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Τρίτη 20 Ιουνίου 2017

Scholar : Ειδοποίηση Μελετητή - [ ΠΑΛΙΝ

Ειδοποίηση Μελετητή:[ ΠΑΛΙΝΔΡΟΜΗΣΗ ]

[PDF] To σύνδρομο της επαγγελματικής εξουθένωσης (Burnout) και η επαγγελματική ικανοποίηση των Καθηγητών Φυσικής Αγωγής

Ε Παπασωτηρίου - 2017
Page 1. ΘΕΜΑ ΔΙΠΛΩΜΑΤΙΚΗΣ ΕΡΓΑΣΙΑΣ «To σύνδρομο της επαγγελματικής εξουθένωσης
(Burnout) και η επαγγελματική ικανοποίηση των Καθηγητών Φυσικής Αγωγής». (Η περίπτωση
των : Κ.Φ.Α. που εργάζονται σε αθλητικούς οργανισμούς των Ο.Τ.Α.) ΑΕΙ ΠΕΙΡΑΙΑ Τ.Τ. ...
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Scholar : Ειδοποίηση Μελετητή - [ ωτα ]

Ειδοποίηση Μελετητή:[ ωτα ]

[HTML] E-SUS: Adesão ao PSE 2017

JFL Junior, G França - 2017
ftypisom*isomiso2avc1mp41*free*¼π├mdat▐*libfaac 1.28Bô *2G*ü** }▄EΘ╜µ┘H╖û,╪
┘#ε∩x264 - core 148 r2579 73ae2d1 - H.264/MPEG-4 AVC codec - Copyleft 2003-2015 -
http://ift.tt/1cmqH4m - options: cabac=0 ref=2 deblock=1:0:0 analyse=0x1:0x111 ...
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Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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Scholar : Ειδοποίηση Μελετητή - [ ΣΤΟΜΑ

Ειδοποίηση Μελετητή:[ ΣΤΟΜΑΤΙΤΙΣ ]

[PDF] Vesicular stomatitis virus pseudotyped with Ebola virus glycoprotein serves as a protective, non-infectious vaccine against Ebola virus challenge in mice

NJ Lennemann, AS Herbert, R Brouillette, B Rhein… - Journal of Virology, 2017
ABSTRACT The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the
potential for a significant public health burden caused by filoviral infections. No vaccine or
antiviral is currently FDA-approved. To expand the vaccine options potentially available, we
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[PDF] Current Diagnosis and Treatment Models of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Lymphadenitis Syndrome

AP Kısaarslan, EK Ünsür, B Sözeri - 2017
Periodic fever, aphthous stomatitis, pharyngitis, and cervical lymphadenitis (PFAPA)
syndrome is the most frequent cause of periodic fever in childhood. The pathogenesis of
PFAPA is still unknown. Differantial diagnosis must be made with cyclic neutropenia and
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[PDF] МОНОЦУКРИДНИЙ СКЛАД РАБДОВІРУСІВ, І3ОЛЬОВАНИХ 3 ТВАРИН ТА РОСЛИН

ЛФ Діденко, ЛД Варбанець, ТЮ Сaбiровa… - Мікробіологія і …, 2017
... K eywords: carbohydrates, rhabdoviruses, vesicular stomatitis virus, curly potato dwarf virus,
spot sweetflag virus. Carbohydrate component of viral glycoproteins plays the leading role in
the virus genome expression. Rhabdoviruses contain 3 % of carbohydrates. ...
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Assessment of nutritional status in children of an orphanage

KS Soudhabi, B Bhat, S Anees, S Bangera - Indian Journal of Clinical Anatomy and …, 2017
(66.249.79.157). Users online: 2783, [ij] [ij] [ij],
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Cerebral venous thrombosis a rare complication of ulcerative colitis–Case report

E Marušić, A Ursic, R Despot, M Simunovic, ML Doric… - European Journal of …, 2017
... The incidence of extraintestinal manifestations/complica- tions in inflammatory bowel disease
in children is around 6% at the beginning of the disease with prevalence gradually increasing
with age. The most common are arthritis, aphthous stomatitis and osteopenia. ...
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Genetic background of Moyamoya syndrome: report of 3 new cases

S Gueden, M Gibaud, J Durigneux, M Delion, E Colin… - European Journal of …, 2017
... The incidence of extraintestinal manifestations/complica- tions in inflammatory bowel disease
in children is around 6% at the beginning of the disease with prevalence gradually increasing
with age. The most common are arthritis, aphthous stomatitis and osteopenia. ...
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Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents

K Klimenko, S Lyakhov, M Shibinskaya, A Karpenko… - Bioorganic & Medicinal …, 2017
... acid intercalators. Earlier obtained experimental data for DNA intercalation affinities
and activities against Vesicular stomatitis virus (VSV) have been used to build,
respectively, pharmacophore and QSAR models. These models ...
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Cerebral venous thrombosis in pediatric patients–Clinical and imaging aspects

