.
https://ift.tt/2JudmjQ
From HSV infection to erythema multiforme through autoimmune crossreactivity
Source:Autoimmunity Reviews
Author(s): Alberta Lucchese
Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180 kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM.
https://ift.tt/2qiJqzB
Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors
Source:Autoimmunity Reviews
Author(s): Milena Tocut, Ronen Brenner, Gisele Zandman-Goddard
The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically morbidity and mortality for these patients.Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome.The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation.In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.
https://ift.tt/2Etakss
Antinuclear antibodies: Is the indirect immunofluorescence still the gold standard or should be replaced by solid phase assays?
Source:Autoimmunity Reviews
Author(s): Dolores Pérez, Boris Gilburd, Danielle Azoulay, Ora Shovman, Nicola Bizzaro, Yehuda Shoenfeld
https://ift.tt/2Ix4c51
Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review
Source:Autoimmunity Reviews
Author(s): Mathilde Thiebaut, David Launay, Sébastien Rivière, Thibaut Mahévas, Syrine Bellakhal, Eric Hachulla, Olivier Fain, Arsène Mekinian
ObjectiveTo describe safety and efficacy of rituximab in patients with systemic sclerosis.MethodsWe included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones.ResultsThirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [−4; 4] vs loss of −7 [−19; 0]; p = 0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [−16.8; 2.5], (p = 0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p = 0.007), 13 [8; 18] at M12 (p = 0.008) and 10 [4; 16] at the last follow-up (p = 0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p = 0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p = 0.04).ConclusionOur personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases.
https://ift.tt/2Jv4cnw
Behçet's disease: New insights into pathophysiology, clinical features and treatment options
Source:Autoimmunity Reviews
Author(s): Antonio Greco, Armando De Virgilio, Massimo Ralli, Andrea Ciofalo, Patrizia Mancini, Giuseppe Attanasio, Marco de Vincentiis, Alessandro Lambiase
Behçet's disease (BD) is a rare systemic vasculitis characterized by oral aphthous ulcers, genital ulcers, ocular lesions and other systemic manifestations. BD occurs most frequently in Eurasian populations along the ancient trading route known as the "Silk Road" which extends from eastern Asia to the Mediterranean basin. The causes of BD are unknown: it is believed to be due to an autoimmune process triggered by an infectious or environmental agent in a genetically predisposed individual. HLA-B51 allele located in the MHC locus, on chromosome 6p has been the most strongly associated risk factor for BD in areas along the Old Silk Route. Herpes simplex virus-1 and Streptococcus have been postulated as possible environmental triggers of BD. T cell homeostasis perturbation, especially Th1 and Th17 expansions and decrease regulation by Tregs are now supposed to be the cornerstone of BD pathogenesis. The histology shows vasculitis that involves both arteries and veins, and vessels of any size. BD is a systemic vasculitis with significant neutrophil infiltration, endothelial cell swelling, and fibrinoid necrosis. The diagnosis of BD is only supported by clinical criteria and requires the exclusion of other diagnoses based on clinical presentation. There are no pathognomonic laboratorial findings of BD. This rare disease often leads to blindness and fatal systemic involvement. Main causes of death include major vessel disease and central nervous system involvement (Neuro-Behcet). Corticosteroids are commonly used to treat clinical manifestations of BD in combination with immunosuppressant drugs. Tumor necrosis factor (TNF)-blocking agents such as Infliximab, Etanercept, and Adalimumab have been reported to have success in patients with BD.
https://ift.tt/2EsIPzs
MECP2 mutation in a boy with severe apnea and sick sinus syndrome
Source:Brain and Development
Author(s): Tsutomu Shioda, Satoru Takahashi, Tadashi Kaname, Toyohiro Yamauchi, Tetsuya Fukuoka
Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene, which encodes methyl-CpG-binding protein 2 (MECP2). It almost exclusively affects the female sex and is considered lethal in the male sex. However, an increasing number of male patients with MECP2 mutations have been reported, including patients who suddenly died of unknown causes. We report a case of MECP2 mutation in a male patient who exhibited neonatal encephalopathy. He developed severe apnea, epilepsy, and psychomotor developmental delay and died suddenly of sick sinus syndrome at 17 months of age. Severe bradycardia had been noticed since 16 months of age. His older brother followed a similar clinical course and died at 30 months of age. The brother had also experienced severe bradycardia. This familial case might help to clarify the causes of sudden death in cases of MECP2 mutations.
