Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2IPhltR
Πέμπτη 17 Μαΐου 2018
NonScarring Diffuse Hair Loss in Women: a Clinico‐Etiological Study from tertiary care center in North‐West India
Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years
Clinical Endocrinology, EarlyView.
https://ift.tt/2rRxWUh
Identification of tumor margins using diffuse reflectance spectroscopy with an extended‐wavelength spectrum in a porcine model
Skin Research and Technology, EarlyView.
https://ift.tt/2INRB1g
Violaceous papules on the hands
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2wR9MOv
A simple and cost‐efficient adherent culture platform for human gastric primary cells, as an in vitro model for Helicobacter pylori infection
Helicobacter, EarlyView.
https://ift.tt/2L5DXot
Glucocorticoid withdrawal affects stress‐induced changes in urocortin 2 gene expression in the rat adrenal medulla and brain
Journal of Neuroendocrinology, Volume 30, Issue 5, May 2018.
https://ift.tt/2k66IVz
Oxytocin levels in saliva correlate better than plasma levels with concentrations in the cerebrospinal fluid of patients in neurocritical care
Journal of Neuroendocrinology, Volume 30, Issue 5, May 2018.
https://ift.tt/2rSU1kq
The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase
Publication date: Available online 17 May 2018
Source:Cell Metabolism
Author(s): Phillip J. White, Robert W. McGarrah, Paul A. Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M. Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L. Lapworth, Inna Astapova, Sarah A. Hannou, Tabitha George, Michelle Arlotto, Lyra B. Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A. Herman, R. Max Wynn, David T. Chuang, Christopher B. Newgard
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Hepatic overexpression of BDK increased ACL phosphorylation and activated de novo lipogenesis. BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding or expression of the ChREBP-β transcription factor. These studies identify BDK and PPM1K as a ChREBP-regulated node that integrates BCAA and lipid metabolism. Moreover, manipulation of the BDK:PPM1K ratio relieves key metabolic disease phenotypes in a genetic model of severe obesity.
Graphical abstract
Teaser
Branched-chain amino acids (BCAA) are strongly associated with metabolic diseases. White et al. demonstrate that the kinase (BDK) and phosphatase (PPM1K) that regulate a rate-limiting BCAA metabolic enzyme, BCKDH, also regulate ATP-citrate lyase, a key lipogenic enzyme, thus identifying a new regulatory node that integrates BCAA and lipid metabolism.https://ift.tt/2wXrDmW
Testosterone induced downregulation of migration and proliferation in human Umbilical Vein Endothelial Cells by Androgen Receptor dependent and independent mechanisms
Publication date: Available online 17 May 2018
Source:Molecular and Cellular Endocrinology
Author(s): Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova
Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools. At a concentration of 1 μM, T downregulated the proliferation of HUVEC by inducing arrest in the G1 cell cycle phase in an Androgen Receptor (AR)-independent manner. We show that upon treatment with 1 μM T also induced downregulation of HUVEC migration. This process was AR-dependent and was associated with persistent phosphorylation of ezrin, radixin and moesin. Regardless of the mechanism of action, the treatment of HUVEC with both supra- and physiological doses of T was associated with posttranscriptional stabilization of the AR upon ligand binding.
https://ift.tt/2rQiPKU
Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Longwang Chen, Yang Lu, Linjun Zhao, Lili Hu, Qiaomeng Qiu, Zhuoling Zhang, Mengfang Li, Guangliang Hong, Bing Wu, Guangju Zhao, Zhongqiu Lu
Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4+CD25+regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis.
https://ift.tt/2Gtvsjx
Molecular analysis in liquid biopsies for diagnostics of primary central nervous system lymphoma: review of literature and future opportunities
Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Laura S. Hiemcke-Jiwa, Roos J. Leguit, Tom J. Snijders, N. Mehdi Jiwa, Jonas. J.W. Kuiper, Roel A. de Weger, Monique C. Minnema, Manon M.H. Huibers
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with a poor prognosis, for which accurate and timely diagnosis is of utmost importance. Unfortunately, diagnosis of PCNSL can be challenging and a brain biopsy (gold standard for diagnosis) is an invasive procedure with the risk of major complications. Thus, there is an urgent need for an alternative strategy to diagnose and monitor these lymphomas.Currently, liquid biopsies from cerebrospinal fluid (CSF) are used for cytomorphologic and flow cytometric analysis. Recently, new biomarkers such as genetic mutations and interleukins have been identified in these liquid biopsies, further expanding the diagnostic armamentarium.In this review we present an overview of genetic aberrations (>70) reported in this unique lymphoma. Of these genes, we have selected those that are reported in ≥3 studies. Half of the selected genes are implicated in the NFκB pathway (CARD11, CD79B, MYD88, TBL1XR1 and TNFAIP3), while the other half are not related to this pathway (CDKN2A, ETV6, PIM1, PRDM1 and TOX). Although this underlines the crucial role of the NFκB pathway in PCNSL, CD79B and MYD88 are at present the only genes mentioned in liquid biopsy analysis.Finally, a stepwise approach is proposed for minimally invasive liquid biopsy analysis and work-up of PCNSL, incorporating molecular analysis. Prioritization and refinements of this approach can be constructed based upon multidisciplinary collaboration as well as novel scientific insights.
