Single-unit implant-supported restoration adjacent to multiple lithium disilicate restorations, an approach to an esthetic challenge: A clinical report

Publication date: Available online 16 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Gelareh Ronaghi, Winston Chee, Stephanie Yeung
This clinical report describes a method for predictably shade matching a highly opaque yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) implant restoration adjacent to relatively translucent lithium disilicate veneers in the maxillary anterior region. To achieve a satisfactory outcome, the milled Y-TZP abutment was layered with low-fusing feldspathic porcelain to match the stump shade of the adjacent prepared teeth; this layer subsequently facilitated adhesive bonding of a veneer to the abutment before insertion.



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Expression and characterization of recombinant bifunctional enzymes with glutathione peroxidase and superoxide dismutase activities

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Tuchen Guan, Jian Song, Yanan Wang, Liying Guo, Lin Yuan, Yingding Zhao, Yuan Gao, Liangru Lin, Yali Wang, Jingyan Wei
To balance the production and decomposition of reactive oxygen species, living organisms have generated antioxidant enzymes and non-enzymatic antioxidant defense systems. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are two important antioxidant enzymes. Apart from their catalytic functions, they protect each other, resulting in more efficient removal of reactive oxygen species, protection of cells against injury, and maintenance of the normal metabolism of reactive oxygen species. SOD catalyzes the dismutation of the superoxide anion (O2^•−) to oxygen (O2) and hydrogen peroxide (H2O2). H2O2 is then detoxified to water by GPx. In this study, human GPx1^Ser and the Alvinella pompejana SOD (ApSOD) gene were used to design and generate several recombinant proteins with both GPx and SOD activities by combining traditional fusion protein technology, a cysteine auxotrophic expression system, and a single protein production (SPP) system. Among the fusion proteins, Se-hGPx1^Ser-L-ApSOD exhibited the highest SOD and GPx activities. Additional research was conducted to better understand the properties of Se-hGPx1^Ser-L-ApSOD. The synergism of Se-hGPx1^Ser-L-ApSOD was evaluated by using an in vitro model. This research may facilitate future studies on the cooperation and catalytic mechanisms of GPx and SOD. We believe that the bifunctional enzyme has potential applications as a potent antioxidant.



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Editorial Board

Publication date: July 2017
Source:Free Radical Biology and Medicine, Volume 108





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Does anaesthesia stop the clock?

Anyone who has undergone general anaesthesia (GA) remembers the strange state of disorientation lasting for quite some time after waking up. Until recently, the idea that one's biological clock had just "paused" for a few hours was not a concept that was considered to explain (part of) this discombobulation. Yet it seems that when we go into the operating room, we come out in another time zone, or rather, time stands still: in other words, GA induces jet-lag. Post-operative recovery may be hindered by circadian disruption and the resulting sleep disturbances, and may also impair mood, alertness, cognitive performance, and even immune function.

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Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific 68Ga- and 44Sc-labeled DOTA-NAPamide in melanoma imaging

Publication date: Available online 16 June 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Gábor Nagy, Noémi Dénes, Adrienn Kis, Judit P. Szabó, Ervin Berényi, Ildikó Garai, Péter Bai, István Hajdu, Dezső Szikra, György Trencsényi
PurposeAlpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors.MethodsDOTA-NAPamide was labeled with Ga-68 and Sc-44 radionuclides. The MC1-R specificity of Ga-68- and Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using MC1-R positive (B16-F10) and negative (A375) melanoma cell lines. For in vivo imaging studies B16-F10 and A375 tumor-bearing mice were injected with ⁴⁴Sc/⁶⁸Ga-DOTA-NAPamide (in blocking studies with α-MSH) and whole body PET/MRI scans were acquired. Radiotracer uptake was expressed in terms of standardized uptake values (SUVs).Results⁴⁴Sc/⁶⁸Ga-labeled DOTA-NAPamide were produced with high specific activity (approx. 19 GBq/μmol) and with excellent radiochemical purity (99%<). MC1-R positive B16-F10 cells showed significantly (p≤0.01) higher in vitro radiotracer accumulation than that of receptor negative A375 melanoma cells. In animal experiments, also significantly (p≤0.01) higher Ga-68-DOTA-NAPamide (SUVmean: 0.38±0.02), and Sc-44-DOTA-NAPamide (SUVmean: 0.52±0.13) uptake was observed in subcutaneously growing B16-F10 tumors, than in receptor negative A375 tumors, where the SUVmean values of Ga-68-DOTA-NAPamide and Sc-44-DOTA-NAPamide were 0.04±0.01 and 0.07±0.01, respectively. Tumor-to-muscle (T/M SUVmean) ratios were approximately 15-fold higher in B16-F10 tumor-bearing mice, than that of A375 tumors, and this difference was also significant (p≤0.01) using both radiotracers after 60 min incubation time.ConclusionOur newly synthesized ⁴⁴Sc-labeled DOTA-NAPamide probe showed excellent binding properties to melanocortin-1 receptor (MC1-R) positive melanoma cell and tumors. Due to its high specificity and sensitivity ⁴⁴Sc-DOTA-NAPamide is a promising radiotracer in molecular imaging of malignant melanoma.



