Adaptive cone-beam CT planning improves long-term biochemical disease-free survival for 125I prostate brachytherapy

Publication date: Available online 16 January 2017
Source:Brachytherapy
Author(s): M. Peters, D.A. Smit Duijzentkunst, H. Westendorp, S.M.G. van de Pol, R. Kattevilder, A. Schellekens, J.R.N. van der Voort van Zyp, M.A. Moerland, M. van Vulpen, C.J. Hoekstra
PurposeDetermining the independent effect of additional intraoperative adaptive C-arm cone-beam CT (CBCT) planning vs. transrectal ultrasound (TRUS)-guided interactive planning alone in ¹²⁵I brachytherapy for prostate cancer (PCa) on biochemical disease-free survival (BDFS).Methods and materialsT1/T2-stage PCa patients receiving TRUS-guided brachytherapy from 2000 to 2014 were analyzed. From October 2006, patients received additional intraoperative adaptive CBCT planning for dosimetric evaluation and subsequent remedial seed placement in underdosed areas. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) risk classification. Kaplan–Meier analysis was used to estimate BDFS (primary outcome), overall survival, and PCa-specific survival (secondary outcomes). Cox regression was used to assess the relation between CBCT use and biochemical failure (BF) and overall mortality.ResultsIn all, 1623 patients were included. Median followup was 99 months (interquartile range 70–115) for TRUS patients (n = 613) and 51 months (interquartile range 29–70) for CBCT patients (n = 1010). BF occurred 203 times and 206 patients died, 26 from PCa. For TRUS and CBCT patients, 7-year BDFS was 87.2% vs. 93.5% (log rank: p = 0.04) for low, 75.9% vs. 88.5% (p < 0.001) for intermediate, and 57.1% vs. 85.0% for high-risk patients (p < 0.001). For TRUS and CBCT patients, 7-year PCa-specific survival was 96.0% vs. 100% (p < 0.0001). After Cox regression, CBCT patients had lower hazard of BF: hazard ratio (HR) 0.25 (95% confidence interval [CI]: 0.18–0.33; p < 0.0001). Corrected for confounders, CBCT remained a predictor of BF: HR 0.51 (95% CI: 0.31–0.86; p = 0.01) but not for overall mortality: HR 0.66 (95% CI: 0.40–1.07; p = 0.09).ConclusionsAdditional intraoperative adaptive CBCT planning in ¹²⁵I prostate brachytherapy leads to a significant increase in BDFS in all NCCN risk groups.



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Cosmetics, Vol. 4, Pages 6: Acknowledgement to Reviewers of Cosmetics in 2016

The editors of Cosmetics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016. [...]

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American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

Publication date: Available online 16 January 2017
Source:Brachytherapy
Author(s): M. Keyes, G. Merrick, S.J. Frank, P. Grimm, M.J. Zelefsky
PurposeProstate brachytherapy (PB) has well-documented excellent long-term outcomes in all risk groups. There are significant uncertainties regarding the role of androgen deprivation therapy (ADT) with brachytherapy. The purpose of this report was to review systemically the published literature and summarize present knowledge regarding the impact of ADT on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS).Methods and MaterialsA literature search was conducted in Medline and Embase covering the years 1996–2016. Selected were articles with >100 patients, minimum followup 3 years, defined risk stratification, and directly examining the role and impact of ADT on bPFS, CSS, and OS. The studies were grouped to reflect disease risk stratification. We also reviewed the impact of ADT on OS, cardiovascular morbidity, mortality, and on-going brachytherapy randomized controlled trials (RCTs).ResultsFifty-two selected studies (43,303 patients) were included in this review; 7 high-dose rate and 45 low-dose rate; 25 studies were multi-institutional and 27 single institution (retrospective review or prospective data collection) and 2 were RCTs. The studies were heterogeneous in patient population, risk categories, risk factors, followup time, and treatment administered, including ADT administration and duration (median, 3–12 months);71% of the studies reported a lack of benefit, whereas 28% showed improvement in bPFS with addition of ADT to PB. The lack of benefit was seen in low-risk and favorable intermediate-risk (IR) disease and most high–dose rate studies. A bPFS benefit of up to 15% was seen with ADT use in patients with suboptimal dosimetry, those with multiple adverse risk factors (unfavorable IR [uIR]), and most high-risk (HR) studies. Four studies reported very small benefit to CSS (2%). None of the studies showed OS advantage; however, three studies reported an absolute 5–20% OS detriment with ADT. Literature suggests that OS detriment is more likely in older patients or those with pre-existing cardiovascular disease. Four RCTs with an adequate number of patients and well-defined risk stratification are in progress. One RCT will answer the question regarding the role of ADT with PB in favorable IR patients and the other three RCTs will focus on optimal duration of ADT in the uIR and favorable HR population.ConclusionsPatients treated with brachytherapy have excellent long-term disease outcomes. Existing evidence shows no benefit of adding ADT to PB in low-risk and favorable IR patients. UIR and HR patients and those with suboptimal dosimetry may have up to 15% improvement in bPFS with addition of 3–12 months of ADT, with uncertain impact on CSS and a potential detriment on OS. To minimize morbidity, one should exercise caution in prescribing ADT together with PB, in particular to older men and those with existing cardiovascular disease. Due to the retrospective nature of this evidence, significant selection, and treatment bias, no definitive conclusions are possible. RCT is urgently needed to define the potential role and optimal duration of ADT in uIR and favorable HR disease.



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Aims and Scope and Editorial Board

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Effects of neuromuscular electrical stimulation during hemodialysis on peripheral muscle strength and exercise capacity: a randomized clinical trial

Publication date: Available online 16 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ana Karla Vieira Brüggemann, Carolina Luana Mello, Tarcila Dal Pont, Deborah de Camargo Hizume Kunzler, Daniel Fernandes Martins, Franciane Bobinski, Wellington Pereira Yamaguti, Elaine Paulin
ObjectiveTo evaluate the effects of neuromuscular electrical stimulation of high and low frequency and intensity, performed during hemodialysis (HD), on physical function and inflammation markers in patients with chronic kidney disease (CKD).DesignRandomized clinical trialSettingHemodialysis clinic.Participants51 CKD patients were randomized into blocks of four by means of opaque envelopes. They were divided into a group of high frequency and intensity neuromuscular electrical stimulation (HG) and a group of low frequency and intensity neuromuscular electrical stimulation (LG).InterventionHG was submitted to neuromuscular electrical stimulation with 50Hz and medium intensity of 72.90mA, and LG used 5Hz and medium intensity of 13.85mA, 3 times per week for one hour, during 12 sessions.Main Outcome MeasuresPeripheral muscle strength, exercise capacity, levels of muscle trophism marker [growth factor similar to insulin type 1 (IGF-1)] and levels of pro- inflammatory [tumor necrosis factor (TNF-alpha)] and anti-inflammatory [Interleukin 10 – (IL-10)] cytokines.ResultsHG showed significant increase in right peripheral muscle strength (155.35±65.32Nm versus 161.60±68.73Nm; p=0.01) and left peripheral muscle strength (156.60±66.51Nm versus 164.10±69.76Nm, p=0.02) after training, which did not occur with LG for both right muscle strength (109.40±32.08Nm versus 112.65±38.44Nm, p=0.50) and left muscle strength (113.65±37.79Nm versus 116.15±43.01Nm; p=0.61). The distance of the 6-minute walk test (6MWTD) increased in both groups: HG (435.55±95.81m versus 457.25±90.64m; p=0.02) and LG (403.80±90.56m versus 428.90±87.42m, p=0.007). The groups did not differ in peripheral muscle strength and in the 6MWTD after the training protocol. In HG, a correlation was observed between initial and final values for 6MWTD and muscle strength. In LG, correlations occurred only between the 6MWTD and the initial muscle strength. Only LG increased levels of IGF-1 (252.38±156.35pg/ml versus 336.97±207.34 pg/ml; p=0.03) and only HG reduced levels of IL-10 (7.26±1.81 pg/ml versus 6.32±1.54 pg/ml; p=0.03). The groups showed no differences in the TNF-alpha concentrations.ConclusionCKD patients on HD improve exercise capacity after peripheral neuromuscular electrical stimulation of high and low frequency and intensity. However, the benefits on muscle and inflammatory outcomes seem to be specific for the adopted strategy.



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Bromodomain and Extraterminal Protein Inhibitor JQ1 Suppresses Thyroid Tumor Growth

http://ssccancermelanoma.blogspot.com/2017/01/bromodomain-and-extraterminal-protein_16.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Production of renewable aromatic hydrocarbons via conversion of canola oil methyl ester (CME) over zinc promoted HZSM-5 catalysts

Publication date: June 2017
Source:Renewable Energy, Volume 106
Author(s): A. Bayat, S.M. Sadrameli
The conversion of canola oil methyl ester (CME) to aromatics was studied over Zn-modified HZSM-5 catalysts. The catalysts were prepared by incipient wetness impregnation method. Several techniques were used in characterization of the catalysts: X-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption and ammonia temperature-programmed desorption. The effects of reaction temperature and Weight Hourly Space Velocity (WHSV) on the aromatics yields were investigated. The reactor was operated at atmospheric pressure, temperatures of 400 and 450 °C and space velocities of 2 and 4 hr⁻¹. The main products were liquid hydrocarbon product (LHP), gases and water. Gas Chromatography (GC) analysis was applied to determine the BTX content of the LHP. Similar aromatic products distributions were obtained in the presence of unpromoted as well as Zn-promoted HZSM-5 catalysts. Toluene was the major aromatic compound followed by para-meta xylenes and benzene. The addition of zinc species to HZSM-5 catalyst promoted the aromatization capacity of the catalyst. The maximum aromatic yield of 42.6% was achieved at 450 °C and 2 h⁻¹ over 4Zn/ZS catalyst.



