Source:DNA Repair, Volume 61
http://ift.tt/2DkxMbm
Τρίτη 26 Δεκεμβρίου 2017
Transitions into young adulthood: Extent to which alcohol use, perceived drinking norms, and consequences vary by education and work statuses among 18–20year olds
Source:Addictive Behaviors, Volume 79
Author(s): Christine M. Lee, Jennifer M. Cadigan, Anne M. Fairlie, Melissa A. Lewis
IntroductionWith many young adults pursuing post-secondary education and many working, understanding the importance of education and work roles on alcohol use are of developmental and clinical importance. Utilizing a sample of 18–20year-olds transitioning from adolescence to young adulthood, the current study examined how social role statuses in education (i.e., not in school, 2-year students, 4-year students) and work status (i.e., unemployed, employed part-time, employed full-time) were associated with alcohol use, alcohol-related consequences, and perceived drinking norms.MethodParticipants were 18–20year old young adults (54% female) participating in a one-time online survey about alcohol use and sexual behavior. Regression models were conducted to examine associations between school status and work status with alcohol related outcomes.ResultsIndividuals who were unemployed had a significantly lower likelihood of any heavy episodic drinking (HED) in the past month, consumed fewer drinks per week, and experienced fewer alcohol-related consequences compared to individuals who worked full-time. Individuals who worked part-time consumed fewer drinks per week and had lower perceived drinking norms compared to individuals who worked full-time. No significant associations were found for alcohol use and consequences by education status.DiscussionWorking full-time is a risk factor for HED, greater weekly drinking and negative alcohol-related consequences when compared to young adults who are unemployed, and to a lesser extent with young adults working part-time. Workplace interventions may be one approach to reach heavy drinking young adults.
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Response to Stephane Renaud et al.
Source:Radiotherapy and Oncology
Author(s): Wen-Chi Yang, Jin-Yuan Shih, Chao-Chi Ho, Feng-Ming Hsu
http://ift.tt/2zAP8hN
Effect of glucocorticoid treatment on BAFF and APRIL expression in patients with immune thrombocytopenia (ITP)
Source:Clinical Immunology
Author(s): Julian Kamhieh-Milz, Nuha Ghosoun, Viktor Sterzer, Abdulgabar Salama
Immune thrombocytopenic purpura (ITP) is an idiopathic bleeding disorder. B cell activating factor (BAFF) and 'A proliferation-inducing ligand' (APRIL) have regulatory effects on B and T cells and may represent relevant factors in the pathogenesis of ITP. Serum levels and gene expression were investigated in ITP patients. Both BAFF and APRIL serum levels were significantly elevated in active ITP. However, gene expression analysis revealed both factors to have a tendency toward downregulation. Glucocorticoid treatment significantly reduced BAFF but not APRIL serum levels, which may be mediated by differences in transcription factor binding sites. The glucocorticoid receptor binding site is present in the BAFF promotor region, but not in the APRIL promotor region. Prednisolone in combination with vitamin D3 may be effective in reducing APRIL serum levels. In conclusion, glucocorticoid treatment exerts different regulatory effects on both BAFF and APRIL, whereas antioxidant supplementation may also be beneficial in reducing serum levels.
http://ift.tt/2pFXjtB
YouTube Medicine
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
From equilibrium lamellae to out-of-equilibrium cylinders in triblock copolymer nanolayers obtained via multilayer coextrusion
Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Juan-Sebastián Montana, Sébastien Roland, Emmanuel Richaud, Guillaume Miquelard-Garnier
Multilayer coextrusion was used to obtain nanolayered films of self-assembled commercial triblock copolymer poly(methyl methacrylate-b-butyl acrylate-b-methyl methacrylate) (MAM) confined by poly(methyl methacrylate) (PMMA). The MAM layer thickness was varied from 30 nm to 500 nm (i.e. roughly 1 to 15–20 nanodomains) by changing either the number of multiplying elements or the chill roll draw ratio. The as-extruded triblock morphology within the layers was identified as cylindrical using transmission electronic microscopy (TEM) and small-angle X-ray scattering (SAXS). Surprisingly, this differs from the lamellar morphology identified at equilibrium in bulk and thin films for this triblock. Moreover, as the triblock layer thickness is decreased, the triblock morphology is constrained into a preferential orientation. Slightly different packings were observed on films with similar layer thicknesses but achieved with different processing routes. This one-step and industrially scalable method allowing long-range control of the self-assembly is of interest for engineering applications with large quantity of materials needed.
Graphical abstract
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Severe ophthalmoplegia and myocarditis following the administration of pembrolizumab
Source:European Journal of Cancer
Author(s): Fadi Nasr, Elie El Rassy, Georgina Maalouf, Carine Azar, Fadi Haddad, Jeanine Helou, Caroline Robert
http://ift.tt/2zAnkdi
When politicians really decide that nation health is a top priority: the Danish model
Source:European Journal of Cancer
Author(s): Marc Hamoir
http://ift.tt/2zA8P9J
Neural stem cells in neuropsychiatric disorders
Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Roberto Sacco, Emanuele Cacci, Gaia Novarino
The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies.