https://ift.tt/2IN5yfD
A network meta-analysis of the treatments for esophageal squamous cell carcinoma in terms of survival
Publication date: Available online 17 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Amin Doosti-Irani, Kourosh Holakouie-Naieni, Abbas Rahimi-Foroushani, Mohammad Ali Mansournia, Peiman Haddad
We aimed to compare treatments for patients with esophageal squamous cell carcinoma (SCC) in terms of survival.Medline, Web of Science, Scopus, the Cochrane Library and Embase were searched. Randomized controlled trials (RCT) that had compared esophageal SCC treatments were included. The hazard ratio (HR) with 95% credible interval (CrI) was used to summarize the effect measures in the Bayesian network meta-analysis.Out of 23256 references, 43 RCTs with 34 treatments were included. Carboplatin and paclitaxel plus radiotherapy plus surgery (carbo-pacli + RT + S) compared with surgery alone decreased risk of death (HR = 0.49; 95% CrI: 0.26, 0.90). The HRs for carbo-pacli + RT + S versus surgery plus cisplatin and fluorouracil and surgery plus cisplatin and vindesine were 0.44 (0.22, 0.86) and 0.41 (0.20, 0.83), respectively. Among all treatments in network, carbo-pacli + RT + S ranked as first treatment.It seems carbo-pacli + RT + S was a better treatment among available treatments in network in terms of survival in patients with esophageal SCC.
https://ift.tt/2x08DEL
Long-term survival after liver metastasectomy in gastric cancer: Systematic review and meta-analysis of prognostic factors.
Publication date: Available online 17 May 2018
Source:Cancer Treatment Reviews
Author(s): Francesco Montagnani, Francesca Crivelli, Giuseppe Aprile, Caterina Vivaldi, Irene Pecora, Rocco De Vivo, Mario Alberto Clerico, Lorenzo Fornaro
BackgroundDespite the amelioration of systemic therapy, overall survival (OS) of metastatic gastric cancer (GC) patients remains poor. Liver is a common metastatic site and retrospective series suggest a potential OS benefit from hepatectomy, with interesting 5-year (5y) and 10-year (10y) OS rates in selected patients. We aim to evaluate the impact of liver resection and related prognostic factors on long-term outcome in this setting.MethodsWe searched Pubmed, EMBASE, and Abstracts/posters from international meetings since 1990. Data were extracted from publish papers. Random effects models meta-analyses and meta-regression models were built to assess 5yOS and the impact of different prognostic factor. Heterogeneity was assessed using between study variance, I2 and Cochran's Q. Funnel plot were used to assess small study bias.ResultsThirty-three observational studies (for a total of 1304 patients) were included. Our analysis demonstrates a 5yOS rate of 22% (95%CI: 18%-26%) and 10yOS rate of 11% (95%CI: 7%-18%) among patients undergoing radical hepatectomy. A favorable effect on OS was shown by several factors linked to primary cancer (lower T and N stage, no lympho-vascular or serosal invasion) and burden of hepatic disease (≤3 metastases, unilobar involvement, greatest lesion <5 cm, negative resection margins). Moreover, lower CEA and CA19.9 levels and post-resection chemotherapy were associated with improved OS.ConclusionsSurgical resection of liver metastases from GC seems associated with a significant chance of 5yOS and 10yOS and compares favourably with results of medical treatment alone. Prospective evaluation of this approach and validation of adequate selection criteria are needed.
https://ift.tt/2L9fvmd
Extracellular matrix expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Majed Felemban, Birthe Dorgau, Nicola Claire Hunt, Dean Hallam, Darin Zerti, Roman Bauer, Yuchun Ding, Joseph Collin, David Steel, Natalio Krasnogor, Jumana Al-Aama, Susan Lindsay, Carla Mellough, Majlinda Lako
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch's membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis.Statement of SignificanceThe expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin were expressed in Bruch's membrane; whereas Brevican, Versican, IMPG1 & IMPG2 in the developing interphotoreceptor matrix (IPM). Retinal organoids were successfully generated from pluripotent stem cells. The expression of ECM components was examined in the retinal organoids found to recapitulate human retinal development in vivo. Using functional blocking experiments, this study also highlight an important role of IMPG1 and CD44 in the development of photoreceptors and IPM formation.
Graphical abstract
https://ift.tt/2GunwOK
Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Linhua Zhang, Yu Qin, Zhiming Zhang, Fan Fan, Chenlu Huang, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Deling Kong, Chun Wang, Hongfan Sun, Xigang Leng, Dunwan Zhu
The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy.Statement of SignificanceThe combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.
Graphical abstract
https://ift.tt/2rQbpr2
ssSupramolecular poly(acrylic acid)/F127 hydrogel with hydration-controlled nitric oxide release for enhancing wound healing
Publication date: Available online 17 May 2018
Source:Acta Biomaterialia
Author(s): Mathilde Champeau, Valéria Póvoa, Lucas Militão, Flávia Cabrini, Guilherme F. Picheth, Florian Meneau, Carlos P. Jara, Eliana P. de Araujo, Marcelo G. de Oliveira
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200 min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40 nmol/g h to 1.5 μmol/g h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5 days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5 to 3.4 days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing.Statement of SignificanceThe topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor Snitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel.
Graphical abstract
https://ift.tt/2rR6R3v
Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer
Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): T. Aparicio, O. Bouché, E. Francois, F. Retornaz, E. Barbier, J. Taieb, S. Kirscher, P.-L. Etienne, R. Faroux, F. Khemissa Akouz, F. El Hajbi, C. Locher, Y. Rinaldi, T. Lecomte, S. Lavau-Denes, M. Baconnier, A. Oden-Gangloff, D. Genet, L. Bedenne, E. Paillaud
BackgroundOlder patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older.Patients and methodsPatients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS).Results102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75–91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status.ConclusionNormal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.
https://ift.tt/2wNzbc5
Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis
Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): Carmen Criscitiello, Mehra Golshan, William T. Barry, Giulia Viale, Stephanie Wong, Michele Santangelo, Giuseppe Curigliano
PurposeWe conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC).Patients and methodsThe primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant.ResultsThirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5–76% across arms with an average BCT of 57% (95% CI 52–62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I2 = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3–60% across studies. The average pCR across all study arms was 24% (95% CI 19–29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27).ConclusionspCR does not increase BCT in patients receiving NST for EBC.
