Ovarian cancer: novel molecular aspects for clinical assessment

Publication date: Available online 17 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches.



http://ift.tt/2rLlzeB

SERI Surgical Scaffold in 2-Stage Breast Reconstruction: 2-Year Data from a Prospective, Multicenter Trial

Background: Soft-tissue support devices are used during breast reconstruction. This study investigated long-term clinical data following SERI Surgical Scaffold (SERI) implantation, a bioresorbable, silk-derived scaffold for soft-tissue support. Methods: This was a prospective, multicenter study in 103 subjects who received SERI during stage 1 of 2-stage breast reconstruction with subpectoral tissue expander placement (Natrelle Style 133V; Allergan plc, Dublin, Ireland) followed by subpectoral breast implant placement. Investigator satisfaction (11-point scale: 0, very dissatisfied and 10, very satisfied) at 6 months was the primary endpoint. Ease of use, satisfaction, scaffold palpability/visibility, breast anatomy measurements via 3D images, SERI integration, histology, and safety were also assessed through 2 years after stage 1 surgery. Results: Analyses were performed on the per-protocol population (103 subjects; 161 breasts) with no protocol deviations that could affect outcomes. Ease of use and subject and investigator satisfaction with SERI were high throughout 2 years. Breast anatomy measurements with 3D images demonstrated long-term soft-tissue stability of the lower breast mound. Key complication rates per breast were tissue/skin necrosis and wrinkling/rippling (8.1% each) and seroma, wound dehiscence, and breast redness (5.0% each). Over 2 years, 4 breasts in 4 subjects underwent reoperation with explantation of any device; 2 breasts required SERI explantation. SERI was retained in 98.8% of breasts (159/161) at 2 years. Conclusions: SERI was associated with high and consistent levels of investigator and subject satisfaction and demonstrated soft-tissue stability in the lower breast through 2 years. SERI provides a safe, long-term benefit for soft-tissue support in 2-stage breast reconstruction.

http://ift.tt/2s94OK3

Personality Traits as Predictors of Quality of Life and Body Image after Breast Reconstruction

Background: It has been suggested that personality traits may influence patient-reported outcomes of breast reconstruction, but the research is limited. We investigated, in a prospective study, whether personality traits predict the achieved body image and quality of life (QoL) after breast reconstruction. Methods: Patients planning to undergo breast reconstruction at a University Hospital were consecutively recruited from January 2014 to January 2016. Participants completed validated measures of personality, body image, and QoL, before and 6 months after breast reconstruction. The influence of personality traits on achieved body image and QoL was explored with multivariate linear regression modelling, adjusting for baseline scores, demographics, and clinical variables. Results: Of 247 eligible patients, 208 (84%) participated. Twelve patients (6%) were excluded due to failed reconstruction. Of the remaining 196 patients, 180 (92%) completed the follow-up questionnaire. When adjusted for baseline QoL scores, higher trait Neuroticism, higher trait Openness, and higher body mass index measured at baseline showed to be independent and statistically significant predictors of deteriorating QoL scores from baseline to 6-month follow-up (P

http://ift.tt/2s8LdcZ

An ultrasensitive stain for negative protein detection in SDS-PAGE via 4′,5′-Dibromofluorescein

Publication date: Available online 19 June 2017
Source:Journal of Proteomics
Author(s): Dongdong Yu, Yang Wang, Shaoqing Zhang, Zhiwei Chen, Mei Xue, Ying Wang, Weitao Cong, Litai Jin, Zhongxin Zhu
A highly sensitive method for brief and economical staining of proteins in 1-D and 2-D sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) by 4′,5′-Dibromofluorescein (DBF) was developed in this study. Down to 0.025–0.05ng protein could be detected within 10min (only 2 steps) by DBF stain, which is approximately 10-fold more sensitive than those of Eosin Y (EY) and SYPRO Ruby stains, and 20-fold more sensitive than that of imidazole-zinc (IZ) negative stain. In addition, the LC-MS/MS results indicated that the newly developed staining method is compatible with the downstream protein identification. Moreover, the mechanism of DBF stain was investigated by molecular docking.



http://ift.tt/2rPAAqW

Highly reproducible improved label-free quantitative analysis of cellular phosphoproteome by optimization of LC-MS/MS gradient and analytical column construction

Publication date: Available online 17 June 2017
Source:Journal of Proteomics
Author(s): Nagib Ahsan, Judson Belmont, Zhuo Chen, James G. Clifton, Arthur R. Salomon
Expanding the sequencing depth of the peptides with a statistically significant quantitative change derived from a biological stimulation is critical. Here we demonstrate that optimization of LC gradient and analytical column construction can reveal over 30,000 unique peptides and 23,000 phosphopeptides at high confidence. The quantitative reproducibility of different analytical workflows was evaluated by comparing the phosphoproteome of CD3/4 stimulated and unstimulated T-cells as a model system. A fritless, 50cm-long column packed with 1.9μm particles operated with a standard pressure HPLC significantly improved the sequencing depth 51% and decreased the selected ion chromatogram peak spreading. Most importantly, under the optimal workflow we observed an improvement of over 300% in detection of significantly changed phosphopeptides in the stimulated cells compared with the other workflows. The discovery power of the optimized column configuration was illustrated by identification of significantly altered phosphopeptides harboring novel sites from proteins previously established as important in T cell signaling including A-Raf, B-Raf, c-Myc, CARMA1, Fyn, ITK, LAT, NFAT1/2/3, PKCα, PLCγ1/2, RAF1, and SOS1. Taken together, our results reveal the analytical power of optimized chromatography using sub 2μm particles for the analysis of the T cell phosphoproteome to reveal a vast landscape of significantly altered phosphorylation changes in response to T cell receptor stimulation.



http://ift.tt/2slbJyM

Proteomic analysis of mesenchymal to Schwann cell transdifferentiation

Publication date: Available online 17 June 2017
Source:Journal of Proteomics
Author(s): Anup D. Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K. Mallapragada, Howard E. Gendelman, Donald S. Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation. Transdifferentiated MSCs secrete significant amounts of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cell-conditioned media that facilitated neurite outgrowth. MSC proteins significantly regulated during Schwann cell transdifferentiation included, but were not limited to, GNAI2, MYL9, ACTN4, ACTN1, ACTB, CAV-1, HSPB1, PHB2, TBB4B, CTGF, TGFI1, ARF6, EZR, GELS, VIM, WNT5A, RTN4, EFNB1. These support axonal guidance, myelination, neural development and neural growth and differentiation. The results unravel the molecular events that underlie cell transdifferentiation that ultimately serve to facilitate nerve regeneration and repair in support of cell transplantation.Significance statementWhile Schwann cells facilitate axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of bone-marrow derived mesenchymal stem cells (MSCs) transdifferentiated to Schwann cell-phenotypes. In the present study, we undertook the first proteomic evaluation of these transdifferentiated cells to uncover the protein contents that affects Schwann cell formulation. Furthermore, these transdifferentiated MSCs secrete significant amounts of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cell-conditioned media that facilitated neurite outgrowth. Our results demonstrate that a number of MSC proteins were significantly regulated following transdifferentiation of the MSCs supporting roles in axonal guidance, myelination, neural development and differentiation. The conclusions of the present work unravel the molecular events that underlie cell transdifferentiation that ultimately serve to facilitate nerve regeneration and repair in support of cell transplantation. Our study was the first proteomic comparison demonstrating the transdifferentiation of MSCs and these reported results can affect a wide field of stem cell biology, tissue engineering, and proteomics.

Graphical abstract

http://ift.tt/2skDjvS

Identification of chickpea seed proteins resistant to simulated in vitro human digestion

Publication date: Available online 17 June 2017
Source:Journal of Proteomics
Author(s): I.C. Ribeiro, C.C. Leclercq, N. Simões, A. Toureiro, I. Duarte, J.B. Freire, M.M. Chaves, J. Renaut, C. Pinheiro
Proteins and peptides able to resist gastrointestinal digestion and reach the intestinal mucosa have the potential to influence human health. Chickpea (Cicer arietinum L.) seed proteins are able to resist cooking (86.9% total protein) and/or in vitro simulated human digestion (15.9% total protein resists soaking, cooking and digestion with pepsin and pancreatin). To identify and characterize proteins resisting digestion we made use of different MS methodologies. The efficiency of several proteases (trypsin, AspN, chymotrypsin and LysC) was tested, and two technologies were employed (MALDI-TOF-TOF and LC-nESI-MS/MS). Digestion with trypsin and AspN were most successful for the identification of seed proteins. When analyzed by MALDI-TOF-TOF, trypsin allowed the identification of at least one protein in 60% of the polypeptide bands, while AspN allows the identification in 48%. The use of LC-ESI-MS/MS, allowed the identification of much more proteins/polypeptides from digested seeds (232 vs 17 using trypsin). The majority of the proteins found to be able to resist simulated digestion were members of the 7S vicilin and 11S legumin seed storage protein classes, which are reported to contain bio-active functions. In addition, we have found proteins that had not yet been described as potentially able to cause an impact on human health.SignificanceThis is the first proteomic study to analyze the effect of processing and simulated human gastrointestinal digestion on the proteome of chickpea seed. Chickpea is reported to have anti-nutritional effects as well as nutraceutical properties, so the identification and characterization of the proteins able to resist digestion is crucial to understand the targets underlying such properties.



http://ift.tt/2sl2oXJ

Erratum to: Toxic potential of the emerging contaminant nicotine to the aquatic ecosystem

http://ift.tt/2tmJzBL

Impairments of cadmium on vitellogenin accumulation in the hepatopancreas of freshwater crab Sinopotamon henanense