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Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
Publication date: Available online 26 December 2017
Source:Immunity
Author(s): Robert K. Abbott, Jeong Hyun Lee, Sergey Menis, Patrick Skog, Meghan Rossi, Takayuki Ota, Daniel W. Kulp, Deepika Bhullar, Oleksandr Kalyuzhniy, Colin Havenar-Daughton, William R. Schief, David Nemazee, Shane Crotty
How precursor frequencies and antigen affinities impact interclonal B cell competition is a particularly relevant issue for candidate germline-targeting HIV vaccine designs because of the in vivo rarity of naive B cells that recognize broadly neutralizing epitopes. Knowing the frequencies and affinities of HIV-specific VRC01-class naive human B cells, we transferred B cells with germline VRC01 B cell receptors into congenic recipients to elucidate the roles of precursor frequency, antigen affinity, and avidity on B cell responses following immunization. All three factors were interdependently limiting for competitive success of VRC01-class B cells. In physiological high-affinity conditions using a multivalent immunogen, rare VRC01-class B cells successfully competed in germinal centers (GC), underwent extensive somatic hypermutation, and differentiated into memory B cells. The data reveal dominant influences of precursor frequency, affinity, and avidity for interclonal GC competition and indicate that germline-targeting immunogens can overcome these challenges with high-affinity multimeric designs.
Graphical abstract
Teaser
It is not clear how precursor frequencies and antigen affinities impact interclonal B cell competition. Abbott et al. show these parameters interdependently limit germinal center B cell fitness. When these variables are matched to the human physiological range, HIV bnAb precursor B cells compete in germinal centers, undergo extensive mutation, and form memory.http://ift.tt/2CaGZnn
Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1
Publication date: Available online 26 December 2017
Source:Immunity
Author(s): Yehudi Bloch, Laura Bouchareychas, Romain Merceron, Katarzyna Składanowska, Lien Van den Bossche, Sammy Detry, Srinath Govindarajan, Dirk Elewaut, Filomeen Haerynck, Melissa Dullaers, Iannis E. Adamopoulos, Savvas N. Savvides
Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. We determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity. Together with structural insights from the interaction of IL-23 with the inhibitory antibody briakinumab and by leveraging additional IL-23:antibody complexes, we propose a mechanistic paradigm for IL-23 and IL-12 whereby cognate receptor binding to the helical cytokine subunits primes recruitment of the shared receptors via the IL-12p40 subunit.
Graphical abstract
Teaser
IL-23, a human cytokine under intense clinical targeting, is pivotal to cellular responses underlying widespread inflammatory and autoimmune diseases, such as psoriasis and rheumatoid arthritis. Bloch et al. determine the structure of IL-23 bound by one of its receptors, IL-23R, and reveal how IL-23R activates IL-23 for recruiting IL-12Rβ1 to the signaling assembly. Together with identifying an interaction hotspot, such findings may contribute to additional approaches for the mechanistic and therapeutic interrogation of receptor complexes mediated by IL-12 family members.http://ift.tt/2C92GE3
Disrupting the Approach to Sudden Cardiac Death: From Vulnerable Ejection Fraction to Vulnerable Patient.
Author: Chugh, Sumeet S. MD
Page: 7-9
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Fasting Versus Nonfasting and Low-Density Lipoprotein Cholesterol Accuracy.
Author: Sathiyakumar, Vasanth MD; Park, Jihwan MA; Golozar, Asieh MD, PhD; Lazo, Mariana MD, PhD; Quispe, Renato MD, MHS; Guallar, Eliseo MD, MPH; Blumenthal, Roger S. MD; Jones, Steven R. MD; Martin, Seth S. MD, MHS
Page: 10-19
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The Future of Low-Density Lipoprotein Cholesterol in an Era of Nonfasting Lipid Testing and Potent Low-Density Lipoprotein Lowering.
Author: Farukhi, Zareen MD; Mora, Samia MD, MHS
Page: 20-23
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Mortality and Cerebrovascular Events After Heart Rhythm Disorder Management Procedures.
Author: Lee, Justin Z. MBBS *,; Ling, Jayna CNP *,; Diehl, Nancy N. BS; Hodge, David O. MS; Padmanabhan, Deepak MBBS; Killu, Ammar M. MBBS; Madhavan, Malini MBBS; Noseworthy, Peter A. MD; Kapa, Suraj MD; McLeod, Christopher J. MBChB, PhD; Cha, Yong-Mei MD; Deshmukh, Abhishek J. MBBS; Srivathsan, Komandoor MD; Kusumoto, Fred M. MD; Shen, Win-Kuang MD; Friedman, Paul A. MD; Munger, Thomas M. MD; Asirvatham, Samuel J. MD; Packer, Douglas L. MD; Mulpuru, Siva K. MD
Page: 24-33
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The Truth Is in the Details: The Case for Not Missing the Trees for the Forest.
Author: Voigt, Andrew MD; Saba, Samir MD
Page: 34-37
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Association of Pediatric Medical Emergency Teams With Hospital Mortality.
Author: Kutty, Shelby MD, PhD, MHCM; Jones, Philip G. MS; Karels, Quentin MBA; Joseph, Navya MD; Spertus, John A. MD, MPH; Chan, Paul S. MD, MSc
Page: 38-46
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Rapid Response Teams in Pediatric Patients: Well Intentioned, but Do They Really Help?.