https://ift.tt/2IviVSE
International Organization of Psychophysiology
Publication date: June 2018
Source:International Journal of Psychophysiology, Volume 128
https://ift.tt/2Iq2wyB
Editorial Board
Publication date: June 2018
Source:International Journal of Psychophysiology, Volume 128
https://ift.tt/2KBL1b5
Kasuistik: Metamizol-induzierte Agranulozytose
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 388-394
DOI: 10.1055/s-0043-115329
Metamizol hat insgesamt ein günstiges Nebenwirkungsprofil – aber es birgt ein höheres Risiko einer medikamenteninduzierten Agranulozytose als andere Schmerzmittel und darf daher nicht unkritisch eingesetzt werden. Dieser Beitrag berichtet von einem Patienten, der nach prothetischem Hüftersatz eine medikamenteninduzierte Agranulozytose – mutmaßlich durch Metamizol – entwickelt und trotz maximaler Therapie im septischen Schock verstirbt.
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Georg Thieme Verlag KG Stuttgart · New York
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Kardioanästhesie: Monitoring der Gerinnung und Gerinnungstherapie
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 364-379
DOI: 10.1055/s-0043-112099
Die Transfusion von allogenen Blutprodukten ist mit einer Erhöhung der perioperativen Morbidität und Letalität assoziiert. Störungen der Hämostase sind insbesondere bei kardiochirurgischen Patienten häufig anzutreffen und können zu transfusionspflichtigen Blutungen führen. Eine zielgerichtete Therapie der häufig komplexen Gerinnungsstörungen erfordert eine differenzierte Diagnostik.
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Georg Thieme Verlag KG Stuttgart · New York
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Kolloide zur Volumentherapie nach Verbrennung geeignet?
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 324-324
DOI: 10.1055/a-0607-6170
Georg Thieme Verlag KG Stuttgart · New York
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Hypertone Lösungen bei hämorrhagischem Schock ohne gesicherten Vorteil
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 327-328
DOI: 10.1055/a-0607-6183
Georg Thieme Verlag KG Stuttgart · New York
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Kardioanästhesie: anästhesiologisches Management
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 346-362
DOI: 10.1055/s-0043-106337
Das anästhesiologische Management herzchirurgischer Patienten hat sich in den letzten Jahren deutlich weiterentwickelt. Diese Übersicht widmet sich vor allem folgenden Bereichen: pharmakologische Kardioprotektion bei herzchirurgischen Eingriffen, Narkosemanagement an der Herz-Lungen-Maschine, Protokolle der „Enhanced Recovery After Cardiac Surgery" sowie innovative minimalinvasive Operationsverfahren wie die kathetergestützte Aortenklappenimplantation.
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Georg Thieme Verlag KG Stuttgart · New York
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Hypotonie nach Spinalanästhesie zur Sectio: Noradrenalin oder Phenylephrin?
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 328-328
DOI: 10.1055/a-0607-6144
Georg Thieme Verlag KG Stuttgart · New York
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Obere Altersgrenze bei ambulanter Anästhesie: Möglichkeiten und Risiken
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 380-386
DOI: 10.1055/s-0042-124408
Zahlreiche Operationen werden heute auch noch in höherem Lebensalter ambulant durchgeführt. Dieser Übersichtsartikel stellt die Vorteile der ambulanten Anästhesie bei älteren Patienten dar, zeigt aber auch die Risiken einer zu frühen Entlassung auf. Für den klinischen Alltag werden praktische Hilfestellungen für die Patientenauswahl gegeben und Risikofaktoren für eine ungeplante stationäre Aufnahme identifiziert.
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Georg Thieme Verlag KG Stuttgart · New York
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Pssst … AINS-Secrets: heute aus der Urologie – TUR-Syndrom
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 395-398
DOI: 10.1055/s-0042-101662
Georg Thieme Verlag KG Stuttgart · New York
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Erratum: Atemwegsmanagement – der schwierige Atemweg beim thoraxchirurgischen Patienten
Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0613-2898
Georg Thieme Verlag KG Stuttgart · New York
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Sauerstoffgabe für die Mutter bei Kaiserschnitt und oxidativer Stress des Kindes
Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 322-322
DOI: 10.1055/a-0607-6131
Georg Thieme Verlag KG Stuttgart · New York
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Preface
Publication date: June 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 3
Author(s): Matti Poutanen, Manuel Tena-Sempere
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Editorial Board
Publication date: June 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 3
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Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Anna M. Nicholson, Cora Olpe, Alice Hoyle, Ann-Sofie Thorsen, Teja Rus, Mathilde Colombé, Roxanne Brunton-Sim, Richard Kemp, Kate Marks, Phil Quirke, Shalini Malhotra, Rogier ten Hoopen, Ashraf Ibrahim, Cecilia Lindskog, Meagan B. Myers, Barbara Parsons, Simon Tavaré, Mark Wilkinson, Edward Morrissey, Douglas J. Winton
We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
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Teaser
Winton and colleagues describe stem cell dynamics in normal human colon to identify the efficiency of clone fixation within the epithelium and the rate of subsequent lateral expansion. Against these benchmarks biased stem cell behaviors advantaged in both fixation and expansion can be quantified to predict the age-related burden of pro-oncogenic mutation.https://ift.tt/2wS4Mtf
High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): Stefan M. Czerniecki, Nelly M. Cruz, Jennifer L. Harder, Rajasree Menon, James Annis, Edgar A. Otto, Ramila E. Gulieva, Laura V. Islas, Yong Kyun Kim, Linh M. Tran, Timothy J. Martins, Jeffrey W. Pippin, Hongxia Fu, Matthias Kretzler, Stuart J. Shankland, Jonathan Himmelfarb, Randall T. Moon, Neal Paragas, Benjamin S. Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening.