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Antiobesity, antioxidant and hepatoprotective effects of Diallyl trisulphide (DATS) alone or in combination with Orlistat on HFD induced obese rats

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Sivakumar Annamalai, Lavanya Mohanam, Veena Raja, Alwin Dev, Venkataraman Prabhu
The increasing rate of obesity in the past years has become a worldwide concern and it causes many diseases. Even though, Orlistat, a synthetic anti-obesity drug approved by FDA, it causes severe side effects. DATS, a natural product from garlic have gained attention in many biological activities. The aim of the study is to determine the impact of Dially trisulpide (DATS) and its combination with Orlistat therapy on obese animals. 30 male Wistar rats (150–180g) were assigned into 5 groups (n=6). Group 1 rats received normal diet and Group 2 fed with high fat diet (HFD) for 14 weeks. Group 3–5 animals fed with HFD for 8 weeks, after that respective drugs were given simultaneously along with HFD for 6 weeks; Group 3: HFD+Orlistat; Group 4: HFD+DATS; Group 5: HFD+Orlistat+DATS. Before and after drug treatment, body weight was measured and blood was collected for assessment of lipid and liver function profiles. After end of the treatment 14 weeks, liver and adipose tissues were collected for antioxidants determination and histological observations. The significantly (p<0.05) increased body weight, serum glucose, total cholesterol, triglycerides, LDL-cholesterol were observed while significantly (p<0.05) decreased HDL-cholesterol and liver function parameters in HFD induced rats when compared to control group. The significantly (p<0.05) decreased activities of SOD, CAT, GPx and GSH levels were observed while significantly (p<0.05) increased LPO in both the tissues of HFD treated group when compared to control. Histopathological changes were observed in both the liver and adipose tissue of HFD treated group. The DATS and its combination with orlistat supplementation restored all the parameters significantly (p<0.05) especially liver function parameters and also retrieved histopathological changes when compared to orlistat alone. DATS and its combination with Orlistat had great effect than Orlistat alone.



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2-Methylpyridine-1-ium-1-sulfonate from Allium hirtifolium: An anti-angiogenic compound which inhibits growth of MCF-7 and MDA-MB-231 cells through cell cycle arrest and apoptosis induction

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Hamid-Reza Mohammadi-Motlagh, Yalda Shokohinia, Mahdi Mojarrab, Hassan Rasouli, Ali Mostafaie
Natural products have well been recognized as sources of drugs in cancer treatment. Some medicinal plants contain the constituents with potent anti-angiogenic and anti-cancer effects, which have offered great hopes of being used as drugs for treating various cancers. The present study aims at identifying the anti-angiogenic effects of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from the ethyl acetate extract (EA) of Persian shallot (Allium hirtifolium). In a concentration-dependent manner, the MPS was able to inhibit endothelial cell migration and angiogenesis in both in vivo and in vitro assays, and also significantly suppressed proliferation of MCF-7 and MDA-MB-231 human breast cancer cell lines. Additionally, treatment with MPS showed a significant reduction in the vascular endothelial growth factor (VEGF) secretion level and production/activity of matrix metalloproteinases (MMP-2 and MMP-9) in the studied cells. The flow cytometry analysis indicated that MPS suppressed growth of MCF-7 and MDA-MB-231 cells at G0/G1 and S phases, respectively. Our results indicated that the induction of cell cycle arrest was correlated with the obvious changes in expression of p21, p27 and p53. According to the DNA fragmentation assay, MPS caused apoptosis in both cell lines, which confirms the results obtained with the growth assay. Moreover, the compound-mediated apoptosis accompanied with the increase in the Bax/Bcl-2 ratio and caspase-3 and −9 activities. Molecular docking results indicated that the MPS compound can surprisingly bind to VEGF and VEGF receptors and interacts with their critical amino acids. Finally, compounds with anticancer inhibitory activity (e.g. MPS) are abundant in nature and can be obtained from several sources. So, our data can be clinically developed for treating angiogenesis and cancer significantly.