Author: Koch, Joshua MD; Das, Sandeep R. MD, MPH
Page: 47-48
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Carotid Stent Fractures Are Not Associated With Adverse Events: Results From the ACT-1 Multicenter Randomized Trial (Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease).
Author: Weinberg, Ido MD; Beckman, Joshua A. MD; Matsumura, Jon S. MD; Rosenfield, Kenneth MD; Ansel, Gary M. MD; Chaturvedi, Seemant MD; Gray, William MD; Metzger, D. Chris MD; Riles, Tom MD; Shu, Yu PhD; Wechsler, Lawrence MD; Jaff, Michael R. DO
Page: 49-56
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Runx1 Deficiency Protects Against Adverse Cardiac Remodeling After Myocardial Infarction.
Author: McCarroll, Charlotte S. BVMS, PhD *,; He, Weihong MD, PhD *,; Foote, Kirsty PhD; Bradley, Ashley MRes; Mcglynn, Karen PhD; Vidler, Francesca MRes; Nixon, Colin; Nather, Katrin PhD; Fattah, Caroline PhD; Riddell, Alexandra Vet, MB, MRes; Bowman, Peter MRes; Elliott, Elspeth B. PhD; Bell, Margaret; Hawksby, Catherine; MacKenzie, Scott M. PhD; Morrison, Liam J. BVMS, PhD; Terry, Anne BSc; Blyth, Karen PhD; Smith, Godfrey L. PhD; McBride, Martin W. PhD; Kubin, Thomas PhD; Braun, Thomas MD, PhD; Nicklin, Stuart A. PhD; Cameron, Ewan R. BVMS, PhD; Loughrey, Christopher M. BVMS, PhD
Page: 57-70
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Honoring 50 Years of Clinical Heart Transplantation in Circulation: In-Depth State-of-the-Art Review.
Author: Stehlik, Josef MD, MPH; Kobashigawa, Jon MD; Hunt, Sharon A. MD; Reichenspurner, Hermann MD, PhD; Kirklin, James K. MD
Page: 71-87
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Effect of Basal Insulin Glargine on First and Recurrent Episodes of Heart Failure Hospitalization: The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention).
Author: Gerstein, Hertzel C. MD, MSc; Jung, Hyejung MSc; Ryden, Lars MD, PhD; Diaz, Rafael MD; Gilbert, Richard E. MBBS, PhD; Yusuf, Salim DPhil; On behalf of the ORIGIN Investigators
Page: 88-90
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Extended-Duration Betrixaban Reduces the Risk of Rehospitalization Associated With Venous Thromboembolism Among Acutely Ill Hospitalized Medical Patients: Findings From the APEX Trial (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban Trial).
Author: Chi, Gerald MD; Yee, Megan K. MPH; Amin, Alpesh N. MD; Goldhaber, Samuel Z. MD; Hernandez, Adrian F. MD; Hull, Russell D. MD; Cohen, Alexander T. MD; Harrington, Robert A. MD; Gibson, C. Michael MS, MD
Page: 91-94
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Letter by Ye et al Regarding Article, "Association Between Fetal Congenital Heart Defects and Maternal Risk of Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies".
Author: Ye, Ziliang MD; Su, Qiang MD, PhD; Li, Lang MD, PhD
Page: 95-96
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Response by Boyd et al to Letter Regarding Article, "Association Between Fetal Congenital Heart Defects and Maternal Risk of Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies".
Author: Boyd, Heather A. PhD; Basit, Saima MSc; Wohlfahrt, Jan MSc, DrMed; Oyen, Nina MD, MPH, DrMed
Page: 97-98
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Letter by Locorotondo et al Regarding Article, "Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients with Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction".
Author: Locorotondo, Gabriella MD, PhD; Manfredi, Riccardo MD, MBA; Crea, Filippo MD, PhD
Page: 99-100
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Response by Halliday et al to Letter Regarding Article, "Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients with Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction".
Author: Halliday, Brian P. MBChB; Pennell, Dudley J. MD; Prasad, Sanjay K. MD
Page: 101-102
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2017 American Heart Association Focused Update on Pediatric Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Author: Atkins, Dianne L. MD, FAHA, Chair; de Caen, Allan R. MD; Berger, Stuart MD, FAHA; Samson, Ricardo A. MD; Schexnayder, Stephen M. MD; Joyner, Benny L. Jr MD, MPH; Bigham, Blair L. MD, MSc; Niles, Dana E. MS; Duff, Jonathan P. MD, MEd; Hunt, Elizabeth A. MD, MPH, PhD; Meaney, Peter A. MD, MPH
Page: e1-e6
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2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Author: Kleinman, Monica E. MD, Chair; Goldberger, Zachary D. MD, MSc, FAHA; Rea, Thomas MD, MPH; Swor, Robert A. DO; Bobrow, Bentley J. MD, FAHA; Brennan, Erin E. MD, MMEd; Terry, Mark MPA, NRP; Hemphill, Robin MD, MPH; Gazmuri, Raul J. MD, PhD; Hazinski, Mary Fran MSN, RN, FAHA; Travers, Andrew H. MD, MSc
Page: e7-e13
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Neural phase locking predicts BOLD response in human auditory cortex
Source:NeuroImage, Volume 169
Author(s): Hiroyuki Oya, Phillip E. Gander, Christopher I. Petkov, Ralph Adolphs, Kirill V. Nourski, Hiroto Kawasaki, Matthew A. Howard, Timothy D. Griffiths
Natural environments elicit both phase-locked and non-phase-locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non-phase-locked power of high-frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase-locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high-gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity.