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Teaser
Organoids derived from human iPSCs have great potential for drug screening, but their complexity poses a challenge for miniaturization and automation. Freedman and colleagues establish a robotic pipeline to manufacture and analyze kidney organoids in microwell arrays. They apply this system to improve differentiation, measure toxicity, and comprehend disease.https://ift.tt/2IPmx0M
Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner
Publication date: Available online 17 May 2018
Source:Cell Stem Cell
Author(s): David Petrik, Michael H. Myoga, Sofia Grade, Niklas J. Gerkau, Melanie Pusch, Christine R. Rose, Benedikt Grothe, Magdalena Götz
One hallmark of adult neurogenesis is its adaptability to environmental influences. Here, we uncovered the epithelial sodium channel (ENaC) as a key regulator of adult neurogenesis as its deletion in neural stem cells (NSCs) and their progeny in the murine subependymal zone (SEZ) strongly impairs their proliferation and neurogenic output in the olfactory bulb. Importantly, alteration of fluid flow promotes proliferation of SEZ cells in an ENaC-dependent manner, eliciting sodium and calcium signals that regulate proliferation via calcium-release-activated channels and phosphorylation of ERK. Flow-induced calcium signals are restricted to NSCs in contact with the ventricular fluid, thereby providing a highly specific mechanism to regulate NSC behavior at this special interface with the cerebrospinal fluid. Thus, ENaC plays a central role in regulating adult neurogenesis, and among multiple modes of ENaC function, flow-induced changes in sodium signals are critical for NSC biology.
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Teaser
Stem cells need to adapt to signals from the environment to regulate their output. Here, we show the key role of a flow-sensitive ion channel in regulating the activation of adult neural stem cells and their output.https://ift.tt/2Kxs9Ks
Non-viral delivery of an optogenetic tool into cells with self-healing hydrogel
Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Fu-Yu Hsieh, Hao-Wei Han, Xiao-Ru Chen, Chii-Shen Yang, Yen Wei, Shan-hui Hsu
Optogenetics offers unique, temporally precise control of neural activity in genetically targeted specific neurons that express light-sensitive opsin molecules. Three-dimensional (3D) delivery of optogenetics can be realized by co-injection of bacteriorhodopsin (HEBR) plasmid with a chitosan-based self-healing hydrogel with strong shear-thinning properties. The HEBR protein shows photoelectrical properties and can be used as an optical switch for cell activation. We optimize the shear force generated during the process of injection (∼100 Pa), which is transient because of the self-healing nature of the hydrogel. This transient force exerted by the self-healing hydrogel may allow the cytosolic delivery of HEBR plasmid with excellent cell viability and a high efficiency approaching 80%. When excited with green light, HEBR-delivered neural stem cells (NSCs) can proliferate and specifically differentiate into neurons in vitro and rescue the function of nerve impaired zebrafish in vivo. This novel optogenetic method combining 3D injectable self-healing hydrogel offers potential temporal-spatial approaches to treat neurodegenerative diseases in the future.
https://ift.tt/2KzfGWJ
Walking the line: The fate of nanomaterials at biological barriers
Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Huan Meng, Wei Leong, Kam W. Leong, Chunying Chen, Yuliang Zhao
Biological systems have developed an efficient multi-tiered defense system to block foreign substances such as engineered nanomaterials (NMs) from causing damage. In a pathological scenario, the disease itself may also pose additional barriers due to the imbalance between abnormal cells and their surrounding microenvironment, and NMs could behave similarly or differently to classic foreign substances, depending on their unique characteristics. Thus, understanding the mechanisms that govern the fate of NMs against these biological barriers, including the strategies that can be used to shift their fate between access and blockage, become key information for NMs design. In this manuscript, we first describe the biological barriers that NMs may encounter, and further discuss how these biological barrier interactions could shift the fate of NMs between toxicity and therapeutic potential. A list of effects that may influence NMs access at nano/bio interface are presented and discussed, followed by personal insights on the important nano/bio topics that require additional research for a better understanding of NM/biological barrier interactions.
https://ift.tt/2k7Z5yb
Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy
Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Ling-xiao Zhang, Xi-xiu Xie, Dong-qun Liu, Zhi Ping Xu, Rui-tian Liu
Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and CpG onto LDH nanoparticles. Using melanoma as the model cancer and Tyrosinase-related protein 2 (Trp2) peptide as the model antigen, we demonstrated that dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth in comparison with aggregated LDH-based vaccine. We further constructed multi-target dispersion-stable LDH-based vaccine by co-loading Trp2, two mutated epitopes (M27 and M30) and CpG, which showed remarkable inhibition of melanoma growth. These results suggest that dispersion-stable LDH nanoparticles are an ideal platform to load multi-antigens and immune stimulants as effective personalized therapeutic cancer vaccines.
Graphical abstract
https://ift.tt/2KyUiAP
Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer
Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results also showed that targeted delivery of siRNA specific for CD44 can efficiently overcome resistance to EGFR targeting in TNBC cells both in vitro and in vivo. Overall, our results establish a new principle to achieve EGFR inhibition in TNBC and limit drug resistance.