S Dana, C Sandu, D Mavrodin, N Butoianu, C Iliescu… - European Journal of …, 2017
... The incidence of extraintestinal manifestations/complica- tions in inflammatory bowel disease
in children is around 6% at the beginning of the disease with prevalence gradually increasing
with age. The most common are arthritis, aphthous stomatitis and osteopenia. ...
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Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations

P Chalasani - Oncology, 2017
... assessed. Stomatitis/oral mucositis are among the most common AEs associated with
everolimus therapy [19, 72] . In the BOLERO-2 study, the incidence of all-grade stomatitis
was 67% in the exemestane plus everolimus group [73] . ...
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Antiherpetic (HSV-1) activity of carrageenans from the red seaweed Solieria chordalis (Rhodophyta, Gigartinales) extracted by microwave-assisted extraction (MAE)

R Boulho, C Marty, Y Freile-Pelegrín, D Robledo… - Journal of Applied …, 2017
... Polysaccharides extracted from Rhodophyta have been shown to exhibit antiviral activity against
a wide spectrum of viruses including important human pathogenic agents such as human
immunodeficiency virus (HIV), Herpes simplex virus (HSV), Vesicular stomatitis virus (VSV ...
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Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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Scholar : Ειδοποίηση Μελετητή - [ Εξωτε

Ειδοποίηση Μελετητή:[ Εξωτερική ωτίτιδα ]

[PDF] Σεξουαλικώς μεταδιδόμενα νοσήματα και ο ρόλος του νοσηλευτή.

Α Αργυροκαστρίτη - 2017
... Τα συνηθέστερα αποτελούν την τριάδα του Hutchinson. α. Διάμεσος κερατίτις β. Μέση πυώδης
ωτίτιδα (κώφωση) γ. Οδóντες του Hutchinson (οδóντες με εντομή) (Κατσάμπας, 2007). ΘΔΡΑΠΔΗΑ
Η θεραπεία γίνεται με αντιβιοτικά ανάλογα με το στάδιο της νóσου. Η ...
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Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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Changes in plasma miR-9, miR-16, miR-205 and miR-486 levels after non-small cell lung cancer resection

Abstract

Purpose

The majority of non-small cell lung cancer (NSCLC) patients presents with an advanced-stage disease and, consequently, exhibits a poor overall survival rate. We aimed to assess changes in plasma miR-9, miR-16, miR-205 and miR-486 levels and their potential as biomarkers for the diagnosis and monitoring of NSCLC patients.

Methods

Plasma was collected from 50 healthy donors and from NSCLC patients before surgery (n = 61), 1 month after surgery (n = 37) and 1 year after surgery (n = 14). microRNA levels were quantified using qRT-PCR.

Results

We found in NSCLC patients before treatment, both with squamous cell carcinoma (SQCC) and adenocarcinoma (ADC), significantly higher plasma miR-16 and miR-486 levels than in healthy individuals. Pre-treatment miR-205 concentrations were found to be significantly higher in SQCC than in ADC patients, and only SQCC patients presented significantly higher circulating miR-205 levels than healthy donors. SQCC plasma miR-9 levels were not different from normal control levels, but in ADC they were found to be significantly decreased. A combination of plasma miR-16, miR-205 and miR-486 measurements was found to discriminate NSCLC patients from healthy persons, with a specificity of 95% and a sensitivity of 80%. Following tumor resection, we found that the miR-9 and miR-205 levels significantly decreased, even below the normal level, whereas the increased miR-486 level persisted up to one year after surgery, and the miR-16 level decreased to normal. After tumor resection, none of the miR levels tested was found to relate to recurrence.

Conclusions

Our data indicate that miR-9, miR-16, miR-205 and miR-486 may serve as NSCLC biomarkers. The observed cancer-related pre- and post-operative changes in their plasma levels may not only reflect the presence of a primary cancer, but also of a systemic response to cancer.



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mRNA transport & local translation in neurons

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Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Caspar Glock, Maximilian Heumüller, Erin M Schuman
Neurons are amongst the most structurally complex cells and exhibit a high degree of spatial compartmentalization. Also, neurons exhibit rapid and dynamic signaling by processing information in a precise and, sometimes, spatially-restricted manner. The signaling that occurs in axons and dendrites necessitates the maintenance and modification of their local proteomes. Local translation of mRNAs into protein is one solution that neurons use to meet synaptic demand and activity. Here we review some of the key findings and recent discoveries that have shaped our understanding of local translation in neuronal function and highlight important new techniques that might pave the way for new insights.