http://ift.tt/2DT7hLc
Effects of a hydroethanolic extract of Boophone disticha bulb on anxiety-related behaviour in naive BALB/c mice
Publication date: 25 March 2018
Source:Journal of Ethnopharmacology, Volume 214
Author(s): William Pote, Shamiso Musarira, Donald Chuma, Louis L. Gadaga, Ellen Mwandiringana, Dexter Tagwireyi
Ethnopharmacological relevanceBoophone disticha is one of the most important medicinal bulbs of Southern Africa. Previous in vitro studies have shown that it's crude ethanolic extracts and some alkaloidal phytoconstituents possesses high affinity for the serotonin transporter protein (SERT) and serotonin receptor 1a (5HT1a) which are both implicated in the pathogenesis and treatment of anxiety disorders. However, there are no in vivo studies that validates the anxiolytic actions of the plant.Aim of the studyThis study was therefore set to determine the anxiolytic-like activity of an orally administered hydroethanolic extract of B. disticha bulbs in naive mice using the behavioural tests of anxiety.Materials and methodsNaïve adult male BALB/c mice were randomly placed into five treatment groups (n=6–10): vehicle control (10ml/kg 0.9% NaCl), positive control (1mg/kg diazepam) and the hydroethanolic extract of B. disticha (10, 25 and 40mg/kg p.o.). Souk test, elevared plus maze and open field tests were used to evaluate the anxiolytic-like activity of the B. disticha extract.ResultsDiazepam-treated mice exhibited higher number of sector visits and line crossings in the ST, rearings in the OF and head dips in the EPM than the control (p<0.05). B. disticha extract treated groups expressed higher sector visits at 10mg/kg, and, unprotected head dips at 25mg/kg in the ST, as well as, open arm time entries at 10mg/kg dose, and unprotected head dips at all doses in the EPM than the control group (p<0.05). The 25mg/kg B. disticha dose group exhibited highest anxiolytic-like activity in both the ST and OF, while the 10mg/kg was most active in the EPM.ConclusionThe extract of B. disticha exerted good anxiolytic-like activity in both the ST and OF at medium dose (25mg/kg), while the low dose (10mg/kg) showed prominent anxiolytic-like activity in the EPM.
Graphical abstract
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Total and fraction content of elements in volcanic soil: Natural or anthropogenic derivation
Publication date: 1 June 2018
Source:Science of The Total Environment, Volume 625
Author(s): Valeria Memoli, Enrique Eymar, Carlos García-Delgado, Francesco Esposito, Lucia Santorufo, Anna De Marco, Rossella Barile, Giulia Maisto
Soil element composition derives from parent material disaggregation during pedogenesis and weathering processes but also by anthropogenic inputs. Elements are present in soils in different chemical forms that affect their availability and mobility. The aim of the study was to evaluate the main derivation, natural or anthropogenic, of elements in the soils of the Vesuvius National Park (a natural environment strongly affected by human impacts). Besides, the effects of age of the lava from which soils derive, different vegetation covers, traffic fluxes along the two roads connecting the Vesuvius crater and altitudes of the sites on the pseudo-total element concentrations and on their contents in different fraction of soil were investigated. To reach the aims, BCR (Bureau Commun de Référence) sequential extraction was performed in order to determine the distribution of elements into: acid-soluble, reducible, oxidizable and residual fractions. The relationship between the main environmental media and distribution of elements was discussed using non-metric multidimensional scaling (NMDS). The findings showed that, with the exception of Cd, Cu, Pb and Zn that would seem to derive also from human activities, the other investigated elements (Al, As, B, Ba, Ca, Cd, Cr, Cu, Fe, K, La, Mg, Mn, Na, Ni, P, Pb, Si, Ti, V, W and Zn) mainly had a natural derivation. Among the investigated elements, only Cd could represent a potential high risk for the studied andosols. The highest element accumulations in the soils at low altitude could be attributable to an integrated effect of plant cover, vicinity of downtowns and traffic flux. The acid-soluble fraction of elements appeared more linked to lava age; the reducible and oxidizable ones to plant cover; the residual one to the chemical composition of the parent material that gave origin to the soils.
