Precision medicine for early breast cancer radiotherapy: opening up new horizons?

Publication date: Available online 18 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jacques Bernier
So far most efforts put forth to test the value of predictive and prognostic tools in the field of breast radiotherapy remained globally disappointing, or at least below the convincing levels reached for systemic therapy. Nevertheless the addition of predictive tools to the clinical armament tends to prevail over the use of the sole prognostic factors, also in radiotherapy. A number of predictive assays, clinically validated or not, have recently elicited significant associations between molecular profiles and tumor biological aggressiveness and/or radiosensitivity levels. Will it take a long time for these radiation-specific assays to provide added value to the – already crowded – constellation of predictive tools in the breast cancer? On the one hand, optimizing radiotherapy through the integration of precision medicine into the breast cancer management still remains a challenging issue. On the other hand, recent advances in predictive assays aimed at distinguishing patients with a more radioresistant tumor that necessitates radiation dose escalation or a switch to therapeutic approaches other than radiotherapy, plea in favor of an increasing role, in a near future, for radiation-specific molecular signatures. Streamlining predictive assays platforms via concerted actions should imperatively be given high priority, also in terms of health economics.



http://ift.tt/2mMMC2h

Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials

Publication date: Available online 18 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Zhiqiang Sun, Fang Zheng, Suwan Wu, Yanjuan Liu, Hehe Guo, Yichen Liu
During the past decades, several prospective trials had been conducted to assess the efficacy and toxicities of triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma (RRMM), but the results were controversial. We thus performed a systematic literature search to identify relevant trials. Summary hazard ratios (HRs), relative risks (RRs), and 95% confidence intervals (95%CIs) were calculated. A total of 3197 RRMM patients were included for analysis. The pooled results demonstrated that triplet combination therapies significantly improve OS (HR 0.83, 95%CI: 0.71–0.94, p=0.004) and PFS (HR 0.68, 95%CI: 0.62–0.74, p<0.001). The pooled RRs of ORR, very good partial response (VGPR) and complete response (CR) with triplets vs. doublets were 1.19 (95%CI: 1.10–1.27), 1.44 (95%CI: 1.18–1.77), and 1.76 (95%CI: 1.04–2.97), respectively, indicating that the RRs of achieving deeper responses were higher with triplets, though the RRs of overall≥grade 3 adverse events (RR 1.11, p=0.001) and ≥grade 3 thrombocytopenia (RR 1.64, p=0.009) was higher with triplets. In conclusion, our meta-analysis demonstrated that triplet regimens result in improved OS, PFS, ORR, VGPR, and CR when compared to doublets, though the risk of grade 3 and 4 adverse events were higher with triplets.



http://ift.tt/2n6QC0d

Lymphoblastic lymphoma

Publication date: Available online 18 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sergio Cortelazzo, Andrés Ferreri, Dieter Hoelzer, Maurilio Ponzoni
Lymphoblastic lymphoma (LBL) is a neoplasm of immature B cells committed to the B-(B-LBL) or T-cell lineage (T-LBL) that accounts for approximately 2% of all lymphomas. Although histological features are usually sufficient to distinguish lymphoblastic from mature B- or T-cell neoplasms, of greater importance for diagnosis is the characterization of immunophenotype by flow cytometry. LBL occurs more commonly in children than in adults, mostly in males. A bone marrow involvement <25% (or 20% according to WHO) formally distinguishes LBL from ALL. The prognosis of LBL has dramatically improved with the use of intensive ALL-type chemotherapy regimens, which includes intensive intrathecal chemotherapy prophylaxis and consolidation with mediastinal irradiation. Patients with adverse prognostic features assessed by postinduction CT/positron emission tomography scans (PET) and minimal residual disease analysis (MRD) should be considered for high-dose chemotherapy and stem cell transplantation. Further therapeutic progresses are expected from the introduction of new drugs and targeting agents.



http://ift.tt/2mMD0ox

Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients

Publication date: Available online 16 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Giovanni Codacci-Pisanelli, Lino Del Pup, Maria Del Grande, Fedro A. Peccatori
Fertility preservation in breast cancer patients is an increasingly relevant topic. In the present paper we review available data on the mechanism of ovarian damage caused by anticancer agents currently used for the treatment of breast cancer. We also describe current methods to preserve fertility including oocytes or ovarian tissue freezing and administration of LH-RHa during chemotherapy.The aim of the paper is to provide clinical oncologists with an adequate knowledge of the subject to enable them to give a correct counselling to young women that must receive chemotherapy and want to increase their possibilities of maintaining fertility.



http://ift.tt/2n6PoCt

Toxicity of Iron Overload and Iron Overload Reduction in the Setting of Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

Publication date: Available online 14 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Heather A. Leitch, Eitan Fibach, Eliezer Rachmilewitz
Iron is an essential element for key cellular metabolic processes. However, transfusional iron overload (IOL) may result in significant cellular toxicity. IOL occurs in transfusion dependent hematologic malignancies (HM), may lead to pathological clinical outcomes, and IOL reduction may improve outcomes. In hematopoietic stem cell transplantation (SCT) for HM, IOL may have clinical importance; endpoints examined regarding an impact of IOL and IOL reduction include transplant-related mortality, organ function, infection, relapse risk, and survival. Here we review the clinical consequences of IOL and effects of IOL reduction before, during and following SCT for HM. IOL pathophysiology is discussed as well as available tests for IOL quantification including transfusion history, serum ferritin level, transferrin saturation, hepcidin, labile plasma iron and other parameters of iron-catalyzed oxygen free radicals, and organ IOL by imaging. Data-based recommendations for IOL measurement, monitoring and reduction before, during and following SCT for HM are made.



http://ift.tt/2mMY1z8

Follow-up program in head and neck cancer

Publication date: Available online 14 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesca De Felice, Marco de Vincentiis, Valentino Valentini, Daniela Musio, Silvia Mezi, Luigi Lo Mele, Valentina Terenzi, Vittorio D'Aguanno, Andrea Cassoni, Martina Di Brino, Gianluca Tenore, Nadia Bulzonetti, Andrea Battisti, Antonio Greco, Giorgio Pompa, Antonio Minni, Umberto Romeo, Enrico Cortesi, Antonella Polimeni, Vincenzo Tombolini
Follow-up program in head and neck cancer (HNC) is an important issue in patients management. It represents the major dilemma in daily practice clinic. Many guidelines have been published in order to better define the best clinical protocol, but a consensus has not been attained yet. We constructed a follow-up program based on specific primary subsite, to standardize patients surveillance after treatment of HNC.



http://ift.tt/2n6QzS5

Immobilization of BSA on ionic liquid functionalized magnetic Fe3O4 nanoparticles for use in surface imprinting strategy

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Liwei Qian, Jiexuan Sun, Chen Hou, Jinfan Yang, Yongwei Li, Dan Lei, Miaoxiu Yang, Sufeng Zhang
Combining template immobilization with surface imprinting technology is an effective strategy to overcome the difficulties associated with macromolecular template removal and to achieve high specific recognition ability. In this work, ionic liquid functionalized Fe3O4 nanoparticles were prepared via a simple two-step modification process and were used as substrate to immobilize bovine serum albumin (BSA). The zeta potential study revealed immobilization of BSA on the nanoparticles through multiple interactions, and the immobilization capacity was about nine times higher compared with that of bare Fe3O4. Subsequently, dopamine was utilized as functional monomer to prepare BSA surface imprinted nanoparticles. Fourier transform infrared spectroscopy, thermo-gravimetric analysis and transmission electron microscopy verified the successful preparation of BSA imprinted nanoparticles with core-shell structure. The influence of imprinted layer thickness on recognition ability of imprinted nanoparticles was investigated, and the results suggested that 20nm was an optimum thickness to achieve the best recognition ability. The adsorption isotherm studies showed that the imprinted nanoparticles had a significantly higher adsorption capacity and stronger binding affinity than the non-imprinted ones. Furthermore, the selective as well as the competitive adsorption studies revealed higher selectivity and recognition ability of the imprinted nanoparticles for BSA. Therefore, the proposed strategy is an effective way to obtain protein imprinted polymers with high adsorption capacity and good recognition ability, thus would be beneficial for the further development and application of protein imprinting technology.

Graphical abstract

http://ift.tt/2nD94iB

Rhenium filament oxidation: Effect on TIMS performance and the roles of carburization and humidity

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Joseph M. Mannion, Charles R. Shick Jr., Glenn A. Fugate, Matthew S. Wellons, Brian A. Powell, Scott M. Husson
This communication presents findings on the effect of rhenium filament oxidation on thermal ionization mass spectrometry (TIMS) analyses of plutonium. Additionally, the roles of atmospheric humidity and carburization on the oxidation characteristics (i.e. aging) of rhenium filaments were studied. Degassed and carburized filaments were aged for up to 79 days under dry and humid conditions, and the growth of oxo-rhenium crystallites was investigated intermittently by scanning electron microscopy (SEM) to construct growth profiles. SEM images were analyzed to determine average crystallite size, number density, and percent surface coverage. Crystallite growth was found to be suppressed by both filament carburization and dry storage conditions (~13% relative humidity). Under humid conditions (75% relative humidity), crystallite growth progressed steadily over the investigatory period, reaching >2.3% surface coverage within 79 days of aging. Atomic ion production of Pu (Pu⁺) was suppressed by approximately 20% and the standard deviation of isotope ratio measurements was increased by 170% when filaments with 1% oxide surface coverage were used in sample loading. Measurement sensitivity and reproducibility are imperative for applications involving ultra-trace analysis of plutonium by TIMS. These findings offer validation for observations regarding the detrimental effect of excessive filament aging post-degassing, improve the understanding of conditions that impel the oxidation of rhenium filaments, and provide practical means to suppress the growth of oxides.