https://ift.tt/2EsGVic
The association of solid-phase assays to immunofluorescence increases the diagnostic accuracy for ANA screening in patients with autoimmune rheumatic diseases
Source:Autoimmunity Reviews
Author(s): Nicola Bizzaro, Ignazio Brusca, Giulia Previtali, Maria Grazia Alessio, Massimo Daves, Stefan Platzgummer, Luigi Cinquanta, Giusy Paura, Maria Infantino, Mariangela Manfredi, Raffaella Faricelli, Danila Bassetti, Maura Musso, Gaia Deleonardi, Maria Teresa Trevisan, Antonella Radice, Marco Liguori, Tiziana Imbastaro, Fiorenza Pesente, Martina Fabris, Elio Tonutti
https://ift.tt/2Jv4hYm
The role of ophthalmic imaging in central nervous system degeneration in systemic lupus erythematosus
Source:Autoimmunity Reviews
Author(s): Arnaldo Dias-Santos, Rita Pinto Proença, Joana Tavares Ferreira, Sofia Pinheiro, João Paulo Cunha, Rui Proença, Maria Francisca Moraes-Fontes
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder that can involve any organ system. Central nervous system involvement can be a severe life threatening complication, ultimately resulting in severe neurodegenerative changes. Magnetic resonance imaging suggests that neurodegeneration, which may have deleterious effects on brain function, may occur early in SLE and experimental models suggest that neuroprotection may be feasible and beneficial.The retina is an extension of the brain. Recent ophthalmic imaging technologies are capable of identifying early changes in retinal and choroidal morphology and circulation that may reflect CNS degeneration. However, their utility in monitoring CNS involvement in SLE has been poorly studied as these have only been performed in small cohorts, in a cross-sectional design, non-quantitatively and without correlation to disease activity.The authors aim to review the current understanding of neurodegeneration associated with SLE, with particular focus on the visual pathway. We describe the neuropathology of the visual system in SLE and the evidence for retinal and choroidal neurodegenerative and microvascular changes using optical coherence tomography technology. We aim to describe the potential role of optical imaging modalities in NPSLE diagnosis and their likely impact on the study of neuronal function.
https://ift.tt/2EqYrn2
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
Source:Autoimmunity Reviews
Author(s): Franziska Sotzny, Julià Blanco, Enrica Capelli, Jesús Castro-Marrero, Sophie Steiner, Modra Murovska, Carmen Scheibenbogen
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.
https://ift.tt/2JudmjQ
Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets
Source:Autoimmunity Reviews
Author(s): Marc Scherlinger, Vivien Guillotin, Marie-Elise Truchetet, Cécile Contin-Bordes, Vanja Sisirak, Pierre Duffau, Estibaliz Lazaro, Christophe Richez, Patrick Blanco
Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two phenotypically distincts inflammatory systemic diseases. However, SLE and SSc share pathogenic features such as interferon signature, loss of tolerance against self-nuclear antigens and increased tissue damage such as fibrosis. Recently, platelets have emerged as a major actor in immunity including auto-immune diseases. Both SLE and SSc are characterized by strong platelet system activation, which is likely to be both the witness and culprit in their pathogenesis. Platelet activation pathways are multiple and sometimes redundant. They include immune complexes, Toll-like receptors activation, antiphospholipid antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once activated, platelet promote immune dysregulation by priming interferon production by immune cells, providing CD40L supporting B lymphocyte functions and providing a source of autoantigens. Platelets are actively implicated in SLE and SSc end-organ damage such as cardiovascular and renal disease and in the promotion of tissue fibrosis. Finally, after understanding the main pathogenic implications of platelet activation in both diseases, we discuss potential therapeutics targeting platelets.
https://ift.tt/2Ix4d95
From HSV infection to erythema multiforme through autoimmune crossreactivity
Source:Autoimmunity Reviews
Author(s): Alberta Lucchese
Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180 kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM.
https://ift.tt/2qiJqzB
Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors
Source:Autoimmunity Reviews
Author(s): Milena Tocut, Ronen Brenner, Gisele Zandman-Goddard
The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically morbidity and mortality for these patients.Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome.The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation.In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.
https://ift.tt/2Etakss
Antinuclear antibodies: Is the indirect immunofluorescence still the gold standard or should be replaced by solid phase assays?