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Synthesis, structure, spectroscopic properties and DFT studies on some 7-hydroxy-4-methyl-8-(arylazo)-2H-1-benzopyran-2-one and their complexes with some divalent transition metal ions

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Samir A. Abdel-Latif, Adel A. Mohamed
A novel 7-hydroxy-4-methyl-8-(p-tolylazo)-2H-1-benzopyran-2-one (coumarin) (L1) and 7-hydroxy-4-methyl-8-(p-anisylazo)-2H-1-benzopyran-2-one (coumarin) (L2) and their metal complexes with Mn(II), Co(II), Ni(II) Cu(II) and Zn(II) have been prepared and characterized by elemental analysis, infrared (IR), proton nuclear magnetic resonance (¹H NMR) and mass spectra. The solid complexes have been also characterized by thermal analyses (TG and DTA), magnetic measurements, electronic transition, molar conductance; mass spectra, and electron spin resonance (ESR). The molecular orbital calculations of the complexes have been performed using the density functional theory (DFT) method and the basis sets 6-31G* and 6-311G**. The computational results revealed that the proposed geometrical structures for the investigated metal complexes suggest trigonal bipyramid for 1:1 and tetrahedral geometry for 1:2 complexes. The 1:1 complexes contain coordinated and lattice held water molecules whereas 1:2 complexes contain only lattice water molecules. The complexes behave as non-electrolytes in dimethyl formamide (DMF).

Graphical abstract

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A Zn-Ni coating with both high electrical conductivity and infrared emissivity prepared by hydrogen evolution method

Publication date: 30 April 2017
Source:Applied Surface Science, Volume 402
Author(s): Jiacheng Guo, Xingwu Guo, Wenbin Xu, Zhicheng Zhang, Jie Dong, Liming Peng, Wenjiang Ding
A Zn-Ni coating with both high electrical conductivity and infrared emissivity was prepared by hydrogen evolution method in order to satisfy the demand of thermal control in space. The maximum infrared emissivity of 0.91 was obtained, meanwhile the electrical resistivity is lower than 0.01mΩ/cm. The infrared emissivity of the coating obtained from the experimental result is proportional to the projected area of pores per unit area in the coating. The addition of NH4SCN in the bath can obviously increase the projected area of pores per unit area in the coating and lead to the formation of NiO and ZnO compounds, which further increase the infrared emissivity of the coating. The porous hierarchical structure of Zn-Ni coating can further improve the infrared emissivity, and the infrared emissivity can be tuned by changing the projected area of pores in the coating. Based on the experimental results, a mathematical relationship between infrared emissivity and the projected area of pores per unit area is established. The bond strength and the mass of volatiles of the design of coatings satisfy the technical standard demanded by the satellites in space.

Graphical abstract

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Magnetic losses versus sintering treatment in Mn-Zn ferrites

Publication date: 1 May 2017
Source:Journal of Magnetism and Magnetic Materials, Volume 429
Author(s): Cinzia Beatrice, Vasiliki Tsakaloudi, Samuel Dobák, Vassilios Zaspalis, Fausto Fiorillo
Mn-Zn ferrites prepared by different sintering schedules at 1325°C, 1340°C, and 1360°C, have been characterized from the structural, electrical, and magnetic viewpoint. Magnetic losses and complex permeability have been, in particular, measured and analyzed from quasi-static excitation up to 1GHz. It is observed that lower sintering temperatures and shorter treatment times lead to more homogeneous grain structure and better soft magnetic response at all frequencies. It is shown, however, that, once the contribution by eddy currents is singled out, the energy losses tend to coincide beyond a few MHz in the differently treated samples. The interpretative approach consists in separating the contributions by the domain wall displacements and the magnetization rotations to complex permeability and losses as a function of frequency. This can be accomplished in a relatively simple way in the low induction region described by the Rayleigh law, where these quantities can be quantitatively related and the linear Landau-Lifshitz-Gilbert equation applies, account being taken of the distribution in amplitude and orientation of the local anisotropy fields.



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16 novel mutations in PNPLA1 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in PNPLA1 that is essential for proper human skin barrier function

Abstract

Background

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause non-syndromic forms of ARCI. To date, only ten distinct pathogenic mutations in PNPLA1 have been reported.

Objectives

To identify new causative PNPLA1 mutations, we screened genetically unresolved cases including our ARCI collection comprising more than 700 families. Here, we report on 16 novel mutations present in patients from 17 families.

Methods

The screening for mutations was performed either by direct Sanger sequencing or in combination with a multi gene panel, followed by sequence and mutation analysis.

Results

While all previously reported mutations and most of our novel mutations are located within the core patatin domain, here we report on five novel PNPLA1 mutations, which are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation.

Conclusions

We estimate the frequency of PNPLA1 mutations amongst ARCI patients to around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotype variation in a small percentage of patients with PNPLA1 mutations.

The variability of the clinical manifestations as well as the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.

This article is protected by copyright. All rights reserved.

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Cell proliferation and differentiation during the three dimensional reconstitution of eccrine sweat glands

Abstract

The aim of this study is to characterize the cell proliferation and proliferating cell types during three-dimensional reconstitution of eccrine sweat glands. Eccrine sweat gland cells suspended in Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 1, 2, 4, 6, 8, 14, 21, 28, 35 and 42 days post-implantation, Matrigel plugs were immunostained for Ki67, to detect cycling cells, and the Ki67 labeling index at different time points was calculated. Three pairs of antibodies, Ki67/K7, Ki67/K14 and Ki67/α-SMA, were used to identify proliferating cell types in the plugs, on days 28, 35 and 42, by immunofluorescence double staining. The Ki67 labeling index on the first day of implantation was 30.53%, rapidly reached a peak value of 81.43% at 2 days post-implantation, and then decreased gradually to a low of 2.87% at 42 days. Double immunofluorescence staining showed that K14/Ki67 double-stained cells accounted for 80% of the Ki67-positive cells, whereas K7/Ki67 and α-SMA/Ki67 double-stained cells each accounted for 10% of the Ki67-positive population on days 28, 35, or 42 post-implantation. We conclude that eccrine sweat gland cells rapidly enter the cell cycle after implantation, but quickly show decreased cell proliferation and increased cell differentiation.

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A Surgeon's View on the Pathogenesis of Atherosclerosis.

Author: Haverich, Axel MD

Page: 205-207

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Wide Variation in Reported Rates of Stroke Across Cohorts of Patients With Atrial Fibrillation.

Author: Quinn, Gene R. MD, MS; Severdija, Olivia N. MD; Chang, Yuchiao PhD; Singer, Daniel E. MD

Page: 208-219

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Adding Rigor to Stroke Rate Investigations in Patients With Atrial Fibrillation.

Author: Nielsen, Peter Bronnum PhD; Lip, Gregory Y. H. MD

Page: 220-223

http://ift.tt/2jDRmWQ

Heart Failure Stages Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

Author: Shah, Amil M. MD, MPH; Claggett, Brian PhD; Loehr, Laura R. MD, PhD; Chang, Patricia P. MD, MHS; Matsushita, Kunihiro MD, PhD; Kitzman, Dalane MD; Konety, Suma MD; Kucharska-Newton, Anna PhD, MPH; Sueta, Carla A. MD, PhD; Mosley, Thomas H. PhD; Wright, Jacqueline D. DrPH; Coresh, Joseph MD, PhD; Heiss, Gerardo MD, PhD; Folsom, Aaron R. MD, MPH; Solomon, Scott D. MD

Page: 224-240

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Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease.

Author: Jones, W. Schuyler MD; Baumgartner, Iris MD; Hiatt, William R. MD; Heizer, Gretchen MS; Conte, Michael S. MD; White, Christopher J. MD; Berger, Jeffrey S. MD, MS; Held, Peter MD, PhD; Katona, Brian G. PharmD; Mahaffey, Kenneth W. MD; Norgren, Lars MD, PhD; Blomster, Juuso MD; Millegard, Marcus MSc; Reist, Craig PhD; Patel, Manesh R. MD; Fowkes, F. Gerry R. MD; On behalf of the International Steering Committee and Investigators of the EUCLID Trial

Page: 241-250

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LPA Gene, Ethnicity, and Cardiovascular Events.

Author: Lee, Sang-Rok MD, PhD; Prasad, Anand MD; Choi, Yun-Seok MD, PhD; Xing, Chao PhD; Clopton, Paul MS; Witztum, Joseph L. MD; Tsimikas, Sotirios MD

Page: 251-263

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Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease.

Author: Baggen, Vivan J.M. MD; van den Bosch, Annemien E. MD, PhD; Eindhoven, Jannet A. MD, PhD; Schut, Anne-Rose W. BSc; Cuypers, Judith A.A.E. MD, PhD; Witsenburg, Maarten MD, PhD; de Waart, Monique; van Schaik, Ron H.N. PhD; Zijlstra, Felix MD, PhD; Boersma, Eric MSc, PhD; Roos-Hesselink, Jolien W. MD, PhD

Page: 264-279

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Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

Author: Abbas, Malak PhD; Jesel, Laurence MD, PhD; Auger, Cyril PhD; Amoura, Lamia; Messas, Nathan MD; Manin, Guillaume MD; Rumig, Cordula PhD; Leon-Gonzalez, Antonio J. PhD; Ribeiro, Thais P. PhD; Silva, Grazielle C. PhD; Abou-Merhi, Raghida PhD; Hamade, Eva PhD; Hecker, Markus PhD; Georg, Yannick MD; Chakfe, Nabil MD, PhD; Ohlmann, Patrick MD, PhD; Schini-Kerth, Valerie B. PhD; Toti, Florence PhD; Morel, Olivier MD, PhD

Page: 280-296

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Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications.