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Administration of a leptin antagonist during the neonatal leptin surge induces alterations in the redox and inflammatory state in peripubertal /adolescent rats

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Publication date: Available online 19 June 2017
Source:Molecular and Cellular Endocrinology
Author(s): Virginia Mela, Oskarina Hernandez, Caroline Hunsche, Francisca Diaz, Julie A. Chowen, Mónica De la Fuente
The importance of the neonatal leptin surge in rodents in neurodevelopmental processes has aroused curiosity in its implication in other physiological systems. Given the role of leptin in neuro-immune interactions, we hypothesized that the neonatal leptin surge could have an effect on the oxidative and inflammatory stress situations of both systems. We blocked the neonatal leptin surge by a leptin antagonist and measured several parameters of oxidative and inflammatory stress in the spleen, hypothalamus and adipose tissue of peripubertal/adolescent rats. The treated rats showed lower activity of several antioxidant enzymes in the spleen and their leukocytes released lower levels of mitogen-stimulated IL-10 and IL-13 and higher levels of TNF-alpha. In conclusion, the neonatal leptin surge may have a key role in the establishment of adequate redox and inflammatory states in the immune system, which is important for the generation of adequate immune responses and to obtain and maintain good health.



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High toxicity of camphene and γ-elemene from Wedelia prostrata essential oil against larvae of Spodoptera litura (Lepidoptera: Noctuidae)

Abstract

The development of eco-friendly biopesticides in the fight against agricultural pests is an important challenge nowadays. The essential oil of Wedelia prostrata Hemsl. is known for its multipurpose biological activities in Chinese folk medicine. However, limited efforts attempted to understand the potential insecticidal activity of its main individual constituents and related mechanism of action. In this research, we investigated the insecticidal activity of W. prostrata against the crop pest Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Toxicity on 4th instar larvae was assessed after 24 h of exposure. The LC50 and LC90 of the W. prostrata essential oil were 167.46 and 322.12 μg/ml, respectively. GC-MS analyses were carried out to shed light on the oil chemical composition. Main constituents were the monoterpene camphene (9.6%) and the sesquiterpenes γ-elemene (7.6%), α-humulene (6.9%), and (E,E)-α-farnesene (7.3%). The pure constituents were evaluated for their insecticidal activity on S. litura 4th instar larvae. The most toxic molecule was camphene (LC50 = 6.28 μg/ml), followed by γ-elemene, (LC50 = 10.64 μg/ml), α-humulene (LC50 = 12.89 μg/ml), and (E,E)-α-farnesene (LC50 = 16.77 μg/ml). Overall, our experiments highlighted the promising potential of camphene and γ-elemene from W. prostrata essential oil against larvae of S. litura, allowing us to propose these two compounds for the development of newer pesticides in the fight against crop pests. Further studies aimed at evaluating the potential synergy between these two molecules, as well as their stability in field conditions are ongoing.



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Effects of perfluorooctanoic acid and perfluorooctane sulfonate on acute toxicity, superoxide dismutase, and cellulase activity in the earthworm Eisenia fetida

Abstract

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the two best-known perfluorinated chemicals and have received much attention due to their ubiquity in the environment. In the present study, we evaluated the effects of PFOS and PFOA on acute toxicity, superoxide dismutase (SOD), and cellulase activities in Eisenia fetida. The results of acute toxicity testing using a filter paper contact test and a natural field soil test showed that PFOA and PFOS exhibited acute toxicity in earthworms, and the toxic effect of PFOS was greater than that of PFOA. The results also showed that avoidance behavior is a more sensitive and easy operation biomarker than acute toxicity and will give us information for early diagnosis of soil pollution, well before the lethal effect becomes apparent. Subchronic exposure to PFOA or PFOS resulted in changes in SOD and cellulase activities in E. fetida, and SOD activity was more sensitive than cellulase activity during early exposure. Based on these findings, we suggest that avoidance behavior and SOD activity in earthworms are suitable biomarkers for evaluating the toxicity of PFOA- and PFOS-contaminated soils. These results indicate that exposure to PFOA and PFOS has a potential impact on soil animals and their environment.



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Distribution, transfer, and health risks of polycyclic aromatic hydrocarbons (PAHs) in soil-wheat systems of Henan Province, a typical agriculture province of China

Abstract

In order to investigate the distribution, transfer, and human health risks of polycyclic aromatic hydrocarbons (PAHs) in the soil-wheat systems, soil samples from 20 farmlands and corresponding wheat tissues were collected from selected regions of Henan Province in June 2013 and were analyzed to estimate the concentration of PAHs. The total concentrations of 15 PAHs (∑15PAHs) in soils from Henan Province varied from 6.91 to 72.4 ng/g. Moreover, two-ring to three-ring PAHs (1.59–29.1 ng/g) were the major species in soils, occupying 56.2% of total PAHs. Principal component analysis (PCA)-multiple linear regression (MLR) revealed that fossil fuel burning dominated the input of PAHs in agricultural soils of Henan Province. The range of ∑15PAHs concentrations in wheat tissues was 13.9–50.9 ng/g, which decreased along the root-straw-grain. Positive correlation among PAHs of soil and wheat tissues showed that PAHs in wheat mainly came from soil and then migrated along root-straw-grain. Moreover, PAHs were accumulated highest in root and lowest in grain. Two-ring to three-ring PAHs were easier to transfer from soil to wheat than five-ring to six-ring PAHs. Consumption of wheat grain created potential risk of cancer in Henan Province.