Source:Autoimmunity Reviews
Author(s): Dolores Pérez, Boris Gilburd, Danielle Azoulay, Ora Shovman, Nicola Bizzaro, Yehuda Shoenfeld
https://ift.tt/2Ix4c51
Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review
Source:Autoimmunity Reviews
Author(s): Mathilde Thiebaut, David Launay, Sébastien Rivière, Thibaut Mahévas, Syrine Bellakhal, Eric Hachulla, Olivier Fain, Arsène Mekinian
ObjectiveTo describe safety and efficacy of rituximab in patients with systemic sclerosis.MethodsWe included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones.ResultsThirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [−4; 4] vs loss of −7 [−19; 0]; p = 0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [−16.8; 2.5], (p = 0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p = 0.007), 13 [8; 18] at M12 (p = 0.008) and 10 [4; 16] at the last follow-up (p = 0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p = 0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p = 0.04).ConclusionOur personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases.
https://ift.tt/2Jv4cnw
Behçet's disease: New insights into pathophysiology, clinical features and treatment options
Source:Autoimmunity Reviews
Author(s): Antonio Greco, Armando De Virgilio, Massimo Ralli, Andrea Ciofalo, Patrizia Mancini, Giuseppe Attanasio, Marco de Vincentiis, Alessandro Lambiase
Behçet's disease (BD) is a rare systemic vasculitis characterized by oral aphthous ulcers, genital ulcers, ocular lesions and other systemic manifestations. BD occurs most frequently in Eurasian populations along the ancient trading route known as the "Silk Road" which extends from eastern Asia to the Mediterranean basin. The causes of BD are unknown: it is believed to be due to an autoimmune process triggered by an infectious or environmental agent in a genetically predisposed individual. HLA-B51 allele located in the MHC locus, on chromosome 6p has been the most strongly associated risk factor for BD in areas along the Old Silk Route. Herpes simplex virus-1 and Streptococcus have been postulated as possible environmental triggers of BD. T cell homeostasis perturbation, especially Th1 and Th17 expansions and decrease regulation by Tregs are now supposed to be the cornerstone of BD pathogenesis. The histology shows vasculitis that involves both arteries and veins, and vessels of any size. BD is a systemic vasculitis with significant neutrophil infiltration, endothelial cell swelling, and fibrinoid necrosis. The diagnosis of BD is only supported by clinical criteria and requires the exclusion of other diagnoses based on clinical presentation. There are no pathognomonic laboratorial findings of BD. This rare disease often leads to blindness and fatal systemic involvement. Main causes of death include major vessel disease and central nervous system involvement (Neuro-Behcet). Corticosteroids are commonly used to treat clinical manifestations of BD in combination with immunosuppressant drugs. Tumor necrosis factor (TNF)-blocking agents such as Infliximab, Etanercept, and Adalimumab have been reported to have success in patients with BD.
https://ift.tt/2EsIPzs
The intersection of men's sexual violence perpetration and sexual risk behavior: A literature review
Source:Aggression and Violent Behavior
Author(s): Kelly Cue Davis, Elizabeth C. Neilson, Rhiana Wegner, Cinnamon L. Danube
According to the Confluence Model of Sexual Violence, men with a strong impersonal sex orientation (i.e., greater engagement in sexual activities with more casual sexual partners) are at increased risk of perpetrating sexual violence. Research from a variety of countries and samples has supported this proposition, finding that men who perpetrate sexual violence are also more likely to engage in risky sexual behavior. The present article reviews this literature, synthesizing research findings from both psychology and public health domains utilizing both domestic and international samples. In particular, this review focuses on the associations between men's perpetration of sexual violence and their sexual partners, condom use, and sexually transmitted infection status, as well as provides recommendations for future research directions and prevention and intervention programming.