Graphical abstract
http://ift.tt/2DX03Gb
Application of selectrodialysis for the removal of As from metallurgical process waters: Recovery of Cu and Zn
Publication date: 29 April 2018
Source:Separation and Purification Technology, Volume 195
Author(s): M. Reig, X. Vecino, C. Valderrama, O. Gibert, J.L. Cortina
In this work, selectrodialysis (SED) was used to separate arsenic (As(V)) from copper (Cu(II)) and zinc (Zn(II)) of acidic metallurgical process streams by integrating non-selective and selective membranes. The separation process is determined by the chemical speciation of the involved elements. In this case, As(V) is mainly present as anionic species (H2AsO4−), while Cu(II) and Zn(II) are mainly present as cationic species although partially complexed as neutral complexes (CuSO4 and ZnSO4). A lab set-up was used to conduct the experimental tests with different type of standard and monovalent selective ion-exchange membranes. The results obtained showed that by SED configuration it was possible to recover around 80 ± 0.2% of Cu(II), 87 ± 0.2% of Zn(II) and 95 ± 0.3% of As(V) from the feed solution to the rich-product streams with an energy consumption of 2.6 ± 0.2 kWh/kg CuSO4+ZnSO4. Furthermore, a Cu/Zn-rich stream with a purity of both divalent cations of 99.8% (0.02% of As(V)) was achieved by means of SED. Overall, the results herein gathered suggest that SED is an efficient separation technology for Cu(II) and Zn(II) recovery from mining and metallurgical acidic streams.
Graphical abstract
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Neurophysiological correlates of word processing deficits in isolated reading and isolated spelling disorders
Publication date: Available online 24 December 2017
Source:Clinical Neurophysiology
Author(s): Sarolta Bakos, Karin Landerl, Jürgen Bartling, Gerd Schulte-Körne, Kristina Moll
ObjectiveIn consistent orthographies, isolated reading disorders (iRD) and isolated spelling disorders (iSD) are nearly as common as combined reading-spelling disorders (cRSD). However, the exact nature of the underlying word processing deficits in isolated versus combined literacy deficits are not well understood yet.MethodsWe applied a phonological lexical decision task (including words, pseudohomophones, legal and illegal pseudowords) during ERP recording to investigate the neurophysiological correlates of lexical and sublexical word-processing in children with iRD, iSD and cRSD compared to typically developing (TD) 9-year-olds.ResultsTD children showed enhanced early sensitivity (N170) for word material and for the violation of orthographic rules compared to the other groups. Lexical orthographic effects (higher LPC amplitude for words than for pseudohomophones) were the same in the TD and iRD groups, although processing took longer in children with iRD. In the iSD and cRSD groups, lexical orthographic effects were evident and stable over time only for correctly spelled words.ConclusionsOrthographic representations were intact in iRD children, but word processing took longer compared to TD. Children with spelling disorders had partly missing orthographic representations.SignificanceOur study is the first to specify the underlying neurophysiology of word processing deficits associated with isolated literacy deficits.
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Bullying and peer violence among children and adolescents in residential care settings: A review of the literature
Source:Aggression and Violent Behavior
Author(s): Angela Mazzone, Annalaura Nocentini, Ersilia Menesini
The present paper offers a review of the phenomena of bullying and peer violence among children and adolescents living in residential care settings (RCS). The review was conducted on four databases (Scopus, Web of Science, PsycINFO and ERIC). Findings of the 31 full-text papers included in the present work showed that bullying and peer violence involve various forms of direct and indirect attacks. While bullying in RCS involves severe and repeated aggressive actions, peer violence seems to be characterized by distinct levels of severity; i.e., low-level attacks are infrequent and isolated, whereas high level attacks may be severe and frequent. Several individual factors, such as age, gender, and length of stay in RCS were found to be associated with both bullying and peer violence. Contextual risk factors such as activities, structure and facility size, along with a residential peer culture characterized by a high level of hierarchy and a poor emotional bond between children and staff, contributed to bullying and peer violence. Furthermore, findings of the studies included in the present review showed that both perpetrators and victims manifest a number of behavioral and psychological problems. Overall, the present study offers a picture of bullying and peer violence among institutionalized children. However, distinct operationalization of constructs among studies, together with the use of different methods and measures, made comparisons among studies difficult. Future research should overcome these limitations in order to promote validity and compatibility of research in this field of study.
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Inhibition of protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase by xanthones from Cratoxylum cochinchinense, and their kinetic characterization
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Zuopeng Li, Yeong Hun Song, Zia Uddin, Yan Wang, Ki Hun Park
Cratoxylum cochinchinense displayed significant inhibition against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase, both of which are key target enzymes to attenuate diabetes and obesity. The compounds responsible for both enzymes inhibition were identified as twelve xanthones (1-12) among which compounds 1 and 2 were found to be new ones. All of them simultaneously inhibited PTP1B with IC50s of (2.4-52.5 µM), and α-glucosidase with IC50 values of (1.7-72.7 µM), respectively. Cratoxanthone A (3) and γ-mangostin (7) were estimated to be most active inhibitors against both PTP1B (IC50 = 2.4 µM for 3, 2.8 µM for 7) and α-glucosidase (IC50 = 4.8 µM for 3, 1.7 µM for 7). In kinetic studies, all isolated xanthones emerged to be mixed inhibitors of α-glucosidase, whereas they behaved as competitive inhibitors of PTP1B. In time dependent experiments, compound 3 showed isomerization inhibitory behavior with following kinetic parameters: Kiapp = 2.4 µM; k5 = 0.05001 µM-1S-1 and k6 = 0.02076µM-1S-1.