Abstract

During ovary maturation of crabs, vitellogenin (Vg), a precursor molecule of vitellin (Vn) needed for embryogenesis, can be produced in large quantities in the hepatopancreas and then transported to the ovary by the hemolymph. In the present study, effects of Cd on Vg accumulation in the hepatopancreas and Vg transportation of the freshwater crab Sinopotamon henanense were investigated. We also studied the impacts of Cd on the mRNA expression of genes involved in energy metabolism, protein metabolism, and metallothionein (MT) and glutathione (GSH) synthesis. After Cd treatment, the Vg concentration and the Vg mRNA expression in the hepatopancreas were downregulated. Pearson's correlation coefficient showed that the Vg level in the hepatopancreas correlated positively with those of the ovary and hemolymph (correlation coefficients 0.844 and 0.749, respectively), suggesting that the Vg transport from the hepatopancreas to the ovary can be impaired by Cd. The levels of carbohydrate and protein in the hepatopancreas of Cd-exposed crabs were decreased, and an inhibited protein metabolism was also observed. Energy production related isocitrate dehydrogenase and cytochrome C oxidase mRNA expressions, and MT and GSH synthesis increased after 10 days of Cd treatment and decreased after 20 days. Cd also caused a time-dependent upregulation of malondialdehyde. Our findings showed that Cd decreased Vg accumulation in the hepatopancreas due to partially excessive energy consumption and an activated defense system in the hepatopancreas, suggesting a possible regulatory mechanism in S. henanense which is the competitive advantage of energy reserves in metabolic Cd stress responses over the high-energy flux during vitellogenesis to ensure a continuous supply of metabolic energy. Moreover, the damage of Vg accumulation in the hepatopancreas caused by Cd could lead to an insufficient accumulation of Vn in the ovary and cause a retardation of oocyte development.

http://ift.tt/2sNe86N

Arsenic sorption by red mud-modified biochar produced from rice straw

Abstract

Red mud-modified biochar (RM-BC) has been produced to be utilized as a novel adsorbent to remove As because it can effectively combine the beneficial features of red mud (rich metal oxide composition and porous structure) and biochar (large surface area and porous structure properties). SEM-EDS and XRD analyses demonstrated that red mud had loaded successfully on the surface of biochar. With the increasing of pH in solution, arsenate (As(V)) adsorption on RM-BC decreased while arsenite (As(III)) increased. Arsenate adsorption kinetics process on RM-BC fitted the pseudo-second-order model, while that of As(III) favored the Elovich model. All sorption isotherms produced superior fits with the Langmuir model. RM-BC exhibited improved As removal capabilities, with a maximum adsorption capacity (Q_max) for As(V) of 5923 μg g⁻¹, approximately ten times greater than that of the untreated BC (552.0 μg g⁻¹). Furthermore, it has been indicated that the adsorption of As(V) on RM-BC may be strongly associated with iron oxides (hematite and magnetite) and aluminum oxides (gibbsite) by X-ray absorption near-edge spectroscopy (XANES), which was possibly because of surface complexation and electrostatic interactions. RM-BC may be used as a valuable adsorbent for removing As in the environment due to the waste materials being relatively abundant.

http://ift.tt/2tmP03s

The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions

http://orlhealth.blogspot.com/2017/06/the-absence-of-cd56-expression-can.html

The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. Aim: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. Statistical Analysis Used: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Results: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. Conclusions: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.

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

6948891480

alsfakia@gmail.com

iACP-GAEnsC: Evolutionary genetic Algorithm based Ensemble Classification of Anticancer Peptides by utilizing Hybridd Feature space

Publication date: Available online 17 June 2017
Source:Artificial Intelligence in Medicine
Author(s): Shahid Akbar, Maqsood Hayat, Muhammad Iqbal, Mian Ahmad Jan
Cancer is a fatal disease, responsible for one-quarter of all deaths in developed countries. Traditional anticancer therapies such as, chemotherapy and radiation, are highly expensive, susceptible to errors and ineffective techniques. These conventional techniques induce severe side-effects on human cells. Due to perilous impact of cancer, the development of an accurate and highly efficient intelligent computational model is desirable for identification of anticancer peptides. In this paper, evolutionary intelligent genetic algorithm-based ensemble model, 'iACP-GAEnsC', is proposed for the identification of anticancer peptides. In this model, the protein sequences are formulated, using three different discrete feature representation methods, i.e., amphiphilic Pseudo amino acid composition, g-Gap dipeptide composition, and Reduce amino acid alphabet composition. The performance of the extracted feature spaces are investigated separately and then merged to exhibit the significance of hybridization. In addition, the predicted results of individual classifiers are combined together, using optimized genetic algorithm and simple majority technique in order to enhance the true classification rate. It is observed that genetic algorithm-based ensemble classification outperforms than individual classifiers as well as simple majority voting base ensemble. The performance of genetic algorithm-based ensemble classification is highly reported on hybrid feature space, with an accuracy of 96.45%. In comparison to the existing techniques, 'iACP-GAEnsC' model has achieved remarkable improvement in terms of various performance metrics. Based on the simulation results, it is observed that 'iACP-GAEnsC' model might be a leading tool in the field of drug design and proteomics for researchers.



http://ift.tt/2skNf8z

Teprotumumab: a new avenue for the management of moderate-to-severe and active Graves’ orbitopathy?

http://ift.tt/2rPKEzT

Microstructural characterisation and experimental determination of a multiaxial yield surface for open-cell aluminium foams

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): A. Jung, S. Diebels
Metal foams are bio-inspired microheterogeneous materials, which exhibit a strong structure-property relationship. Their global mechanical properties depend strongly on the local micromechanical properties of the struts and on the pore geometry of the foams. A solid micromechanical and macromechanical understanding of the yield behaviour of the foams under realistic complex stress states is essential in order to be able to design components made of foams. However, up to now, experimental yield surface data for foams are very limited.The present contribution deals with the structural characterisation of open-cell aluminium foams of different pore sizes by X-ray computed tomography (CT). The strut geometry e.g. regarding cross-sectional shape and the mass distribution along the struts is evaluated from the CT data. Yield surfaces for 10, 20 and 30ppi foams are experimentally probed by performing uniaxial tensile and compression tests, pure torsion as well as combined compression-torsion and tension-torsion tests. This results in one of the most comprehensive experimental data sets in the literature ever reported for open-cell aluminium foams. The shape of the yield surface and its degree of asymmetry were connected to the geometric data from the structural characterisation. It provides a deeper understanding of aluminium foams under complex multiaxial stress states.

Graphical abstract

http://ift.tt/2rxX3Jx

Assessment of modified lignin cationic emulsifier for bitumen emulsions used in road paving

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): A. Yuliestyan, M. García-Morales, E. Moreno, V. Carrera, P. Partal
The utilization of Kraft lignin as cationic emulsifier in the preparation of bitumen emulsions has been assessed in this work. Thus, Kraft lignin was previously modified in alkaline medium in presence of tetraethylene pentamine (TEPA) and formaldehyde, according to the Mannich reaction. Solubility in water phase as a function of pH demonstrated the amphoteric nature of the reaction product, which enables its potential application in cationic bitumen emulsions. Bitumen emulsions stabilized by modified Kraft lignin (MKL) were further studied. Different B/W ratios, which mainly affected the high-shear-rate-limiting viscosities, yielded more similar mean droplet diameters than different pHs, whose effect on viscosity was mainly at low shear rates. Moreover, viscous flow and linear viscoelasticity tests revealed enhanced rheological performance of the MKL bitumen residue if compared to the parent base bitumen. Finally, half warm mix asphalt (HWMA) specimens containing reclaimed asphalt pavement (RAP) were studied, and the results compared with those corresponding to virgin aggregate. In both cases, the preparation of HWMA with a selected 60/40 MKL bitumen emulsion at 80°C by gyratory compaction was successful. Compared to the virgin aggregate, the specimen derived from 100% RAP showed much higher mechanical resistance due to a partial blending of fresh binder with RAP aged binder.

Graphical abstract

http://ift.tt/2ry6p8h

Ovarian cancer: novel molecular aspects for clinical assessment

Publication date: Available online 17 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches.



http://ift.tt/2rLlzeB

Unsuccessful treatment of progressive macular hypomelanosis with oral isotretinoin

http://ift.tt/2tmK1zS

Inoperable infiltrative basal cell carcinoma successfully treated with vismodegib

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer but usually has a good prognosis. However, there is a subset of BCC cases with a less favorable prognosis. For patients with locally advanced, recurrent or metastatic BCCs who are not suitable for surgery or radiotherapy, small-molecule drug inhibitors of hedgehog pathway are a new therapeutic opportunity. Here, we present a case of infiltrative BCC with multiple recurrences. Wide excision with reconstructive plastic surgery was performed initially with adjuvant radiotherapy. Due to multiple recurrences afterward, radiotherapy, topical imiquimod and oral itraconazole were used but were not effective. Finally, the patient was treated with vismodegib which led to a complete response. Moreover, the patient's symptoms due to the locally diffused cancer resolved.

http://ift.tt/2sN88ef

Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Yang-bo Guan, Dong-rong Yang, Shao-jun Nong, Jian Ni, Chun-hui Hu, Jian Li, Jin Zhu, Yu-xi Shan
Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics.



http://ift.tt/2sN6rxe

Analysis of immunostimulatory activity of polysaccharide extracted from Yu-Ping-Feng in vitro and in vivo