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Evaluation in situ of genotoxicity and stress in South American common toad Rhinella arenarum in environments related to fluorite mine

Abstract

Little attention has been paid to the impact of wastewater generated by mining activities on fluoride. In this study, we evaluated the hematology responses of common South American toad Rhinella arenarum inhabiting natural and artificial environments associated with a fluorite mine from central Argentina. We analyzed three sampling stations associated with the fluorite mine: (I) Los Cerros Negros stream (CN), which runs on granitic rock with a high fluorite content; (II) Los Vallecitos stream (LV), which runs on metamorphic rock with low fluorite content; and (III) artificial decantation ponds (DP) containing sediments produced by fluorite flotation process. We calculated frequencies of micronuclei, erythrocyte nuclear abnormalities, mitosis, and immature erythrocytes. In addition, we performed a differential leukocyte count and determined neutrophils/lymphocyte ratio as a stress response estimator. We found high micronucleus (MN) and erythrocyte nuclear abnormality (ENA) frequencies in DP and CN but low frequencies in LV. The neutrophil/lymphocyte ratio was different among sites, with a significant increase in individuals from DP. Values registered in DP could be caused by exposure to mixture of compounds registered in dams that hold wastewater, while high values registered in CN stream might be due to natural concentrations of fluoride. Our results suggest that blood is an effective and non-destructive sensitive indicator for monitoring genotoxic agents in freshwater ecosystems.



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Perceptual statistical learning over one week in child speech production

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Publication date: Available online 17 June 2017
Source:Journal of Communication Disorders
Author(s): Peter T. Richtsmeier, Lisa Goffman
What cognitive mechanisms account for the trajectory of speech sound development, in particular, gradually increasing accuracy during childhood? An intriguing potential contributor is statistical learning, a type of learning that has been studied frequently in infant perception but less often in child speech production. To assess the relevance of statistical learning to developing speech accuracy, we carried out a statistical learning experiment with four- and five-year-olds in which statistical learning was examined over one week. Children were familiarized with and tested on word-medial consonant sequences in novel words. There was only modest evidence for statistical learning, primarily in the first few productions of the first session. This initial learning effect nevertheless aligns with previous statistical learning research. Furthermore, the overall learning effect was similar to an estimate of weekly accuracy growth based on normative studies. The results implicate other important factors in speech sound development, particularly learning via production.



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Speech-language pathologists’ preferences for patient-centeredness

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Publication date: Available online 17 June 2017
Source:Journal of Communication Disorders
Author(s): Monica L. Bellon-Harn, Jamie Hartwell Azios, Ashley L. Dockens, Vinaya Manchaiah




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SIRT1 Enzymatically Potentiates 1,25-Dihydroxyvitamin D3 Signaling via Vitamin D Receptor Deacetylation

Publication date: Available online 19 June 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Marya S. Sabir, Chengcheng Hu, Zainab Khan, Michael A. Galligan, Christopher M. Dussik, Sanchita Mallick, Angelika Dampf Stone, Shane F. Batie, Elizabeth T. Jacobs, G.Kerr Whitfield, Mark R. Haussler, Michael C. Heck, Peter W. Jurutka
The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR-deacetylation, vitamin-D-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kidney and TE85 bone cells, co-transfection of low amounts (1–5ng) of a SIRT1-expression vector elicits a reproducible and statistically significant enhancement (1.3- to 2.6-fold) in transcription mediated by VDREs from the CYP3A4 and cyp24a1 genes, where the magnitude of response to 1,25D-ligand is 6- to 30-fold. Inhibition of SIRT1 via EX-527, or utilization of a SIRT1 loss-of-function mutant (H363Y), resulted in abrogation of SIRT1-mediated VDR potentiation. Studies with a novel, non-acetylatable VDR mutant (K413R) showed that the mutant VDR possesses enhanced responsiveness to 1,25D, in conjunction with reduced, but still significant, sensitivity to exogenous SIRT1, indicating that acetylation of lysine 413 is relevant, but that other acetylated residues in VDR contribute to modulation of its activity. We conclude that the acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This regulatory loop is reversed by SIRT1-catalyzed deacetylation of VDR to amplify VDR signaling and 1,25D actions.