https://ift.tt/2IrC03T
Hydroxycoumarins: New, effective plant-derived compounds reduce Ralstonia pseudosolanacearum populations and control tobacco bacterial wilt
Publication date: Available online 17 May 2018
Source:Microbiological Research
Author(s): Liang Yang, Lintong Wu, Xiaoyuan Yao, Shiyuan Zhao, Jiao Wang, Shili Li, Wei Ding
Plant wilt disease caused by the soilborne bacterial pathogen Ralstonia pseudosolanacearum is one of the most devastating plant diseases; however, no effective protection against this disease has been developed. Coumarins are important natural plant-derived compounds with a wide range of bioactivities and extensive applications in medicine and agriculture. In the present study, three hydroxycoumarins (Hycs), umbelliferone (UM), esculetin (ES) and daphnetin (DA) significantly inhibited the growth of R. pseudosolanacearum on solid medium in a concentration-dependent manner, and the minimum inhibitory concentration (MICs) of these compounds was 325 mg·L−1, 125 mg·L−1 and 75 mg·L−1, respectively. The percentage of live cells of R. pseudosolanacearum when supplemented with UM, ES, and DA was 63.61%, 17.81% and 7.23%, respectively, which were significantly lower than the DMSO treatment with 92%. Furthermore, irrigating roots with hydroxycoumarins (Hycs) 24 h before inoculation with R. pseudosolanacearum significantly delayed the occurrence of tobacco bacterial wilt, with the control efficiency of the DA treatment (the most efficient of Hycs treatment) 80.03%, 69.83%, 59.19%, 45.49%, 44.12%, 38.27% at 6, 8, 10, 12, 14, and 16 days after inoculation, respectively. Compared with the DMSO treatment, the pathogen populations of tobacco stems supplemented with 100 mg L−1 DA were the lowest, with population significantly reduced by 22.46%, 27.34%, and 18.06% at 4, 7, and 10 days after inoculation, respectively. Based on this study, these Hycs could be applied as potential protective agents in the management of tobacco bacterial wilt.
https://ift.tt/2wP9U13
Masthead
Publication date: May–June 2018
Source:Brachytherapy, Volume 17, Issue 3
https://ift.tt/2rOvEFq
Table of Contents
Publication date: May–June 2018
Source:Brachytherapy, Volume 17, Issue 3
https://ift.tt/2GusT0r
A Novel Approach to Probabilistic Characterisation of Neural Firing Patterns
Publication date: Available online 17 May 2018
Source:Journal of Neuroscience Methods
Author(s): Gorana Mijatović, Tatjana Lončar-Turukalo, Emmanuel Procyk, Dragana Bajić
BackgroundThe advances in extracellular neural recording techniques result in big data volumes that necessitate fast, reliable, and automatic identification of statistically similar units. This study proposes a single framework yielding a compact set of probabilistic descriptors that characterise the firing patterns of a single unit.New MethodProbabilistic features are estimated from an inter-spike-interval time series, without assumptions about the firing distribution or the stationarity. The first level of proposed firing patterns decomposition divides the inter-spike intervals into bursting, moderate and idle firing modes, yielding a coarse feature set. The second level identifies the successive bursting spikes, or the spiking acceleration/deceleration in the moderate firing mode, yielding a refined feature set. The features are estimated from simulated data and from experimental recordings from the lateral prefrontal cortex in awake, behaving rhesus monkeys.ResultsAn efficient and stable partitioning of neural units is provided by the ensemble evidence accumulation clustering. The possibility of selecting the number of clusters and choosing among coarse and refined feature sets provides an opportunity to explore and compare different data partitions.ConclusionsThe estimation of features, if applied to a single unit, can serve as a tool for the firing analysis, observing either overall spiking activity or the periods of interest in trial-to-trial recordings. If applied to massively parallel recordings, it additionally serves as an input to the clustering procedure, with the potential to compare the functional properties of various brain structures and to link the types of neural cells to the particular behavioural states.
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Highlights
https://ift.tt/2GrpQGB
Longitudinal Observations Using Simultaneous fMRI, Multiple Channel Electrophysiology Recording, and Chemical Microiontophoresis in The Rat Brain
Publication date: Available online 17 May 2018
Source:Journal of Neuroscience Methods
Author(s): Saul Jaime, Jose E. Cavazos, Yihong Yang, Hanbing Lu
BackgroundfMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity.New MethodsSimultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection.ResultsIntracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4 T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) enhanced dopaminergic neuronal activity in the ventral tegmental area (VTA) and altered LFP signal and fMRI functional connectivity in the striatum.Comparisons with Existing Method(s)Nanomanufacturing advances permit the production of MRI-compatible microelectrode arrays (with 16 or more channels), extending research beyond conventional methods limited to fewer channels. Our method permits longitudinal data collection of LFP and rsMRI and our algorithm effectively detects and replaces fMRI-induced electrophysiological noise, permitting rsMRI data collection concomitant with LFP recordings.ConclusionsOur model consists of longitudinal concurrent fMRI and multichannel intracortical electrophysiological recording during microinjection of pharmacological agents to modulate neural activity in the rat brain. We used commercial micro-electrodes and recording system and can be readily generalized to other labs.
https://ift.tt/2IqhkgR
Feasibility of imaging evoked activity throughout the rat brain using electrical impedance tomography
Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Mayo Faulkner, Sana Hannan, Kirill Aristovich, James Avery, David Holder
Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 μm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode. Impedance changes of −0.16 ± 0.08% at 12.9 ± 1.4 ms and −0.41 ± 0.14% at 8.8±1.9 ms were recorded from the cortex and VPL respectively. For imaging purposes, two 57-channel epicortical electrode arrays were used with one placed on each hemisphere of the rat brain. Despite using parameters optimised toward measuring thalamic activity and undertaking extensive averaging, reconstructed activity was constrained to the cortical somatosensory forepaw region and no significant activity at a depth greater than 1.6 mm below the surface of the cortex could be reconstructed. An evaluation of the depth sensitivity of EIT was investigated in simulations using estimates of the conductivity change and noise levels derived from experiments. These indicate that EIT imaging with epicortical electrodes is limited to activity occurring 2.5 mm below the surface of the cortex. This depth includes the hippocampus and so EIT has the potential to image activity, such as epilepsy, originating from this structure. To image deeper activity, however, alternative methods such as the additional implementation of depth electrodes will be required to gain the necessary depth resolution.