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Wentao Fan, Pimiao Zheng, Yang Wang, Pan Hao, Jianzhu Liu, Xiaona Zhao
As a traditional Chinese multiherbal formula, Yu-Ping-Feng (YPF) is frequently used to treat cold, flu and inflammation-associated diseases. We aimed to evaluate the immunostimulatory effects of polysaccharide isolated from YPF (YPF-PS) in vitro and in vivo. In in vitro experiment, macrophage cell proliferation, phagocytosis rate, cytokine and costimulatory molecule release, T lymphocyte proliferation, cell cycle distribution, CD4⁺ and CD8⁺ T cell percentages were determined. To investigate the in vivo effects of YPF-PS treatment, different doses YPF-PS were administered to chicken vaccinated against Newcastle disease. The immune organ index, lymphocyte proliferation, antibody titer, cell cycle distribution, and the cell percentage of CD4⁺ and CD8⁺ were assessed. In vitro results indicated that YPF-PS at 15.62μgmL⁻¹ could increase the LPS-induced macrophage cell proliferation and phagocytosis rate significantly. The levels of cytokine (nitric oxide, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon beta) and costimulatory molecules (CD80 and CD86) were also considerably enhanced. Moreover, YPF-PS could significantly enhance T lymphocyte proliferation individually or synergistically with phytohemagglutinin. It promoted lymphocyte entry into S and G2/M phases and increased the percentages of CD4⁺ and CD8⁺ T cells effectively. In addition, in vivo experiments showed that YPF-PS could enhance serum HI antibody titer. The results about T lymphocyte proliferation, cell cycle distribution, CD4⁺ and CD8⁺ cell percentages in chickens were also confirmed. YPF-PS has efficacious immunomodulatory properties and could be used as a new potential immune stimulator for food and medical purposes.



http://ift.tt/2tmKO3O

Young leaves of reed (Phragmites communis) suppress melanogenesis and oxidative stress in B16F10 melanoma cells

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Mi-Ok Sim, Ju Ri Ham, Mi-Kyung Lee
This study investigated the effects young leaves of reed (Phragmites communis) water extract (YLR) on melanogenesis and oxidative stress using B16F10 cells. YLR decreased the intracellular melanin content, protein expression and enzyme activity of tyrosinase in a dose-dependent manner. YLR significantly decreased the gene and protein expression of melanogeneis-related proteins, such as microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 and -2. In addition, YLR up-regulated the melanogenesis inhibitory proteins, extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), while it dose-dependently down-regulated p38 and cAMP response element-binding protein (CREB). Moreover, YLR significantly reduced H2O2-induced reactive oxygen species levels in B16F10 cells and showed antioxidant activity based on DPPH and ABTS free radical scavenging activity and SOD-like activity. These results suggest that YLR have anti-melanogensis properties that function through regulation of the CREB/MITF/tyrosinase pathway in B16F10 cells and antioxidant activity. Overall, these findings indicate that YLR has the potential for use in treatment of skin disorders and skin-whitening.



http://ift.tt/2sNe4ny

Inhibition effect of tacrolimus and platelet-derived growth factor-BB on restenosis after vascular intimal injury

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xu Ma, Chunyu Jiang, Yuehua Li, Lishuai Feng, Jingjing Liu, Jianbo Wang
Excessive proliferation and migration of vascular smooth muscle cells(VSMCs) and delayed proliferation and migration of endothelial cells(ECs) were the main cause of restenosis after endovascular interventional therapy. Since tacrolimus has proved to be more sensitive to inhibiting VSMCs' proliferation,and platelet-derived growth factor-BB(PDGF-BB) benefitted ECs' and VSMCs' proliferation, this study was aimed to identify combined effect of tacrolimus and PDGF-BB, investigate any mechanisms underneath and demonstrate combined effect of two drugs in vivo. As the results showed we confirmed differential effect of PDGF-BB and tacrolimus on ECs and VSMCs. On the concentration level of 2–5μg/ml tacrolimus plus 10ng/ml PDGF-BB, combination of drugs could effectively promote ECs proliferation and migration, and meanwhile inhibit VSMCs proliferation and migration, and the inhibition of p-mTOR's expression within VSMCs played an important role in this differentiated effect. Raising concentration level of PDGF-BB would weaken inhibitory effect of tacrolimus on both kinds of cell. For injured intima, the mix solution of two drugs could promote intima healing and suppress excessive intimal hyperplasia.



http://ift.tt/2sMWjof

Synthesis, screening and pro-apoptotic activity of novel acyl spermidine derivatives on human cancer cell lines

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Syed Shoeb Razvi, Hany Choudhry, Said Salama Moselhy, Taha Abduallah Kumosani, Mohammed Nihal Hasan, Mazin A. Zamzami, Khalid Omer Abualnaja, Abdulrahman Labeed Al-Malki, Mahmoud Alhosin, Tadao Asami
The polyamines putrescine, spermidine, and spermine are polycationic, alkyl polyamines which play a significant role in eukaryotic cell proliferation. The polyamine metabolism and function are dysregulated in tumor cells making them an attractive therapeutic target by employing polyamine analogs. These analogs have a high degree of similarity with the structure of polyamines but not with their function. Multidrug resistance is a major factor in the failure of many chemotherapeutic drugs which necessitates further research and exploration of better novel alternatives. In the present study, Twenty-six novel acylspermidine derivatives were synthesized and evaluated for their anti-proliferative and pro-apoptotic activities on human breast cancer cells and T-lymphoblastic leukemia cells. The cell proliferation and apoptosis assays using WST-1 and annexin-V/7AAD staining respectively suggest that Compound 1 (C19H41N3O2), Compound 7(C25H51N3O2) and Compound 8 (C29H59N3O) significantly reduced cancer cell viability in a dose- and time-dependent manner. Interestingly, compounds 7, 8 and 9 had slight or no effect on cell proliferation of non-cancerous cells. These studies speculate that these novel acylspermidine derivatives could be promising candidates in designing an anti-proliferative drug, targeting both solid and blood cancer cells.



http://ift.tt/2tmZEr1

Pharmaceutical counselling about different types of tablet-splitting methods based on the results of weighing tests and mechanical development of splitting devices

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): O. Somogyi, A. Meskó, L. Csorba, P. Szabó, R. Zelkó
The division of tablets and adequate methods of splitting them are a complex problem in all sectors of health care. Although tablet-splitting is often required, this procedure can be difficult for patients.Four tablets were investigated with different external features (shape, score-line, film-coat and size). The influencing effect of these features and the splitting methods was investigated according to the precision and "weight loss" of splitting techniques. All four types of tablets were halved by four methods: by hand, with a kitchen knife, with an original manufactured splitting device and with a modified tablet splitter based on a self-developed mechanical model. The mechanical parameters (harness and friability) of the products were measured during the study.The "weight loss" and precision of splitting methods were determined and compared by statistical analysis. On the basis of the results, the external features (geometry), the mechanical parameters of tablets and the mechanical structure of splitting devices can influence the "weight loss" and precision of tablet-splitting. Accordingly, a new decision-making scheme was developed for the selection of splitting methods. In addition, the skills of patients and the specialties of therapy should be considered so that pharmaceutical counselling can be more effective regarding tablet-splitting.

Graphical abstract

http://ift.tt/2rPxlzB

The effect of altitude, patch size and disturbance on species richness and density of lianas in montane forest patches

Publication date: August 2017
Source:Acta Oecologica, Volume 83
Author(s): Dharmalingam Mohandass, Mason J. Campbell, Alice C. Hughes, Christos Mammides, Priya Davidar
The species richness and density of lianas (woody vines) in tropical forests is determined by various abiotic and biotic factors. Factors such as altitude, forest patch size and the degree of forest disturbance are known to exert strong influences on liana species richness and density. We investigated how liana species richness and density were concurrently influenced by altitude (1700–2360 m), forest patch size, forest patch location (edge or interior) and disturbance intensity in the tropical montane evergreen forests, of the Nilgiri and Palni hills, Western Ghats, southern India. All woody lianas (≥1 cm dbh) were enumerated in plots of 30 × 30 m in small, medium and large forest patches, which were located along an altitudinal gradient ranging from 1700 to 2360 m. A total of 1980 individual lianas were recorded, belonging to 45 species, 32 genera and 21 families, from a total sampling area of 13.86 ha (across 154 plots). Liana species richness and density decreased significantly with increasing altitude and increased with increasing forest patch size. Within forest patches, the proportion of forest edge or interior habitat influenced liana distribution and succession especially when compared across the patch size categories. Liana species richness and density also varied along the altitudinal gradient when examined using eco-physiological guilds (i.e. shade tolerance, dispersal mode and climbing mechanism). The species richness and density of lianas within these ecological guilds responded negatively to increasing altitude and positively to increasing patch size and additionally displayed differing sensitivities to forest disturbance. Importantly, the degree of forest disturbance significantly altered the relationship between liana species richness and density to increasing altitude and patches size, and as such is likely the primary influence on liana response to montane forest succession. Our findings suggest that managing forest disturbance in the examined montane forests would assist in conserving local liana diversity across the examined altitudinal range.



http://ift.tt/2rxrkZ6

Sugar secretion and ant protection in Ficus benguetensis: Toward a general trend of fig–ant interactions

Publication date: Available online 17 June 2017
Source:Acta Oecologica
Author(s): Shang-Yang Lin, Lien-Siang Chou, Anthony Bain
The relationship between plants and ants is often mediated by the presence of extrafloral nectaries (EFNs) that attract ants and provide rewards by protecting plants from herbivores or parasites. Ficus trees (Moraceae) and their pollinators (Hymenoptera: Agaonidae) are parasitized by many nonpollinating fig wasp species (Hymenoptera: Chalcidoidea) that decrease the reproductive output of the mutualistic partners. Previous studies have shown that ants living on and patrolling Ficus species can efficiently deter parasitic wasps. The aim of this study was to verify the presence of EFNs on figs of Ficus benguetensis and test the hypothetical protection service provided by ants. Figs in different developmental stages were collected from Fu-Yang Eco Park, Taipei, Taiwan. Sugars on the fig surface were collected and analyzed through high-performance anion-exchange chromatography. Moreover, ants were excluded from the figs to determine the effect of ants on the nonpollinating fig wasps. We identified three oligosaccharides whose relative proportions varied with the fig developmental phase. In addition, results showed that the ant-excluded figs were heavily parasitized and produced three times less pollinators than did the control figs. Finally, the specific interactions of Ficus benguetensis with ants and the relationship between figs and ants in general are discussed.