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One year on: Test your knowledge from the previous year

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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Contents

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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Surgical Treatment of Splenic Artery Aneurysm

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1
Author(s): P. Berek, P. Štefanič




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Editorial Board

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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Spanish Translated Abstracts

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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A Retrograde Endo-bypass to Revascularise an Isolated Internal Iliac Artery

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1
Author(s): E. Girsowicz, N. Chakfé




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Selected Abstracts from the July Issues of the Journal of Vascular Surgery and the Journal of Vascular Surgery: Venous and Lymphatic Disorders

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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Forthcoming Events

Publication date: July 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 1





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Hydroxyapatite/chemically reduced graphene oxide composite: Environment-friendly synthesis and high-performance electrochemical sensing for hydrazine

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Publication date: 15 November 2017
Source:Biosensors and Bioelectronics, Volume 97
Author(s): Feng Gao, Qingxiang Wang, Ningning Gao, Yizhen Yang, Fuxian Cai, Mayoka Yamane, Fei Gao, Hidekazu Tanaka
It is unexpectedly found that, the in-situ growth of hydroxyapatite (HAP) on graphene oxide (GO) under a moderate temperature (85°C) can effectively trigger the reduction of GO, which needs neither extra reducing agents nor high-temperature thermal treatment. The transmission electron microscope (TEM) experiment demonstrates that the rod-like HAP particles are well attached on the surface of reduced GO (rGO) to form the composite. Electrochemical sensing assays show that the synthesized HAP-rGO nanocomposite presents excellent electrocatalytic capacity for the oxidation of a toxic chemical of hydrazine. When the HAP-rGO modified electrode was utilized as an electrochemical sensor for hydrazine detection, outstanding performances in the indexes of low fabrication cost, short response time (~2s), wide linear range, low detection limit (0.43μM), and good selectivity were achieved. The developed sensor also shows satisfactory results for the detection of hydrazine in real industrial wastewater sample were achieved.



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How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey

Abstract

Objective

Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated.

Methods

The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey.

Results

One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time.

Conclusion

Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.



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Macromolecules of polycarboxybetaine poly(4-N,N-diallyl-N-methylammonio) butanoate: Synthesis and molecular characteristics

Publication date: Available online 19 June 2017
Source:Polymer
Author(s): N.V. Tsvetkov, A.A. Lezov, P.S. Vlasov, A.S. Gubarev, A.A. Lezova, E.V. Lebedeva, G.E. Polushina, N.S. Domnina
A series of water-soluble poly(carboxybetaines) (poly(4-(diallyl(methyl)ammonio)butanoates), poly(DAMAB)) was synthesized. Detailed studies of the solution properties of these poly(carboxybetaines) were performed using viscometry, static and dynamic light scattering, velocity sedimentation and flow birefringence. Molar masses, other molecular parameters and conformational characteristics of the macromolecules were determined in water and 1 MNaCl solutions. The Mark-Kuhn-Houwink and scaling equations were obtained for poly(DAMAB). It was established that 1 M NaCl solution is a thermodynamically good solvent for poly(DAMAB). In water, the conformation of poly(DAMAB) molecules is similar to that of a polymer coil under θ-conditions. The Kuhn segment length for poly(DAMAB) molecules was A=7nm in water and in 1 MNaCl solution. Data on the thermal stability of DAMAB and its polymer were obtained. Thorough consideration of contributions of optical effects of micro- and macroform into the observed flow birefringence in copolymer solutions allowed us to estimate optical characteristics of copolymer macromolecules. Optical anisotropy of polarizability of the monomer unit of the studied poly(DAMAB) was negative. This fact indicates that the main anisotropic groups are located along the longer axis of their optical polarizabilities at high angles to the direction of the polymer chain growth.

Graphical abstract

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Employment Stability in Veterans and Service Members with Traumatic Brain Injury:A VA Traumatic Brain Injury Model Systems Study

Publication date: Available online 17 June 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Christina Dillahunt-Aspillaga, Mary Jo Pugh, Bridget A. Cotner, Marc A. Silva, Adam Haskin, Xinyu Tang, Marie E. Saylors, Risa Nakase-Richardson
ObjectiveTo examine incidence and predictors of employment stability in Veterans and Military Service Members (V/SM) with traumatic brain injury (TBI) who return to work.DesignProspective observational cohort study.SettingFour Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs).Participants110 V/SM with mild (26%), moderate (22%), or severe (52%) TBI enrolled in the VA PRC TBI Model Systems database within 2 years of injury who were discharged between January 2009 and June 2015.Main Outcome MeasuresEmployment stability as reflected by competitive employment at 1- and/or 2-year follow-up.ResultsOver half (n=61, 55%) had stable employment at the time the first competitive employment date was recorded. Individuals with stable employment were more likely to be Caucasian (79%) and to have slightly higher cognitive and motor discharge scores on the Functional Independence Measure (FIMTM). Based on univariate analysis, more severe TBI and higher FIMTM motor scores at discharge were significantly associated with employment stability. At follow up, compared with V/SM who had unstable employment, those with stable employment had higher scores on motor and cognitive FIMTM and lower scores of self-report symptoms on the Neurobehavioral Symptom Inventory, the 9-item Patient Health Questionnaire-Depression , the 7-item Generalized Anxiety Disorder Questionnaire, and the PTSD Checklist-Civilian version.ConclusionsA number of unique factors affect employment stability in V/SM with TBI. Study findings identify V/SM who have stable employment and predictors of employment stability.