Author: Bertrand, Philippe B. MD, MSc, PhD; Schwammenthal, Ehud MD, PhD; Levine, Robert A. MD; Vandervoort, Pieter M. MD

Page: 297-314

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Effect of Clopidogrel by Smoking Status on Secondary Stroke Prevention.

Author: Ovbiagele, Bruce MD; Wang, Jing MD; Johnston, S. Claiborne MD, PhD; Wang, Anxin MS; Wang, David DO; Wang, Yongjun MD; Zhao, Xingquan MD, PhD; Wang, Yilong MD, PhD

Page: 315-316

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Letter by Colli and Gerosa Regarding Article, "Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience".

Author: Colli, Andrea MD, PhD; Gerosa, Gino MD

Page: e16-e17

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Response by Gammie et al to Letter Regarding Article, "Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience".

Author: Gammie, James S. MD; Wilson, Peter BSMET; Bartus, Krzysztof MD, PhD; Gackowski, Andrzej MD, PhD; Hung, Judy MD; D'Ambra, Michael N. MD; Kolsut, Piotr MD, PhD; Bittle, Gregory J. MD; Szymanski, Piotr MD, PhD; Sadowski, Jerzy MD, PhD; Kapelak, Boguslaw MD, PhD; Bilewska, Agata MD, PhD; Kusmierczyk, Mariusz MD; Ghoreishi, Mehrdad MD

Page: e18-e19

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Letter by Dhruva and Redberg Regarding Article, "Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure: Findings From the Get With The Guidelines-Heart Failure Program".

Author: Dhruva, Sanket S. MD; Redberg, Rita F. MD, MSc

Page: e20-e21

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Response by Hess et al to Letter Regarding Article, "Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure: Findings From the Get With The Guidelines-Heart Failure Program".

Author: Hess, Paul L. MD, MHS; Hernandez, Adrian F. MD, MHS; Bhatt, Deepak L. MD, MPH; Hellkamp, Anne S. MS; Yancy, Clyde W. MD, MSc; Schwamm, Lee H. MD; Peterson, Eric D. MD, MPH; Schulte, Phillip J. PhD; Fonarow, Gregg C. MD; Al-Khatib, Sana M. MD, MHS

Page: e22-e23

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pH/thermo-responsive poly(N-isopropylacrylamide-co-maleic acid) hydrogel with a sensor and an actuator for biomedical applications

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Gheorghe Fundueanu, Marieta Constantin, Sanda Bucatariu, Paolo Ascenzi
Poly(N-isopropylacrylamide-co-maleic acid) (poly(NIPAAm-co-MAc)) with an appropriate comonomer ratio was designed and synthesized as an appealing pH/thermo-responsive copolymer. In simulated physiological fluids (phosphate buffer solution (PBS) at pH = 7.4 and T = 36 °C), both carboxylic groups of MAc in copolymer (pKa1 = 3.45, pKa2 = 6.09) are in the ionized form, more hydrophilic and consequently the copolymer loses the thermosensitive properties. However, when the carboxylate groups present in the copolymer are protonated or interact ionically with positively-charged compounds with hydrophobic character (e.g. diphenhydramine, DPH), the copolymer takes back the thermosensitive properties at the physiological pH and temperature. Therefore, microgels obtained from poly(NIPAAm-co-MAc) are in the swollen state in PBS at T = 36 °C, i.e. they are in the "inactive" state. However, after ionic interactions with hydrophobic compounds, taken as triggering agents, the microgels become "activated" and collapse. Therefore, the triggering agent is the key factor controlling the thermosensitivity of the hydrogel.

Graphical abstract

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Corrigendum to “Molecules in seminal plasma related to platelets in preeclampsia” [Med. Hypotheses 93 (2016) 27–29]

Publication date: March 2017
Source:Medical Hypotheses, Volume 100
Author(s): Iván Antonio García-Montalvo, Gabriel Mayoral Andrade, Laura Perez-Campos Mayoral, Socorro Pina Canseco, Ruth Martinez Cruz, Margarito Martínez-Cruz, Edgar Zenteno, Eduardo Perez-Campos Mayoral, Itandehui Gallegos Velasco, Maria Teresa Hernandez-Huerta, Diana Matias-Perez, Eduardo Pérez-Campos




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Primary trigeminal neuralgia and the role of pars oralis of the spinal trigeminal nucleus

Publication date: Available online 16 January 2017
Source:Medical Hypotheses
Author(s): Selcuk Peker, Alperen Sirin
Trigeminal neuralgia is a painful condition that causes great discomfort. Although this disease has been known for more than 1,000 years, there is still no consensus on its underlying mechanism or treatment. Many hypotheses have been reported to explain the cause and nature of trigeminal neuralgia. These include theories about peripheral mechanisms and central mechanisms. We put forward a new hypothesis that trigeminal neuralgia is associated with the pars oralis of the spinal trigeminal nucleus (POSTN). The main basis for this is the close similarity between trigger point distribution and the area of influence of the POSTN. We also highlight that the areas of influence for the trigeminal nerve divisions do not match the trigger point distribution; therefore, peripheral theories should be further investigated.



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Impaired Illness Awareness and Leftward Visuospatial Inattention in Schizophrenia Are Attributable to a Common Neural Deficit – Posterior Parietal Hemispheric Imbalance

Publication date: Available online 16 January 2017
Source:Medical Hypotheses
Author(s): Julia Kim, Eric Plitman, Shinichiro Nakajima, Jun Ku Chung, Youssef Alshehri, Yusuke Iwata, Fernando Caravaggio, Bruce G. Pollock, Dave Pothier, Ariel Graff-Guerrero, Philip Gerretsen




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Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Michelle S. Miller, Sweta Maheshwari, Fiona M. McRobb, Kenneth W. Kinzler, L. Mario Amzel, Bert Vogelstein, Sandra B. Gabelli
PIK3CA, the gene that encodes the catalytic subunit of phosphatidylinositol 3-kinase α (PI3Kα), is frequently mutated in breast and other types of cancer. A specific inhibitor that targets the mutant forms of PI3Kα could maximize treatment efficiency while minimizing side-effects. Herein we describe the identification of novel binding pockets that may provide an opportunity for the design of mutant selective inhibitors. Using a fragment-based approach, we screened a library of 352 fragments (MW <300 Da) for binding to PI3Kα by X-ray crystallography. Five novel binding pockets were identified, each providing potential opportunities for inhibitor design. Of particular interest was a binding pocket near Glu542, which is located in one of the two most frequently mutated domains.

Graphical abstract

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Identification of Novel Inverse Agonists of Estrogen-Related Receptors ERRγ and ERRβ

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Donna D. Yu, Janice M. Huss, Hongzhi Li, Barry M. Forman
Estrogen-related receptors (ERRs, α, β, and γ) are orphan nuclear receptors most closely related in sequence to estrogen receptors (ERα and ERβ). Much attention has been paid recently to the functions of ERRs for their potential roles as new therapeutic targets implicated in the etiology of metabolic disorders. While no endogenous ligand has been identified for any of the ERR isoforms to date, the potential for using synthetic small molecules to modulate their activity has been demonstrated. In the present study, a series of novel inverse agonists of ERRγ and ERRβ were synthesized using regio- and stereo-specific direct substitution of triarylethylenes. These compounds were evaluated for their ability to modulate the activities of ERRs. The rational directed substitution approach and extensive SAR studies resulted in the discovery of compound 4a (DY40) as the most potent ERRγ inverse agonist described to date with mixed ERRγ/ERRβ functional activities, which potently suppressed the transcriptional functions of ERRγ with IC50 = 0.01 μM in a cell-based reporter gene assay and antagonized ERRγ with a potency approximately 60 times greater than its analog Z-4-OHT (Z-4-hydroxytamoxifen). In addition, compound 3h (DY181) was identified as the most potent synthetic inverse agonist for the ERRβ that exhibited excellent selectivity over ERRα/γ in functional assays. This selectivity was also supported by computational docking models that suggest DY181 forms more extensive hydrogen bound network with ERRβ which should result in higher binding affinity on ERRβ over ERRγ.

Graphical abstract

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Synthesis of new spirooxindole-pyrrolothiazoles derivatives: Anti-cancer activity and molecular docking

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Gehad Lotfy, Mohamed M. Said, El Sayed H. El Ashry, El Sayed H. El Tamany, Abdullah Al-Dhfyan, Yasmine M. Abdel Aziz, Assem Barakat
The 1,3-dipolar cycloadditions of an azomethine ylide generated from isatin and thiazolidinecarboxylic acid to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded new di-spiro heterocycles incorporating pyrrolidine and oxindole rings in quantitative yields and chemo-, regio-, and stereoselectively. The newly synthesized compounds were characterized using spectroscopic techniques. Furthermore, the molecular structures of 4a, 4e, and 4n were confirmed by X-ray crystallography. These newly synthesized compounds were screened for their in vitro activity against breast cancer cell line MCF-7 and K562-leukemia. 4k was found to be the most potent compound of this series in targeting MCF-7 breast cancer cells and K562-leukemia, with IC50 values of 15.32 ± 0.02 and 14.74 ± 0.7 μM, respectively. The molecular studies of the synthesized compounds were investigated.