http://ift.tt/2sQJSY0

Impact of evolving isoprene mechanisms on simulated formaldehyde: An inter-comparison supported by in situ observations from SENEX

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Margaret R. Marvin, Glenn M. Wolfe, Ross J. Salawitch, Timothy P. Canty, Sandra J. Roberts, Katherine R. Travis, Kenneth C. Aikin, Joost A. de Gouw, Martin Graus, Thomas F. Hanisco, John S. Holloway, Gerhard Hübler, Jennifer Kaiser, Frank N. Keutsch, Jeff Peischl, Ilana B. Pollack, James M. Roberts, Thomas B. Ryerson, Patrick R. Veres, Carsten Warneke
Isoprene oxidation schemes vary greatly among gas-phase chemical mechanisms, with potentially significant ramifications for air quality modeling and interpretation of satellite observations in biogenic-rich regions. In this study, in situ observations from the 2013 SENEX mission are combined with a constrained 0-D photochemical box model to evaluate isoprene chemistry among five commonly used gas-phase chemical mechanisms: CB05, CB6r2, MCMv3.2, MCMv3.3.1, and a recent version of GEOS-Chem. Mechanisms are evaluated and inter-compared with respect to formaldehyde (HCHO), a high-yield product of isoprene oxidation. Though underestimated by all considered mechanisms, observed HCHO mixing ratios are best reproduced by MCMv3.3.1 (normalized mean bias = −15%), followed by GEOS-Chem (−17%), MCMv3.2 (−25%), CB6r2 (−32%) and CB05 (−33%). Inter-comparison of HCHO production rates reveals that major restructuring of the isoprene oxidation scheme in the Carbon Bond mechanism increases HCHO production by only ∼5% in CB6r2 relative to CB05, while further refinement of the complex isoprene scheme in the Master Chemical Mechanism increases HCHO production by ∼16% in MCMv3.3.1 relative to MCMv3.2. The GEOS-Chem mechanism provides a good approximation of the explicit isoprene chemistry in MCMv3.3.1 and generally reproduces the magnitude and source distribution of HCHO production rates. We analytically derive improvements to the isoprene scheme in CB6r2 and incorporate these changes into a new mechanism called CB6r2-UMD, which is designed to preserve computational efficiency. The CB6r2-UMD mechanism mimics production of HCHO in MCMv3.3.1 and demonstrates good agreement with observed mixing ratios from SENEX (−14%). Improved simulation of HCHO also impacts modeled ozone: at ∼0.3 ppb NO, the ozone production rate increases ∼3% between CB6r2 and CB6r2-UMD, and rises another ∼4% when HCHO is constrained to match observations.



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Effects of Three Different Chair-Based Exercise Programs on People Older Than 80 Years

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2rJK3VD

Neuromuscular Electrical Stimulation Combined with Protein Ingestion Preserves Thigh Muscle Mass But Not Muscle Function in Healthy Older Adults During 5 Days of Bed Rest

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2stMkkJ

Lifecourse Adversity and Telomere Length in Older Women from Northeast Brazil

Rejuvenation Research , Vol. 0, No. 0.


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It Is Time to End the Dualistic Short Versus Long Duration of Dual Antiplatelet Therapy Debates.

Author: Levine, Glenn N. MD; Bates, Eric R. MD

Page: 2451-2453

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Optimizing a Drone Network to Deliver Automated External Defibrillators.

Author: Boutilier, Justin J. BSc; Brooks, Steven C. MD; Janmohamed, Alyf; Byers, Adam MDEM; Buick, Jason E. MSc; Zhan, Cathy MSc; Schoellig, Angela P. PhD; Cheskes, Sheldon MD; Morrison, Laurie J. MD; Chan, Timothy C. Y. PhD; On behalf of the Rescu Epistry Investigators

Page: 2454-2465

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Drone-Based Automatic External Defibrillators for Sudden Death?: Do We Need More Courage or More Serenity?.

Author: Mark, Daniel B. MD, MPH; Hansen, Steen M. MD; Starks, Monique L. MD; Cummings, Mary L. PhD

Page: 2466-2469

http://ift.tt/2rxRevM

Thresholds for Ambulatory Blood Pressure Among African Americans in the Jackson Heart Study.

Author: Ravenell, Joseph MD, MS; Shimbo, Daichi MD; Booth, John N. III MS; Sarpong, Daniel F. PhD; Agyemang, Charles MPH, PhD; Beatty Moody, Danielle L. PhD; Abdalla, Marwah MD, MPH; Spruill, Tanya M. PhD; Shallcross, Amanda J. ND, MPH; Bress, Adam P. PharmD, MS; Muntner, Paul PhD; Ogedegbe, Gbenga MD, MS, MPH

Page: 2470-2480

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Defining Ambulatory Blood Pressure Thresholds for Decision Making in Hypertension: The Effect of Race and Methodology.

Author: Stergiou, George S. MD, PhD; Ntineri, Angeliki MD, MSc; Kollias, Anastasios MD, PhD

Page: 2481-2484

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Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplantation.

Author: Flyer, Jonathan N. MD; Zuckerman, Warren A. MD; Richmond, Marc E. MD, MS; Anderson, Brett R. MD, MBA, MS; Mendelsberg, Tamar G. BSN, RN, MS, FNP; McAllister, Jennie M. BA; Liberman, Leonardo MD; Addonizio, Linda J. MD; Silver, Eric S. MD

Page: 2485-2493

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Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

Author: Khera, Amit V. MD *; Demler, Olga V. PhD *; Adelman, Steven J. PhD; Collins, Heidi L. PhD; Glynn, Robert J. PhD; Ridker, Paul M MD, MPH; Rader, Daniel J. MD; Mora, Samia MD, MHS

Page: 2494-2504

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SOX17 Regulates Conversion of Human Fibroblasts Into Endothelial Cells and Erythroblasts by Dedifferentiation Into CD34+ Progenitor Cells.

Author: Zhang, Lianghui MD, PhD; Jambusaria, Ankit BS; Hong, Zhigang MD, PhD; Marsboom, Glenn PhD; Toth, Peter T. PhD; Herbert, Brittney-Shea PhD; Malik, Asrar B. PhD; Rehman, Jalees MD

Page: 2505-2523

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A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative.

Author: Hess, Connie N. MD, MHS; Norgren, Lars MD, PhD; Ansel, Gary M. MD; Capell, Warren H. MD; Fletcher, John P. MD, MS; Fowkes, F. Gerry R. PhD; Gottsater, Anders MD, PhD; Hitos, Kerry BSc, PhD; Jaff, Michael R. DO; Nordanstig, Joakim MD, PhD; Hiatt, William R. MD

Page: 2534-2555

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P2X7 Deficiency Blocks Lesional Inflammasome Activity and Ameliorates Atherosclerosis in Mice.

Author: Stachon, Peter MD *; Heidenreich, Adrian MS *; Merz, Julian MSc; Hilgendorf, Ingo MD; Wolf, Dennis MD; Willecke, Florian MD; von Garlen, Sunaina MS; Albrecht, Philipp MS; Hardtner, Carmen PhD; Ehrat, Nicolas MSc; Hoppe, Natalie BSc; Reinohl, Jochen MD; von zur Muhlen, Constantin MD; Bode, Christoph MD; Idzko, Marco MD +; Zirlik, Andreas MD +

Page: 2524-2533

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Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement From the American Heart Association.

Author: Cook, Jennifer L. MD, FAHA, Chair; Colvin, Monica MD, FAHA, Co-Chair; Francis, Gary S. MD, FAHA; Grady, Kathleen L. PhD, RN, MS, FAHA; Hoffman, Timothy M. MD, FAHA; Jessup, Mariell MD, FAHA; John, Ranjit MD; Kiernan, Michael S. MD, FAHA; Mitchell, Judith E. MD, FAHA; Pagani, Francis D. MD, PhD, FAHA; Petty, Michael PhD, RN; Ravichandran, Pasala MD; Rogers, Joseph G. MD, FAHA; Semigran, Marc J. MD, FAHA; Toole, J. Matthew MD, FAHA; On behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; and Council on Cardiovascular Surgery and Anesthesia

Page: e1145-e1158

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2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Author: Nishimura, Rick A. MD, MACC, FAHA, Co-Chair; Otto, Catherine M. MD, FACC, FAHA, Co-Chair; Bonow, Robert O. MD, MACC, FAHA +; Carabello, Blase A. MD, FACC *+; Erwin, John P. III MD, FACC, FAHA +; Fleisher, Lee A. MD, FACC, FAHA ++; Jneid, Hani MD, FACC, FAHA, FSCAI [S]; Mack, Michael J. MD, FACC *%7c%7c; McLeod, Christopher J. MBChB, PhD, FACC, FAHA +; O'Gara, Patrick T. MD, MACC, FAHA +; Rigolin, Vera H. MD, FACC [P]; Sundt, Thoralf M. III MD, FACC *#; Thompson, Annemarie MD **

Page: e1159-e1195

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Highlights From the Circulation Family of Journals.

Author:

Page: 2556-2561

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Coverage and Cardioprotective Benefits of PCSK9 Take Center Stage at the American College of Cardiology Meeting.

Author: Kuehn, Bridget M.

Page: 2562-2563

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Out-of-Hospital Cardiac Arrest: An Underlying Reversible Cause.

Author: Robert, Jimmy MD; Derkenne, Clement MD; Jost, Daniel MD; Tourtier, Jean-Pierre PhD

Page: 2564-2566

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Of a Tortuous Nature: An Unusual Cause of Peripartum Congestive Heart Failure.

Author: Rubin, Geoffrey Allan MD; Grinspan, Lauren Tal MD, PhD; Ginns, Jonathan MD

Page: 2567-2571

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Estimation of Eligibility for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Associated Costs Based on the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk): Insights From the Department of Veterans Affairs.