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Theoretical Research in Structure Characteristics of Different Inhibitors and Differences of Binding Modes with CBP Bromodomain
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xue-Song Wang, Qing-Chuan Zheng
The CBP (CREB (cAMP responsive element binding protein) binding protein) bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor suppressor protein p53 which the mutation of encoding gene might cause human cancers. CBP-BRD serves as a promising drug target for several disease pathways and a series of effective drug have been discovered. In this study, molecular dynamics (MD) simulations and molecular mechanics generalized born surface area (MM-GB/SA) approaches were performed to investigate the different binding modes between five inhibitors with CBP-BRD. Based on the energy and conformation analyses, a potent core fragment is chosen to act as the starting point for new inhibitor design by means of LUDI and rational drug design approaches. Then, T.E.S.T and molinspirition were applied to evaluate oral bioavailability and drug promiscuity of the new molecules. These results shed light on the idea for further inhibitor design.
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A cell surface clicked navigation system to direct specific bone targeting
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Young Kim, Zhe Zhang, Jae-Hyuck Shim, Tae Sup Lee, Ching-Hsuan Tung
Cell therapies are promising up-and-coming therapeutic strategies for many diseases. For maximal therapeutic benefits, injected cells have to navigate their way to a designated area, including organ and tissue; unfortunately, the majority of therapeutic cells are currently administered without a guide or homing device. To improve this serious shortcoming, a functionalization method was developed to equip cells with a homing signal. Its application was demonstrated by applying an Azadibenzocyclooctyne-bisphosphonate (ADIBO-BP) and azide paired bioorthogonal chemistry on cells for bone specific homing. Jurkat T cells and bone marrow derived stromal cells (BMSCs) were cultured with tetraacetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) to place unnatural azido groups onto the cell's surface; these azido groups were then reacted with ADIBO-BP. The tethered bisphosphonates were able to bring Jurkat cells to hydroxyapatite, the major component of bone, and mineralized SAOS-2 cells. The incorporated BP groups also enhanced the specific affinity of BMSCs to mouse femur bone fragments in vitro. The introduced navigation strategy is expected to have a broad application in cell therapy, because through the biocompatible ADIBO and azide reactive pair, various homing signals could be efficiently anchored onto therapeutic cells.
Graphical abstract
http://ift.tt/2l1Cbck
One-step Synthesis of Carbohydrate Esters as Antibacterial and Antifungal Agents
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Madher N. AlFindee, Qian Zhang, Yagya Prasad Subedi, Jaya P. Shrestha, Yukie Kawasaki, Michelle Grilley, Jon Y. Takemoto, Cheng-Wei Tom Chang
Carbohydrate esters are biodegradable, and the degraded adducts are naturally occurring carbohydrates and fatty acids which are environmentally friendly and non-toxic to human. A simple one-step regioselective acylation of mono-carbohydrates has been developed that leads to the synthesis of a wide range of carbohydrate esters. Screening of these acylated carbohydrates revealed that several compounds were active against a panel of bacteria and fungi, including Staphylococcus aureus. methicillin-resistant S. aureus (MRSA), Candida albicans, Cryptococcus neoformans, Aspergillus flavus and Fusarium graminearum. Unlike prior studies on carbohydrate esters that focus only on antibacterial applications, our compounds are found to be active against both bacteria and fungi. Furthermore, the synthetic methodology is suitable to scale-up production for a variety of acylated carbohydrates. The identified lead compound, MAN014, can be used as an antimicrobial in applications such as food processing and preservation and for treatment of bacterial and fungal diseases in animals and plants.
Graphical abstract
http://ift.tt/2l256NL
New branched amino acids for high affinity dendrimeric DC-SIGN ligands
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Laurent Cattiaux, Vanessa Porkolab, Franck Fieschi, Jean-Maurice Mallet
A branched amino acid was synthesized from methyl glucopyranoside; this amino acid presents three amino groups protected by Fmoc and one acid group and can be used in classic peptide synthesis. In parallel, similar azido terminated blocks were synthesized.Successive coupling reaction and deprotection afforded dendrimers with up to 27 azido functional groups. As an example of application, D-mannose and L-fucose residues were linked through CuAAC coupling and resulting glycodendrimers were evaluated in their interaction with DC-SIGN using SPR competition assay.
Graphical abstract
http://ift.tt/2kZMn5g
A review on the hybrids of hydroxycinnamic acidas multi-target-directed ligands against Alzheimer's disease
Publication date: Available online 26 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xiao Zhang, Xixin He, Qiuhe Chen, Junfeng Lu, Simona Rapposelli, Rongbiao Pi
Alzheimer's disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids,including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD.