Graphical abstract

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Chiral resolution of serial potent and selective σ1 ligands and biological evaluation of (-)-[18F]TZ3108 in rodent and the nonhuman primate brain

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xuyi Yue, Hongjun Jin, Zonghua Luo, Hui Liu, Xiang Zhang, Ethan D. McSpadden, Linlin Tian, Hubert P. Flores, Joel S. Perlmutter, Stanley M. Parsons, Zhude Tu
Twelve optically pure enantiomers were obtained using either crystallization or chiral high performance liquid chromatography (HPLC) separation methodologies to resolve six racemic sigma-1 (σ1) receptor ligands. The in vitro binding affinities of each enantiomer for σ1, σ2 receptors and vesicular acetylcholine transporter (VAChT) were determined. Out of the 12 optically pure enantiomers, five displayed very high affinities for σ1 (Ki < 2 nM) and high selectivity for σ1 versus σ2 and VAChT (>100-fold). The minus enantiomer, (-)-14a ((-)-TZ3108)) (Ki-σ1 = 1.8 ± 0.4 nM, Ki-σ2 = 6960 ± 810 nM, Ki-VAChT = 980 ± 87 nM), was chosen for radiolabeling and further in vivo evaluation in rodents and nonhuman primates (NHPs). A biodistribution study in Sprague Dawley rats showed brain uptake (%ID/gram) of (-)-[¹⁸F]TZ3108 reached 1.285 ± 0.062 at 5 min and 0.802 ± 0.129 at 120 min. NHP microPET imaging studies revealed higher brain uptake of (-)-[¹⁸F]TZ3108 and more favorable pharmacokinetics compared to its racemic counterpart. Pretreatment of the animal using two structurally different σ1 ligands significantly decreased accumulation of (-)-[¹⁸F]TZ3108 in the brain. Together, our in vivo evaluation results suggest that (-)-[¹⁸F]TZ3108 is a promising positron emission tomography (PET) tracer for quantifying σ1 receptor in the brain.

Graphical abstract

http://ift.tt/2ivyix4

Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPARγ and SURs agonists

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed.K. Ibrahim, Ibrahim H. Eissa, AbdallahE. Abdallah, Ahmed M. Metwaly, M.M. and M.A. Radwan ElSohly
In our effort to develop potent anti-hyperglycemic agents with potential agonistic activities toward PPARγ and SURs, three novel series of quinoxaline derivatives bearing sulfonylurea or sulfonylthiourea moieties with different linkers were designed and synthesized. Some of the newly synthesized compounds were evaluated in vivo for their anti-hyperglycemic activities in STZ-induced hyperglycemic rats. Compounds 15a, 15e, 19b and 24a exhibited the highest anti-hyperglycemic activities with% reduction in blood glucose level of (50.58, 43.84, 45.10 and 49.62, respectively). Additionally, eight compounds revealed potent anti-hyperglycemic activities were further evaluated in vitro for their PPARγ binding affinity and insulin-secreting ability as potential mechanisms for anti-hyperglycemic activity. Four compounds (15a, 15b, 15d and 15e) significantly bound to PPARγ with IC50 values of 0.482, 0.491, 0.350 and 0.369 μM, respectively. Moreover, Compounds 15a and 15b have demonstrated induction of insulin-secretion with EC50 values of 0.92 and 0.98 μM, respectively. Furthermore, molecular docking and pharmacophore generation techniques were carried out to investigate binding patterns and fit values of the designed compounds with PPARγ and SUR, respectively.

Graphical abstract

http://ift.tt/2ivCMnw

Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy

Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): Justin G. Lees, Preet G.S. Makker, Ryan S. Tonkin, Munawwar Abdulla, Susanna B. Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN. Here, we discuss recent findings, which provide insight into this complex process of neuroimmune interactions. Findings show limited infiltration of leukocytes into the nervous system of CIPN animals and varying degrees of peripheral and central glial activation depending on the chemotherapeutic drug, dose, schedule, and timing. Most evidence suggests an increase in pro-inflammatory cytokine expression and changes in immune signalling pathways. There is, however, limited evidence available from human studies and it remains unclear whether neuroinflammatory responses are the cause of neuropathy or a bystander effect of the chemotherapy treatment.



http://ift.tt/2jq3D42

Strategy for constructing vascularized adipose units in poly(L-glutamic acid) hydrogel porous scaffold through inducing in-situ formation of ASCs spheroids

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Kunxi Zhang, Li Song, Jia Wang, Shifeng Yan, Guifei Li, Lei Cui, Jingbo Yin
Vascularization is of great importance to adipose tissue regeneration. Here we introduced a paradigm that using scaffold to induce ASC spheroids, so to promote vascularized adipose tissue regeneration. Poly (L-glutamic acid) (PLGA) was activated by EDC, followed by being cross-linked by Adipic dihydrazide (ADH) to form a homogeneous hydrogel. Lyophilization was then carried out to create porous structure. The PLGA hydrogel scaffold possessed a significant swollen hydrophilic network to weaken cell-scaffold adhesion but drive ASCs to aggregate to form spheroids. Increase of seeding cell density was proved to result in the increase of spheroid size, upregulating angiogenic genes (VEGF and FGF-2) expression by enhancing the hypoxia-induced paracrine secretion. Also, the adipogenic differentiation of ASCs was achieved in spheroids in vitro. Moreover, the in vivo vascularized adipose tissue regeneration was evaluated in the dorsum of nude mice. After 12 weeks post-implantation, the significant angiogenesis was found in both adipogenic induced and non-induced engineered tissue. In adipogenic induced group, the clear ring-like morphology, the large vacuole in the middle of the cell and the Oil red O staining demonstrated adipose tissue formation.Statement of SignificanceVascularization is of great importance to adipose tissue regeneration. Adipose derived stem cell (ASC) spheroids possessed not only the high efficiency of vascularization, but also the improved differentiation ability. Several research works have illustrated the advantage of ASC spheroids in vascularization. However, in adipose regeneration, ASC spheroid was rarely used. Even so, it is reasonable to believe that ASC spheroids hold a great promise in vascularized adipose tissue engineering. Thus in the present study, we introduced a method to create lots of ASC spheroids that acted as lots of individual adipogenesis and angiogenesis units inside of a porous hydrogel scaffold. Then, the scaffold carrying ASC spheroids was implanted subcutaneously in nude mice to preliminarily evaluate the adipose tissue generation and blood vessel formation.

Graphical abstract

http://ift.tt/2jikB1W

Fabrication of nanofibrous electrospun scaffolds from a heterogeneous library of co- and self-assembling peptides

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Mahboubeh Maleki, Antonino Natalello, Raffaele Pugliese, Fabrizio Gelain
Self-assembling (SAPs) and co-assembling peptides (CAPs) are driving increasing enthusiasm as synthetic but biologically inspired biomaterials amenable of easy functionalization for regenerative medicine. On the other hand, electrospinning (ES) is a versatile technique useful for tailoring the nanostructures of various biomaterials into scaffolds resembling the extracellular matrices found in organs and tissues. The synergistic merging of these two approaches is a long-awaited advance in nanomedicine that has not been deeply documented so far. In the present work, we describe the successful ES of a library of diverse SAPs and CAPs into biomimetic nanofibrous mats. Our results suggest that suitable ES solutions are characterized by high concentrations of peptides, providing backbone physical chain entanglements, and by random coil/α-helical conformations while β-sheet aggregation may be detrimental to spinnability. The resulting peptide fibers feature interconnected seamless mats with nanofibers average diameters ranging from ∼100 nm to ∼400 nm. Also, peptide chemical nature and ES set up parameters play pivotal roles in determining the conformational transitions and morphological properties of the produced nanofibers. Far from being an exhaustive description of the just-opened novel field of ES-assembled peptides, this seminal work aims at shining a light on a still missing general theory for the production of electrospun peptidic biomaterials bringing together the spatial, biochemical and biomimetic of these two techniques into unique scaffolds for tissue engineering.Statement of SignificanceConstruction of peptide hydrogels has received considerable attention due to their potential as nanostructures amenable of easy functionalization and capable of creating microenvironments suited for culturing cells and triggering tissue regeneration. They display a superior biocompatibility unmatched by other known synthetic biomaterials so far. However, their applications are confined to body fillers because most of them do spontaneously form hydrogels, while effective tissue regeneration often requires well-defined fibrous scaffolds. In this work, we developed electrospun fibers of various peptides (cross-beta self-assembling, hierarchically assembling, functionalized, co-assembling) and we provided a deep understanding of the crucial phenomena to be taken into account when peptides fibers fabrication. These results open new venues for exploring novel regenerative applications of peptide nanofibrous scaffolds.

Graphical abstract

http://ift.tt/2jijaAt

Composite material consisting of microporous β-TCP ceramic and alginate for delayed release of antibiotics

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Michael Seidenstuecker, Juergen Ruehe, Norbert P. Suedkamp, Annerose Serr, Annette Wittmer, Marc Bohner, Anke Bernstein, Hermann O. Mayr
ObjectiveThe aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days.Material and MethodsUsing the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28 days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA.ResultsThe release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2 ± 1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14 days. The burst release here was 61.9 ± 4.3%. The native alginate's burst release was 54.1 ± 7.8%; that of the sterile alginate 40.5 ± 6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0 μg/mL against Staphylococcus aureus.Statement of SignificanceDrug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the "granule in hydrogel" composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work.

Graphical abstract

http://ift.tt/2ji8H86

Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Zefeng Zheng, Jisheng Ran, Weishan Chen, Yejun Hu, Ting Zhu, Xiao Chen, Zi Yin, Boon Chin Heng, Gang Feng, Huihui Le, Chenqi Tang, Jiayun Huang, Yangwu Chen, Yiting Zhou, Pioletti Dominique, Weiliang Shen, Hong-wei Ouyang
Rotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10mg/ml), pore diameter (108.43 ± 7.25 μm) and porosity (97.94 ± 0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24 hours. TSPCs formed intercellular contacts and deposited extracellular matrix after 7 days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72 ± 3.75 vs. 44.26 ± 5.03 nm) that had better alignment and mechanical properties (139.85 ± 49.36 vs. 99.09 ± 33.98 N) at 12 weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering.Statement of SignificanceMassive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced cellular infiltration and tenogenic differentiation of stem/progenitor cells from both the tendon itself and surrounding tissues. Hence, it can potentially be a clinically useful application for tendon tissue engineering.