https://ift.tt/2JtgyfZ
Genomic Profile of Appendiceal Goblet Cell Carcinoid Is Distinct Compared to Appendiceal Neuroendocrine Tumor and Conventional Adenocarcinoma
Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Kwun Wah Wen, James P. Grenert, Nancy M. Joseph, Nafis Shafizadeh, Anne Huang, Mojgan Hosseini, Sanjay Kakar
Goblet cell carcinoid (GCC) is a rare appendiceal tumor with unique morphologic features that shows glandular and neuroendocrine differentiation on immunohistochemistry. An additional component of adenocarcinoma (AC) can be present (GCC-AC). Both GCC and GCC-AC are staged and treated like AC. The histogenesis and genetic alterations underlying GCC and GCC-AC are unclear. Capture-based next-generation DNA sequencing targeting 479 cancer genes was performed on 19 appendiceal tumors: 4 GCC, 9 GCC-AC, 3 neuroendocrine tumors (NET), and 3AC (2 conventional, 1 mucinous). Somatic coding mutations were not seen in any NET. Pathogenic (P)/likely pathogenic (LP) mutations were present in 1 GCC, 8 GCC-AC and all 3AC cases. P/LP mutations in chromatin remodeling genes were seen in 4 (44.4%) GCC-AC cases, but not in NET, GCC or AC. In GCC-AC, P/LP mutations in ARID1A and RHOA were each present in 3 cases, and KDM6A and SOX9 mutations were each seen in 2 cases. APC and KRAS mutations were present in 1 conventional AC case, but were not observed in any GCC or GCC-AC. This limited series reveals mutations in SOX9, RHOA, and chromatin-modifier genes in goblet cell tumors, and shows that the mutational profile of GCC/GCC-AC is distinct from NET and conventional appendiceal AC.
https://ift.tt/2GDo0Hk
High expression of synthesis of cytochrome c oxidase 2 and TP53-induced glycolysis and apoptosis regulator can predict poor prognosis in human lung adenocarcinoma
Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Jiabin Liu, Funian Lu, Yan Gong, Chen Zhao, Qi Pan, Stephanie Ballantyne, Xianda Zhao, Sufang Tian, Honglei Chen
Synthesis of cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) are two p53-mediated proteins that can play a regulatory role in cancer energy metabolism. However, no study has examined the association of SCO2 and TIGAR with the prognosis of patients with lung adenocarcinoma (AC). In our study, the expression of SCO2 and TIGAR proteins in lung AC was detected, and the potential relation to prognosis was evaluated, aiming to take a further view of lung AC progression. Quantum dots–based immunofluorescence histochemistry staining was performed to observe the expression of p53, SCO2, and TIGAR in 75 specimens of lung AC. Of these, 51 (68.0%) showed high expression of SCO2, and 59 (78.7%) showed high expression of TIGAR. High TIGAR expression was significantly associated with a history of smoking (P = .017) and being male (P = .006). The correlation between high SCO2 expression and age also was significant (P = .042). Moreover, high TIGAR expression was positively correlated with high SCO2 expression (P = .019; rs = 0.271). High expression of the SCO2 and TIGAR proteins predicted poorer survival and a higher mortality rate (P = .024 and .030, respectively). High expression of SCO2 and TIGAR proteins is significantly associated with lung AC progression, suggesting their potential use as prognostic markers and therapeutic targets.
https://ift.tt/2qh3IZ4
Somatic polymerase epsilon mutations as another route leading to loss of DNA MMR protein expression in endometrial carcinoma
Publication date: Available online 7 April 2018
Source:Human Pathology
Author(s): Pieter J. Westenend, Winand N. Dinjens
https://ift.tt/2GIKze0
Pseudolaric acid B attenuates atherosclerosis progression and inflammation by suppressing PPARγ-mediated NF-κB activation
Source:International Immunopharmacology, Volume 59
Author(s): Tan Li, Wei Wang, Yu-Xiu Li, Xiao Li, Wen-Jie Ji, Yong-Qiang Ma, Hong Chen, Ji-Hong Zhao, Xin Zhou
Aims/objectiveAtherosclerosis is a progressive disease of large arteries characterized with chronic inflammation and aberrant immune response. Pseudolaric acid B (PB) has been found to exert multiple effects by inhibiting inflammatory response. However, there is no comprehensive assessment of the effects of PB on atherosclerosis using relevant in vivo and in vitro models.Material and methodsMale ApoE−/− mice were treated with PB orally with a high fat diet (HFD) to clarify its anti-atherosclerotic activities. RAW264.7 macrophage line, a well-accepted cell model of atherosclerosis, was used to investigate anti-inflammatory effects and molecular mechanisms of PB.ResultsPB significantly attenuated atherosclerotic lesions by modulating plasma lipid profiles as well as inhibiting inflammatory responses in macrophages of atherosclerotic mice. Meanwhile, PB markedly suppressed the expression of pro-inflammatory cytokines, and regulated cholesterol efflux related genes in oxidative low density lipoprotein (ox-LDL)-loaded macrophages. The cellular uptake of Dil-labeled ox-LDL was significantly inhibited by PB either. Moreover, the ability of PB to suppress nuclear factor kappa B (NF-κB) and activate peroxisome proliferator-activated receptor gamma (PPARγ) was confirmed using luciferase reporter assays. Conversely, the selective PPARγ antagonist GW9662 reversed the influence of PB in macrophages.ConclusionTogether, these findings indicate that PB exerts its protective effects on atherosclerosis by inhibiting macrophage-mediated inflammatory response and cellular ox-LDL uptake, and promoting cholesterol efflux by suppressing NF-κB activation PPARγ-dependently. Therefore, PB may be a promising agent for inflammatory and atherosclerotic diseases.