Author: Virani, Salim S. MD, PhD; Akeroyd, Julia M. MPH; Nambi, Vijay MD, PhD; Heidenreich, Paul A. MD, MS; Morris, Pamela B. MD; Nasir, Khurram MD; Michos, Erin D. MD, MHS; Bittner, Vera A. MD, MSPH; Petersen, Laura A. MD, MPH; Ballantyne, Christie M. MD

Page: 2572-2574

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Early Myocardial Strain Changes During Potentially Cardiotoxic Chemotherapy May Occur as a Result of Reductions in Left Ventricular End-Diastolic Volume: The Need to Interpret Left Ventricular Strain With Volumes.

Author: Jordan, Jennifer H. PhD; Sukpraphrute, Bunyapon MD; Melendez, Giselle C. MD; Jolly, Marie-Pierre PhD; D'Agostino, Ralph B. Jr PhD; Hundley, W. Gregory MD

Page: 2575-2577

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Letter by Barakat et al Regarding Article, "Implantable Cardioverter-Defibrillator for Nonischemic Cardiomyopathy: An Updated Meta-Analysis".

Author: Barakat, Amr F. MD; Saad, Marwan MD, PhD; Elgendy, Islam Y. MD

Page: e1196-e1197

http://ift.tt/2rxedqQ

Letter by Nery et al Regarding Article, "Implantable Cardioverter-Defibrillator for Nonischemic Cardiomyopathy: An Updated Meta-Analysis".

Author: Nery, Pablo B. MD; Lewis, Krystina B. RN, PhD(c); Birnie, David H. MBChB, MD

Page: e1198-e1199

http://ift.tt/2sQyKKP

Enhancing sensitivity of pH-weighted MRI with combination of amide and guanidyl CEST

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Tao Jin, Ping Wang, T. Kevin Hitchens, Seong-Gi Kim
Amide-proton-transfer weighted (APTw) MRI has emerged as a non-invasive pH-weighted imaging technique for studies of several diseases such as ischemic stroke. However, its pH-sensitivity is relatively low, limiting its capability to detect small pH changes. In this work, computer simulations, protamine phantom experiments, and in vivo gas challenge and experimental stroke in rats showed that, with judicious selection of the saturation pulse power, the amide-CEST at 3.6ppm and guanidyl-CEST signals at 2.0ppm changed in opposite directions with decreased pH. Thus, the difference between amide-CEST and guanidyl-CEST can enhance the pH measurement sensitivity, and is dubbed as pHenh. Acidification induced a negative contrast in APTw, but a positive contrast in pHenh. In vivo experiments showed that pHenh can detect hypercapnia-induced acidosis with about 3-times higher sensitivity than APTw. Also, pHenh slightly reduced gray and white matter contrast compared to APTw. In stroke animals, the CEST contrast between the ipsilateral ischemic core and contralateral normal tissue was −1.85 ± 0.42% for APTw and 3.04 ± 0.61% (n = 5) for pHenh, and the contrast to noise was 2.9 times higher for pHenh than APTw. Our results suggest that pHenh can be a useful tool for non-invasive pH-weighted imaging.



http://ift.tt/2sJrFLG

Cyclooxygenase-2 inhibitors and free flap complications after autologous breast reconstruction, a retrospective cohort study

A key component of modern analgesics is the use of multimodal opioid sparing analgesia (MOSA). In the past, our analgesic regime after autologous breast reconstruction (ABR) included either NSAID or a selective cyclooxygenase-2 inhibitor (COX-2). COX-2 inhibitors could be superior to NSAID due to the well-known side effects from NSAID (bleeding/gastrointestinal ulcers). However, COX-2 inhibitors have been suggested to increase flap failure rates. We report our experience with using COX-2 inhibitors as part of our postoperative MOSA after ABR using free flaps.

http://ift.tt/2tHjPzi

Elucidating the interactions between individual differences and noninvasive brain stimulation effects in visual working memory by using tDCS, tACS and EEG

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Chi-Hung Juan, Wei-Kuang Liang, Neil G. Muggleton, Philip Tseng, Tzu-Yu Hsu




http://ift.tt/2sQPTnA

Editorial Board

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





http://ift.tt/2rxJj1o

E-meditation: A novel paradigm using tDCS to enhance mindfulness meditation

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Bashar W. Badran, Chris W. Austelle, Nicole R. Smith, Chloe E. Glusman, Brett Froeliger, Eric L. Garland, Jeffrey J. Borckardt, Mark S. George, Baron Short




http://ift.tt/2sQIS6p

Table of Contents

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





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Information for Authors

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





http://ift.tt/2sQnqhG

Transcranial Direct Current Stimulation and Mobility Functioning in Older Adults with Knee Osteoarthritis Pain: A Double-Blind, Randomized, Sham-Controlled Pilot Clinical Study

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Hyochol Ahn, Adam J. Woods, Eunyoung Choi, Nikhil Padhye, Roger Fillingim




http://ift.tt/2rxbBZX

Individual Differences in tDCS Augmented Working Memory Training

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Benjamin Katz, Jacky Au, Martin Buschkuehl, Tessa Abagis, Chelsea Zabel, Susanne M. Jaeggi, John Jonides




http://ift.tt/2sQo8fb

Masthead

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





http://ift.tt/2rxlvuK

The Effects of High Definition Transcranial Direct Current Stimulation (HD-tDCS) on Memory and Metamemory by Task Difficulty

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Sandry Garcia, Rifat Ahmed, Elizabeth F. Chua




http://ift.tt/2sQpiqP

tDCS metaplasticity and astrocytic calcium in mice

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Hajime Hirase, Hiromu Monai




http://ift.tt/2rxsaVQ

Feasibility and Dose Tolerability of High Definition Transcranial Direct Current Stimulation in healthy adults

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Christopher A. Turski, Alanna Kessler-Jones, Bruce Hermann, David Hsu, Jana Jones, Susanne Seeger, Rick Chappell, Chrysanthy Ikonomidou




http://ift.tt/2sQF4SK

Off-line rTMS of left Dorsolateral Prefrontal Cortex reduces food cravings in females but not males

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Valentina Cazzato, Huw Williams, Stergios Makris




http://ift.tt/2rxfHkZ

Repetitive Transcranial Magnetic Stimulation in Oromandibular Dystonia

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Noriyuki Narita, Kazunobu Kamiya, Tomohhiro Ishii, Teruyasu Hirayama




http://ift.tt/2sQvjUg

Do rTMS and tDCS really affect synaptic plasticity?

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): J.C. Rothwell




http://ift.tt/2rxbzRP

Control of Rhythmic Neural Activity with Periodic Stimulation: Computational Insights

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Iman Kamali Sarvestani, Jérémie Lefebvre




http://ift.tt/2sQgaCx

Electroconvulsive therapy in a patient with left ventricular assist device following deliberate disconnection of the device driveline

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): M. Augustin, C.S. Bruells, A. Moza, B. Gillmann, L. Mevissen, M. Grözinger




http://ift.tt/2rxraAT

The effect of tDCS and phonemic decoding ability on learning to read

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Jessica Wise Younger, James R. Booth




http://ift.tt/2rxkOl9

A case of coenesthetic hallucinations treated with low-frequency repetitive transcranial magnetic stimulation

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Allam Nasser, Juliana Sousa Batista, Pedro Brandão, Talyta Grippe




http://ift.tt/2sQxQ0Y

The current level of evidence for using transcranial direct current stimulation (tDCS) to improve naming ability in post-stroke aphasia: a critical review

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Mohammed F. ALHarbi, Susan Armijo-Olivo, Esther S. Kim




http://ift.tt/2rxs4gW

Direct current stimulation modulates LTP and LTD: activity dependence and dendritic effects

Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Greg Kronberg, Morgan Bridi, Ted Abel, Marom Bikson, Lucas C. Parra




http://ift.tt/2sQ1pzI

Size partitioning and mixing behavior of trace metals and dissolved organic matter in a South China estuary

Publication date: 15 December 2017
Source:Science of The Total Environment, Volumes 603–604
Author(s): Wenhao Wang, Min Chen, Laodong Guo, Wen-Xiong Wang
The Jiulong River estuary, located in the southeastern China, suffered from metal pollution due to industrial effluent releases. Mixing of effluent and estuarine water may have significantly affected the size distribution of trace metals and their environmental fate. In the present study, colloidal size distribution of organic matter and selected metals were quantified using asymmetric flow field-flow fractionation (AF4) and ICP-MS. We demonstrated a dominance of dissolved metals in the 1–10kDa fraction, and metals such as Cu, Zn, Ni, Co, Pb, Cd and Mn were mostly regulated by terrestrial fulvic acid. The larger inorganic colloids played a limited role, although Fe reduction was likely to affect the size partitioning of colloidal Mn. The holding pond represented a source of trace metals and chromophoric and humic-like dissolved organic matter to the estuary. Scavenging or removal behavior became evident following the intermittent mixing, and the small sized colloidal organic complexes were responsible for binding and stabilizing trace metals. Variations in particle size distributions indicated different sources, fates and geochemical controls of the metals. Our results highlighted the impacts of both natural and anthropogenic processes on the transformation of trace metals among phases in this dynamic estuary system.