Graphical abstract

http://ift.tt/2nDlV4d

Falling under the umbrella cells: A single institutional experience and literature review of urothelial carcinoma presenting as a primary pancreatic mass on endoscopic ultrasound-guided fine-needle aspiration

Michael Chambers, Konrad Krall, Shantel Hébert-Magee

CytoJournal 2017 14(1):6-6

Metastases to the pancreas are much less common than primary pancreatic lesions, and there are few reports in the literature of metastatic urothelial carcinoma (UC) found in the pancreas. We report two cases of metastatic UC mimicking a primary pancreatic lesion. Two female patients, aged 48 and 83 years, presented with isolated pancreatic lesions causing obstructive jaundice suspicious for pancreatic adenocarcinoma and underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE). On cytopathology, the lesions were found to be UC, confirmed with immunohistochemical (IHC) staining. UC rarely metastasizes to the pancreas, and diagnosis through EUS-FNA can be challenging. However, the utilization of ROSE, dedicated cell block passes, and IHC have proved to be effective in obtaining this unusual pancreatic diagnosis by EUS-FNA.

http://ift.tt/2nsg0i2

Next-generation sequencing of non-small cell lung cancer using a customized, targeted sequencing panel: Emphasis on small biopsy and cytology

David M DiBardino, David W Rawson, Anjali Saqi, Jonas J Heymann, Carlos A Pagan, William A Bulman

CytoJournal 2017 14(1):7-7

Background: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. Materials and Methods: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015. The customized NGS panel sequences 467 cancer-associated genes with exonic and intronic sequences obtained from purified tumor DNA. Genomic alterations, patient characteristics, and success of testing were determined. Results: The majority of samples tested were metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5 (22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology specimens. Twenty-one (95%) of the specimens were adequate for full sequencing and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which 17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2, KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes. Conclusions: NGS using a comprehensive gene panel was performed successfully in 95% of all NSCLC cases in this series, including 94% small biopsy and cytology specimens and 100% surgical resections. This custom assay was performed on a range of tumor specimens and demonstrates that small specimens are able to provide a similar depth of information as larger ones. As many patients present at an advanced stage and only small specimens are obtained, the information these provide has the potential for guiding treatment in highly selected patients with advanced lung adenocarcinoma.

http://ift.tt/2nKr1IX

Editorial Board

Publication date: April 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 4





http://ift.tt/2nKzhZh

Raltitrexed and Paclitaxel for Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions:   Gastric Cancer;   Gastroesophageal Junction Adenocarcinoma
Interventions:   Drug: Raltitrexed;   Drug: Paclitaxel
Sponsor:   Chinese Academy of Medical Sciences
Recruiting - verified December 2016

http://ift.tt/2n0yrYA

Study of LN-145 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck

Condition:   Squamous Cell Carcinoma of the Head and Neck
Intervention:   Biological: LN-145
Sponsor:   Lion Biotechnologies
Recruiting - verified March 2017

http://ift.tt/2mkZRuZ

Estimating body size in early primates: The case of Archicebus and Teilhardina

Publication date: Available online 19 March 2017
Source:Journal of Human Evolution
Author(s): Marian Dagosto, Daniel Gebo, Xijun Ni, Thierry Smith
Obtaining accurate estimations of the body mass of fossil primates has always been a subject of interest in paleoanthropology because mass is an important determinant for so many other aspects of biology, ecology, and life history. This paper focuses on the issues involved in attempting to reconstruct the mass of two early Eocene haplorhine primates, Teilhardina and Archicebus, which pose particular problems due to their small size and temporal and phylogenetic distance from extant primates. In addition to a ranking of variables from more to less useful, the effect of using models of varying taxonomic and size compositions is examined. Phylogenetic correction is also applied to the primate database. Our results indicate that the choice of variable is more critical than the choice of model. The more reliable variables are the mediolateral breadth across the femoral condyles and the area of the calcaneocuboid facet of the calcaneus. These variables suggest a body mass of 39 g (range 33–46 g) for Archicebus and 48 g (range 44–56 g) for Teilhardina. The width of the distal femur is found to be the most consistent estimator across models of various composition and techniques. The effect of phylogenetic correction is small but the choice of branch length assumption affects point estimates for the fossils. The majority of variables and models predict the body mass of Archicebus and Teilhardina to be in the range of the smaller extant mouse lemurs, as expected.



http://ift.tt/2nJWHhG

Irinotecan-induced bile acid malabsorption is associated with down-regulation of ileal Asbt (Slc10a2) in mice

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): A-xi Shi, Yan Zhou, Xiao-yi Zhang, Yan-shu Zhao, Hong-yan Qin, Yan-ping Wang, Xin-an Wu
Irinotecan, (CPT-11), an antitumor agent primarily used for the treatment of solid tumors, has often compromised clinical application due to the inducement of severe delay-onset diarrhea. Bile acid malabsorption (BAM) is widely accepted as the common cause of diarrhea. However, whether CPT-11-induced diarrhea has correlation with BAM is unknown. The aim of this study was to investigate the effect of CPT-11 on the bile acid homeostasis in mice. The mice were administrated with CPT-11 intravenously for four consecutive days. The total bile acids (TBAs) levels in the small intestine, colon, feces, liver, serum and gallbladder were evaluated by automatic biochemical analyzer, and the individual bile acids were also measured by LC-MS/MS. Real-time qPCR and Western blot techniques were used to evaluate the mRNA and protein expressions of Cyp7a1, Cyp27a1, Asbt, Ostα/β. In situ loop method was carried out to evaluate the function of apical Na⁺-dependent bile salt transporter (Asbt). Results showed that the bile acid pool size was significantly reduced by 17%, 25%, and 40% respectively at 2, 3, and 4days post CPT-11 treatment. The fecal excretions of TBAs were significantly increased by 2.1-fold at 3 and 4days post CPT-11 treatment. The ileal expression of Asbt was significantly decreased at mRNA and protein levels, and the transport ability of Asbt was also attenuated after CPT-11 treatment. Moreover, the incidence of CPT-11-induced delay-onset diarrhea was also decreased after cholestyramine administration in CPT-11-treated mice. These results indicated that BAM may be partially responsible for CPT-11-induced delay-onset diarrhea, and the underlying mechanism may have correlation with down-regulation of the Asbt in the ileum of mice.

Graphical abstract

http://ift.tt/2n0g2v6

Environmental exposure to arsenic and chromium in an industrial area

Abstract

Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of chromium, inorganic arsenic, and methylated metabolites, in the urine samples of 279 subjects residing in Taranto and neighboring areas. Qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and controlling for confounding factors. The biological monitoring data showed high urinary concentrations of both the heavy metals investigated, particularly Cr. On this basis, it will be necessary to carry out an organized environmental monitoring program, taking into consideration all exposure routes so as to correlate the environmental concentrations of these metals with the biomonitoring results.

http://ift.tt/2nrNRHV

Magnetic EDTA functionalized CoFe 2 O 4 nanoparticles (EDTA-CoFe 2 O 4 ) as a novel catalyst for peroxymonosulfate activation and degradation of Orange G

Abstract

EDTA functionalized CoFe₂O₄ nanoparticles (EDTA-CoFe₂O₄) synthesized using a facile one-pot solvothermal method were employed as catalysts to activate peroxymonosulfate (PMS) with Orange G (OG) as the target pollutant. Effects of operating parameters including initial solution pH, catalyst dosage, PMS dosage, and water matrix components such as Cl⁻, NO₃⁻, CO₃²⁻, and humic acid were evaluated. A degradation efficiency of 93% was achieved in 15 min with 1 mM PMS and 0.2 g/L EDTA-CoFe₂O₄ catalyst, while only 57% of OG was degraded within 15 min in CoFe₂O₄/PMS system. The degradation of OG followed pseudo-first-order kinetics, and the apparent first-order date constant (k _obs) for OG in EDTA-CoFe₂O₄/PMS and CoFe₂O₄/PMS system was determined to be 0.152 and 0.077 min⁻¹, respectively. OG degradation by EDTA-CoFe₂O₄/PMS was enhanced with the increase of catalyst and PMS doses at respective range of 0.1–2.0 g/L and 0.5–10.0 mM. Higher efficiency of OG oxidation was observed within a wide pH range (3.0–9.0), implying the possibility of applying EDTA-CoFe₂O₄/PMS process under environmental realistic conditions. Humic acid (HA) at low concentration accelerated the removal of OG; however, a less apparent inhibitive effect was observed at HA addition of 10 mg/L. The k _obs value was found to decrease slightly from 0.1601 to 0.1274, 0.1248, and 0.1152 min⁻¹ with the addition of NO₃⁻, CO₃²⁻, and Cl⁻, respectively, but near-complete removal of OG could still be obtained after 15 min. Both of the sulfate radicals and hydroxyl radicals were produced in the reaction, and sulfate radicals were the dominant according to the scavenging tests and electron paramagnetic resonance (EPR) tests. Finally, a degradation mechanism was proposed, and the stability and reusability of the EDTA-CoFe₂O₄ were evaluated.

http://ift.tt/2mHU2D8

Thermoactivated persulfate oxidation of pesticide chlorpyrifos in aquatic system: kinetic and mechanistic investigations

Abstract

The widespread occurrence of organophosphorus pesticides (OPPs) in the environment poses risks to both ecologic system as well as human health. This study investigated the oxidation kinetics of chlorpyrifos (CP), one of the typical OPPs, by thermoactivated persulfate (PS) oxidation process, and evaluated the influence of key kinetic factors, such as PS concentrations, pH, temperature, bicarbonate, and chloride ions. The reaction pathways and mechanisms were also proposed based on products identification by LC-MS techniques. Our results revealed that increasing initial PS concentration and temperature favored the decomposition of CP, whereas the oxidation efficiency was not affected by pH change ranging from 3 to 11. Bicarbonate was found to play a detrimental role on CP removal rates, while chloride showed no effect. The oxidation pathways including initial oxidation of P=S bond to P=O, dechlorination, dealkylation, and the dechlorination-hydroxylation were proposed, and the detailed underlying mechanisms were also discussed. Molecular orbital (MO) calculations indicated that P=S bond was the most favored oxidation site of the molecule. The toxicity of reaction solution was believed to increase due to the formation of products with P=O structures. This work demonstrates that OPPs can readily react with SO₄^·− and provides important information for further research on the oxidation of these contaminants.