Graphical abstract
http://ift.tt/2l24UOx
A Propensity Matched Comparison for Open and Endovascular Treatment of Post-carotid Endarterectomy Restenosis
Publication date: Available online 26 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Walter Dorigo, Aaron Fargion, Elena Giacomelli, Raffaele Pulli, Fabrizio Masciello, Sara Speziali, Giovanni Pratesi, Carlo Pratesi
ObjectivesTo compare results of open and endovascular management of post-carotid endarterectomy (CEA) restenosis.MethodsThis was a retrospective single centre matched case control study. From 2005 to 2015, 148 consecutive interventions for post-CEA restenosis were performed: 80 cases received carotid artery stenting (CAS) and 68 cases received redo CEA. Propensity score based matching was performed in a 1:1 ratio to compare outcomes. Coronary artery disease, degree of the carotid restenosis, timing of the re-intervention with respect to the primary intervention (greater or less than 24 months) and the presence of ipsilateral brain lesions were the covariates included in the matching. Peri-operative outcomes were analysed with χ2 tests, while late results were estimated by Kaplan–Meier methods.ResultsAfter propensity matching, 32 CAS interventions were matched with 32 redo CEAs. There were no peri-operative deaths or strokes. Cranial nerve palsy occurred in seven patients in the redo CEA group. Median duration of follow-up was 36 months (interquartile range 24–60; range 6–120). The estimated 5 year survival rate was 94% in the CAS group and 72% in the redo CEA group (p=.1, log rank 2.4). There were no significant differences between the groups in terms of stroke free survival. In the CAS group, no severe restenosis were found, while in the redo CEA group eight patients had severe restenosis or occlusion of the operated carotid artery. Freedom from secondary restenosis at 4 years was 100% in the CAS group and 72.5% in the redo CEA group (p=.005, log rank 7.9). The corresponding figures in terms of freedom from secondary re-intervention were 100% and 83%, respectively (p=.02, log rank 4.8).ConclusionsCAS and redo CEA in patients with post-CEA restenosis provided similar peri-operative results in a sample of equivalent patients. CAS patients had better follow-up results in terms of secondary restenosis and re-interventions. Further analysis is required with a larger number of patients and a longer follow-up time.
http://ift.tt/2CcFQhD
Short-term effects of electrical nerve stimulation on spinal reciprocal inhibition depend on gait phase during passive stepping
Source:Journal of Electromyography and Kinesiology
Author(s): Hiroki Obata, Tetsuya Ogawa, Matija Milosevic, Noritaka Kawashima, Kimitaka Nakazawa
A combination of electrical nerve stimulation (ENS) and passive or active cyclic movements (i.e., pedaling and stepping) has been suggested to induce stronger short-term effects in spinal circuits as compared to either intervention alone. The purpose of the present study is to determine whether the effects of ENS during passive stepping are dependent on the timing of the stimulation during the stepping cycle. A total of 10 able-bodied participants were recruited for the study. Two interventions were assessed during passive ground stepping: 1) ENS of the common peroneal nerve (CPN) during the swing phase (ENSswing) and 2) stance phase (ENSstance). ENS was applied at the motor threshold intensity on the tibialis anterior muscle for a total of 30 min. Spinal reciprocal inhibition (RI) was assessed by conditioning the H-reflex in the soleus muscle with electrical stimulation to the CPN before (baseline), as well as 5, 15, and 30 min after each intervention. Compared to the baseline, the amount of RI was increased 5 and 15 min after the ENSswing intervention, whereas it was decreased after the ENSstance intervention. This suggests that ENS has a phase-dependent effect on RI during passive stepping. Overall, the results imply that phase-dependent timing of ENS is essential for guiding plasticity in the spinal circuits.
http://ift.tt/2lcJ6yM
The effect of age and gender on the genetic regulation of serum 25-hydroxyvitamin D - the FIN-D2D Population-Based Study
Publication date: Available online 26 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Maija E Miettinen, Melissa C Smart, Leena Kinnunen, Sirkka Keinänen-Kiukaanniemi, Leena Moilanen, Hannu Puolijoki, Juha Saltevo, Heikki Oksa, Graham A. Hitman, Jaakko Tuomilehto, Markku Peltonen
In addition to sunlight and dietary sources, several genes in the metabolic pathway of vitamin D affect serum 25-hydroxyvitamin D (25OHD) concentration. It is not known whether this genetic regulation is influenced by host characteristics. We investigated the effect of age and gender on the genetic regulation of serum 25OHD concentration.In total, 2868 Finnish men and women aged 45-74 years participated in FIN-D2D population-based health survey in 2007. Of the 2822 participants that had serum 25OHD concentration available, 2757 were successfully genotyped. Age and gender-dependent association of SNPs with serum 25OHD concentration was studied in 10 SNPs with previously found association with vitamin D metabolites.Associations of 3 SNPs with serum 25OHD concentration were dependent on age with greater effects on younger (≤60 y) than older (>60y) adults (rs10783219 in VDR, rs12512631 in GC and rs3794060 in NADSYN1/DHCR7; pinteraction=0.03, 0.02 and 0.01, respectively). The results suggested a novel association between serum 25OHD concentration and rs8082391 in STAT5B gene in men but not in women (pinteraction=0.01). After multiple testing correction with false discovery rate method, two age-dependent interactions (rs3794060 in NADSYN1/DHCR7 gene and rs12512631 in GC gene) remained statistically significant.This is the first study to suggest that genetic regulation of serum 25OHD concentration is age-dependent. Our results also indicated a novel association between serum 25OHD concentration and SNP in STAT5B gene in men. The results need to be confirmed in future studies preferably in a larger sample.