Graphical abstract

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Editorial board

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4





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Accelerated Lymph Flow in Early-Stage Secondary Lymphedema Detected by Indocyanine Green Fluorescence Lymphography

J reconstr Microsurg
DOI: 10.1055/s-0037-1603740

Background The purpose of this study was to evaluate the lymph function of the lower extremities and to identify early symptoms of lymph dysfunction in secondary lymphedema by observing lymph flow with indocyanine green (ICG) fluorescence lymphography (LG). Methods We retrospectively evaluated the lymph flow of 108 limbs in 54 female patients with leg lymphedema secondary to pelvic lymphadenectomy for gynecological carcinoma and 14 limbs in 7 female controls without a history of pelvic lymphadenectomy or radiotherapy. ICG was injected into four points at the distal part of the lower extremity. Lymph flow was evaluated by measuring the proximal point where the ICG could be observed 5 minutes after rest and 15 minutes after a walking exercise. Results In the controls, lymph flow was stable at rest and was well enhanced by exercise. In patients with early-stage lymphedema, lymph flow was already enhanced at rest (p = 0.005) and was further enhanced by exercise. In advanced-stage lymphedema, lymph flow was not enhanced, even by exercise (p = 0.001). Conclusion ICG-LG could evaluate lymph flow and functions of lymph systems and detect accelerated lymph flow in early-stage secondary lymphedema. Detecting accelerated lymph flow may facilitate early detection and treatment of secondary lymphedema.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2sMoqnE

Early Markers of Angiogenesis and Ischemia during Bowel Conduit Neovascularization

J reconstr Microsurg
DOI: 10.1055/s-0037-1603905

Background Bowel flaps are a good and reliable method to restore the continuity of the aerodigestive tract. Radiated fields, contaminated recipient sites, or depleted recipient vessels may increase the risk for ischemic injury after transfer. During ischemic events, we believe that bowel conduits with serosa have a delayed neovascularization process at its new recipient site.We conducted an ischemia/reperfusion murine model to understand the difference among bowel conduits with and without serosa. Materials and Methods Two groups of rats were compared: control group (jejunal conduit with serosa) and a target group (jejunal conduit without serosa). These conduits were harvested from the peritoneal cavity and transferred into a subcutaneous pocket. After 72 hours of transfer and pedicle ligation, histological changes related to ischemia/reperfusion were assessed. In addition, tissue markers of angiogenesis (CD34), ischemia (lactate dehydrogenase [LDH]), and inflammation (interleukin [IL]-1β and IL-6) were analyzed. Results Two groups (n = 20) of male rats were analyzed. Histology showed intact jejunal mucosa in the target group. The control group showed decreased number of mucin, globet cells, decreased height, and fragmentation of villi with the absence of intestinal glands. Markers of angiogenesis (CD34) were higher in the target group. In addition, markers of ischemia (LDH) (p = 0.0045) and inflammation (IL-1b, p = 0.0008, and IL-6, p = 0.0008) were significantly lower in the target group as compared with the control group. Conclusions In circumstances in which the recipient site does not offer an adequate and healthy bed or a vascular insult occurs, bowel flaps with less amount of serosa may be able to neovascularize faster thereby increasing its chances of survival.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2sMf5Mj

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease

Summary

Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing's syndrome and only a few cases have been reported in the literature. Differentiating between Cushing's disease and ectopic Cushing's syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing's disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing's syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing's disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing's disease.

Learning points:

The discrimination between a Cushing's disease and ectopic Cushing's syndrome is challenging and has many caveats.

Ectopic ACTH/CRH co-secreting tumors are very rare.

Dynamic tests as well as BIPSS may be compatible with Cushing's disease in ectopic CRH-secretion.

High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.

Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing's syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing's syndrome and lead to further investigations.

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A comparative study of hospital admissions for respiratory diseases during normal and dusty days in Iran

Abstract

During the last century, most of people around the world moved from communicable to non-communicable diseases, mainly due to air pollution. Air pollutants and dust storm increase risk of morbidity, for cardiovascular and respiratory diseases, and increase the number of deaths. The city of Ahvaz is considered as the focal point of air pollution and dust storm in Iran. The aim of this study was to determine the number of Hospital Admission Respiratory Disease (HARD) including asthma attacks, acute bronchitis and chronic obstructive pulmonary disease attributed to PM₁₀ by a descriptive study during normal and dust event days in Ahvaz during the time period 2010–2012. The hourly PM₁₀ data was collected from the Iranian Environmental Protection Agency and Razi hospital. The annual PM₁₀ mean concentrations reached 282, 288 and 278 μg/m³ in 2010, 2011 and 2012, respectively. The number of HARD attributed to PM₁₀ was 1438, 1945 and 1393 people, respectively, and the highest number of daily admissions was attributed to the highest daily PM₁₀ concentration in Ahvaz. The average number of daily HARD during dusty days was higher than normal days, and a significant positive correlation, between the number of hospital admissions and dusty days, was found. Dust had significant impact on HARD in Ahvaz.

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Toxicity of cypermethrin on the embryo and larvae of Gangetic mystus, Mystus cavasius

Abstract

The objective of the present study was to elucidate the effects of cypermethrin on the embryo and the larvae of Gangetic mystus, Mystus cavasius. Therefore, fertilized eggs (n = 100) and 1-day-old larvae (n = 100) were exposed to six different concentrations of cypermethrin (0, 2, 4, 8, 16 and 32 μg L⁻¹) in each of the 18 plastic bowls. Each of the treatment and control was maintained in three replicates. The LC₁₀ and LC₅₀ values for Gangetic mystus embryos and larvae were calculated using probit analysis. Results showed the mortality of embryos significantly increased with increasing cypermethrin concentrations. The 24-h LC₁₀ and LC₅₀ (with 95% confidence interval) values of cypermethrin for embryo were 0.42 (0.14–0.81) and 5.60 (4.16–7.19) μg L⁻¹, respectively. Hatching success decreased and mortality of larvae increased significantly with increasing cypermethrin concentrations. The 24-h LC₁₀ and LC₅₀ values (with 95% confidence limits) of cypermethrin for larvae were 1.72 (1.24–2.20) and 11.57 (10.09–13.42) μg L⁻¹, respectively; the 48-h LC₁₀ and LC₅₀ for larvae were 1.34 (0.83–1.89) and 8.25 (6.87–9.91) μg L⁻¹, respectively; the 72-h LC₁₀ and LC₅₀ for larvae were 1.13 (0.63–1.66) and 6.12 (4.91–7.47) μg L⁻¹, respectively. Furthermore, results showed several malformations in embryos and larvae when exposed to the two highest concentrations of cypermethrin. The findings of the study suggest that 2 μg L⁻¹ cypermethrin concentration in the aquatic environment may have deleterious effects on the development and the reproduction of Gangetic mystus.

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ASCIZ/ATMIN is dispensable for ATM signaling in response to replication stress

Publication date: Available online 17 June 2017
Source:DNA Repair
Author(s): Rui Liu, Ashleigh King, Nicolas C. Hoch, Catherine Chang, Gemma L. Kelly, Andrew J. Deans, Jörg Heierhorst
The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was unaffected in both immortalized and primary ASCIZ/ATMIN-deficient murine embryonic fibroblasts compared to control cells. Similar results were also obtained in human ASCIZ/ATMIN-deleted lymphoma cells. The results demonstrate that ASCIZ/ATMIN is dispensable for ATM activation, and contradict the previously reported dependence of ATM on ASCIZ/ATMIN.



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Artery first approach for resecting ganglioneuroma encasing superior mesenteric artery

Publication date: Available online 17 June 2017
Source:Medical Journal Armed Forces India
Author(s): Jayant Kumar Banerjee, Ramanathan Saranga Bharathi, Rajat Jagani, Giriraj Singh




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Functional outcome after arthroscopic management of traumatic recurrent dislocation shoulder using Bankart repair and Remplissage techniques

Publication date: Available online 17 June 2017
Source:Medical Journal Armed Forces India
Author(s): Munish Sood, Amresh Ghai
BackgroundRecurrent dislocation shoulder is one of the common shoulder injuries encountered by the orthopedic surgeon in clinical practice. Bankart repair using the arthroscopic method has become one of the standard techniques in the management of recurrent dislocation shoulder. Remplissage technique can be used as adjunct to Bankart repair in certain conditions.MethodIn this case series, we have assessed the functional outcome and return to activity at midterm follow-up after arthroscopic management.Results51 patients with traumatic shoulder dislocation were operated using the shoulder arthroscopic technique. Rowe score improved significantly at the latest follow-up. No major complication was noticed in our case series.ConclusionThe shoulder arthroscopy procedure requires special instrumentation and expertise. We believe that this is a less invasive and safe procedure and provides an additional tool in the management of instabilities including in cases of complex recurrent dislocation of the shoulder.



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The psychological morbidity in the long term after war related bilateral lower limb amputation

Publication date: Available online 17 June 2017
Source:Medical Journal Armed Forces India
Author(s): Batool Mousavi, Mehdi Masoumi, Mohammadreza Soroush, Shekoufe Shahriar, Ali Firoozabadi
BackgroundTo determine the psychological morbidity in the long term after war related bilateral lower limb amputation.MethodsMental health status was determined by the Symptom Checklist-90-R (SCL-90-R) and a structured psychiatrist interview using Structured Clinical Interview for DSM Disorders-IV (SCID-IV) in 327 male amputees. The survey was 22.3 (SD=3.9) years after amputation. A one-sample t-test was conducted to compare our results with a survey carried out in a rural Iranian population.ResultsThe mean age of the participants was 42 years (SD=6.3). Only 22 persons had psychiatric diagnosis and were under treatment. The most common problems on SCL-90-R were somatization, obsessive-compulsive, interpersonal sensitivity, anxiety, and depression. Global severity index (GSI) of the bilateral lower limb amputees (BLLA) (0.88±0.63) was significantly higher than Iranian population (0.35±0.28) (p<0.001). BLLA had significantly higher scores in all subscales of Scl-90-R compared with general population (p<0.001). Of the total amputees about 39.1% (128 out 327) diagnosed with at least one psychiatric disorder in psychiatrist interview. About 83.9% (N=115) of the psychiatrist diagnosed disorders were new cases. Mood disorders 37.3% (depression 28.7%) and anxiety disorders 12.2% (obsessive compulsive disorder 9.8%) were the most common disorders in the study group. There was not any relationship between demographic variables and mental disorder (p>0.05).ConclusionThe high prevalence and especially the large proportion of undiagnosed mental disorders high-light the need for targeted and appropriate psychological interventions in this vulnerable population.