http://ift.tt/2nrRrlw

Numerical simulation of reactive extraction of benzoic acid from wastewater via membrane contactors

Abstract

Membrane-based non-dispersive solvent extraction is used in many chemical processes due to its significant benefits such as straightforward scale-up and low energy consumption. A mechanistic model was developed to predict recovery of benzoic acid (BA) from wastewater using membrane contactors. Model equations were derived for benzoic acid transport in the membrane module, and solved using FEM. The model findings were compared with experimental results, and an average deviation of 4% was observed between experimental and simulation results. Simulations showed that change in organic phase flowrate and initial concentration of BA does not have considerable effect on the removal efficiency of benzoic acid. In addition, increasing feed flowrate leads to the enhancement of convective mass transfer flux in the tube side of membrane contactor which decreases removal efficiency of benzoic acid.

http://ift.tt/2mHTz4a

Direct detection of two different tumor-derived extracellular vesicles by SAM-AuNIs LSPR biosensor

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Abhimanyu Thakur, Guangyu Qiu, Siu-Pang NG, Jintao Guan, Jianbo Yue, Youngjin Lee, Chi-Man Lawrence Wu
Extracellular vesicles (EVs) are abundant in various biological fluids including blood, saliva, urine, as well as extracellular milieu. Accumulating evidence has indicated that EVs, which contain functional proteins and small RNAs, facilitate intercellular communication between neighbouring cells, and are critical to maintain various physiological processes. In contrast, EV-derived toxic signals can spread out over the tissues adjacent to the injured area in certain diseases, including brain tumors and neurodegenerative disorders. This demands better characterization of EVs which can be employed for liquid biopsy clinically as well as for the study of intercellular signalling. Exosomes and microvesicles share a number of similar characteristics, but it is important to distinguish between these two types of EVs. Here, we report for the first time that our in-house developed Localized Surface Plasmon Resonance biosensor with self-assembly gold nanoislands (SAM-AuNIs) can be used to detect and distinguish exosomes from MVs isolated from A-549 cells, SH-SY5Y cells, blood serum, and urine from a lung cancer mouse model. Exosomes, compared with MVs, produced a distinguishable response to the bare LSPR biosensor without functionalization, suggesting a different biophysical interaction between exosomes and MVs with SAM AuNIs. This sensor attains the limit of detection to 0.194µg/ml, and the linear dynamic range covers 0.194–100µg/ml. This discovery not only reveals great insight into the distinctive membrane property of tumor-derived exosomes and MVs, but also facilitate the development of novel LSPR biosensors for direct detection and isolation of heterogeneous EVs.



http://ift.tt/2mHPnB8

Bovine serum albumin as an effective sensitivity enhancer for peptide-based amperometric biosensor for ultrasensitive detection of prostate specific antigen

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Zhongxue Tang, Yuanyuan Fu, Zhanfang Ma
Bovine serum albumin (BSA) was firstly implemented as an effective sensitivity enhancer for a peptide-based amperometric biosensor for the ultrasensitive detection of prostate specific antigen (PSA). A porous and conductive substrate of chitosan-lead ferrocyanide-(poly(diallyldimethylammonium chloride)-graphene oxide) was in-situ generated on a glassy carbon electrode (GCE), in which Pb2[Fe(CN)6] served as a novel redox species with strong current signal at −0.46 V (vs. Ag/AgCl). Poly(diallyldimethylammonium chloride)-graphene oxide was applied to improve conductivity of the substrate. After adsorbing Pb²⁺ for signal amplification, chitosan provided active sites to simultaneously immobilize peptides and 1-aminopropyl-3-methylimidazolium chloride by glutaraldehyde. To enhance the sensitivity, BSA was chemically linked to the immobilized peptide, behaving as a serious decrease of current signal for BSA hindering the electron transfer. The dramatic increase of current signal of the biosensor was obtained by PSA cleaving the immobilized BSA-peptide. The proposed biosensor exhibited a detection limit of 1fgmL⁻¹ for PSA and its sensitivity was seven-fold higher than previous works.



http://ift.tt/2nqHG6V

Differentiating motivational from affective influence of performance-contingent reward on cognitive control: the wanting component enhances both proactive and reactive control

Publication date: Available online 18 March 2017
Source:Biological Psychology
Author(s): Anne-Clémence Chaillou, Anne Giersch, Marc Hoonakker, Rémi L. Capa, Anne Bonnefond
Positive affect strongly modulates goal-directed behaviors and cognitive control mechanisms. It often results from the presence of a pleasant stimulus in the environment, whether that stimulus appears unpredictably or as a consequence of a particular behavior. The influence of positive affect linked to a random pleasant stimulus differs from the influence of positive affect resulting from performance-contingent pleasant stimuli. However, the mechanisms by which the performance contingency of pleasant stimuli modulates the influence of positive affect on cognitive control mechanisms have not been elucidated. Here, we tested the hypothesis that these differentiated effects are the consequence of the activation of the motivational "wanting" component specifically under performance contingency conditions. To that end, we directly compared the effects on cognitive control of pleasant stimuli (a monetary reward) attributed in a performance contingent manner, and of random pleasant stimuli (positive picture) not related to performance, during an AX-CPT task. Both proactive and reactive modes of control were increased specifically by performance contingency, as reflected by faster reaction times and larger amplitude of the CNV and P3a components. Our findings advance our understanding of the respective effects of affect and motivation, which is of special interest regarding alterations of emotion-motivation interaction found in several psychopathological disorders.



http://ift.tt/2nVwDiC

Visual object separation resolves competitive interactions in somatosensory cortex evoked signals during concurrent vibrotactile stimulation of the left and right hand

Publication date: Available online 18 March 2017
Source:Biological Psychology
Author(s): Cheuk Yee Pang, Matthias M. Müller
We investigated the effect of visual separation of the left and right hemispaces within peripersonal space to sustained tactile spatial attention processing and show that visually perceived object separation weakens the competitive interaction for concurrent vibrotactile stimulation to two hands. Participants received concurrent vibrotactile stimulation at different frequencies on two hands (right: 20Hz; left: 24Hz) for 4500ms to elicit steady-state somatosensory evoked potentials (SSSEPs). They attended to one of the stimulated hands and reacted to rare transient events embedded in the attended ongoing stream. Behavioral and neurophysiological results reveal that separation of spatial representation of tactile event locations could facilitate bilateral tactile spatial selection in sustained attention processing. Visual separation by a gap between hands increased the magnitude of attentional gain in SSSEPs compared to the situation when no gap was present. Results suggest that visual separation resolved the competition between concurrent tactile stimulation on two hands.



http://ift.tt/2nryVtu

Implementing a negative-pressure isolation ward for a surge in airborne infectious patients

Publication date: Available online 20 March 2017
Source:American Journal of Infection Control
Author(s): Shelly L. Miller, Nicholas Clements, Steven A. Elliott, Shobha S. Subhash, Aaron Eagan, Lewis J. Radonovich
BackgroundDuring a large-scale airborne infectious disease outbreak, the number of patients needing hospital-based health care services may exceed available negative-pressure isolation room capacity.MethodsTo test one method of increasing hospital surge capacity, a temporary negative-pressure isolation ward was established at a fully functioning hospital. Negative pressure was achieved in a 30-bed hospital ward by adjusting the ventilation system. Differential pressure was continuously measured at 22 locations, and ventilation airflow was characterized throughout the ward.ResultsThe pressure on the test ward relative to the main hospital hallway was −29 Pa on average, approximately 10 times higher than the Centers for Disease Control and Prevention guidance for airborne infection control. No occurrences of pressure reversal occurred at the entrances to the ward, even when staff entered the ward. Pressures within the ward changed, with some rooms becoming neutrally or slightly positively pressurized.ConclusionsThis study showed that establishing a temporary negative-pressure isolation ward is an effective method to increase surge capacity in a hospital.



http://ift.tt/2mZYmQb

Microorganisms present on peripheral intravenous needleless connectors in the clinical environment

Publication date: Available online 20 March 2017
Source:American Journal of Infection Control
Author(s): Karen Slater, Marie Cooke, Michael Whitby, Fiona Fullerton, Joel Douglas, Jennine Hay, Claire Rickard
The aim of this study was to quantify culturable microorganisms on needleless connectors (NCs) attached to peripheral intravenous catheters in hospitalized adult medical patients. Half (50%) of 40 NCs were contaminated with microorganisms commonly found on the skin or mouth. Staphylococcus capitis and Staphylococcus epidermidis were most commonly isolated. Emergency department insertion and higher patient dependency were statistically associated with positive NC microorganism growth. These results reaffirm the need for NC decontamination prior to access.



http://ift.tt/2nCMB5a

Anti-inflammatory mechanism of ulinastatin: Inhibiting the hyperpermeability of vascular endothelial cells induced by TNF-α via the RhoA/ROCK signal pathway

Publication date: May 2017
Source:International Immunopharmacology, Volume 46
Author(s): Fu Wei, Siyi Liu, Li Luo, Nina Gu, Yan Zeng, Xiaoying Chen, Shan Xu, Dan Zhang
ObjectiveUlinastatin reduces the high permeability of vascular endothelial cells induced by tumor necrosis factor alpha (TNF-α). This study investigated the molecular mechanism behind this effect, with the aim of understanding the action of ulinastatin in sepsis therapy and exploring novel therapeutic strategies for sepsis patients.MethodsA TNF-α treated human umbilical vein endothelial cell line (EA.hy926) was employed as an inflammation model. Horseradish peroxidase permeability assays and an epithelial voltmeter method were used to measure the permeability of EA.hy926 cells. Immunocytochemistry was used to assay the expression of p-MYPT1 and the distribution and morphology of F-actin; the expression of the key molecules related to vascular endothelial permeability (RhoA, ROCK2, MYPT1, p-MYPT1 and VE-cadherin) was detected by immunocytochemistry assays, western blotting and quantitative real-time polymerase chain reaction.ResultsAfter incubation with TNF-α or septic serum, the transendothelial electrical resistance of EA.hy926 cells decreased and the permeability of the cells increased significantly (all P<0.05). The expression of p-MYPT1 was higher and VE-cadherin was lower compared with the control group, and F-actin was redistributed, with the formation of additional stress fibers in the cells. Ulinastatin treatment moderated these phenomena. The immunocytochemistry assays and western blots showed that the expression of RhoA and ROCK2 was significantly upregulated in cells treated with TNF-α (P<0.05); however, ulinastatin could inhibit the high expression of these two proteins. Under treatment with TNF-α and ulinastatin, compared with normal EA.hy926 cells, overexpression of RhoA upregulated expression of RhoA, ROCK2 and p-MYPT1, downregulated expression of VE-cadherin, and restored the hyperpermeability of vascular endothelial cells due to TNF-α treatment (P<0.05).ConclusionsUlinastatin inhibited the hyperpermeability of vascular endothelial cells induced by TNF-α. This inhibitory effect of ulinastatin may be related to the RhoA/ROCK signaling pathway.