Graphical abstract

http://ift.tt/2jiinQ5

Effect of construction of TiO2 nanotubes on platelet behaviors: Structure-property Relationships

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Qiaoling Huang, Yun Yang, Dajiang Zheng, Ran Song, Yanmei Zhang, Pinliang Jiang, Erwin A. Vogler, Changjian Lin
Blood compatibility of TiO2 nanotubes (TNTs) has been assessed in rabbit platelet-rich plasma (PRP), which combines activation of both blood plasma coagulation and platelets. We find that (i) amorphous TiO2 nanotubes (TNTs) with relatively larger outer diameters led to reduced platelet adhesion/activation, (ii) TNTs with relatively smaller outer diameters in a predominately rutile phase also inhibited platelet adhesion and activation, and (iii) a pervasive fibrin network formed on larger outer diameter TNTs in a predominately anatase phase. Thus, this study suggests that combined effect of crystalline phase and surface chemistry controls blood-contact behavior of TNTs. A more comprehensive mechanism is proposed for understanding hemocompatibility of TiO2 which might prove helpful as a guide to prospective design of TiO2-based biomaterials.Statement of SignificanceTo realize optimal design and construction of biomaterials with desired properties for blood contact materials, a comprehensive understanding of structure-property relationships is required. In the existing literature, TiO2 nanotube has been reported to be a good candicate for biomedical applications. However, it is noticeable that the blood compatibility of TiO2 nanotubes (TNTs) remains obscure or even inconsistent in the previously published works. The inconsistency could derive from different research protocols, material properties or blood sources. Thus, a thorough investigation of the effect of suface properties on blood compatibility is crucial to the development of titanium based materials. In this paper, we explored the effect of surface properties on the response of platelet-rich plasma, especially surface morphology, chemistry, wettability and crystalline phase. The results indicated that cyrstalline phase was a dominant factor in platelet behaviors. Reduced adhesion and activation of platelets were observed on amorphous and rutile dominated TNTs, whereas anatase dominated TNTs activated the formation of fibrin network. We further proposed a hypothetical mechanism for better understanding of how surface properties affect the response of platelet-rich plasma. Therefore, this study expands the fundamental understanding of the structure-property relationships of titanium based materials.

Graphical abstract

http://ift.tt/2jikyDi

Surface Modification of PDLLGA Microspheres with Gelatine Methacrylate: Evaluation of Adsorption, Entrapment, and Oxygen Plasma Treatment Approaches

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Abdulrahman Baki, Cheryl V. Rahman, Lisa J. White, David J. Scurr, Omar Qutachi, Kevin M. Shakesheff
Injectable poly (DL-lactic-co-glycolic acid) (PDLLGA) microspheres are promising candidates as biodegradable controlled release carriers for drug and cell delivery applications; however, they have limited functional groups on the surface to enable dense grafting of tissue specific biocompatible molecules. In this study we have evaluated surface adsorption, entrapment and oxygen plasma treatment as three approaches to modify the surfaces of PDLLGA microspheres with gelatine methacrylate (gel-MA) as a biocompatible and photo cross-linkable macromolecule. Time of flight secondary ion mass spectroscopy (TOF SIMS) and X-ray photoelectron spectroscopy (XPS) were used to detect and quantify gel-MA on the surfaces. Fluorescent and scanning electron microscopies (SEM) were used to image the topographical changes. Human mesenchymal stem cells (hMSCs) of immortalised cell line were cultured on the surface of gel-MA modified PDLLGA microspheres and Presto-Blue assay was used to study the effect of different surface modifications on cell proliferation. Data analysis showed that the oxygen plasma treatment approach resulted in the highest density of gel-MA deposition. This study supports oxygen plasma treatment as a facile approach to modify the surface of injectable PDLLGA microspheres with macromolecules such as gel-MA to enhance proliferation rate of injected cells and potentially enable further grafting of tissue specific molecules.Statement of SignificancePoly (DL lactic-co-glycolic) acid (PDLLGA) microspheres offer limited functional groups on their surface to enable proper grafting of tissue specific bioactive molecules. To overcome this limitation, previous approaches have suggested using alkaline solutions to introduce active groups to the surface; however, they may compromise surface topography and lose any potential surface patterns. Plasma polymerisation of bioactive monomers has been suggested to enhance surface biocompatibility; however, it is not applicable on low vapour pressure macromolecules such as most extracellular matrix (ECM) proteins and growth factors. This study aims to evaluate three different approaches to modify the surface of PDLLGA microspheres with gelatine-methacrylate (gel-MA) to enable further grafting of cross-linkable biomolecules without compromising the surface topography or the biocompatibility of the system.

Graphical abstract

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Vitamin B3 metal-organic frameworks as potential delivery vehicles for therapeutic nitric oxide

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Rosana V. Pinto, Fernando Antunes, João Pires, Vanessa Graça, Paula Brandão, Moisés L. Pinto
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2(μ2-H2O)(μ-vitamin B3)4]·2H2O contain two crystallographic distinct divalent metal centers connected by a bridging water and carboxylate group from vitamin B3. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0 μmol NO mgsolid^-1, on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Hemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, showing low toxicity of the compounds at concentrations below 180 μg cm^-3. The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery.Significance statementThe synthesis and characterization of new vitamin B3 porous metal-organic frameworks (MOFs) is presented in this work for the first time. Few other examples of porous MOFs build up of vitamin exist in the literature with adsorbing capacity like our materials.The ligand (vitamin B3) in these MOFs is much more biocompatible than the usual ligands like, for example, benzene carboxylic acids (terephthalic acid or trimesic acid) and imidazole based ligands.No other vitamin based MOFs have been studied for NO storage.The effects on cell cultures of the materials loaded with NO are studied for the first time and the cell line used is a human primary cell line representative of the human skin. This is relevant for future applications related to wound healing.

Graphical abstract

http://ift.tt/2jija3r

The Effectiveness of Free Vascularized Fibular Flaps in Osteonecrosis of the Femoral Head and Neck: A Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0036-1594294

Background Free vascularized fibular flaps (FVFFs) are accepted surgical options to treat osteonecrosis of the femoral head and neck (ONFHN) to prevent conversion to total hip replacement (THR), yet many studies are single institution cohorts, with little generalizability. Purpose The purpose of this study was to perform a systematic review examining the comparative effectiveness of FVFF to treat ONFHN, particularly preventing conversion to a THR and improving hip function/symptoms. Methods We searched PubMed and EMBASE databases using femoral head, free fibula, and femoral neck keywords. Articles were excluded if not translated into English, n < 10 hips, article was a compilation/review, outcomes were not relevant, or prior to 1994. If from the same institution, we included the largest cohort and excluded others within the same timeline. Two investigators independently reviewed articles and reported number of patients/hips, average age/follow-up time/graft survival before THR, Harris hip score, THR rate, complications, and radiographic progression rates. Results We identified 128 and 157 articles from PubMed and EMBASE. After screening/duplicate removal, 21 studies were included from 14 institutions in 9 countries. Overall, 71% were level IV evidence. The average patient number was 129, number of hips was 166, age at surgery was 34 years, and follow-up time was 92 months. HHS improved on average 21.7 points, with the number of patients requiring THR being 19.4%. Graft survival before THR was 5.2 years, and 47.7% of hips had radiographic progression. Conclusions There is a significant amount of level IV evidence describing the favorable role of FVFF to treat ONFHN. Although efficacious, there is a need for higher level evidence. The level of evidence is 3.
[...]

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The Impact of Changes in Distress Tolerance on PTSD Symptom Severity Post-Treatment among Veterans in Residential Trauma Treatment

Publication date: Available online 16 January 2017
Source:Journal of Anxiety Disorders
Author(s): Anne N. Banducci, Kevin M. Connolly, Anka A. Vujanovic, Jennifer Alvarez, Marcel O. Bonn-Miller
Given that rates of PTSD, particularly among military populations, are increasing, it is critical to gain a better understanding of factors associated with treatment response. Low distress tolerance (DT), conceptualized as the perceived or actual inability to tolerate negative emotional states, may impacts veterans' responses to PTSD treatment. Low DT has been associated with more severe PTSD symptoms in clinical and non-clinical samples; however, its impact on PTSD symptomatology across treatment has yet to be assessed. We examined the impact of changes in DT, from intake to discharge, on post-treatment PTSD symptom severity within two samples of veterans recruited from Veterans Affairs residential PTSD treatment facilities in the northwestern and southern United States (Total N=86; 87% male; 46% White, 39% Black, 9% Latino, 6% Other). Veterans completed the Distress Tolerance Scale and PTSD Checklist (PCL) at intake and discharge from residential PTSD treatment. Regression analyses revealed that, within each veteran sample, those with the greatest improvements in DT had the lowest PCL total and subscale scores at discharge after controlling for respective intake PCL scores. This suggests increases in DT across treatment help explain the degree of benefits experienced by veterans following PTSD treatment.



http://ift.tt/2jt33SQ

Heroin use is associated with lower levels of restriction factors and type I interferon expression and facilitates HIV-1 replication

Publication date: Available online 16 January 2017
Source:Microbes and Infection
Author(s): Jia-Wu Zhu, Feng-Liang Liu, Dan Mu, De-Yao Deng, Yong-Tang Zheng
Heroin use is associated with increased incidence of infectious diseases such as HIV-1 infection, as a result of immunosuppression to a certain extent. Host restriction factors are recently identified cellular proteins with potent antiviral activities. Whether heroin use impacts on the in vivo expression of restriction factors that result in facilitating HIV-1 replication is poorly understood. Here we recruited 432 intravenous drug users (IDUs) and 164 non-IDUs at high-risk behaviors. Based on serological tests, significantly higher prevalence of HIV-1 infection was observed among IDUs compared with non-IDUs. We included those IDUs and non-IDUs without HIV-1 infection, and found IDUs had significantly lower levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β expression than did non-IDUs. We also directly examined plasma viral load in HIV-1 mono-infected IDUs and non-IDUs and found HIV-1 mono-infected IDUs had significantly higher plasma viral load than did non-IDUs. Moreover, intrinsically positive correlation between type I interferon and TRIM5α or TRIM22 was observed, however, which was dysregulated following heroin use. Collectively, heroin use benefits HIV-1 replication that may be partly due to suppression of host restriction factors and type I interferon expression.