https://ift.tt/2JtubeQ
Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis
Source:International Immunopharmacology, Volume 59
Author(s): Veronika Caisová, Ondřej Uher, Pavla Nedbalová, Ivana Jochmanová, Karolína Kvardová, Kamila Masáková, Gabriela Krejčová, Lucie Paďouková, Jindřich Chmelař, Jan Kopecký, Jan Ženka
Immunotherapy emerges as a fundamental approach in cancer treatment. Up to date, the efficacy of numerous different immunotherapies has been evaluated. The use of microorganisms or their parts for immune cell activation, referred to as Pathogen-Associated Molecular Patterns (PAMPs), represents highly promising concept. The therapeutic effect of PAMPs can be further amplified by suitable combination of different types of PAMPs such as Toll like receptor (TLR) agonists and phagocytosis activating ligands. Previously, we used the combination of phagocytosis activating ligand (mannan) and mixture of TLR agonists (resiquimod (R-848), poly(I:C), inactivated Listeria monocytogenes) for successful treatment of melanoma in murine B16-F10 model. In the present study, we optimized the composition and timing of previously used mixture. Therapeutic mixture based on well-defined chemical compounds consisted of mannan anchoring to tumor cell surface by biocompatible anchor for membranes (BAM) and TLR agonists resiquimod, poly(I:C), and lipoteichoic acid (LTA). The optimization resulted in (1) eradication of advanced stage progressive melanoma in 83% of mice, (2) acquisition of resistance to tumor re-transplantation, and (3) potential anti-metastatic effect. After further investigation of mechanisms, underlying anti-tumor responses, we concluded that both innate and adaptive immunity are activated and involved in these processes.We tested the efficacy of our treatment in Panc02 murine model of aggressive pancreatic tumor as well. Simultaneous application of agonistic anti-CD40 antibody was necessary to achieve effective therapeutic response (80% recovery) in this model.Our results suggest that herein presented immunotherapeutic approach is a promising cancer treatment strategy with the ability to eradicate not only primary tumors but also metastases.
https://ift.tt/2GH2ugJ
Investigational agents to enhance the efficacy of chemotherapy or radiation in pancreatic cancer
Source:Critical Reviews in Oncology/Hematology
Author(s): Myrna Hurtado, Umesh T. Sankpal, Amalendu Ranjan, Rajasekhar Maram, Jamboor K. Vishwanatha, Ganji Purnachandra Nagaraju, Bassel F. El-Rayes, Riyaz Basha
Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays. Cur has a low level of toxicity and promising anti-cancer activity, however, its clinical development has been limited by low bioavailability. Cur analogs and nanoparticles were synthesized to improve Cur's efficacy and bioavailability. These compounds were found to be effective in enhancing the therapeutic effects of chemotherapy in pre-clinical models. Small molecules such as NSAIDs have also been tested for the anti-cancer activity and induction of response of chemotherapy and radiation. Interest in TA, a NSAID, has recently increased due to promising preclinical data demonstrating its anti-cancer properties with minimum toxicity. TA also synergistically increased the response of XRT in PC cells and in an orthotropic mouse model. With strong preclinical evidence, research aimed at developing less toxic therapies for PC using Cur analogues or TA is ready for translation into clinical testing.