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Insight into pathogenesis of Sjögren's syndrome: Dissection on autoimmune infiltrates and epithelial cells

Publication date: Available online 19 March 2017
Source:Clinical Immunology
Author(s): Andreas V. Goules, Efstathia K. Kapsogeorgou, Athanasios G. Tzioufas
Sjögren's syndrome (SS) is a chronic autoimmune disease with broad clinical spectrum, extending from benign exocrinopathy to severe systemic disease and lymphoma development. The glandular and extraglandular dysfunction of SS is associated with lymphocytic infiltrates that invade the epithelial structures of affected organs. The in-depth study of autoimmune lesions in the minor salivary glands (MSG), which are the major target-organ of SS responses, revealed that the lymphocytic infiltrates vary in severity and composition among SS-patients, are full-blown at diagnosis and remain unchanged thereafter. Although the pathogenetic pathways underlying SS have not yet elucidated, it is well-established that glandular epithelial cells are central regulators of local autoimmune responses. Moreover, chronic inflammation affects epithelial function and phenotype, which strengthens or weakens their immunoregulatory/secretory function, leading to deterioration of autoimmune phenomena. Herein, the current findings regarding the autoimmune lesions, the role of epithelial cells and their interaction with infiltrating lymphocytic cells are discussed.



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Development and Validation of a Novel Questionnaire for Adherence with Topical Treatments in Psoriasis (QATOP)

Abstract

Background

Self-report measures are the most used methodologies for the evaluation of adherence to psoriasis topical treatment, although currently there is no standard questionnaire for this purpose.

Objective

The present study aimed at developing a novel questionnaire (Questionnaire for Adherence to TOPical treatment [QATOP]) for the assessment of adherence to topical treatment in psoriasis.

Methods

A questionnaire containing nine items organized into two parts (part 1: current patient treatment; part 2: adherence to treatment, amount used, and treatment-associated variables) was developed, supported by a systematic literature review, qualitative patient focus interviews, and expert-group input. Its content validity was determined by a pilot study of six patients. Adherence to topical treatment was then assessed in 35 patients with psoriasis, after 45 days of treatment, using the QATOP and a medication log. Associations between different items of the QATOP and the log were investigated.

Results

Adherence results were 63.5 ± 29.2% for the log and 60.9 ± 24.4% for the QATOP, and were strongly correlated (R = 0.819, p < 0.001). Distinct posologic regimens were reported by patients, which, in some cases, were not the usual doses. Patients also reported using doses of medicine on each application that were markedly lower than required.

Conclusion

The QATOP is a valid and reliable self-report measure of adherence to topical treatment in patients with psoriasis. The use of this standard questionnaire could improve the methodological quality of adherence studies. Improvement of the clarity of posologic instructions is clearly urgently needed.

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Giant adenoid basal cell carcinoma of the scalp with intracranial involvement—successful management strategies for a rare entity

Abstract

Adenoid basal cell carcinoma (BCC) is a rare but aggressive histologic subtype of BCC. The aim of this report is to present our multidisciplinary management strategy and a literature review on this seldom reported entity. A 72-year-old female with fungating giant BCC of the scalp, ear, and bone underwent preoperative biopsy revealing adenoid histology with infiltrating and nodular components. The patient underwent radical resection of the biparietal and occipital scalp, auriculectomy and craniectomy with dural resection. Immediate reconstruction of the intracranial and bony defect was performed with dural substitute and a titanium cranioplasty. The soft tissue defect was reconstructed with a latissimus dorsi free flap and split thickness skin graft using the right superficial temporal artery and vein as recipient vessels. Adjuvant external beam radiation was initiated postoperatively. Nearly 2 years postoperatively, she presented mesh exposure necessitating secondary reconstruction with debridement, hardware removal, and an anterolateral thigh (ALT) free flap, followed by flap debulking. Four years following initial presentation, she remains disease-free. To our knowledge, this is the only reported case of a giant, locally invasive scalp BCC with the adenoid subtype treated with composite resection and single stage reconstruction. Using an aggressive multimodal management paradigm, treatment and surveillance of the rarely reported, giant, locally invasive scalp BCC with adenoid subtype can result in a durable disease-free response and a functional, esthetic reconstruction. Evidence-based medicine level.

Level of Evidence: Level V, therapeutic study.

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Identification of putative effector genes and their transcripts in three strains related to ‘Candidatus Phytoplasma aurantifolia’

Publication date: Available online 19 March 2017
Source:Microbiological Research
Author(s): Ameneh Anabestani, Keramat Izadpanah, Simona Abbà, Luciana Galetto, Abozar Ghorbani, Sabrina Palmano, Majid Siampour, Flavio Veratti, Cristina Marzachì
Anabestani A., Izadpanah K., Abbà S., Galetto L., Ghorbani A., Palmano S., Siampour M., Veratti F., Marzachì C. 2016. Identification of putative effector genes and their transcripts in three strains related to 'Candidatus Phytoplasma aurantifolia'.Molecular mechanisms underlying phytoplasma interactions with host plants are largely unknown. In this study attempts were made to identify effectors of three phytoplasma strains related to 'Ca. P. aurantifolia', crotalaria phyllody (CrP), faba bean phyllody (FBP), and witches' broom disease of lime (WBDL), using information from draft genome of peanut witches' broom phytoplasma. Seven putative effectors were identified in WBDL genome (SAP11, SAP21, Eff64, Eff115, Eff197, Eff211 and EffSAP67), five (SAP11, SAP21, Eff64, Eff99 and Eff197) in CrP and two (SAP11, Eff64) in FBP. No homologs to Eff64, Eff197 and Eff211 in phytoplasmas of other phylogenetic groups were found. SAP11 and Eff64 homologs of 'Ca. P. aurantifolia' strains shared at least 95.9% identity and were detected in the three phytoplasmas, supporting their role within the group. Five of the putative effectors (SAP11, SAP21, Eff64, Eff115, and Eff99) were transcribed from total RNA extracts of periwinkle plants infected with these phytoplasmas. Transcription profiles of selected putative effectors of CrP, FBP and WBDL indicated that SAP11 transcripts were the most abundant in the three phytoplasmas. SAP21 transcript levels were comparable to those of SAP11 for CrP and not measurable for the other phytoplasmas. Eff64 had the lowest transcription level irrespective of sampling date and phytoplasma isolate. Eff115 transcript levels were the highest in WBDL infected plants. This work reports the first sequence information for 14 putative effectors in three strains related to 'Ca. P. aurantifolia', and offers novel insight into the transcription profile of five of them during infection of periwinkle.



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Functional characterisation of Burkholderia pseudomallei biotin protein ligase: A toolkit for anti-melioidosis drug development

Publication date: Available online 19 March 2017
Source:Microbiological Research
Author(s): Thomas E.H. Bond, Alanna E. Sorensona, Patrick M. Schaeffer
Burkholderia pseudomallei (Bp) is the causative agent of melioidosis. The bacterium is responsible for 20% of community-acquired sepsis cases and 40% of sepsis-related mortalities in northeast Thailand, and is intrinsically resistant to aminoglycosides, macrolides, rifamycins, cephalosporins, and nonureidopenicillins. There is no vaccine and its diagnosis is problematic. Biotin protein ligase (BirA) which is essential for fatty acid synthesis has been proposed as a drug target in bacteria. Very few bacterial BirA have been characterized, and a better understanding of these enzymes is necessary to further assess their value as drug targets. BirA within the Burkholderia genus have not yet been investigated. We present for the first time the cloning, expression, purification and functional characterisation of the putative Bp BirA and orthologous B. thailandensis (Bt) biotin carboxyl carrier protein (BCCP) substrate. A GFP-tagged Bp BirA was produced and applied for the development of a high-throughput (HT) assay based on our differential scanning fluorimetry of GFP-tagged proteins (DSF-GTP) principle as well as an electrophoretic mobility shift assay. Our biochemical data in combination with the new HT DSF-GTP and biotinylation activity assay could facilitate future drug screening efforts against this drug-resistant organism.



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Pre-clinical investigation of Diabetes Mellitus as a risk factor for schizophrenia

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Alexandra S. Almeida Heylmann, Lara Canever, Katia Gress, Sarah T. Gomes, Isadora Fachim, Carolina Michels, Geórgia C. Stopassoli, Gustavo A. Mastella, Amanda V. Steckert, Adriani P. Damiani, Vanessa M. de Andrade, João Quevedo, Alexandra I. Zugno
This study investigated the behavioral and biochemical parameters of DM1 as a risk factor in an animal model of schizophrenia (SZ). All groups: 1 Control (saline+saline); 2 Alloxan (alloxan+saline); 3 Ketamine (saline+ketamine); 4 (Alloxan+Ketamine) were fasted for a period of 18h before the subsequent induction of DM via a single intraperitoneal (i.p) injection of alloxan (150mg/kg). From the 4th to the 10th days, the animals were injected i.p with ketamine (25mg/kg) or saline, once a day, to induce a model of SZ and 30min after the last administration were subjected to behavioral testing. After, the animals were decapitated and the brain structures were removed. Ketamine induced hyperactivity and in the social interaction, ketamine, alloxan and the association of alloxan+ketamine increased the latency and decreased the number of contacts between animals. The animals from the ketamine, alloxan and alloxan+ketamine groups showed a prepulse startle reflex (PPI) deficit at the three intensities (65, 70 and 75dB). Ketamine was shown to be capable of increasing the activity of acetylcholinesterase (AChE) in the brain structures. Combination of alloxan+ketamine seems to have an exacerbated effect within the cholinergic system. For lipid peroxidation and protein carbonyls, alloxan+ketamine appear to have intensified lipid and protein damage in the three structures. Ketamine and the combination of ketamine+alloxan induced DNA damage in both frequency and damage index. This research found a relationship between DM1 and SZ.