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Brain stem death certification protocol

Publication date: Available online 17 June 2017
Source:Medical Journal Armed Forces India
Author(s): Vikas Srivastava, Monish Nakra, Anand Shankar K., Pawan Dhull, R. Ramprasad, N.S. Lamba
Transplantation of Human Organs is guided by laid down specific Laws in India. The organs which are targeted to be transplanted are liver, kidney and cornea. The waiting list is enormous but the donor pool is meagre. This document has been made with a view that the donor pool can be enlarged by identifying patients who are 'Brain Dead' while still not having 'Cardiac Death'. The steps include the prerequisite conditions which must be satisfied by patients who have suspicion of being brain dead, detailed examination of the patient, confirmation of the Brain Death and Counselling of the relatives for organ donation.



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Family food talk, child eating behavior, and maternal feeding practices

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Elizabeth Roach, Gail B. Viechnicki, Lauren B. Retzloff, Pamela Davis-Kean, Julie C. Lumeng, Alison L. Miller
Families discuss food and eating in many ways that may shape child eating habits. Researchers studying how families talk about food have examined this process during meals. Little work has examined parent-child food-related interactions outside of mealtime. We assessed family food talk at home outside of mealtime and tested whether food talk was associated with obesogenic child eating behaviors, maternal feeding practices, or child weight. Preschool and school-aged mother-child dyads (n = 61) participated in naturalistic voice recording using a LENA (Language ENvironment Analysis) recorder. A coding scheme was developed to reliably characterize different types of food talk from LENA transcripts. Mothers completed the Children's Eating Behavior Questionnaire (CEBQ) and Child Feeding Questionnaire (CFQ) to assess child eating behaviors and maternal feeding practices. Child weight and height were measured and body mass index z-score (BMIz) calculated. Bivariate associations among food talk types, as a proportion of total speech, were examined and multivariate regression models used to test associations between food talk and child eating behaviors, maternal feeding practices, and child BMIz. Proportion of child Overall Food Talk and Food Explanations were positively associated with CEBQ Food Responsiveness and Enjoyment of Food (p's < 0.05). Child food Desire/Need and child Prep/Planning talk were positively associated with CEBQ Enjoyment of Food (p < 0.05). Child Food Enjoyment talk and mother Overt Restriction talk were positively associated with CEBQ Emotional Over-Eating (p < 0.05). Mother Monitoring talk was positively associated with CFQ Restriction (p < 0.05). Mother Prep/Planning talk was negatively associated with child BMIz. Food talk outside of mealtimes related to child obesogenic eating behaviors and feeding practices in expected ways; examining food talk outside of meals is a novel way to consider feeding practices and child eating behavior.



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A walnut-containing meal had similar effects on early satiety, CCK, and PYY, but attenuated the postprandial GLP-1 and insulin response compared to a nut-free control meal

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Cheryl L. Rock, Shirley W. Flatt, Hava-Shoshana Barkai, Bilge Pakiz, Dennis D. Heath
Regular nut consumption is associated with lower adiposity and reduced weight gain in adulthood. Walnut feeding studies have observed minimal effect on body weight despite potential additional energy intake. Several mechanisms may explain why consuming nuts promotes weight control, including increased early phase satiety, possibly reflected in postprandial response of gastrointestinal and pancreatic peptides hypothesized to affect appetite. The purpose of this study was to compare postprandial insulin, glucagon and gastrointestinal peptide response and satiety following a meal with ∼54% of energy from walnuts or cream cheese, using a within-subject crossover study design in overweight/obese adults (N = 28). Sixty minutes after the walnut-containing meal, glucagon-like peptide-1 was lower than after the reference meal (p=0.0433), and peptide YY, cholecystokinin and ghrelin did not differ after the two meals. Sixty and 120 min after the walnut-containing meal, pancreatic polypeptide (p = 0.0014 and p = 0.0002) and glucose-dependent insulinotropic peptide (p < 0.0001 and p = 0.0079) were lower than after the reference meal, and 120 min after the walnut-containing meal, glucagon was higher (p=0.0069). Insulin and C-peptide increased at 60 min in response to both meals but were lower at 120 min after the walnut-containing meal (p=0.0349 and 0.0237, respectively). Satiety measures were similar after both meals. These findings fail to support the hypothesis that acute postprandial gastrointestinal peptide response to a walnut-containing meal contributes to increased satiety. However, inclusion of walnuts attenuated the postprandial insulin response, which may contribute to the more favorable lipid profile observed in association with regular walnut consumption.



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Incentivizing healthy eating in children: An investigation of the “ripple” and “temporal” effects of a reward-based intervention

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Saied Toossi
Although previous studies have established the effectiveness of using small reward-based incentives in inducing the choice and consumption of healthier foods among children, little is known about their impact outside of experimental settings or their effectiveness over time when administered daily. This paper presents the results of a field experiment conducted to provide insight on these matters. The study employs a removed treatment within-subject design and was conducted at a summer program catering to low-income children between the ages of 5 and 12. The month long experiment—wherein participants were offered a small prize for choosing a fruit cup for dessert after lunch in lieu of cookies—involved 23 children between the ages of 5 and 8. Corroborating existing studies, the introduction of small reward-based incentives in this context was found to induce large increases in the number of children choosing the healthy dessert options after lunch, but disaggregating the results by week and day suggests that their impact diminished over time. Attempts to ascertain their effect outside of experimental settings did not indicate that the introduction of rewards had any adverse effects, but also did not provide definitive conclusions.



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Educational nutrition messaging at breakfast reduces snack intake and influences snack preferences in adult men and women

Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Jamie I. Baum, Brianna L. Gaines, Gabrielle C. Kubas, Charlayne F. Mitchell, Sarah L. Russell
Breakfast skipping is associated with increased risk of weight gain and obesity in young adults, possibly due to increased snacking later in the day. Recent research suggests that providing and animal versus a plant source of protein at breakfast can reduce snack intake later in the day. In addition, providing nutrition information via a nutrition label, front-of-pack information, or via text messaging has been shown to help individuals make healthier food choices. The objective of this study was to determine if educational nutrition messaging and protein source influenced snack intake 2 h following the breakfast meal. Participants (n = 33) were randomly assigned to one of two groups: educational nutrition messaging (EM; n = 16) or no messaging (NM; n = 17) group. The study was conducted using a randomized, cross-over design in which each participant received each of two breakfast beverages, whey protein- (WP) and pea protein (PP)- based. Appetite was assessed at 0, 15, 30, 60, 90, and 120 min after each test breakfast using visual analog scales. Participants were then provided with a selection of healthy and unhealthy snacks for 60 min. There was no effect of protein source on appetite or snack intake. However, participants presented with EM had reduced snack intake over the snacking period compared to NM (P = 0.058) and, of the snacks consumed, the EM group consumed a higher percentage of healthy versus unhealthy snacks compared to NM (P < 0.0001), resulting in lower calorie intake. Taken together these data suggest that protein source, as part of a higher protein breakfast, does not affect appetite response or snack intake, but EM may help play a role in reducing snack intake between meals.



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Effect of Endothelin-1 on proliferation, migration and fibrogenic gene expression in human RPE cells

Publication date: Available online 17 June 2017
Source:Peptides
Author(s): Dong Qin, Li Zhang, Xuemin Jin, Zhaoxia Zhao, Yanrong Jiang, Zijun Meng
The pathology of the fibrotic proliferative vitreoretinopathy (PVR) membrane represents an excessive wound healing response characterised by cells' proliferation, migration and secretion of extracellular matrix molecules (ECMs). Retinal pigment epithelial (RPE) cells are a major cellular component of the fibrotic membrane. Endothelin-1 (ET-1) has been reported to be involved in the development of PVR in vivo research. However, little is known about the role of ET-1 in RPE cells in vitro. In the present study, we investigated the role of ET-1 in the proliferation, migration and secretion of ECMs (such as type I collagen and fibronectin) in RPE cells in vitro. Our results illustrated that ET-1 promoted the proliferation, migration and secretion of ECMs through the protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) signaling pathways in RPE cells in vitro. These findings strongly suggested that ET-1 may play a vital role in the development of PVR.



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Letter to Editor: “Intra-operative assessment of excised breast tumour margins using clear edge imaging device”

Publication date: Available online 19 June 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): A.S. Chekavar, A.K. Verma, A. Agarwal, S. Mayilvahanan, T. Sundarram, G. Johri, S. Bothra




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Novel FKRP mutations in a Japanese MDC1C sibship clinically diagnosed with Fukuyama congenital muscular dystrophy

Publication date: Available online 17 June 2017
Source:Brain and Development
Author(s): Mieko Yoshioka, Kazuhiro Kobayashi, Tatsushi Toda
IntroductionFukuyama congenital muscular dystrophy (FCMD), caused by fukutin mutations, is the most common form of Japanese CMD. We followed a Japanese CMD sibship without fukutin mutation, and herein identified new FKRP mutations causing MDC1C rarely reported in Oriental countries.PatientsTwo affected siblings, individuals 1 (I-1, male) and 2 (I-2, female), were born uneventfully to unaffected, non-consanguineous parents. Severe hypotonia was soon apparent and serum CK levels were elevated: I-1: 1025 IU/L (normal range <130 IU/L) and I-2: 5350 IU/L. I-1 had neither shown head control, nor said any words until he died of pneumonia at the age of 23months. I-2 learned to sit at 4years and 10months and spoke sentences at 6years and 5months. She had received respiratory support since 9years of age and died at 22years. Both showed a low-density area in the cerebral white matter on CT. MRI of I-2 revealed diffuse hyperintensity in the cerebral white matter on T2-WI, polymicrogyria over the frontal and parietal lobes, and disorganized folia and cysts in the cerebellum.Methods and resultsNext generation and Sanger sequencing were performed for I-2. Heterozygous FKRP mutations were identified in exon 4: c.1167_1168delGC, p.Gly391Leufs∗72 and c.501_502GT>CC, p.Arg167Ser, p.Cys168Arg.DiscussionRecently, fukutin and FKRP were identified as sequentially acting ribitol 5-phosphate transferases involved in the post-translational modification of α-dystroglycan. This may explain the clinical similarities between the two disorders.