https://ift.tt/2IAy7Ju
The role of heme iron molecules derived from red and processed meat in the pathogenesis of colorectal carcinoma
Source:Critical Reviews in Oncology/Hematology
Author(s): S.M.K. Gamage, Lakal Dissabandara, Alfred King-Yin Lam, Vinod Gopalan
Emerging evidence that heme iron in red meat is a risk factor for colorectal carcinogenesis is a topic that has received recent scrutiny. This review aims to summarise the mechanism of colorectal carcinogenesis by heme contained in red and processed meat. Heme iron can induce cytotoxicity by 'cytotoxic heme factor' and promote surface epithelial cell apoptosis and compensatory epithelial hyperplasia. Heme, induces peroxidation of lipids, leading to free radical formation and generation of DNA adducts in colorectal epithelial cells. In addition, heme catalyses the formation of N-nitroso-compounds, which in turn results in the initiation of colorectal carcinogenesis. Emerging data suggest that intestinal dysbiosis can promote carcinogenic properties of heme. Heme induces multiple genetic alterations by regulating WNT signalling pathway and causing mutations in major colon cancer genes such as APC, TP53 and KRAS. However, a balanced diet containing green vegetables, olive oil and calcium may reduce the carcinogenic effects of heme.
https://ift.tt/2qbf162
The identification and isolation of CTCs: a Biological Rubik’s Cube
Publication date: Available online 7 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Cristina Mansilla, Elena Soria, Natalia Ramírez
Liquid biopsy represents an alternative to conventional biopsies for the evaluation of tumors mainly due to its easy sampling. One of the main applications is the enumeration of Circulating Tumor Cells (CTCs) to evaluate tumor progression or response to treatment. The analysis of the functional characteristics of CTCs could give us much more information about their role in order to establish a more personalized treatment for the patients. The major issue that has to be solved is the isolation of the CTC population. Multiple protocols have been developed, however none of them has demonstrated to be the definitive one. In fact, a combination of these techniques has often been performed in order to obtain a purer and viable population of CTCs. In this review we have summarized for the first time the different combinatorial approaches used in the last years to optimize the isolation of CTCs and their limitations.
https://ift.tt/2qd12ga
Utilidad del diagnóstico por la imagen en el mielolipoma extraadrenal
Publication date: Available online 7 April 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): J. Salvador García, P. Abreu Sánchez, F. Delgado Cordón, P. Soriano Sarrió, B. Cueto Cañadas, I. Latorre Agraz
https://ift.tt/2qfyIcd
Influence of epidermal basement membrane integrity on cutaneous permeability barrier function
Publication date: Available online 6 April 2018
Source:Journal of Dermatological Science
Author(s): Shunsuke Iriyama, Yuko Matsuura-Hachiya, Makoto Tsunenaga
https://ift.tt/2GGCtT4
Emerging Applications of Eye-Tracking Technology in Dermatology
Publication date: Available online 6 April 2018
Source:Journal of Dermatological Science
Author(s): Kevin K. John, Jakob D. Jensen, Andy J. King, Manusheela Pokharel, Douglas Grossman
Eye-tracking technology has been used within a multitude of disciplines to provide data linking eye movements to visual processing of various stimuli (i.e., x-rays, situational positioning, printed information, and warnings). Despite the benefits provided by eye-tracking in allowing for the identification and quantification of visual attention, the discipline of dermatology has yet to see broad application of the technology. Notwithstanding dermatologists' heavy reliance upon visual patterns and cues to discriminate between benign and atypical nevi, literature that applies eye-tracking to the study of dermatology is sparse; and literature specific to patient-initiated behaviors, such as skin self-examination (SSE), is largely non-existent. The current article provides a review of eye-tracking research in various medical fields, culminating in a discussion of current applications and advantages of eye-tracking for dermatology research.