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A new and accurate predictive model for the efficacy of extracorporeal shock wave therapy in managing patients with chronic plantar fasciitis

Publication date: Available online 17 June 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mengchen Yin, Ni Chen, Quan Huang, Anastasia Sulindro Marla, Junming Ma, Jie Ye, Wen Mo
ObjectivesTo identify factors for the outcome of a minimum clinically successful therapy and to establish a predictive model of extracorporeal shock wave therapy (ESWT) in managing patients with chronic plantar fasciitis.DesignRandomized controlled, prospective study.SettingOutpatient of local medical center settings.ParticipantsPatients treated for symptomatic chronic plantar fasciitis between 2014 and 2016 (N=278).InterventionsESWT was performed by the principal authors to treat chronic plantar fasciitis. ESWT was administered in 3 sessions, with an interval of 2 weeks (±4 days). In the low, moderate and high-intensity group, 2400 impulses total of ESWT with an energy flux density of 0.2mJ/mm2, 0.4mJ/mm2, 0.6mJ/mm2 respectively (a rate of 8 impulses per second) were appliedMain outcome measuresThe demographic and clinical characteristics independent variables were patient age, gender, BMI, affected side, duration of symptoms, Roles and Maudsley score, VAS when taking first steps in the morning, oedema, bone spurs and intensity grade of ESWT. A minimal reduction of 50% in the VAS was considered as minimum clinically successful therapy (MCST). The correlations between the achievement of MCST and independent variables were analyzed. The statistically significant factors identifies were further analyzed by multivariate logistic regression, and the predictive model was established.ResultsThe success rate of ESWT was 66.9%. Univariate analysis found that VAS when taking first steps in the morning, oedema and the presence of heel spur in X-ray significantly affected the outcome of the treatment. Logistic regression draw the equation: MCST=[1+e(0.011+42.807∗heel spur+0.109∗ Oedema+5.395∗VAS)]-1.The sensitivity of predictive factors was 96.77%, 87.63% and 86.02%, respectively. The specificity 45.65%, 42.39% and 85.87%, respectively. The AUC was 0.751, 0.650 and 0.859, respectively. Youden index was 0.4243, 0.3003 and 0.7189, respectively. Hosmer-Lemeshow test showed a good fitting of the predictive model with an overall accuracy of 89.6%.ConclusionsThe study establishes a new and accurate predictive model for the efficacy of ESWT in managing patients with chronic plantar fasciitis. The use of these parameters, in the form of a predictive model for ESWT efficacy, has the potential to improve decision-making in the application of ESWT.



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Attenuated error-related potentials in amyotrophic lateral sclerosis with executive dysfunctions

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Publication date: August 2017
Source:Clinical Neurophysiology, Volume 128, Issue 8
Author(s): Caroline Seer, Max Joop, Florian Lange, Christian Lange, Reinhard Dengler, Susanne Petri, Bruno Kopp
ObjectiveExecutive dysfunctions affect up to 50% of the patients with amyotrophic lateral sclerosis (ALS). Executive dysfunctions have been identified as negative prognostic factor and can affect quality of life in patients and their caregivers. Assessment of executive dysfunction may be impeded by the patients' motor impairments. Event-related potentials (ERP) have been proposed as a tool to overcome these assessment difficulties. The error(-related) negativity (Ne/ERN) is an ERP which can be recorded with minimal motor requirements for the patient.MethodsWe compared response-synchronized ERP amplitudes of 18 ALS patients and 19 healthy controls (HC) obtained on error trials on a flanker task. We also evaluated the relation between Ne/ERN amplitudes and executive functions as assessed by standardized neuropsychological measures.ResultsWhile response-synchronized ERP amplitudes were generally unaffected by ALS, we found an ALS-associated relation between Ne/ERN amplitudes and executive functions. ALS patients with poorer executive functioning showed attenuated Ne/ERN amplitudes.ConclusionsOur data suggest that Ne/ERN amplitudes reflect ALS-associated impairment of executive functions, potentially due to disturbances in neural networks that involve the anterior cingulate cortex.SignificanceAssessment of Ne/ERN amplitudes might provide a cost-efficient and non-invasive marker for executive dysfunction in ALS.