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Discovery of a series of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton as potential FAK inhibitors

Publication date: Available online 19 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Juan Sun, Shen-Zhen Ren, Xiao-Yuan Lu, Jing-Jing Li, Fa-Qian Shen, Chen Xu, Hai-Liang Zhu
Focal adhesion kinase (FAK) is an important drug target that plays a fundamental role in mediating signal transduction system. We report herein the discovery of a novel class of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton with improved potency toward FAK. All of the 17 new synthesized compounds were assayed for the anticancer activities against four cancer cells, HepG2, Hela, SW116 and BGC823. Because of the combination of 1,4-benzodioxan, 1,3,4-oxadiazole and piperazine ring, most of them exhibited remarkable antitumor activities. Notably, compound 5m showed the most potent biological activities (IC50=5.78 μM for HepG2, and IC50=47.15 μM for SW1116), and its anti-FAK inhibitory activity (IC50=0.78 μM) was also the best. Computational docking studies also showed that compound 5m has interaction with FAK key residues in the active site.

Graphical abstract

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PIFA–BF3·OEt2 mediated intramolecular regioselective domino cyclization of ynamides: A novel method for the synthesis of tetrahydroisoquinoline-oxazol-2(3H)-ones

Publication date: Available online 19 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Winai Ieawsuwan, Somsak Ruchirawat
The transition metal-free intramolecular regioselective domino cyclization of N-Boc protected ynamides has been developed to provide the corresponding tetrahydroisoquinoline-oxazo-2(3H)-ones in moderate to good yields.

Graphical abstract

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Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function

Publication date: Available online 19 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Wei Bi, Yue Bi, Xiang Gao, Pengfei Li, Shanshan Hou, Yanrong Zhang, Cathy Bammert, Steffen Jockusch, Thomas D. Legalley, K. Michael Gibson, Lanrong Bi
Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/ reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.

Graphical abstract

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Design, Synthesis and Anti-tumor Activity Study of Novel Histone Deacetylase Inhibitors Containing Isatin-based Caps and O-phenylenediamine-based Zinc Binding Groups

Publication date: Available online 19 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Shuai Gao, Jie Zang, Qianwen Gao, Xuewu Liang, Qinge Ding, Xiaoyang Li, Wenfang Xu, C. James Chou, Yingjie Zhang
As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605 µM, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311 µM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.

Graphical abstract

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Perceived impact of Nepalese food and food culture in diabetes

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Sujata Sapkota, Jo-anne E Brien, Josephine Gwynn, Victoria Flood, Parisa Aslani
Consuming a healthy diet forms an important component of diabetes management; however, adhering to a healthy diet is challenging. Dietary behaviour is often guided by socio-cultural, environmental and emotional factors, and not necessarily by physical and nutritional needs. This study explored Nepalese patients' perceptions of the impact of diet, diet management requirement for diabetes and how Nepalese food culture in particular influenced diet management.Interviews were conducted with Nepalese participants with type 2 diabetes in Sydney and Kathmandu; and data was thematically analysed. Diet was recognized as a cause of, and a key treatment modality, in diabetes. Besides doctors, participants in Nepal received a large amount of dietary information from the community. Dietary changes formed a major component of lifestyle modifications adopted after diagnosis, and mostly consisted of removal of foods with added sugar and foods with high total sugar content from the diet, and a reduction in overall quantity of foods consumed.Perceived dietary restriction requirements created social and emotional discomfort to patients. Most participants perceived the Nepalese food culture as a barrier to effective diet management. Meals high in carbohydrates, limited food choices, and food preparation methods were identified as barriers, particularly in Nepal. In Australia, participants reported greater availability and easier access to appropriate food, and healthier cooking options. The socio-cultural aspects of food behaviour, mainly, food practices during social events were identified as significant barriers.Although diet was acknowledged as an important component of diabetes care, and most adopted changes in their diet post-diagnosis, effective and sustained changes were difficult to achieve. Future public health campaigns and education strategies should focus on improving diet knowledge, awareness of food options for diabetes, and effective dietary management.



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The application of defaults to optimize parents' health-based choices for children

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Katharine L. Loeb, Cynthia Radnitz, Kathleen Keller, Marlene B. Schwartz, Sue Marcus, Richard N. Pierson, Michael Shannon, Danielle DeLaurentis
Optimal defaults is a compelling model from behavioral economics and the psychology of human decision-making, designed to shape or "nudge" choices in a positive direction without fundamentally restricting options. The current study aimed to test the effectiveness of optimal (less obesogenic) defaults and parent empowerment priming on health-based decisions with parent-child (ages 3–8) dyads in a community-based setting. Two proof-of-concept experiments (one on breakfast food selections and one on activity choice) were conducted comparing the main and interactive effects of optimal versus suboptimal defaults, and parent empowerment priming versus neutral priming, on parents' health-related choices for their children. We hypothesized that in each experiment, making the default option more optimal will lead to more frequent health-oriented choices, and that priming parents to be the ultimate decision-makers on behalf of their child's health will potentiate this effect. Results show that in both studies, default condition, but not priming condition or the interaction between default and priming, significantly predicted choice (healthier vs. less healthy option). There was also a significant main effect for default condition (and no effect for priming condition or the interaction term) on the quantity of healthier food children consumed in the breakfast experiment. These pilot studies demonstrate that optimal defaults can be practicably implemented to improve parents' food and activity choices for young children. Results can inform policies and practices pertaining to obesogenic environmental factors in school, restaurant, and home environments.



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Peculiar extensibility of swollen statistical hydrogels with structural nanoheterogeneities

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Ryosuke Mishima, Ayuka Nakao, Shinichi Sakurai, Kenji Urayama
An inherent structural nanoheterogeneity in statistical hydrogels leads to a peculiarity in macroscopic tensile properties. Some types of statistical hydrogels with considerable degrees of non-uniform distribution of cross-link, which are formed via free radical copolymerization of mono- and bi-functional monomers, are unusually extensible: The elongation at break before and after equilibrium swelling remains almost unchanged, although the gels undergo a significant increase in volume by swelling, i.e., a finite degree of pre-stretching of network strands. This peculiar extensibility emerges exclusively in uniaxial stretching whereas it is not observed in biaxial stretching including equi-biaxial and planar extension. The concentration ranges of the mono- and bi-functional monomers which result in the gels with the peculiar extensibility are revealed. The two-dimensional SAXS patterns of the uniaxially stretched swollen gels with marked extensibility show the presence of a spatially long-range structure of ca. 50 nm which results from the significantly non-affine deformation of the networks composed of densely and loosely cross-linked regions.

Graphical abstract

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Polylactide (PLA) and acrylonitrile butadiene rubber (NBR) blends: The effect of ACN content on morphology, compatibility and mechanical properties

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Mahshid Maroufkhani, AliAsghar Katbab, Wangcheng Liu, Jinwen Zhang
In this study, attempts have been put to prepare toughened polylactide (PLA) through melt blending with acrylonitrile butadiene rubber (NBR) via melt mixing process. The influences of acrylonitrile (ACN) content on the compatibility, microstructure, tensile properties and impact resistance have been investigated. A matrix-dispersed droplet morphology was noted for all blend samples, and the rubber particle size decreased with decreasing ACN content of NBR. This droplet size, impact strength and elongation all corresponded well to the interfacial interaction that was evidenced by surface tension analysis and melt rheology. It was noted that the interfacial tension decreased with decrease in ACN content, accordingly, the results from both Cole-Cole curves and Han plots indicated high homogeneity of the PLA blend with NBR containing lower ACN contents. On the other hand, all blends exhibited very similar glass transition temperatures and crystallinity. It is concluded that extent of thermodynamic compatibility of PLA and NBR determines the improvement of toughness. Incorporation of only 10 wt% NBR resulted in dramatic improvements of elongation at break and impact strength of PLA and largely retained the high tensile strength of neat PLA.

Graphical abstract

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Symmetric and uniform coalescence of ink-jetting printed polyfluorene ink drops by controlling the droplet spacing distance and ink surface tension/viscosity ratio

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Zhonghui Du, Rubo Xing, Xinxiu Cao, Xinhong Yu, Yanchun Han
The film quality is the core to produce long-life and efficient organic light emitting devices by ink-jetting printing technology which is deeply related to the ink droplet coalescence process, especially the coalescence bead morphology and thickness. However, the fluid flow from impacted drop to the previously deposited drops (drop to bead flow) usually leads to an asymmetry and heterogeneity of coalescence beads during droplets coalescence process in the substrate. Here we reduce the spreading speed of impacted drops to achieve a symmetric and homogeneous coalescence effect, by controlling the drops to deposit firstly and then coalescence. A uniform linear line morphology with a smooth straight edge and symmetric ends was obtained at drop distance 1.35 ≤ y ≤ 1.60. Via adjusting the chloride benzene (CB)/cyclohexylbenzene (ChB) proportion of ink formula, when the γ/η value decreases to 4.73 m/s, the h1/h2 value is nearly 1.04, homogeneous bead obtained. Uniform and homogeneous bead was formed for 80/20 CB/ChB sample with a 4.73 m/s surface tension/viscosity ratio. The appropriate matching of the relationships of the spreading and coalescence speed of impacted drops plays a critical role for the final bead morphology during the droplet coalescence. The spreading and coalescence speed have a finite matching for the 80/20 CB/ChB sample with a 4.73 γ/η value, forming uniform beads.