https://ift.tt/2qeoPLG
Resident and monocyte-derived Langerhans cells are required for imiquimod-induced psoriasis-like dermatitis model
Publication date: Available online 6 April 2018
Source:Journal of Dermatological Science
Author(s): Minseok Lee, Sung Hee Kim, Tae-Gyun Kim, Jeyun Park, Jae Won Lee, Min-Geol Lee
BackgroundLangerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated.ObjectiveTo explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice.Methods5% IMQ cream was topically applied on the skins. Clinical and histopathological features were evaluated. Psoriasis-related gene expression was analyzed by quantitative polymerase chain reaction. The production of psoriasis-related cytokines including IL-17A and IL-22 by T cells were assessed by flow cytometry from the lesional skins.ResultshuLang-DTA mice showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang-DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring erythema, scales, and thickness compared with wild-type mice. Psoriatic lesions from huLang-DTA mice had a decreased level of Il23a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from γdlow T cells. mLCs revealed a significantly greater level of IL-23 expression compared to rLCs in response to topical IMQ treatment.ConclusionAlthough both rLCs and mLCs are involved in the development of IMQ-induced psoriasis-like dermatitis, inflammation-induced mLCs present a superior capacity for producing IL-23 in this murine experimental model of psoriasis.
https://ift.tt/2GFTnRR
Disentangling Intolerance of Uncertainty and Threat Appraisal in Everyday Situations
Source:Journal of Anxiety Disorders
Author(s): E. Pepperdine, C. Lomax, M.H. Freeston
Intolerance of Uncertainty is a transdiagnostic risk and maintenance factor in a range of anxiety disorders and major depressive disorder. However, the mechanism of action in the development and maintenance of anxiety disorders is poorly understood, with the relationship between the constructs of uncertainty and threat appraisal remaining unclear. Most research to date has investigated IU in situations that are explicitly or implicitly threatening (i.e. where they have a negative outcome), which makes it difficult to establish whether it is the uncertainty or the prospect of a negative outcome (or threat) that people find aversive. If the construct of IU is about uncertainty (and not threat), it should also be operating in situations where there are no negative outcomes possible. Participants (N = 224) completed a battery of online measures in tasks designed to evaluate level of situational uncertainty and perception of threat level. These tasks required responses to scenarios which displayed or implied varying levels of estimated threat. Regression analyses indicated that IU was related to perceiving threat and uncertainty in negative situations and positive situations, with the greatest contribution from uncertainty within the situations, supporting the conceptualisation of IU as a response to uncertainty that is largely independent of threat although may contribute to perceptions of threat.
https://ift.tt/2HipB2C
A rare case of septic shock due to Neisseria meningitidis serogroup B infection despite prior vaccination in a young adult with paroxysmal nocturnal haemoglobinuria receiving eculizumab
Source:Vaccine
Author(s): Dominik Reher, Valentin Fuhrmann, Stefan Kluge, Axel Nierhaus
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease which causes defects in complement inhibiting proteins. The disease presents classically with the triad of haemolytic anaemia, pancytopenia and thrombosis. Eculizumab, a humanized antibody that blocks the cleavage of complement factor 5, was approved for PNH treatment in 2007 and has improved patients' survival since then. However, several cases of invasive meningococcal disease (IMD) have been reported in eculizumab-treated patients, mostly caused by serogroup B infection which was not covered by the previously administered vaccine (MenACWY). We report a rare case of septic shock due to infection with Neisseria meningitis serogroup B despite prior vaccination with 4CMenB in a young PNH patient treated with eculizumab. There are increasing doubts over whether vaccination ensures sufficient immunoprotection against IMD in patients receiving eculizumab. Therefore, besides monitoring the immune response, lifelong chemoprophylaxis should be considered.
https://ift.tt/2GGfhjz
Hemifacial microsomia (oculo-auriculo-vertebral spectrum) in an individual from the Teramo Sant’Anna archaeological site (7th–12th centuries of the Common Era, Italy)
Source:Archives of Oral Biology
Author(s): Joan Viciano, Ruggero D'Anastasio
BackgroundThis study is based in an analysis of the skeletal remains of an adult male from the Teramo Sant'Anna archaeological site (7th–12th centuries of the Common Era, Teramo, Italy).Results and DiscussionThe individual shows distinct abnormalities that principally involve asymmetric hypoplasia and dysmorphogenesis of the facial skeleton. The combination of these findings and the absence of abnormalities of the spine strongly suggest diagnosis of the congenital malformation known as hemifacial microsomia. This very heterogeneous syndrome affects primarily aural, ocular, oral and mandibular development. Despite the lack of clinical information and the absence of soft tissue, it was possible to perform a differential diagnosis for this palaeopathological case. Mastication was probably altered considering that the mandible is extremely asymmetric and lacks true condyles. The temporomandibular joints are present, but the right one is hypoplastic and abnormal in shape. There is evidence of bilateral dislocation, and the facial muscles are hypertrophic.ConclusionsThis case represents an important contribution to the palaeopathological literature because this is an uncommon condition that has not been widely documented in ancient skeletal remains.