https://ift.tt/2wLvdR8
Contextualizing action observation in the predictive brain: Causal contributions of prefrontal and middle temporal areas
Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Lucia Amoruso, Alessandra Finisguerra, Cosimo Urgesi
Context facilitates the recognition of forthcoming actions by pointing to which intention is likely to drive them. This intention is thought to be estimated in a ventral pathway linking MTG with frontal regions and to further impact on the implementation of sensory predictions within the action observation network (AON). Additionally, when conflicting intentions are estimated from context, the DLPFC may bias action selection. However, direct evidence for the contribution of these areas to context-embedded action representations in the AON is still lacking. Here, we used a perturb-and-measure TMS-approach to disrupt neural activity, separately in MTG and DLPFC and subsequently measure cortico-spinal excitability while observing actions embedded in congruent, incongruent or ambiguous contexts. Context congruency was manipulated in terms of compatibility between observed kinematics and the action goal suggested by the ensemble of objects depicted in the environment. In the control session (vertex), we found an early facilitation and later inhibition for kinematics embedded in congruent and incongruent contexts, respectively. MTG stimulation altered the differential modulation of M1 response to congruent vs. incongruent contexts, suggesting this area specifies prior representations about appropriate object graspability. Interestingly, all effects were abolished after DLPFC stimulation highlighting its critical role in broader contextual modulation of the AON activity.
https://ift.tt/2L7D6DA
Response of the multiple-demand network during simple stimulus discriminations
Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Tanya Wen, Daniel J. Mitchell, John Duncan
The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control.
https://ift.tt/2L9pnfB
Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits
Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Marta Brocka, Cornelia Helbing, Daniel Vincenz, Thomas Scherf, Dirk Montag, Jürgen Goldschmidt, Frank Angenstein, Michael Lippert
Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data.
https://ift.tt/2wZzzED
Oscillatory networks of high-level mental alignment: A perspective-taking MEG study
Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): R.A. Seymour, H. Wang, G. Rippon, K. Kessler
Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3–7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations.
https://ift.tt/2LazVLj
The neural basis of free language choice in bilingual speakers: Disentangling language choice and language execution
Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Carlo Reverberi, Anna K. Kuhlen, Shima Seyed-Allaei, R.Stefan Greulich, Albert Costa, Jubin Abutalebi, John-Dylan Haynes
For everyday communication, bilingual speakers need to face the complex task of rapidly choosing the most appropriate language given the context, maintaining this choice over the current communicative act, and shielding lexical selection from competing alternatives from non-target languages. Yet, speech production of bilinguals is typically flawless and fluent. Most of the studies available to date constrain speakers' language choice by cueing the target language and conflate language choice with language use. This left largely unexplored the neural mechanisms underlying free language choice, i.e., the voluntary situation of choosing the language to speak. In this study, we used fMRI and Multivariate Pattern Analysis to identify brain regions encoding the target language when bilinguals are free to choose in which language to name pictures. We found that the medial prefrontal cortex encoded the chosen language prior to speaking. By contrast, during language use, language control recruited a wider brain network including the left inferior frontal lobe, the basal ganglia, and the angular and inferior parietal gyrus bilaterally. None of these regions were involved in language choice. We argue that the control processes involved in language choice are different from those involved in language use. Furthermore, our findings confirm that the medial prefrontal cortex is a domain-general region critical for free choice and that bilingual language choice relies on domain general processes.
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Scholar : Canadian Water Resources Journal / Revue canadienne des ressources hydriques, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online
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Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online
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Scholar : These new articles for Annals of GIS are available online
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Hand Sensibility in Healthy Young Children
Source:Pediatric Neurology
Author(s): Sonja M. Buitenhuis, Willem Pondaag, Ron Wolterbeek, Martijn J.A. Malessy
Aim: The aims of the study were (1) to assess hand sensibility in healthy young children using instruments validated for adults; (2) to identify which test tools are suitable; and (3) to compare the dominant and non-dominant sides.Methods: Twenty-five healthy children aged 7-11 years (mean 9.5 years) were investigated. Sensibility was assessed with the Semmes-Weinstein Monofilament test (SW), two-point discrimination (2PD), localization test (LOC) and stereognosis object recognition (SOR). Sensory stimuli were administered to fingertips.Results: The thinnest SW filament (D; 2.83mm) was felt at 94% of examined points. A 2PD at the smallest distance of 2 mm was found in the thumb in 84% of children and in the index finger in 94%. Only 60% felt this distance in the fifth digit. The difference between little finger and index finger was statistically significant (p= 0.001). Near-maximum value on the LOC was scored in both hands. All children had a 100% score for both hands in the SOR.Interpretation: Most children can detect touch in the digits at low pressure. The majority are able to discern two points 2 mm apart in the first and second digits, but significantly less so in the fifth digit. Children are well able to localize on which side of a fingertip pressure is applied. Objects are recognized very well, and occasionally too quickly to record. There appear to be no differences between the dominant and non-dominant hands in either test. Adjustment of sensory test protocols routinely used in adults is necessary to optimize hand sensation testing in children, in view of the detection limits.
https://ift.tt/2LbxLeC
Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.
Continuous low-dose antibiotic prophylaxis reduced the frequency of symptomatic, antibiotic-treated urinary tract infection by 48%, although antimicrobial resistance of bacteria isolated from the urine of those taking prophylaxis increased
https://ift.tt/2IMbCFn
Posterior Ischemic Optic Neuropathy After Blepharoplasty
No abstract availablehttps://ift.tt/2IsEpj3
Rehabilitation of Visual Loss: Where We Are and Where We Need to Be
Background: Spontaneous recovery of visual loss resulting from injury to the brain is variable. A variety of traditional rehabilitative strategies, including the use of prisms or compensatory saccadic eye movements, have been used successfully to improve visual function and quality-of-life for patients with homonymous hemianopia. More recently, repetitive visual stimulation of the blind area has been reported to be of benefit in expanding the field of vision. Evidence Acquisition: We performed a literature review with main focus on clinical studies spanning from 1963 to 2016, including 52 peer-reviewed articles, relevant cross-referenced citations, editorials, and reviews. Results: Repetitive visual stimulation is reported to expand the visual field, although the interpretation of results is confounded by a variety of methodological factors and conflicting outcomes from different research groups. Many studies used subjective assessments of vision and did not include a sufficient number of subjects or controls. Conclusions: The available clinical evidence does not strongly support claims of visual restoration using repetitive visual stimulation beyond the time that spontaneous visual recovery might occur. This lack of firm supportive evidence does not preclude the potential of real benefit demonstrated in laboratories. Additional well-designed clinical studies with adequate controls and methods to record ocular fixation are needed.