http://ift.tt/2l1gNE5
A case of radiation-induced bullous morphea/lichen sclerosus overlap in a breast cancer patient
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 1
Author(s): Erik Petersen, Laila Yazdani, Sharon R. Hymes
Radiation induced morphea (RIM) is an increasingly common complication of radiation treatment for malignancy as early detection has made more patients eligible for non-surgical treatment options. In many cases, the radiation oncologist is the first person to learn of the initial skin changes, often months before a dermatologist sees them. In this paper we present a breast cancer patient who developed a rare bullous variant of RIM, which delayed her diagnosis and subsequent treatment. It is imperative to diagnose RIM early as it carries significant morbidity and permanent deformity if left untreated. The lesions typically present within 1 year of radiation therapy and extend beyond the radiated field. RIM is often mistaken for radiation dermatitis or cellulitis. Bullae, when present, are often hemorrhagic in appearance, which can serve as another clinical clue. It is important to refer these patients for a full gynecologic exam as there can be concurrent anogenital lichen sclerosus et atrophicus which is both debilitating and carries a long term risk for squamous cell carcinoma. Treatment with systemic agents is often necessary, and can be managed by a dermatologist. The most proven regimen in the literature appears to be methotrexate, with our without concurrent narrow band UVB phototherapy.
http://ift.tt/2l1Jh0D
Poly (ethylene-co-vinyl alcohol) is a suitable substrate for human olfactory neuroepithelial cell differentiation in vitro through a defined regulatory pathway
Publication date: Available online 26 December 2017
Source:Acta Biomaterialia
Author(s): Sheng-Tien Li, Tai-Horng Young, Tsung-Wei Huang
Olfactory dysfunction significantly influences patients' life quality, but currently has no adequate treatment. Poly (ethylene-co-vinyl alcohol) (EVAL) mediates cell adhesion, growth and modulates differentiation of neural stem cells. However, whether EVAL is a suitable substrate to establish an in vitro culture system that can promote development and differentiation of human olfactory neuroepithelial cells (HONCs) remains unexplored. This study isolates and cultures HONCs on controls and EVAL films for 21 days. The effects of treatment are assessed using immunocytochemistry, microarray analysis, quantitative PCR, ELISA and western blots following culturing. Most of the cell morphology on controls is epithelial and expresses markers of sustatencular cells (SCs), cadherin-1 and cytokeratin18, whereas the main population on EVAL presents as morphology with extended thin processes and possesses markers of mature olfactory sensory neurons (OSNs), olfactory marker protein (OMP). Microarray analyses reveal neuropeptide Y (NPY) and amphiregulin (AREG) are the two important regulating factors on EVAL films. HONCs cultured on EVAL films enhance the development of mature OSNs through NPY signaling, and significantly decrease the growth of SCs by blocking epidermal growth factor receptor (EGFR) activation. EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future.Statement of significanceOlfaction not only contributes to enjoyments of food, but provides a clue to escape from dangerous environmental hazards. However, loss of smell is commonly progressive and there is no good prognostic approach for olfactory dysfunction. Here, we use poly (ethylene-co-vinyl alcohol) (EVAL) to establish an in vitro culture system that promotes development and differentiation of human olfactory neuroepithelial cells. We show that EVAL not only enhances the development of mature olfactory sensory neurons through neuronpeptide Y signaling, but significantly protects the olfactory neuroepithelium from metaplasia by inhibiting EGFR activation. Therefore, EVAL is a potential biomaterial to serve as an ideal substrate for treating olfactory dysfunction in the future.
Graphical abstract
http://ift.tt/2BHfDE0
Corrigendum to “Projections from the lowest lumbar and sacral-caudal segments to the cerebellar cortex in the rat: An anterograde tracing study” [Neurosci. Res. 114 (January) (2017) 43–54]
Source:Neuroscience Research
Author(s): Matsuo Matsushita
http://ift.tt/2pwQ9Yu
The Potential Therapeutic Effects of Ergothioneine in Pre-eclampsia
Publication date: Available online 25 December 2017
Source:Free Radical Biology and Medicine
Author(s): Robert N. Kerley, Cathal McCarthy, Douglas B. Kell, Louise C. Kenny
Ergothioneine (ERG), is a water-soluble amino acid that is derived entirely from dietary sources. It has received much attention as a therapeutic agent due to its anti-oxidant properties, and there are claims of preferential accumulation within high oxidative stress organs. Pre-eclampsia, a condition accompanied by increased oxidative stress, is one of the leading causes of maternal morbidity and mortality. Despite intense research efforts, its aetiologies remain somewhat unclear and there are still no effective treatment options. Clinical trials of the anti-oxidants vitamin C and vitamin E have proven largely ineffective with little improvement in clinical outcome or even a negative response. This could be explained in part by their inability to permeate the plasma and mitochondrial membranes and scavenge mitochondria-derived superoxide species, and for the former by the fact that it is actually a pro-oxidant in the presence of unliganded iron. ERG accumulates within tissues through the action of a specific organic cation transporter, SLC22A4 (previously referred to as OCTN1), which is possibly also expressed in mammalian mitochondria. Mitochondrial dysfunction has been implicated in a variety of vascular diseases including pre-eclampsia. This review discusses the use of ERG as a possibly mitochondrial-targeted anti-oxidant, focusing on its physical properties, potential mechanisms of action, safety profile and administration in relation to pregnancies complicated by pre-eclampsia.
Graphical abstract
http://ift.tt/2C7UdDI
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