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Degeneration of the vestibular nerve in unilateral Meniere’s disease evaluated by galvanic vestibular-evoked myogenic potentials

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Publication date: Available online 19 June 2017
Source:Clinical Neurophysiology
Author(s): Chih-Ming Chang, Yi-Ho Young, Fu-Shan Jaw, Chi-Te Wang, Po-Wen Cheng
ObjectiveThe staging system of Meniere's disease utilizes audiograms to probe cochlear dysfunction. We explored the addition of galvanic vestibular-evoked myogenic potentials (VEMP) to further explore vestibular function.MethodsSeventy patients with unilateral Meniere's disease were enrolled in this study. Within 2 weeks of diagnosis, all subjects underwent pure tone audiometry, cervical and ocular VEMP, and caloric test. The prevalence of abnormal tests and the VEMP characteristic parameters such as latencies and amplitudes were analyzed.ResultsIn affected ears, the abnormal rate of acoustic cVEMPs, galvanic cVEMPs, vibratory oVEMPs and galvanic oVEMPs was 37%, 17%, 20% and 9%, respectively. No significant differences existed in VEMP latencies and amplitudes between affected ears and unaffected ears.ConclusionsThe impairment of otolithic organs was found to be more than that of vestibular afferents. The deterioration of the saccule was more than that of the utricle, whereas retrolabyrinthine degeneration of sacculo-collic reflex and vestibulo-ocular reflex was similar.SignificanceThis study is the first to use an electrophysiological test to evaluate the retrolabyrinthine function of patients with unilateral Meniere's disease.



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Complementary and Alternative Therapies for Restless Leg Syndrome: An Evidence-Based Systematic Review

Restless leg syndrome (RLS) is defined as an irresistible urge to move the legs, which is usually accompanied by paresthesias or dysesthesias, and affects 2% to 4% of adults in Europe and North America at least twice weekly. This systematic review assesses the current complementary and alternative options for RLS and the potential benefits of those treatments on sleep quality, mood disorder, and quality of life. A systematic search of the PubMed, Embase, Cochrane, and Web of Science databases was conducted.

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Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Yasuyo Suga, Kenji Takehana
S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b+TIM-4+ cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b+TIM-4+ cells.



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Roles of serum in innate immune responses of human leukocytes to synthetic lipopeptide

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Terukazu Sanui, Masaaki Takeshita, Takao Fukuda, Urara Tanaka, Rehab Alshargabi, Yoshitomi Aida, Fusanori Nishimura
Tripalmitoyl-S-glyceryl-l-Cys-Ser-(Lys)4 (Pam3CSK4) is a highly conserved molecular motif found in various classes of lipoproteins. The requirement for leukocyte to respond to synthetic Pam3CSK4 were studied. Pam3CSK4 primed neutrophils for a respiratory burst in a serum-dependent manner. Pam3CSK4 upregulated CD11b, CD14, and cytochrome b558, and downregulated Leu-8. Treatment of neutrophils with anti-CD14 antibodies and treatment of serum with anti-LPS binding protein (LBP) antibodies resulted in the inhibition of priming for respiratory burst by Pam3CSK4. It should be noted that LBP could not replicate the effects of serum in priming of neutrophils for respiratory burst by Pam3CSK4. Serum LBP bound to immobilized Pam3CSK4. Pam3CSK4 induced the interleukin-8 (IL-8) production by leukocytes in a serum-dependent manner. Further, Pam3CSK4-induced priming of neutrophils for respiratory burst was not inhibited by the LPS antagonists LA-14-PP, Rhodobacter sphaeroides LPS, or E5531, and Pam3CSK4-induced IL-8 production by leukocytes was not affected by LPS antagonist, E5531, indicating that Pam3CSK4 was recognized by a different receptor than LPS. Thus, Pam3CSK4 and LPS had similar biological activities and similar requirement to act on leukocytes, but were recognized by different receptors. Serum in the action of Pam3CSK4 on leukocytes was not replicated by LBP, suggesting that Pam3CSK4 might be disaggregated by serum to result in the activation of leukocytes.



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An altered REDOX environment, assisted by over-expression of fetal hemoglobins, protects from inflammatory colitis and reduces inflammatory cytokine expression

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): R.M. Gorczynski, C. Alexander, K. Brandenburg, Z. Chen, A. Heini, D. Neumann, J.P. Mach, E.T. Rietschel, A. Tersikh, A.J. Ulmer, Kai Yu, U. Zahringer, I. Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents. We speculated that this combination led to an altered tissue redox environment in which the immune response developed, thus regulating inflammation. Accordingly, we used wild-type (WT) C57BL/6 mice, or mice lacking either murine beta Hemoglobin major (HgbβmaKO) or minor (HgbβmiKO) as recipients of DSS in their drinking water, and followed development of colitis both clinically and by inflammatory cytokine production, before/after oral treatment of mice with a crude fetal liver extract. Mice lacking an intact fetal hemoglobin chain (HgbβmiKO) developed severe colitis, with enhanced colonic expression of inflammatory cytokines, which could not be rescued by extract, unlike WT and HgbβmaKO animals. Moreover, disease in both WT and HgbβmaKO animals could also be attenuated by exposure to 5-hydroxymethyl furfural (5HMF), hydroxyurea or rapamycin. The former has been used as an alternative means of stabilizing the conformation of adult hemoglobin in a manner which mimicks the oxygen-affinity of fetal hemoglobin, while we show that both hydroxyurea and rapamycin augment expression of murine fetal hemoglobin chains. Our data suggests there may be a clinical value in exploring agents which alter local REDOX environments as an adjunctive treatment for colitis and attenuating inflammatory cytokine production.