https://ift.tt/2wS8J0W
https://ift.tt/2wS8J0W
Optic Disc Drusen in Children: The Copenhagen Child Cohort 2000 Eye Study
Background: Optic disc drusen (ODD) are seen in up to 2.4% of the general population, but the etiology and pathophysiology of the condition is still unknown. The purpose of this study was to determine the prevalence of ODD in a population-based child cohort and to determine if scleral canal diameter and fetal birth and pubertal parameters are associated with the presence of ODD. Methods: This observational, longitudinal population-based birth cohort study, with a nested case–control, included 1,406 children. Eye examinations were performed when the children were between 11 and 12 years of age. Assessment was performed of optical coherence tomography (OCT) scans from 1,304 children with gradable enhanced depth imaging scans of the optic disc. Results: ODD in one or both eyes were found in 13 (1.0%) of all children. All but one of the cases were found in children with scleral canal diameter in the lowest quartile (1,182–1,399 μm) in the nested case–control study. Children with ODD had a mean disc diameter of 1,339 μm (interquartile range, 30 μm), whereas it was 1,508 μm (interquartile range, 196 μm) in the 130 controls without ODD (Phttps://ift.tt/2IqFckn
Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function
Objective: To determine whether at the time of diagnosis, the intraocular pressure (IOP) in patients with optic nerve head drusen (ONHD) correlates with the perimetric mean deviation (PMD) and the mean retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT). Methods: This retrospective chart review included adults with ONHD from 2 academic medical centers. Inclusion criteria were age older than 18 years, definitive diagnosis of ONHD, measurement of IOP, and an automated visual field (VF) within 3 months of diagnosis. Exclusion criteria were unreliable VFs, use of IOP-lowering therapy, and visually significant ocular comorbidities. Data were collected from the initial visit. Age, IOP, method of diagnosis of ONHD, mean RNFL thickness, and PMD were recorded. Multiple and logistic regression models were used to control for potential confounders in statistical analyses. Results: Chart review identified 623 patients, of which 146 patients met inclusion criteria. Mean age was 44.2 years (range: 19–82 years). Average PMD of 236 eyes was −5.22 dB (range, −31.2 to +1.21 dB). Mean IOP was 15.7 mm Hg (range: 6–24 mm Hg). Forty eyes (16.9%) underwent RNFL measurement using OCT; mean RNFL thickness was 79.9 μm (range: 43–117 μm). There was no statistically significant association between IOP and PMD (P = 0.13) or RNFL thickness (P = 0.65). Eyes with ocular hypertension tended to have less depressed PMD than those without (P= 0.031). Stratified analyses of visible and buried subgroups yielded similar results. Conclusions: Lowering IOP in patients with ONHD has been proposed as a means to prevent progression of optic neuropathy. Our study demonstrated that among predominately normotensive eyes, higher IOP was not associated with greater VF loss or thinner RNFL at the time of presentation. This suggests that lowering IOP may not be beneficial in preventing visual loss in normotensive eyes with ONHD.https://ift.tt/2IM6T6p
The Shifting Landscape of Disease-Modifying Therapies for Relapsing Multiple Sclerosis
Background: Multiple sclerosis (MS) is the most common nontraumatic neurological disorder of young adults, and roughly 85% of patients present with the relapsing form of the disease. Over the past 2 decades, the treatment arsenal for relapsing MS has expanded and evolved from mildly effective and relatively benign injectable agents to potent cell-depleting monoclonal agents. The latter have the potential to achieve disease remission coupled with risk of moderate to severe adverse events with which all MS care providers will need to acquaint themselves. Methods: This review is based on a detailed assessment of MS pivotal trials, extension studies, and expert reviews of the agents discussed. Results/Conclusions: The following review should aid those practitioners directly and indirectly involved in the care of MS patients in understanding the benefits and risks associated with the medications they prescribe.https://ift.tt/2Io9Cnb
Evaluation of Retinal Changes in Progressive Supranuclear Palsy and Parkinson Disease
Background: Differentiating Parkinson disease (PD) from progressive supranuclear palsy (PSP) can be challenging early in the clinical course. The aim of our study was to see if specific retinal changes could serve as a distinguishing feature. Methods: We used spectral domain optical coherence tomography (SD-OCT) with automatic segmentation to measure peripapillary nerve fiber layer thickness and the thickness and volume of retinal layers at the macula. Results: Thicknesses of superior peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer, inner plexiform layer, inner nuclear layer, and macular volume were more affected in PSP compared with PD (Phttps://ift.tt/2wPyBKQ
More Than Meets the Eye: The Eye and Migraine—What You Need to Know
Abstract: Migraine has long been associated with disturbances of vision, especially migraine with aura. However, the eye plays an important role in sensory processing as well. We have found that the visual quality of life is reduced in migraine. In this review, we discuss how the migraine and eye pain pathways are similar and affect many of the common complaints which are seen in ophthalmology and neuro-ophthalmology offices, such as dry eye and postoperative eye pain. We also review other related phenomena, including visual snow and photophobia, which also are related to altered sensory processing in migraine.https://ift.tt/2IqmTvI
Delayed Onset Cranial Nerve Palsies After Endovascular Coil Embolization of Direct Carotid-Cavernous Fistulas
Background: Late recurrence of visual symptoms associated with carotid-cavernous fistula (CCF), including diplopia, is uncommon and raises concern for new or recurrent fistula formation. Methods: We report 2 patients with traumatic CCFs, where cranial nerve paresis resolved after endovascular CCF treatment only to reappear years later. Results: No evidence of recurrent or new fistula formation was found. Both were treated successfully with strabismus surgery. Conclusions: Although the cause of delayed onset diplopia after successful treatment is still unknown, theories include late compression of cranial nerves within the cavernous sinus due to coil mass that can cause chronic ischemia, delayed inflammation due to a thrombophilic nidus created by the coil mass, or injury to the cranial nerves that manifests later due to decompensated strabismus.https://ift.tt/2GsCrsW