http://ift.tt/2jpZ5e0

Thyroid High-Impact Articles

FREE ACCESS through January 30, 2017.
Read now:

Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association

3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes
Nancy Schanze, Simon Friedrich Jacobi, Eddy Rijntjes, Stefan Mergler, Marta del Olmo, Carolin Stephanie Hoefig, Noushafarin Khajavi, Ina Lehmphul, Heike Biebermann, Jens Mittag, Josef Köhrle

Differences in Brain Glucose Metabolism During Preparation for ¹³¹I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin
Hyeonseok S. Jeong, Eun Kyoung Choi, In-Uk Song, Yong-An Chung, Jong-Sik Park, Jin Kyoung Oh

RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review
Alireza Najafian, Salem Noureldine, Faris Azar, Chady Atallah, Gina Trinh, Eric B. Schneider, Ralph P. Tufano, Martha A. Zeiger

Thyroglobulin Liquid Chromatography—Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies
Umal Azmat, Kyle Porter, Leigha Senter, Matthew D. Ringel, Fadi Nabhan

Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?
Kai-Pun Wong, Kin-Pan Au, Shi Lam, Brian Hung-Hin Lang

 

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Check out the ten TOP-viewed articles in 2016 for Clinical Thyroidology for the Public

1. THYROID NODULES Risk of thyroid cancer based on thyroid ultrasound findings Vol 7 Issue 1 p.6-7, Jamshid Farahiti, MD

2. HYPOTHYROIDISM Desiccated thyroid extract vs Levothyroxine in the treatment of hypothyroidism Vol 6 Issue 8 p.3, Angela M. Leung, MD, MSc

3. HYPOTHYROIDISM When is the best time to take thyroid hormone? Vol 4 Issue 5 p.7, Whitney Woodmansee, MD

4. THYROID HORMONE THERAPY Taking levothyroxine with breakfast may be fine for many patients Vol 6 Issue 11 p.4, Heather Hofflich, DO

5. THYROID CANCER High risk of thyroid cancer in patients with multinodular goiter Vol 6 Issue 11 p.6-7, Jamshid Farahiti, MD

6. THYROID AND CHOLESTEROL Does thyroid stimulating hormone (TSH) affect cholesterol levels? Vol 5 Issue 12 p.3, Angela Leung, MD

7. THYROID AND PREGNANCY First Trimester TSH levels between 2.5 and 5.0 are associated with increased pregnancy loss Vol 3 Issue 8 p.5-6, Whitney Woodmansee, MD

8. HYPERTHYROIDISM Thyroid tests on newborns within the first five days will detect neonatal hyperthyroidism Vol 7 Issue 7 p.5, Heather Hofflich, DO

9. HYPERTHYROIDISM Some patients with apparent Graves' disease do not have an autoimmune thyroid disorder Vol 7 Issue 2 p.4-5, Glenn D. Braunstein, M.D.

10. HYPOTHYROIDISM Patients with Hashimoto's thyroiditis and negative thyroid antibodies have a milder form of the disease Vol 7 Issue 9 p.10-1, Heather Hofflich, DO

The post Check out the ten TOP-viewed articles in 2016 for Clinical Thyroidology for the Public appeared first on American Thyroid Association.

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Proteomic analysis of the Rett syndrome experimental model mecp2Q63X mutant zebrafish

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Alessio Cortelazzo, Thomas Pietri, Claudio De Felice, Silvia Leoncini, Roberto Guerranti, Cinzia Signorini, Anna Maria Timperio, Lello Zolla, Lucia Ciccoli, Joussef Hayek
Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs. wild-type larvae and adult zebrafish. We found a total of 20 proteins differentially expressed between wild-type and mutant zebrafish, suggesting skeletal and cardiac muscle functional defects, a stunted glycolysis and depleted energy availability. This molecular evidence is directly linked to the mecp2-null zebrafish observed phenotype. In addition, we identified changes in expression of proteins critical for a proper redox balance, suggesting an enhanced oxidative stress, a phenomenon also documented in human patients and RTT murine models. The molecular alterations observed in the mecp2-null zebrafish expand our knowledge on the molecular cascade of events that lead to the RTT phenotype.Biological significanceWe performed a proteomic study of a non-mammalian vertebrate model (zebrafish, Danio rerio) for Rett syndrome (RTT) at larval and adult stages of development. Our results reveal major protein expression changes pointing out to defects in energy metabolism, redox status imbalance, and muscle function, both skeletal and cardiac. Our molecular analysis grants the mecp2-null zebrafish as a valuable RTT model, triggering new research approaches for a better understanding of the RTT pathogenesis and phenotype expression. This non-mammalian vertebrate model of RTT strongly suggests a broad impact of Mecp2 dysfunction.

Graphical abstract

http://ift.tt/2izBLGi

Host–microbiota interactions: epigenomic regulation

Publication date: February 2017
Source:Current Opinion in Immunology, Volume 44
Author(s): Vivienne Woo, Theresa Alenghat
The coevolution of mammalian hosts and their commensal microbiota has led to the development of complex symbiotic relationships between resident microbes and mammalian cells. Epigenomic modifications enable host cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which mammalian cells can transcriptionally respond, transiently or stably, to environmental cues. Advances in genome-wide approaches are accelerating our appreciation of microbial influences on host physiology, and increasing evidence highlights that epigenomics represent a level of regulation by which the host integrates and responds to microbial signals. In particular, bacterial-derived short chain fatty acids have emerged as one clear link between how the microbiota intersects with host epigenomic pathways. Here we review recent findings describing crosstalk between the microbiota and epigenomic pathways in multiple mammalian cell populations. Further, we discuss interesting links that suggest that the scope of our understanding of epigenomic regulation in the host-microbiota relationship is still in its infancy.



http://ift.tt/2j251Xi

Spatio-temporal variation of septage characteristics of a semi-arid metropolitan city in a developing country

Abstract

Septage is the solid sludge that accumulates in septic tanks over a period of time. Many of the developing countries in the world face the challenging task of septage management. Due to the high variability in the nature of septage, there is a need to study its physical and chemical characteristics in order to suggest a sustainable treatment methodology. The present study deals with the characterization of septage collected from different locations of Chennai city in India, in two different seasons (summer and winter). The characterization includes parameters such as solids, organics, inorganics, nutrients and heavy metals. Septage showed significant difference in concentrations of pollutants from one season to the other (p > 0.05). The average total solids concentration is found to be 1.6 times higher during winter season than compared to summer season. Average concentrations of solids were 2185 ± 1070 and 3555 ± 2935 mg/L during summer and winter, respectively. Liquid characterization of septage showed total chemical oxygen demands (COD) of 905 ± 603 mg/L (summer) and 1460 ± 1295 mg/L (winter). Similarly, average soluble biochemical oxygen demand (sBOD) was found to be 117 ± 54 mg/L during summer and 211 ± 220 mg/L during winter season. Studies also showed that septage was rich in nutrients such as total nitrogen (4–500 mg/L), ammoniacal nitrogen (2–129 mg/L), total phosphate (5–236 mg/L) and heavy metals such as copper, zinc, lead and manganese. Overall characterization indicates that the collected septage samples are highly variable in nature with respect to sources, season and locations of collection. As the septage is rich in organic matter and nutrients, it can be used as a resource like soil conditioner or as a substitute for chemical fertilizer in agriculture, after proper treatment, leading to a new evolution in sanitation.

http://ift.tt/2jPPvgZ

Polycyclic aromatic hydrocarbons (PAHs) determined by pine needles and semipermeable membrane devices along an altitude profile in Taurus Mountains, Turkey

Abstract

Polycyclic aromatic hydrocarbons (PAHs) were analyzed at different altitudes of Taurus Mountains in semipermeable membrane devices (SPMD) and in half-, one-and-a-half-, and two-and-a-half-year-old pine needles. SPMDs were deployed for three different exposure periods: March to September (Summer), September to March (Winter), and March to March (whole year) at eight sites where needle samples were collected. The values of PAHs in needles were between 4.4 to 6066 pg g/fw in half-year-old, 7.2 to 111,115 pg g/fw in 1.5-year-old, and 9.7 to 85,335 pg g/fw in 2.5-year-old needles. Mass of PAHs collected by SPMDs varied from <MDL to 8060 ng/SPMD in winter, from 0.98 to 585 ng/SPMD in summer, and <MDL to 9360 ng/SPMD in whole year deployment, respectively. PAH profiles were dependent on the seasonal differences and locations. Roughly, clear decreasing trends with altitude were observed both with SPMD and needles for many individual and groups of PAHs except for the SPMD-summer short-time data. A cross-plot of Fluo/(Fluo+Pyr) vs Ant/(Ant+Phe) diagnostic ratios indicated grass/wood burning (possibly due to forest fires) in summer and petrogenic combustion in winter. Results of the study showed that SPMD and conifer needles are effective passive samplers to measure PAHs in the environment.

http://ift.tt/2jo0qBZ

Allocation and simulation study of carbon emission quotas among China’s provinces in 2020