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Editors, contents and cover information

Publication date: July 2017
Source:Trends in Biochemical Sciences, Volume 42, Issue 7





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Iodine and Freeze-Drying Enhanced High-Resolution MicroCT Imaging for Reconstructing 3D Intraneural Topography of Human Peripheral Nerve Fascicles

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Publication date: Available online 17 June 2017
Source:Journal of Neuroscience Methods
Author(s): Liwei Yan, Yongze Guo, Jian Qi, Qingtang Zhu, Liqiang Gu, Canbin Zheng, Tao Lin, Yutong Yu, Zitao Zeng, Sha Yu, Shuang Zhu, Xiang Zhou, Xi Zhang, Yunfei Du, Zhi Yao, Yao Lu, Xiaolin Liu
BackgroundThe precise annotation and accurate identification of the topography of fascicles to the end organs are prerequisites for studying human peripheral nerves.New methodIn this study, we present a feasible imaging method that acquires 3D high-resolution (HR) topography of peripheral nerve fascicles using an iodine and freeze-drying (IFD) micro-computed tomography (microCT) method to greatly increase the contrast of fascicle images.ResultsThe enhanced microCT imaging method can facilitate the reconstruction of high-contrast HR fascicle images, fascicle segmentation and extraction, feature analysis, and the tracing of fascicle topography to end organs, which define fascicle functions.Comparison with existing methodsThe complex intraneural aggregation and distribution of fascicles is typically assessed using histological techniques or MR imaging to acquire coarse axial three-dimensional (3D) maps. However, the disadvantages of histological techniques (static, axial manual registration, and data instability) and MR imaging (low-resolution) limit these applications in reconstructing the topography of nerve fascicles.ConclusionsThus, enhanced microCT is a new technique for acquiring 3D intraneural topography of the human peripheral nerve fascicles both to improve our understanding of neurobiological principles and to guide accurate repair in the clinic. Additionally, 3D microstructure data can be used as a biofabrication model, which in turn can be used to fabricate scaffolds to repair long nerve gaps.



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A non-invasive restraining system for awake mouse imaging

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Publication date: Available online 17 June 2017
Source:Journal of Neuroscience Methods
Author(s): Dan Madularu, Axel P. Mathieu, Chathura Kumaragamage, Lauren Reynolds, Jamie Near, Cecilia Flores, M.Natasha Rajah
BackgroundPreclinical neuroimaging allows for the assessment of brain anatomy, connectivity and function in laboratory animals, such as mice and rats. Most of these studies are performed under anesthesia to avoid movement during the scanning sessions.MethodDue to the limitations associated with anesthetized imaging, recent efforts have been made to conduct rodent imaging studies in awake animals, habituated to the restraint systems used in these instances. As of now, only one such system is commercially available for mouse scanning (Animal Imaging Research, Boston, MA, USA) integrating the radiofrequency coil electronics with the restraining element, an approach which, although effective in reducing head motion during awake imaging, has some limitations. In the current report, we present a novel mouse restraining system that addresses some of these limitations.Results/Comparison to other methodsThe effectiveness of the restraining system was evaluated in terms of three-dimensional linear head movement across two consecutive functional MRI scans (total 20min) in 33 awake mice. Head movement was minimal, recorded in roughly 12% of the recorded time-series. Respiration rate during the acclimation procedure dropped while the bolus count remained unchanged. Body movement during functional acquisitions did not have a significant effect on magnetic field (B0) homogeneity.Conclusion/noveltyCompared to the commercially available system, the benefit of the current design is two-fold:1) it is compatible with a range of commercially-available coils, and 2) it allows for the pairing of neuroimaging with other established techniques involving intracranial cannulation (i.e. microinfusion and optogenetics).



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Dying for a Cause: Regulated Necrosis of Tissue-Resident Macrophages upon Infection

Publication date: Available online 20 June 2017
Source:Trends in Immunology
Author(s): Florent Ginhoux, Camille Bleriot, Marc Lecuit




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Δευτέρα 19 Ιουνίου 2017

Ovarian cancer: novel molecular aspects for clinical assessment

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



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

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

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

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

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

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



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

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



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Proteomic analysis of mesenchymal to Schwann cell transdifferentiation

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

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

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



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



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

Abstract

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



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