Graphical abstract

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Mutations in C19orf12 and intronic repeat expansions in C9orf72 not observed in Iranian Parkinson’s disease patients

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): Afagh Alavi, Maryam Malakouti Nejad, Gholamali Shahidi, Elahe Elahi
Various neurodegenerative disorders share some clinical features that sometimes renders differential diagnosis challenging. Genetic based classification also has limitations as mutations in the same gene are sometimes associated with different clinically based diagnoses. In this light, we screened the C19orf12 neurodegeneration with brain iron accumulation (NBIA) causing gene and the C9orf72 intronic expansion mutation that is cause of amyotrophic lateral sclerosis (ALS) in 186 Iranian Parkinson's disease (PD) patients. C19orf12 has previously been screened in PD patients in only one study, and to the best of our knowledge neither gene has ever been screened in a PD cohort from a Middle East population. The study was justified because mutations in C19orf12 had previously been shown to be common in Iranian NBIA patients and all the patients with mutations in this gene had exhibited Parkinsonism features. The C9orf72 intronic expansion mutation was screened because the mother of an Iranian ALS patient with the expansion who had been diagnosed with PD also harbored the expansion. The screenings did not identify disease causing variations in either of the genes among the PD patients screened.



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Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

Publication date: Available online 18 March 2017
Source:Neurobiology of Aging
Author(s): David J. Madden, Emily L. Parks, Catherine W. Tallman, Maria A. Boylan, David A. Hoagey, Sally B. Cocjin, Lauren E. Packard, Micah A. Johnson, Ying-hui Chou, Guy G. Potter, Nan-kuei Chen, Rachel E. Siciliano, Zachary A. Monge, Jesse A. Honig, Michele T. Diaz
Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19-79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.



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Periorbital melasma: Hierarchical cluster analysis of clinical features in Asian patients

Background

Studies have shown melasma lesions to be distributed across the face in centrofacial, malar, and mandibular patterns. Meanwhile, however, melasma lesions of the periorbital area have yet to be thoroughly described.

Methods

We analyzed normal and ultraviolet light-exposed photographs of patients with melasma. The periorbital melasma lesions were measured according to anatomical reference points and a hierarchical cluster analysis was performed.

Results

The periorbital melasma lesions showed clinical features of fine and homogenous melasma pigmentation, involving both the upper and lower eyelids that extended to other anatomical sites with a darker and coarser appearance. The hierarchical cluster analysis indicated that patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face. Significant differences between cluster 1 and cluster 2 were found in lateral distance and inferolateral distance, but not in medial distance and superior distance. Comparing the two clusters, patients in cluster 2 were found to be significantly older and more commonly accompanied by melasma lesions of the temple and medial cheek.

Conclusion

Our hierarchical cluster analysis of periorbital melasma lesions demonstrated that Asian patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face.

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Clinical features and in vivo reflectance confocal microscopy of an atypical presentation of Herpesvirus-2 and Cytomegalovirus co-infection of the intergluteal sulcus

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Deciphering the role of ectosomes in cancer development and progression: focus on the proteome

Abstract

Ectosomes are small heterogeneous membrane vesicles generated by budding from the plasma membrane in a variety of cell types and, more frequently, in tumor cells. They are shed into the extracellular space and are proposed as a novel form of intracellular communication in which information is transmitted from the originating cell to recipient cells without direct cell-to-cell contact. This review focuses on a single population of extracellular vesicles—ectosomes. We summarize recent studies of tumor-derived ectosomes which examine their biogenesis and protein cargo, and their influence on different aspects of cancer progression. We discuss possible clinical implications involving ectosomes as potential biomarkers, diagnostic tools and treatment targets in oncology. The unique composition of the molecules (cargo) that ectosomes carry, and their functional role, depends largely on the state of their originating cell. Through horizontal transfer of a variety of biologically active molecules (including proteins, lipids and nucleic acids) between donor and recipient cells, tumor-derived ectosomes may play functional roles in oncogenic transformation, tumor progression, invasion, metastasis, angiogenesis promotion, escape from immune surveillance, and drug resistance, thereby facilitating disease progression. The presence of tumor-derived ectosomes in body fluids such as the blood and urine of cancer patients makes them potentially useful prognostic and predictive biomarkers. Tumor-derived ectosomes also offer possible targets for multiple therapeutic strategies.

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Effects of laser-arc distance on corrosion behavior of single-pass hybrid welded stainless clad steel plate

Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Kai Kang, Yosuke Kawahito, Ming Gao, Xiaoyan Zeng
Single pass laser-arc hybrid welding of stainless clad steel plate was first carried out to develop alternatives to multi-pass welding with low efficient or single pass welding with poor corrosion resistance. The results demonstrated that the weld corrosion resistance increased with the increase of laser-arc distance (DLA), and the corrosion morphologies changed from big and deep 'nail' pits to small and shallow hemispherical pits. The weld with nearly equal corrosion resistance to the base metal (BM) could be obtained at the DLA of 9mm, where the charge transfer resistance increased to 89% of the BM and the corrosion current density decreased by ten times to close to the BM, only 0.13μA·cm⁻² lower. The corrosion resistance improvement had a good agreement with the microstructure homogenization and the increase of Cr content. The microstructure formation was discussed by the molten pool behavior and the laser-arc interaction. The corrosion resistance improvement was explained by the formation and damage mechanism of the passive film.

Graphical abstract

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Tribute

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Treatment of Nevus lipomatosus cutaneous superficialis with CO2 laser

Summary

Nevus lipomatosus cutaneous superficialis (NLCS) is an uncommon lesion characterized by ectopic adipose tissue in the dermis and can be generalized or localized. It presents as a soft skin colored to yellowish papules or cerebriform plaques occurring usually on the buttock or thigh in a segment distribution. We report a case of NLCS in 38-year-old female, which was treated using the ultrapulse mode CO₂ Laser. We describe the scientific logic and clinical results of using the ultrapulse mode in relation to the pathology of NLCS.

http://ift.tt/2mKU7qE

Reconstruction of Wassel Type VI Radial Polydactyly with Triphalangeal Thumb Using an On-top Osteotomy

Background: The purpose of this study was to present a novel surgical technique using an on-top osteotomy and to assess the clinical and radiographic outcomes for the triphalangeal Wassel type VI thumb duplication patients. Methods: The surgical technique involves ablation of the radial thumb at distal one-third of the metacarpal, corresponding metacarpal osteotomy of the ulnar thumb, with amalgamation of 2 metacarpals and reconstruction of the ulnar thumb by a series of soft tissue procedures. Clinical and radiologic outcomes were evaluated by using the Japanese Society for Surgery of the Hand evaluation form at a minimum of 30 months. The size of the metacarpal was measured and compared to the opposite one to assess the growth of the thumb. Results: Five patients, including 4 males and 1 female, were observed for an average of 37 months. All amalgamated metacarpal showed bone union in 6 weeks after surgery and revealed growth with the age. The average length of the metacarpal was 86% of the opposite one at the final follow-up. Motion at the metacarpophalangeal and interphalangeal joints showed no restriction after surgery, and they reached excellent function for gripping and pinching. According to the JHHS scoring system, the results were excellent in 3 cases, good in 2. Conclusions: This novel surgical technique for the reconstruction of Wassel type VI radial polydactyly with triphalangeal shows encouraging results in both clinical and radiologic evaluations; meanwhile long-term results are under evaluation.

http://ift.tt/2m05hGE

Obesity-related Risk Factors in Implant-based Breast Reconstruction Using AlloDerm

With a population in which 70% of the patients were overweight or obese, we reviewed retrospectively 135 breasts of 70 consecutive patients who underwent implant-based immediate breast reconstruction using freeze-dried AlloDerm as the acellular dermal matrix. Several obesity-related parameters were evaluated to determine their possible correlation to early postoperative complications. We found that breast width and surface area of AlloDerm usage correlated with the development of infection and mastectomy skin flap necrosis. Increased breast width and size of AlloDerm matrix implanted were correlated with higher rates of both minor and significant skin necrosis and of cellulitis. Body mass index was correlated with the development of cellulitis and minor and major skin necrosis but not with seroma or reconstruction failure. Preexisting breast cup size correlated with the development of seroma but not the other complications. We observed no statistically significant association between reconstruction failure and any of the parameters reviewed, but this is likely due to the small number of failures in our data set (n = 10).

http://ift.tt/2m0199Q

A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture

Publication date: Available online 15 March 2017
Source:Acta Histochemica
Author(s): Andrew J. Valente, Lucas A. Maddalena, Ellen L. Robb, Fereshteh Moradi, Jeffrey A. Stuart
Mitochondria exist in a dynamic cycle of fusion and fission whose balance directly influences the morphology of the 'mitochondrial network', a term that encompasses the branched, reticular structure of fused mitochondria as well as the separate, punctate individual organelles within a eukaryotic cell. Over the past decade, the significance of the mitochondrial network has been increasingly appreciated, motivating the development of various approaches to analyze it. Here, we describe the Mitochondrial Network Analysis (MiNA) toolset, a relatively simple pair of macros making use of existing ImageJ plug-ins, allowing for semi-automated analysis of mitochondrial networks in cultured mammalian cells. MiNA is freely available at http://ift.tt/2nUekdO. The tool incorporates optional preprocessing steps to enhance the quality of images before converting the images to binary and producing a morphological skeleton for calculating nine parameters to quantitatively capture the morphology of the mitochondrial network. The efficacy of the macro toolset is demonstrated using a sample set of images from SH-SY5Y, C2C12, and mouse embryo fibroblast (MEF) cell cultures treated under different conditions and exhibiting hyperfused, fused, and fragmented mitochondrial network morphologies.