Abstract

China will form its carbon market in 2017 to focus on the allocation of regional carbon emission quota in order to cope with global warming. The rationality of the regional allocation has become an important consideration for the government in ensuring stable growth in different regions that are experiencing disparity in resource endowment and economic status. Based on constructing the quota allocation indicator system for carbon emission, the emission quota for each province in different scenarios and schemes in 2020 is simulated by the multifactor hybrid weighted Shannon entropy allocation model. The following conclusions are drawn: (1) The top 5 secondary-level indicators that influence provincial quota allocation in weight are as follows: per capita energy consumption, openness, per capita carbon emission, per capita disposable income, and energy intensity. (2) The ratio of carbon emission in 2020 is different from that in 2013 in many scenarios, and the variation is scenario 2 > scenario 1 > scenario 3, with Hubei and Guangdong the provinces with the largest increase and decrease ratios, respectively. (3) In the same scenario, the quota allocation varies in different reduction criteria emphases; if the government emphasizes reduction efficiency, scheme 1 will show obvious adjustment, that is, Hunan, Hubei, Guizhou, and Yunnan will have the largest decrease. The amounts are 4.28, 8.31, 4.04, and 5.97 million tons, respectively.

http://ift.tt/2jPSRkk

Study of the genotoxicity of organic extracts from wastewater-irrigated vegetables using in vitro and in vivo biological tests

Abstract

The purpose of this study was to explore genotoxicity due to organic pollutants in wastewater-irrigated vegetables using biological and chemical analyses. Chinese cabbages from wastewater-irrigated farmland were taken as the research object. For the in vitro test, DNA damage was characterized in rat hepatocytes exposed to organic extracts from the cabbages using the comet assay. For the in vivo tests, mice were exposed to organic extracts from the cabbages. DNA damage was assessed in mouse peripheral blood lymphocytes (PBLs), and chromosome damage was assessed in bone marrow cells using the comet assay and micronucleus test, respectively. For the chemical analysis, gas chromatography-mass spectrometry (GC/MS) was used to analyze the organic compounds in the organic vegetable extracts. The in vitro test results showed that the comet tail lengths of the DNA in rat hepatocytes were significantly increased in the group dosed with 0.36 g/ml (P < 0.05), and the comet tailing rates of the hepatocytes were significantly increased in the groups dosed with 0.24 and 0.36 g/ml (P < 0.05). The in vivo test results indicated that the comet tail lengths of the DNA in mouse PBLs were increased in the low- and high-dose groups and that the comet tailing rate of the PBLs was increased in the high-dose group (P < 0.05). The chemical analysis results showed that the total organic content in the organic vegetable extracts from the wastewater-irrigated area (1.355 mg/kg) was significantly higher than the content in the cabbage samples from the clean-water-irrigated area (0.089 mg/kg). This finding indicated that wastewater irrigation can cause organic pollution with genetic toxicity in vegetables. This study also showed that in vivo and in vitro biological tests can reflect the joint toxicity of organic pollutants, and the test results were in accordance with the chemical analysis of the organic pollutant compositions.

http://ift.tt/2jnT81j

Evaluation of laboratory-scale in situ capping sediments with purple parent rock to control the eutrophication

Abstract

In this study, the effectiveness of controlling the eutrophication using purple parent rock to cap the sediments was evaluated in the laboratory scale. Sediments were collected from Sanxikou reservoir (China) in July 2013. Then, three types of purple parent rock (T₁f, J₃p, and J₂s) which are distributed widely in southwest China were used to cap the sediments. Limestone and calcite were used as the contrast group, because they had been reported as effective controls on eutrophication. Then, they were incubated at 20 °C for 46 days. The results indicated that the application of purple parent rock as a barrier material can effectively inhibit the release of nutrient elements in sediments, and the inhibition rates of total nitrogen (TN), total phosphorus (TP), ammonium (NH₄–N), and nitrate (NO₃–N) were much better than that of limestone and calcite. Among the three types of purple parent rock, J₃p exhibited the best inhibitory effect on the release of nitrogen in sediments, and the inhibition efficiency of TN, NH₄–N, and NO₃–N was 59.7, 77.6, and 45.1%, respectively. As for T₁f, it exhibited the best inhibitory effect on the release of TP in sediments with the inhibition rate of 94.4%. Whereas all these capping materials showed weak inhibition on release of organic matter in sediments, and the inhibition efficiencies were less than 20%. Moreover, these treatments could also cause distinct changes in the microbial community in sediments and overlying water, and the contents of TN and TP in all capping materials increased. All results demonstrated that purple parent rock could inhibit the release of nutrient in sediments through mechanical interception, physical adsorption, and chemical absorption as well as changing the microbial activity in the covering layer, sediments, or overlying water.

http://ift.tt/2jsP67b

Complications during Ketogenic diet Initiation: Prevalence, Treatment and Influence on Seizure outcomes

Publication date: Available online 16 January 2017
Source:Pediatric Neurology
Author(s): Abigail Lin, Zahava Turner, Sarah C. Doerrer, Anthony Stanfield, Eric H. Kossoff
IntroductionMany centers still admit children for several days to start the ketogenic diet (KD). The exact incidence of adverse effects during the admission, as well as their potential later impact on seizure reduction, has not been widely studied.MethodsWe performed a retrospective study of children with intractable epilepsy electively admitted for KD initiation at our institution from 2011-2016. Charts were reviewed for adverse effects during the admission period and then examined for seizure reduction and compliance at 3 months. A rating scale (1-4) was created for severity of any adverse events.Results158 children were included, mean age 4.6 years. Potentially attributable adverse effects occurred in 126 (80%), most commonly emesis, food refusal, and hypoglycemia. Seventy-three (46%) received some form of intervention by the medical team, most commonly juice (24%). Younger age was correlated with an increased likelihood of moderate-severe adverse effects during admission, often repeated hypoglycemia (3.6 versus 4.9 years, p=0.04). Fasting was more likely to result in lethargy and a single blood glucose in the 30-40 mg/dL range, but was not correlated with emesis, repeated hypoglycemia, or higher adverse effect scores. There was no statistically significant correlation between the severity of adverse effects and 3-month seizure reduction.ConclusionsMild, easily-treated adverse effects were seen in the majority of children admitted for the ketogenic diet. Younger children were at greater risk for significant difficulties, and should be monitored closely. As fasting led to more lethargy and hypoglycemia, it may be prudent to avoid this in younger children.



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Sustained Attention and Heart Rate Variability in children and adolescents with ADHD

Publication date: Available online 15 January 2017
Source:Biological Psychology
Author(s): Kristi R. Griffiths, Daniel S. Quintana, Daniel F. Hermens, Chris Spooner, Tracey W. Tsang, Simon Clarke, Michael R. Kohn
The autonomic nervous system (ANS) plays an important role in attention and self-regulation by modulating physiological arousal to meet environmental demands. Core symptoms of ADHD such as inattention and behavioral disinhibition may be related to dysregulation of the ANS, however previous findings have been equivocal. We examined autonomic activity and reactivity by assessing heart rate variability (HRV) in a large sample of un-medicated children and adolescents (6-19 years) with ADHD (n=229) compared to typically-developing controls (n=244) during rest and sustained attention. Four heart rate variability measures were extracted: Root mean square of successive differences between inter-beat-intervals (rMSSD), absolute high frequency (HFA) power, absolute low frequency (LFA) power and ratio of low frequency power to high frequency power (LF/HF). There were no group differences in HFA or rMSSD, even when assessing across child and adolescent groups separately, by gender or ADHD subtype. LF/HF however was higher in ADHD during both rest and sustained attention conditions, particularly in male children. Sustained attention was impaired in ADHD relative to controls, and a higher LF/HF ratio during sustained attention was associated with poorer performance in both groups. Lower rMSSD and HFA were associated with higher anxiety, oppositional behaviors and social problems, supporting prevailing theories that these measures index emotion regulation and adaptive social behavior. Different measures of heart rate variability provide important insights into the sustained attention and emotional and behavioral regulation impairments observed in ADHD and may aid in delineating ADHD pathophysiology.



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A visual screen for diet-regulated proteins in the Drosophila ovary using GFP protein trap lines

Publication date: Available online 16 January 2017
Source:Gene Expression Patterns
Author(s): Hwei-Jan Hsu, Daniela Drummond-Barbosa
The effect of diet on reproduction is well documented in a large number of organisms; however, much remains to be learned about the molecular mechanisms underlying this connection. The Drosophila ovary has a well described, fast and largely reversible response to diet. Ovarian stem cells and their progeny proliferate and grow faster on a yeast-rich diet than on a yeast-free (poor) diet, and death of early germline cysts, degeneration of early vitellogenic follicles and partial block in ovulation further contribute to the ∼60-fold decrease in egg laying observed on a poor diet. Multiple diet-dependent factors, including insulin-like peptides, the steroid ecdysone, the nutrient sensor Target of Rapamycin, AMP-dependent kinase, and adipocyte factors mediate this complex response. Here, we describe the results of a visual screen using a library of green fluorescent protein (GFP) protein trap lines to identify additional factors potentially involved in this response. In each GFP protein trap line, an artificial GFP exon is fused in frame to an endogenous protein, such that the GFP fusion pattern parallels the levels and subcellular localization of the corresponding native protein. We identified 53 GFP-tagged proteins that exhibit changes in levels and/or subcellular localization in the ovary at 12–16 h after switching females from rich to poor diets, suggesting them as potential candidates for future functional studies.



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Cost of Hospital Admissions in Medicare Patients With Atrial Fibrillation Taking Warfarin, Dabigatran, or Rivaroxaban

http://ift.tt/2jXZsND

Substrate Ablation Without Pulmonary Vein Isolation: A Reasonable Proposition for Atrial Fibrillation Ablation?

http://ift.tt/2j1F21W

Post-Approval U.S. Experience With Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation

AbstractBackground

Left atrial appendage closure (LAAC) was approved by the U.S. Food and Drug Administration (FDA) as a stroke prevention alternative to warfarin for patients with nonvalvular atrial fibrillation. However, clinical decision-making is confounded by the fact that although LAAC attenuates the anticoagulant-related lifetime risk of bleeding, implantation is associated with upfront complications. Thus, enthusiasm for LAAC as a treatment option has been appropriately tempered, particularly as the therapy is introduced beyond the clinical trial sites into general clinical practice.