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Impact of Changes in Consensus Diagnostic Recommendations on the Echocardiographic Prevalence of Diastolic Dysfunction

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Ideal Cardiovascular Health, Mortality, and Vascular Events in Elderly Subjects: The Three-City Study

AbstractBackground

The benefit of ideal cardiovascular health (CVH) on health-related outcomes in middle-aged patients is firmly established. In the growing elderly population, the high prevalence of comorbidities and medications for chronic diseases may offset such benefit.

Objectives

This study analyzed the association of ideal CVH with mortality, incident coronary heart disease, and stroke events in elderly individuals from the community.

Methods

Between 1999 and 2001, 9,294 men and women, noninstitutionalized and aged 65 years and over were examined, and thereafter followed up for the occurrence of vascular events and mortality within the Three-City Study. Hazard ratios (HRs) were estimated by Cox proportional hazard model and compared subjects with 3 to 4 and subjects with 5 to 7 ideal metrics with those with 0 to 2 ideal metrics, respectively.

Results

The mean age was 73.8 ± 5.3 years, and 36.7% were men. Only 5% of the participants had ≥5 metrics at the ideal level. After a median follow-up of 10.9 years and 8.6 years, respectively 1,987 deaths and 680 adjudicated coronary heart disease or stroke events had occurred. In multivariate analysis, the risk of mortality and of vascular events decreased across the categories of ideal metrics. In particular, in subjects with ≥5 metrics at the ideal level (compared with those with ≤2), there was a 29% (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.55 to 0.90) decreased risk of all-cause mortality and 67% (HR: 0.33; 95% CI: 0.19 to 0.57) for coronary heart disease and stroke combined (p for trend <0.001).

Conclusions

Even in the elderly, higher CVH status is highly beneficial regarding mortality and vascular event risks.

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HIV-1-Associated Atherosclerosis: Unraveling the Missing Link

Abstract

Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation. There is a pressing need to experimentally unravel the missing link between HIV and atherosclerosis. Understanding these mechanisms will help to better develop and design novel therapeutic interventions for the treatment of HIV-associated cardiovascular disease. HIV mainly infects T cells and macrophages resulting in the induction of oxidative and endoplasmic reticulum stress, the formation of the inflammasome, and the dysregulation of autophagy. These mechanisms may contribute to HIV-associated atherogenesis. In this review, we will summarize our current understanding and propose potential mechanisms of HIV-associated atherosclerosis.

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Low-Hanging Fruit for a Healthy Old Age

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Reply: The Feasibility of Transcatheter Mitral Valve Replacement for Patients With Symptomatic Mitral Regurgitation

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Hospitalization for Recently Diagnosed Versus Worsening Chronic Heart Failure: From the ASCEND-HF Trial

AbstractBackground

It is unclear how patients hospitalized for acute heart failure (HF) who are long-term chronic HF survivors differ from those with more recent HF diagnoses.

Objectives

The goal of this study was to evaluate the influence of HF chronicity on acute HF patient profiles and outcomes.

Methods

The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 hospitalized patients with acute HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. The present analysis compared patients according to duration of HF diagnosis before index hospitalization by using pre-specified cutoffs (0 to 1 month [i.e., "recently diagnosed"], >1 to 12 months, >12 to 60 months, and >60 months).

Results

Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (recently diagnosed, n = 1,536; >1 to 12 months, n = 1,020; >12 to 60 months, n = 1,653; and >60 months, n = 1,532). Across HF duration groups, mean age ranged from 64 to 66 years, and mean ejection fraction ranged from 29% to 32%. Compared with patients with longer HF duration, recently diagnosed patients were more likely to be women with nonischemic HF etiology, higher baseline blood pressure, better baseline renal function, and fewer comorbidities. After adjustment, compared with recently diagnosed patients, patients with longer HF duration were associated with more persistent dyspnea at 24 h (>1 to 12 months, odds ratio [OR]: 1.20; 95% confidence interval [CI]: 0.97 to 1.48; >12 to 60 months, OR: 1.34; 95% CI: 1.11 to 1.62; and >60 months, OR: 1.31; 95% CI: 1.08 to 1.60) and increased 180-day mortality (>1 to 12 months, hazard ratio [HR]: 1.89; 95% CI: 1.35 to 2.65; >12 to 60 months, HR: 1.82; 95% CI: 1.33 to 2.48; and >60 months, HR: 2.02; 95% CI: 1.47 to 2.77). The influence of HF duration on mortality was potentially more pronounced among female patients (interaction p = 0.05), but did not differ according to age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23).

Conclusions

In this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852)

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Effect of Changes in Visa Policies and Procedures on Fellows-in-Training and Early Career Cardiologists

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Acute Heart Failure: One Syndrome or Many?

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Reply: History Repeating? The Logics of History

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Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure

AbstractBackground

Acute heart failure (AHF) is a life-threatening disease requiring urgent treatment, including a recommendation for immediate initiation of loop diuretics.

Objectives

The authors prospectively evaluated the association between time-to-diuretic treatment and clinical outcome.

Methods

REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure) was a prospective, multicenter, observational cohort study that primarily aimed to assess the association between time to loop diuretic treatment and clinical outcome in patients with AHF admitted through the emergency department (ED). Door-to-furosemide (D2F) time was defined as the time from patient arrival at the ED to the first intravenous furosemide injection. Patients with a D2F time <60 min were pre-defined as the early treatment group. Primary outcome was all-cause in-hospital mortality.

Results

Among 1,291 AHF patients treated with intravenous furosemide within 24 h of ED arrival, the median D2F time was 90 min (IQR: 36 to 186 min), and 481 patients (37.3%) were categorized as the early treatment group. These patients were more likely to arrive by ambulance and had more signs of congestion compared with the nonearly treatment group. In-hospital mortality was significantly lower in the early treatment group (2.3% vs. 6.0% in the nonearly treatment group; p = 0.002). In multivariate analysis, earlier treatment remained significantly associated with lower in-hospital mortality (odds ratio: 0.39; 95% confidence interval: 0.20 to 0.76; p = 0.006).

Conclusions

In this prospective multicenter, observational cohort study of patients presenting at the ED for AHF, early treatment with intravenous loop diuretics was associated with lower in-hospital mortality. (Registry focused on very early presentation and treatment in emergency department of acute heart failure syndrome; UMIN000014105)

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JACC Instructions for Authors

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Door-to-Furosemide Therapy in the ED: New Quality Metric or Just a Piece of the Puzzle?

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The Continued Search for Physiological Pacing: Where Are We Now?

Abstract

Cardiac pacing is an effective treatment for patients with bradycardia due to sinus node dysfunction or atrioventricular block. Despite decades of technological advances, the optimal ventricular pacing site to mimic normal human ventricular physiology and best hemodynamic response remains elusive. Beginning with atrial synchronous right ventricular (RV) apical pacing, the search has continued through alternate RV pacing sites, minimizing RV pacing, biventricular pacing, left ventricular (LV) pacing, and His-bundle pacing. Understanding the deleterious effects of long-term RV apical pacing in vulnerable populations has created tremendous interest in alternate pacing options. This paper reviews the current status of available pacing options, with particular focus on His-bundle pacing. Permanent His-bundle pacing has emerged as the leading candidate for physiological pacing because it provides nearly normal electrical activation of both ventricles and thereby avoids ventricular dyssynchrony. Synchronized LV pacing, multisite LV pacing, and LV endocardial pacing offer promise as novel pacing options in select patients.

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Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents

AbstractBackground

Recent evidence suggests that bioresorbable vascular scaffolds (BVS) are associated with an excess of thrombotic complications compared with metallic everolimus-eluting stents (EES).

Objectives

This study sought to investigate the comparative effectiveness of the Food and Drug Administration–approved BVS versus metallic EES in patients undergoing percutaneous coronary intervention at longest available follow-up.

Methods

The authors searched MEDLINE, Scopus, and web sources for randomized trials comparing BVS and EES. The primary efficacy and safety endpoints were target lesion failure and definite or probable stent thrombosis, respectively.

Results

Seven trials were included: in sum, 5,583 patients were randomized to receive either the study BVS (n = 3,261) or the EES (n = 2,322). Median time of follow-up was 2 years (range 2 to 3 years). Compared with metallic EES, risk of target lesion failure (9.6% vs. 7.2%; absolute risk difference: +2.4%; risk ratio: 1.32; 95% confidence interval: 1.10 to 1.59; number needed to harm: 41; p = 0.003; I² = 0%) and stent thrombosis (2.4% vs. 0.7%; absolute risk difference: +1.7%; risk ratio: 3.15; 95% confidence interval: 1.87 to 5.30; number needed to harm: 60; p < 0.0001; I² = 0%) were both significantly higher with BVS. There were no significant differences in all-cause or cardiovascular mortality between groups. The increased risk for ST associated with BVS was concordant across the early (<30 days), late (30 days to 1 year), and very late (>1 year) periods (p_interaction = 0.49).

Conclusions

Compared with metallic EES, the BVS appears to be associated with both lower efficacy and higher thrombotic risk over time. (Bioresorbable vascular scaffold compare to everolimus stents in long term follow up; CRD42017059993).

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Subcutaneous Implantable Cardioverter-Defibrillator Implantation Without Defibrillation Testing

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First-Generation Bioresorbable Vascular Scaffolds: Disappearing Stents or Disappearing Evidence?

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History Repeating?: The Logics of History

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Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias

AbstractBackground

Cardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT).

Objectives

This study assessed the value of CSD and the characteristics associated with outcomes in this population.

Methods

Patients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD.

Results

Between 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided–only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up.

Conclusions

CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided–only procedure.

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