http://ift.tt/2nqf79X

Increased nuclear localization of substance P in human gastric tumor cells

Publication date: Available online 18 March 2017
Source:Acta Histochemica
Author(s): Miguel Muñoz, Marisa Rosso, Andrés Carranza, Rafael Coveñas
Gastric cancer (GC) is an aggressive disease that remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. Treatment of advanced or metastatic GC has seen little progress and median overall survival in this group remains <1 year. It is urgent to investigate new mechanisms to understand GC progression. It is known that substance P (SP), after binding to the neurokinin-1 (NK-1) receptor, elicits GC proliferation; that GC cells and samples express NK-1 receptors; that NK-1 receptor antagonists, in a concentration dependent manner, inhibit the proliferation of GC cells and that these cells die by apoptosis. However, the presence of SP in GC and normal gastric cells is unknown. In order to know more on the involvement of the SP/NK-1 receptor system in GC, we studied in thirty human GC and normal gastric samples the immunolocalization of SP after using an immunohistochemical technique. SP was observed in the cytoplasm and in the nucleus of GC and normal gastric cells. The nuclear expression of SP was higher in GC cells than in normal cells. No significant difference was observed when the cytoplasmatic expression of SP in normal and GC cells was compared. The findings suggest that SP plays an important role in both nuclear function and GC.



http://ift.tt/2nqf6Tr

Lanthanide-integrated supramolecular polymeric nanoassembly with multiple regulation characteristics for multidrug-resistant cancer therapy

Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Weihong Jin, Qiwen Wang, Min Wu, Yang Li, Guping Tang, Yuan Ping, Paul K. Chu
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes. The PCD/siRNA nanocomplex is further decorated with the exterior neodymium (Nd)-integrated PC (Nd-PC) layer to obtain the PCD/siRNA/Nd-PC nanoassembly in which the interior PC serves as an efficient carrier for simultaneous delivery of Dox and siRNA to the human breast cancer cell line, Dox-resistant MCF-7 (MCF-7/ADR) both in vitro and in vivo. The exterior Nd-PC layer improves the drug sensitivity to the MCF-7/ADR cells as a result of the improved nanoassembly uptake, reduced drug efflux, and enhanced apoptosis, as evidenced by multiple regulation of a series of intracellular proteins related to MDR. Furthermore, in vivo delivery of the PCD/siRNA/Nd-PC nanoassembly is demonstrated to inhibit tumor growth in the mouse model with MCF-7/ADR tumor xenografts as a result of reduced angiogenesis and increased necrosis at the tumor site. This study reveals a simple and universal strategy to transform polymer-based nanoassemblies into advanced organic-inorganic nanotherapeutics suitable for cancer MDR therapy.



http://ift.tt/2mGBW4A

Staphylococcus aureus colonization in atopic eczema and its association with filaggrin gene mutations

Abstract

Background

Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus (S. aureus) has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD. The primary aim of the present study was to assess differences in S. aureus colonization in AD patients with and without filaggrin gene (FLG) mutations. Secondarily, to assess disease severity in relation to S. aureus colonization. Exploratory analyses were performed to investigate S. aureus genetic lineages in relation to FLG mutations and disease severity (SCORAD).

Methods

101 adult AD patients were included in the study. Bacterial swabs were taken from lesional skin, non-lesional skin and nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type assigned. Patients were characterized with respect to disease severity (SCORAD) and FLG mutations (n=88). Fischer's exact test was used to analyze differences in S. aureus colonization in relation to FLG mutations.

Results

Of the 101 patients included, 74 patients (73%) were colonized with S. aureus. Of the colonized patients, 70 patients (95%) carried only one CC type in all three different sampling sites. In lesional skin S. aureus was found in 24 patients with FLG mutations (n=31), versus 24 wild-type patients (n=54) (p=0.0004). S. aureus CC1 clonal lineage was more prevalent in patients with FLG mutations (n=10) than in wild-type patients (n=2) (p=0.003). No specific bacterial lineage was linked to disease severity.

Conclusion

Increased S. aureus colonization in AD patients with FLG mutations, and increased prevalence of CC1 in patients with FLG mutations, suggest that host-microbe interactions and clonal differences in S. aureus are important for colonization of AD skin.

This article is protected by copyright. All rights reserved.

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ERα and GnRH co-localize in the hypothalamic neurons of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Abstract

Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal axis. Estradiol (E₂) affects GnRH synthesis and delivery. Hypothalamic estrogen receptors (ER) modulate GnRH expression acting as transcription factors. The South American plains vizcacha, Lagostomus maximus, is able to ovulate up to 800 oocytes per reproductive cycle, and shows continuous folliculogenesis with pre-ovulatory follicle formation and an ovulatory event at mid-gestation. The aim of this work was to analyze the hypothalamic expression of ER in the vizcacha at different gestational time-points, and its relationship with GnRH expression, serum luteinizing hormone (LH) and E₂. The hormonal pattern of mid-gestating vizcachas was comparable to ovulating-females with significant increases in GnRH, LH and E₂. Hypothalamic protein and mRNA expression of ERα varied during pregnancy with a significant increase at mid-gestation whereas ERβ mRNA expression did not show significant variations. Hypothalamic immunolocalization of ERα was observed in neurons of the diagonal band of Brocca, medial preoptic area (mPOA), periventricular, suprachiasmatic, supraoptic (SON), ventromedial, and arcuate nuclei, and medial eminence, with a similar distribution throughout gestation. In addition, all GnRH neurons of the mPOA and SON showed ERα expression with no differences across the reproductive status. The correlation between GnRH and ERα at mid-gestation, and their co-localization in the hypothalamic neurons of the vizcacha, provides novel information compared with other mammals suggesting a direct action of estrogen as part of a differential reproductive strategy to assure GnRH synthesis during pregnancy.

http://ift.tt/2nTLavv

“Effects of exergames on quality of life, pain and disease impact in women with Fibromyalgia: A randomized controlled trial”

Publication date: Available online 18 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Daniel Collado-Mateo, Francisco Javier Dominguez-Muñoz, Jose Carmelo Adsuar, Miguel Angel Garcia-Gordillo, Narcis Gusi
ObjectiveTo evaluate the effects of an exergame-based intervention in a population sample of women with fibromyalgia.DesignThis study was a single-blinded, randomized controlled trial for 8-week intervention.SettingFibromyalgia center.ParticipantsParticipants (only women) were divided into two groups: an exercise group (n=42; mean age ± SD, 52.52 ± 9.73) and a control group (n=41; mean age ± SD, 52.47 ± 8.75).InterventionWomen in the exercise group completed an 8-week exergame-based training program, which was focused on postural control and coordination of the upper and lower limbs, aerobic conditioning, strength, and mobility. Women (groups of three) were encouraged to exercise for 120 minutes (over two sessions) per week.Main Outcome MeasuresPain and disease impact were assessed with the Fibromyalgia Impact Questionnaire (FIQ), a specific measure to be applied in fibromyalgia. Secondary outcome measure included quality of life, which was assessed with the European Quality of life-5 Dimensions-5 Levels generic instrument (EQ-5D-5L).ResultsThe results showed that 97.62% of participants in the exercise group completed the 8-week intervention. The exercise group showed a significant improvement (p < .05) in the EQ-5D-5L utility index, and in three of five dimensions. For the FIQ, significant improvements were observed in the dimensions "pain", "stiffness", "anxiety", and "feel good". FIQ score was also reduced. The mean between-group improvement (95% CI) was 8.25 (2.85-13.65).ConclusionsThe results and levels of compliance/adherence suggest that this exergame-based training program is an effective intervention for reducing pain and increasing health-related quality of life in women with fibromyalgia.



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Increased Seat Dump Angle in a Manual Wheelchair is Associated with Changes in Thoracolumbar Lordosis and Scapular Kinematics during Propulsion

Publication date: Available online 18 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Beth A. Cloud, Kristin D. Zhao, Arin M. Ellingson, Ahmad Nassr, Anthony J. Windebank, Kai-Nan An
ObjectiveTo quantify and compare spinal curvature and shoulder kinematics throughout the manual wheelchair propulsion cycle for individuals with spinal cord injury (SCI) who were seated at 2 different seat dump angles.DesignSingle-group, repeated-measures study.SettingAcademic medical center.ParticipantsTwenty-eight individuals completed the telephone screening; 21 were eligible and completed the study.InterventionsParticipants' personal manual wheelchairs were modified to have seat dump angles of 0° or 14°, with a vertical backrest. Participants completed at least 3 propulsion cycles in each condition, during which spine and shoulder motion data were collected with fiber optic and electromagnetic sensors, respectively.Main Outcome MeasuresThoracolumbar spinal curvature, glenohumeral kinematics, and scapulothoracic kinematics at the start of push (SP), mid push (MP), end of push (EP), and mid recovery (MR).ResultsParticipants had significantly less lordosis in the 14° condition for all propulsion events. Median differences ranged from 2.0° to 4.6°. Lordosis differences were more pronounced in those with low SCI. Scapulothoracic internal rotation was increased in the 14° condition at SP and MP (mean differences of 2.5° and 2.7°, respectively). Relative downward rotation increased in the 14° condition at SP and MP (mean differences of 2.4° and 2.1°, respectively). Scapulothoracic differences were more pronounced in those with high SCI. No glenohumeral rotations were significantly different between the conditions.ConclusionsScapulothoracic kinematics and spinal curvature differences during propulsion may be associated with the position of other body segments or postural stability. Because no differences were observed at the glenohumeral joint, risk of subacromial impingement may not be affected by this seat angle change.



http://ift.tt/2mYqKSN

Feasibility and safety of a powered exoskeleton for assisted walking for persons with multiple sclerosis: a single-group preliminary study