Literature Commentary
In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles: Nazarian S, Hansford R, Rahsepar AA, Weltin V, McVeigh D, Gucuk Ipek E, Kwan A, Berger RD, Calkins H, Lardo AC, Kraut MA, Kamel IR, Zimmerman SL, Halperin HR. Safety of magnetic resonance imaging in patients with cardiac devices. N Engl J Med. 2017;377:2555–2564.Martin DR, Kalb B, Mittal A, Salman K, Vedantham S, Mittal PK. No incidence of nephrogenic systemic fibrosis after gadobenate dimeglumine administration in patients undergoing dialysis or those with severe chronic kidney disease. Radiology. 2018;286:113–119.Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O'Brien F, Wang JJ, Mantegazza R; REGAIN Study Group. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (REGAIN): a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Lancet Neurol. 2017;16:976–986. Erratum in: Lancet Neurol. 2017;16:954.Dosunmu EO, Hatt SR, Leske DA, Hodge DO, Holmes JM. Incidence and etiology of presumed fourth cranial nerve palsy: a population-based study. Am J Ophthalmol. 2018;185:110–114.Eade EL, Hardy TG, McKelvie PA, McNab AA. Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle enlargement. Br J Ophthalmol. [published online ahead of print January 19, 2018] doi: 10.1136/bjophthalmol-2017-311147.Nath S, Badhiwala JH, Alhazzani W, et al. Atraumatic versus traumatic lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2018;391:1197–1204. © 2018 by North American Neuro-Ophthalmology Society
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Tacrolimus Optic Neuropathy
Background: Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. Methods: Case series and review of the literature. Results: We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. Conclusions: Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.https://ift.tt/2wOxuel
Erythropoietin in Treatment of Methanol Optic Neuropathy
Background: Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. Methods: In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. Results: Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90–0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90–0.00 logMAR). VA significantly increased in the last follow-up examination (Phttps://ift.tt/2wP1Eye
Evolution of Visual Outcomes in Clinical Trials for Multiple Sclerosis Disease-Modifying Therapies
From the Section Editor: In March 2018, the Journal of Neuro-Ophthalmology (JNO) launched its inaugural "Disease of the Year" section, featuring multiple sclerosis (MS). Beginning from a "Bench" perspective, Meltzner and colleagues presented an elegant overview of the pathogenic mechanisms believed to underpin central nervous system (CNS) injury in MS. To complement these efforts, Backner and Levin highlighted how the afferent visual pathway, as a putative model of CNS inflammation, can be interrogated with measures of structure and function to capture clinical and sub-clinical evidence disease activity in MS patients. Building on these concepts in this issue of the JNO, Nolan et al summarize how visual outcomes have been employed as outcome measures in MS clinical trials. In addition, Burton and Freedman advance us closer to the "Bedside" arena of clinical care, by surveying the rapidly changing therapeutic landscape, and providing a framework for escalating treatments in MS patients. In the Bench-to-Bedside section of this issue of the JNO, Cree provides a historical account of the how treatment paradigms have evolved over the years, to the modern era in which immunosuppressive agents have taken center stage. Specific emphasis is given to ocrelizumab, which targets CD2O B lymphocytes, as promising new treatment for relapsing remitting and progressive MS patients. Probstel and Hauser broaden the discussion around ocrelizumab by reviewing the role of B-cell depleting agents in the treatment of MS. In their review, they also discuss the development of related biomarkers that may be used to monitor treatment response, as our understanding of MS care continues to advance. Background: The visual pathways are increasingly recognized as an ideal model to study neurodegeneration in multiple sclerosis (MS). Low-contrast letter acuity (LCLA) and optical coherence tomography (OCT) are validated measures of function and structure in MS. In fact, LCLA was the topic of a recent review by the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) to qualify this visual measure as a primary or secondary clinical trial endpoint with the Food and Drug Administration (FDA) and other regulatory agencies. This review focuses on the use of LCLA and OCT measures as outcomes in clinical trials to date of MS disease-modifying therapies. Methods: A Pubmed search using the specific key words "optical coherence tomography," "low-contrast letter acuity," "multiple sclerosis," and "clinical trials" was performed. An additional search on the clinicaltrials.gov website with the same key words was used to find registered clinical trials of MS therapies that included these visual outcome measures. Results: As demonstrated by multiple clinical trials, LCLA and OCT measures are sensitive to treatment effects in MS. LCLA has been used in many clinical trials to date, and findings suggest that 7 letters of LCLA at the 2.5% contrast level are meaningful change. Few clinical trials using the benefits of OCT have been performed, although results of observational studies have solidified the ability of OCT to assess change in retinal structure. Continued accrual of clinical trial and observational data is needed to validate the use of OCT in clinical trials, but preliminary work suggests that an intereye difference in retinal nerve fiber layer thickness of 5–6 μm is a clinically meaningful threshold that identifies an optic nerve lesion in MS. Conclusions: Visual impairment represents a significant component of overall disability in MS. LCLA and OCT enhance the detection of visual pathway injury and can be used as measures of axonal and neuronal integrity. Continued investigation is ongoing to further incorporate these vision-based assessments into clinical trials of MS therapies.https://ift.tt/2IOF7Gk
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