Objectives

This study evaluated the acute procedural performance and complication rates for all cases performed in the United States since FDA approval.

Methods

In the absence of a formal national clinical registry since regulatory approval in March 2015, we obtained procedural data on implantation procedures. Every LAAC procedure requires the presence of a manufacturer clinical specialist and for procedural parameter and periprocedural complication data to be collected using a standardized process and forms.

Results

In 3,822 consecutive cases, implantation was successful in 3,653 (95.6%), with a median procedure time of 50 min (range 10 to 210 min). Implanting physicians performing these procedures (n = 382) included 71% new, nonclinical trial implanters, who performed 50% of the procedures. Procedural complication rates included 39 pericardial tamponades (1.02%) (24 treated percutaneously, 12 surgically, and 3 fatal); 3 procedure-related strokes (0.078%); 9 device embolizations (0.24%) (6 requiring surgical removal); and 3 procedure-related deaths (0.078%).

Conclusions

Despite a large fraction of previously inexperienced operators, in the real-world post-FDA approval experience of LAAC, procedural success was high and complication rates were low.

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Reply: Routine Ischemic Work-Up for Patients With New-Onset Heart Failure

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Assessing the Safety of Early U.S. Commercial Application of Left Atrial Appendage Closure

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Comparison of Propensity Score Methods and Covariate Adjustment: Evaluation in 4 Cardiovascular Studies

Abstract

Propensity scores (PS) are an increasingly popular method to adjust for confounding in observational studies. Propensity score methods have theoretical advantages over conventional covariate adjustment, but their relative performance in real-word scenarios is poorly characterized. We used datasets from 4 large-scale cardiovascular observational studies (PROMETHEUS, ADAPT-DES [the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents], THIN [The Health Improvement Network], and CHARM [Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity]) to compare the performance of conventional covariate adjustment with 4 common PS methods: matching, stratification, inverse probability weighting, and use of PS as a covariate. We found that stratification performed poorly with few outcome events, and inverse probability weighting gave imprecise estimates of treatment effect and undue influence to a small number of observations when substantial confounding was present. Covariate adjustment and matching performed well in all of our examples, although matching tended to give less precise estimates in some cases. PS methods are not necessarily superior to conventional covariate adjustment, and care should be taken to select the most suitable method.

http://ift.tt/2j1F75Z

Outcomes Among Older Patients Receiving Implantable Cardioverter-Defibrillators for Secondary Prevention: From the NCDR ICD Registry

AbstractBackground

Clinical trials of implantable cardioverter-defibrillators (ICDs) for secondary prevention of sudden cardiac death were conducted nearly 2 decades ago and enrolled few older patients.

Objectives

This study assessed morbidity and mortality of older patients receiving ICDs for secondary prevention in contemporary clinical practice.

Methods

We identified 12,420 Medicare beneficiaries from the National Cardiovascular Data Registry ICD Registry undergoing first-time secondary prevention ICD implantation between 2006 and 2009 in 956 U.S. hospitals. Risks of death, hospitalization, and admission to a skilled nursing facility (SNF) were assessed over 2 years in age strata (65 to 69, 70 to 74, 75 to 79, and ≥80 years of age) using Medicare claims. The adjusted association between age and outcomes was evaluated using multivariable models.

Results

The mean age was 75 years at the time of implantation; 25.3% were <70 years of age and 25.7% were ≥80 years of age. Overall, the risk of death at 2 years was 21.8%, ranging from 14.7% among those <70 years of age to 28.9% among those ≥80 years of age (adjusted risk ratio [aRR]: 2.01; 95% confidence interval [CI]: 1.85 to 2.33; p for trend <0.001). The cumulative incidence of hospitalizations was 65.4%, ranging from 60.5% in those <70 years of age to 71.5% in those ≥80 years of age (aRR: 1.27; 95% CI: 1.19 to 1.36; p for trend <0.001). The cumulative incidence of admission to a SNF ranged from 13.1% among those <70 years of age to 31.9% among those ≥80 years of age (aRR: 2.67; 95% CI: 2.37 to 3.01; p for trend <0.001); SNF admission risk was highest in the first 30 days.

Conclusions

Almost 1 in 5 older patients receiving a secondary prevention ICD survives at least 2 years. High hospitalization and SNF admission rates, particularly among the oldest patients, identify substantial care needs after device implantation.

http://ift.tt/2jXWCs5

Routine Ischemic Work-Up for Patients With New-Onset Heart Failure

http://ift.tt/2j1qFek

The Conundrum of Defibrillators in the Elderly

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Instructions For Authors

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Percutaneous Mechanical Circulatory Support Versus Intra-Aortic Balloon Pump in Cardiogenic Shock After Acute Myocardial Infarction

AbstractBackground

Despite advances in treatment, mortality in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains high. Short-term mechanical circulatory support devices acutely improve hemodynamic conditions.

Objectives

The aim of this study was to determine whether a new percutaneous mechanical circulatory support (pMCS) device (Impella CP, Abiomed, Danvers, Massachusetts) decreases 30-day mortality when compared with an intra-aortic balloon pump (IABP) in patients with severe shock complicating AMI.

Methods

In a randomized, prospective, open-label, multicenter trial, 48 patients with severe CS complicating AMI were assigned to pMCS (n = 24) or IABP (n = 24). Severe CS was defined as systolic blood pressure <90 mm Hg or the need for inotropic or vasoactive medication and the requirement for mechanical ventilation. The primary endpoint was 30-day all-cause mortality.

Results

At 30 days, mortality in patients treated with either IABP or pMCS was similar (50% and 46%, respectively; hazard ratio with pMCS: 0.96; 95% confidence interval: 0.42 to 2.18; p = 0.92). At 6 months, mortality rates for both pMCS and IABP were 50% (hazard ratio: 1.04; 95% confidence interval: 0.47 to 2.32; p = 0.923).

Conclusions

In this explorative randomized controlled trial involving mechanically ventilated patients with CS after AMI, routine treatment with pMCS was not associated with reduced 30-day mortality compared with IABP. (IMPRESS in Severe Shock; NTR3450)

http://ift.tt/2jY32az

Challenges in Infective Endocarditis

Abstract

Infective endocarditis is defined by a focus of infection within the heart and is a feared disease across the field of cardiology. It is frequently acquired in the health care setting, and more than one-half of cases now occur in patients without known heart disease. Despite optimal care, mortality approaches 30% at 1 year. The challenges posed by infective endocarditis are significant. It is heterogeneous in etiology, clinical manifestations, and course. Staphylococcus aureus, which has become the predominant causative organism in the developed world, leads to an aggressive form of the disease, often in vulnerable or elderly patient populations. There is a lack of research infrastructure and funding, with few randomized controlled trials to guide practice. Longstanding controversies such as the timing of surgery or the role of antibiotic prophylaxis have not been resolved. The present article reviews the challenges posed by infective endocarditis and outlines current and future strategies to limit its impact.

http://ift.tt/2jXRXGy

Mechanical Support for Cardiogenic Shock: Lost in Translation?

http://ift.tt/2j1wAjv

Percutaneous Mechanical Circulatory Support Versus Intra-Aortic Balloon Pump for Treating Cardiogenic Shock: Meta-Analysis

http://ift.tt/2jY11ew

Cardiac Autonomic Dysfunction and Incidence of Atrial Fibrillation: Results From 20 Years Follow-Up

AbstractBackground

Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear.

Objectives

This study sought to study the association between HRV and risk of AF.

Methods

This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011.

Results

During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate <60 beats/min was associated modestly with an increased risk of AF. Lower overall HRV as well as increased sympathetic/parasympathetic tone were associated independently with a higher risk of AF; the hazard ratio for each 1 SD lower SD of normal-to-normal RR intervals was 1.14 (95% confidence interval: 1.08 to 1.21), for HF was 1.12 (95% confidence interval: 1.06 to 1.17), and for low frequency/HF was 1.08 (95% confidence interval: 1.03 to 1.14).

Conclusions

Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF.

http://ift.tt/2j1y4tV

Treatment Nuances in Cardiac Sarcoidosis

http://ift.tt/2jY2mBM

Autonomic Tone and Atrial Fibrillation: A Double-Edged Sword?

http://ift.tt/2j1Evxd

Reply: Treatment Nuances in Cardiac Sarcoidosis

http://ift.tt/2jXUmB0

AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach

AbstractBackground

The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results.

Objectives

The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF.

Methods

The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF.

Results

Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver.

Conclusions

The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949)

http://ift.tt/2j1vUKZ

Cardiac Autonomic Dysfunction and Incidence of Atrial Fibrillation: Results From 20 Years Follow-Up

AbstractBackground

Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear.

Objectives

This study sought to study the association between HRV and risk of AF.

Methods

This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011.

Results

During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate <60 beats/min was associated modestly with an increased risk of AF. Lower overall HRV as well as increased sympathetic/parasympathetic tone were associated independently with a higher risk of AF; the hazard ratio for each 1 SD lower SD of normal-to-normal RR intervals was 1.14 (95% confidence interval: 1.08 to 1.21), for HF was 1.12 (95% confidence interval: 1.06 to 1.17), and for low frequency/HF was 1.08 (95% confidence interval: 1.03 to 1.14).

Conclusions

Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF.

http://ift.tt/2j1y4tV

Treatment Nuances in Cardiac Sarcoidosis

http://ift.tt/2jY2mBM

Autonomic Tone and Atrial Fibrillation: A Double-Edged Sword?

http://ift.tt/2j1Evxd

Reply: Treatment Nuances in Cardiac Sarcoidosis

http://ift.tt/2jXUmB0

AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach

AbstractBackground

The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results.

Objectives

The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF.

Methods

The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF.

Results

Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver.

Conclusions

The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949)

http://ift.tt/2j1vUKZ