Publication date: Available online 16 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Allan J. Kozlowski, Michelle Fabian, Dipan Lad, Andrew Delgado
ObjectiveTo examine the feasibility, safety, and secondary benefit potential of exoskeleton-assisted walking with one device for persons with multiple sclerosis (MS)DesignSingle-group longitudinal preliminary study with 8-week baseline, 8-week intervention, and 4-week follow-up.SettingOutpatient MS clinic at tertiary care hospital.ParticipantsThe 13 participants were mostly female who ranged in age from 38-62 years and on Expanded Disability Status Scale scores from 5.5-7.0.InterventionsExoskeleton-assisted walk trainingMain Outcome MeasuresPrimary outcomes were accessibility (enrollment/screen-pass), tolerability (completion/drop-out), learnability (time to event for standing, walking, and sitting with little or no assistance), acceptability (satisfaction on the device subscale of the Quebec User Evaluation of Satisfaction with assistive Technology version 2, or QUEST 2.0), and safety (event rates standardized to person-time exposure in the powered exoskeleton). Secondary outcomes were walking without the device (Timed 25 Foot Walk Test and 6 Minute Walk Test distance), spasticity (Modified Ashworth Scale), and health-related quality of life (PROMIS Pain Interference and Neuro-QoL fatigue, sleep disturbance, depression, and positive affect and well-being).ResultsThe device was accessible to 11 and tolerated by 5 participants. Learnability was moderate, with 5-15 sessions required to walk with minimal assistance. Safety was good; the highest adverse event rate was for skin issues at 151/1000 hours exposure. Acceptability ranged from 'not very satisfied' to 'very satisfied.' Participants who walked routinely improved qualitatively on sitting, standing, or walking posture. Two participants improved and 2 worsened on one or more quality of life domain. The pattern of spasticity scores may indicate potential benefit.ConclusionsThe device appeared feasible and safe for about a third of our sample, for whom routine exoskeleton-assisted walking may offer secondary benefits.



http://ift.tt/2mijW5l

Validation and refinement of prediction models to estimate exercise capacity in cancer survivors using the Steep Ramp Test

Publication date: Available online 18 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Martijn M. Stuiver, Caroline S. Kampshoff, Saskia Persoon, Wim Groen, Willem van Mechelen, Mai JM. Chinapaw, Johannes Brug, Frans Nollet, Marie-José Kersten, Goof Schep, Laurien M. Buffart
ObjectiveTo further test the validity and clinical usefulness of the Steep Ramp Test (SRT) for estimating exercise tolerance in cancer survivors, by external validation and extension of previously published prediction models for VO2peak and Wpeak.DesignCross-sectional study.SettingMulticenter.ParticipantsCardiopulmonary exercise tests (CPET) and SRT data from cancer survivors (n=283) in two randomized exercise trials.InterventionNot applicableMain outcome measuresPrediction model accuracy was assessed by intra class correlation coefficients (ICCs) and Limits of Agreement (LOA). Multiple linear regression was used for model extension. Clinical performance was judged by the percentage of accurate endurance exercise prescriptions.ResultsICCs of SRT-predicted VO2peak and Wpeak with these values as obtained by CPET were 0.61 and 0.73 respectively, using the previously published prediction models. 95%LOA were +/- 705 ml/min with a bias of 190 mL/min for VO2peak, and +/- 59W with a bias of 5W for Wpeak. Modest improvements were obtained by adding body weight and sex to the regression equation for prediction of VO2peak (ICC= 0.73, 95% LOA +/- 608 ml/min), and age, height and sex for prediction of Wpeak (ICC=0.81, 95%LOA +/- 48W). Accuracy of endurance exercise prescription improved from 57% accurate prescriptions to 68% accurate prescriptions with the new prediction model for Wpeak.ConclusionPredictions of VO2peak and Wpeak based on the SRT are adequate at the group level, but insufficiently accurate in individual patients. The multivariable prediction model for Wpeak can be used cautiously (e.g. supplemented with a Borg score) to aid endurance exercise prescription.



http://ift.tt/2nB6U2X

Response to Growth hormone deficiency in mitochondrial disorders

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2nHdQbC

Environmental and genetic determinants of two vitamin D metabolites in healthy Australian children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2nbf6pC

Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2nH5rFe

Antimicrobial Photodynamic Therapy combined to periodontal treatment: experimental model

Publication date: Available online 19 March 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Estéfani L. Belinello-Souza, Letícia H. Alvarenga, Cintia Lima-Leal, Patrícia Almeida, Carolina Guimarães Leite, Tairine R. Lima, Jhosepher Previati-Oliveira, Lucas de Pretto, Anderson Zanardi de Freitas, Adjaci U. Fernandes, Rodrigo L. Marcos, Renato A. Prates
BackgroundAntimicrobial photodynamic therapy (aPDT) has been used as an adjuvant treatment for periodontitis. It combines a photosensitizer with a light source to induce reactive oxygen species and kill microbial cells. PpNetNI is a protoporphyrin derivative, and it has a chemical binding site at biofilm and great affinity to microbial cells. The aim of this study was to investigate the effects of aPDT as an adjuvant treatment for periodontitis.MethodsThirty healthy male rats Wistar (Rattus norvegicus) were used in this study (Approved by UNINOVE Ethical committee AN0029/2015). Periodontitis was induced by placing a cotton ligature around the first mandibular molar in a subgengival position. The contralateral mandibular first molar received neither a ligature nor any treatment, and was used as a control. After 7 days, the ligature was removed and all animals received scaling and root planing (SRP) and were divided according to the following treatments: SRP group (received SRP and irrigation with PpNetNI, 10μM) and aPDT group (PpNetNI 10μM followed by LED irradiation). aPDT was performed with a LED (630nm) with an output power of 400mW (fluence-rate 200mW/cm²; fluence 18J/cm²). Rats were euthanized at 24h, 48h and 7days postoperatively. The area of bone loss in vestibular region of the first molar was evaluated by Optical Coherence Tomography (OCT, THORLABS LTD., Ely, UK). Data were analyzed statistically (ANOVA and Tukey tests, p<0.05).ResultsThe animals treated by aPDT showed bone gain of approximately 30% compared to the SRP group following 7days from the treatment.ConclusionaPDT promoted bone recover 7days after periodontal periodontal intervention.



http://ift.tt/2mK1jDp

ALA-PDT suppressing the cell growth and reducing the lipogenesis in human SZ95 sebocytes by mTOR signaling pathway in vitro

Publication date: Available online 19 March 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Jiang Tuo, Qianqian Wang, Ye Liu, Ying Ma, Li Ma, Jiayi Ying, Chengfeng Zhang, Leihong Xiang
Background5-Aminolevulinic acid mediated −photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, thetherapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate theeffects and mechanisms of ALA-PDTon the cell growth and lipogenesis of human SZ95 sebocytes.Material and methodsHuman SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells.ResultsALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cellsin suppressing the cell growth and reducing the secretion of lipids.ConclusionALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling, and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγsignaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes.



http://ift.tt/2n4FMrK

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): K.C.J.M. Kraal, G.M. Bleeker, B.L.F. van Eck-Smit, N.K.A. van Eijkelenburg, F. Berthold, M.M. van Noesel, H.N. Caron, G.A.M. Tytgat
Aim of the studyRadiolabelled meta-iodobenzylguanidine (MIBG) is an effective option in treatment of neuroblastoma (NBL) tumours. We studied feasibility, toxicity and efficacy of upfront ¹³¹I-MIBG and induction treatment in stage 4 NBL patients.Patients and methodsRetrospective, multi-centre (AMC and EMC) pilot regimen (1/1/2005–2011). Newly diagnosed stage 4 NBL patients, were treated with 2 courses of ¹³¹I-MIBG, GPOH 2004 NBL protocol, myeloablative therapy (MAT) and autologous stem cell rescue (ASCT). ¹³¹I-MIBG was administered in a fixed dose. Response rate (RR) was defined as complete remission, very good partial response and partial response.ResultsThirty-two patients, (median age [range] 2.9 [0–11.4] years), 21 received ¹³¹I-MIBG therapy, 11 did not because of: MIBG non-avid (N = 5) and poor clinical condition (N = 6). In 95% of eligible patients ¹³¹I-MIBG treatment was feasible within 2 weeks from diagnosis. Interval between chemotherapy courses was 25 days (¹³¹I-MIBG group) versus 22 days (chemotherapy group). No stem cell support was needed after ¹³¹I-MIBG therapy. Stem cell harvest in both groups was feasible, neutrophil recovery was comparable, but platelet recovery post MAT, ASCT was slower for ¹³¹I-MIBG-treated patients. RR post ¹³¹I-MIBG was 38%, post MAT + ASCT was 71% (¹³¹I-MIBG group), 36% (chemotherapy group) and overall 59%.ConclusionsInduction therapy with ¹³¹I-MIBG before the HR GPOH NB 2004 protocol is feasible, tolerable and effective in newly diagnosed stage 4 NBL patients. ¹³¹I-MIBG upfront therapy induces early responses.



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Multi-phase distribution and comprehensive ecological risk assessment of heavy metal pollutants in a river affected by acid mine drainage

Publication date: July 2017
Source:Ecotoxicology and Environmental Safety, Volume 141
Author(s): Jianbo Liao, Xuan Ru, Binbin Xie, Wanhui Zhang, Haizhen Wu, Chaofei Wu, Chaohai Wei
To date, there is a lack of a comprehensive research on heavy metals detection and ecological risk assessment in river water, sediments, pore water (PW) and suspended solids (SS). Here, the concentrations of heavy metals, including Cu, Zn, Mn, Cd, Pb and As, and their distribution between the four phases was studied. Samples for analysis were taken from twelve sites of the Hengshi River, Guangdong Province, China, during the rainy and dry seasons. A new comprehensive ecological risk index (CERI) based on considering metal contents, pollution indices, toxicity coefficients and water categories is offered for prediction of potential risk on aquatic organisms. The results of comprehensive analysis showed that the highest concentrations of Cu, Zn and Mn of 6.42, 87.17 and 98.74mg/L, respectively, in PW were comparable with those in water, while concentrations of Cd, Pb and As of 609.5, 2757 and 96.38μg/L, respectively, were 2–5 times higher. The sum of the exchangeable and carbonate fractions of target metals in sediments followed the order of Cd > Mn > Zn > Pb > Cu > As. The distribution of heavy metals in phases followed the order of sediment > SS > water > PW, having the sum content in water and PW lower than 2% of total. The elevated ecological risk for a single metal and the phase were 34,585 for Cd and 1160 for water, respectively, implied Cd as a priority pollutant in the considered area. According to the CERI, the maximum risk value of 769.3 was smaller than 1160 in water, but higher than those in other phases. Out of considering the water categories and contribution coefficients, the CERI was proved to be more reliable for assessing the pollution of rivers with heavy metals. These results imply that the CERI has a potential of adequate assessment of multi-phase composite metals pollution.

Graphical abstract

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