https://ift.tt/2HhI0fS
Hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves on Streptococcus mutans biofilm and tooth demineralization
Source:Archives of Oral Biology
Author(s): Juliana Gonçalves Pires, Sara Salustiano Zabini, Aline Silva Braga, Rita de Cássia Fabris, Flaviana Bombarda de Andrade, Rodrigo Cardoso de Oliveira, Ana Carolina Magalhães
ObjectivesThis study evaluated the effect of the hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves (alone or combined) on the viability of Streptococcus mutans biofilm and on the prevention of enamel demineralization.MethodsStrain of S. mutans (ATCC 21175) was reactivated in BHI broth. Minimum inhibitory concentration, minimum bactericidal concentration, minimum inhibition biofilm concentration and minimum eradication biofilm concentration were determined in order to choose the concentrations to be tested under biofilm model. S. mutans biofilm (5 × 105 CFU/ml) was produced on bovine enamel, using McBain saliva under 0.2% sucrose exposure, for 3 days. The biofilm was daily treated with the extracts for 1 min. The biofilm viability was tested by fluorescence and the enamel demineralization was measured using TMR.ResultsMyracrodruon urundeuva All. (Isolated or combined) at the concentrations ≥ 0.625 mg/ml was able to reduce bacteria viability, while Qualea Grandflora Mart. alone had antimicrobial effect at 5 mg/ml only (p < 0.05). On the other hand, none of the extracts were able to reduce enamel demineralization.ConclusionsThe hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves (isolated or combined) have antimicrobial action; however, they do not prevent enamel caries under S. mutans biofilm model.
https://ift.tt/2GFc5oA
Physician assessed and patient reported lower limb edema after definitive radio(chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: A report from the EMBRACE study
Source:Radiotherapy and Oncology
Author(s): Dina Najjari Jamal, Richard Pötter, Christine Haie-Meder, Jacob C. Lindegaard, Ina Maria Juergenliemk-Schulz, Umesh Mahantshetty, Barbara Segedin, Kjersti Bruheim, Peter Hoskin, Bhavana Rai, Ericka Wiebe, Rachel Cooper, Kari Tanderup, Kathrin Kirchheiner
Background/purposeTo evaluate the pattern of manifestation and risk factors for lower limb edema (LLE) within the prospective, observational, multi-center EMBRACE study on radiochemotherapy and MRI-guided brachytherapy in locally advanced cervical cancer (LACC).Material/methodsLLE was prospectively assessed according to the physician-reported CTCAE v.3 and patient-reported EORTC QLQ-CX24 questionnaire at baseline and regular follow-up.ResultsIn total, 1176 patients were evaluated with a median follow-up of 27 months. Actuarial analyses revealed 3/5-year estimates of 27%/31% of CTCAE G ≥ 1, 6.1%/6.6% of G ≥ 2 and 0.5%/0.5% for G ≥ 3.Prevalence rates for G ≥ 1 LLE at 3 months, 1, 3 and 5 years after end of treatment were 7%, 12%, 12%, 15% for physician-assessed and 25%, 30%, 30%, 34% for any patient-reported symptoms and showed a steady increase over time.Invasive lymph node staging and obesity at diagnosis are independent significant risk factors for G ≥ 1 LLE, whereas nodal boost has no impact. Extended radiation fields including para-aortic and/or inguinal nodes show a tendency to increase the risk.ConclusionSevere LLE after definitive radiochemotherapy in LACC is rare. However, the risk for mild LLE is considerable, and related to patient-, diagnostic- and treatment characteristics.Less invasive diagnostic surgical procedures or non-invasive assessment, less invasive radiotherapy management and active rehabilitation are important pathways for future developments.
https://ift.tt/2qcwP0y
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