Graphical abstract

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Fusaric acid (FA) protects heart failure induced by isoproterenol (ISP) in mice through fibrosis prevention via TGF-β1/SMADs and PI3K/AKT signaling pathways

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β −myosin heavy chain (β-MHC) in vitro and in vivo. Additionally, FA reduced collagen accumulation and fibrosis-related signals, including α- smooth muscle actin (α-SMA), Collagen type I and Collagen type III. Transforming growth factor-β1 (TGF-β1)/SMADs and mitogen-activated protein kinases (MAPKs), including p38, extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), signalling pathways were highly activated for ISP induction, which were prevented due to FA administration. Further, FA suppressed ISP-induced PI3K/AKT activity in a dose dependent manner. Of note, FA-reduced MAPKs phosphorylation was associated with phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT) activity caused by ISP. However, PI3K/AKT activation showed no effects on TGF-β1/SMADs expression in FA-treated cells after ISP exposure. Together, FA might be an effective candidate agent for preventing cardiac fibrosis by modulating TGF-β1/SMADs and PI3K/AKT signalling pathways.



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Abcb1a (P-glycoprotein) limits brain exposure of the anticancer drug candidate seliciclib in vivo in adult mice

Publication date: Available online 16 June 2017
Source:Brain Research Bulletin
Author(s): Franciska Erdő, Ildikó Nagy, Beáta Tóth, Annamária Bui, Éva Molnár, Zoltán Tímár, Rémi Magnan, Peter Krajcsi
Seliciclib displayed limited brain exposure in vivo in adult rats with mature blood-brain barrier (BBB). Selicilib was shown to be a specific substrate of human ABCB1 in vitro.To demonstrate that ABCB1/Abcb1 can limit brain exposure in vivo in mice we are showing that seliciclib is a substrate of mouse Abcb1a, the murine ABCB1 ortholog expressed in the BBB as LLC-PK-Abcb1a cells displayed an efflux ratio (ER) of 15.31±3.54 versus an ER of 1.44±0.10 in LLC-PK1-mock cells. Additionally, in the presence of LY335979, an ABCB1/Abcb1a specific inhibitor, the observed ER for seliciclib in the LLC-PK1-mMdr1a cells decreased to 1.05±0.25. To demonstrate in vivo relevance of seliciclib transport by Abcb1a mouse brain microdialysis experiments were carried out that showed that the AUCbrain/AUCblood ratio of 0.143 in anesthetized mice increased about two-fold to 0.279 in the presence of PSC833 another ABCB1/Abcb1a specific inhibitor. PSC833 also increased the brain exposure (AUCbrain) of seliciclib close to 2-fold (136 vs 242) in awake mice.In sum, Abcb1a significantly decreases seliciclib permeability in vitro and is partly responsible for limited brain exposure of seliciclib in vivo in mice.

Graphical abstract

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Reply to: ‘Patients with low-risk cutaneous squamous cell carcinoma do not require extended out-patient follow-up’

We read with great interest the paper entitled 'Patients with low-risk cutaneous squamous cell carcinoma do not require extended out-patient follow-up,' by Rose et al.1 The article raised some excellent points regarding the necessity and sustainability of regular specialist follow-up of low-risk squamous cell carcinoma (SCC). We too have recently conducted an analysis of SCC recurrence and follow-up schedules via a retrospective analysis of SCCs excised by the senior author over a 2-year period from January 2014 to January 2016.

http://ift.tt/2tcjkhe

Delaying Implant-Based Mammary Reconstruction After Radiotherapy Does Not Decrease Capsular Contracture: An In Vitro Study

The most common complication of irradiated implant-based mammary reconstruction is fibrosis and capsular contracture. The indications for post mastectomy adjuvant radiotherapy have significantly broadened. Facing an increased number of patients who will require radiotherapy, most guidelines recommend delaying reconstruction after radiotherapy to prevent long-term fibrotic complications. Does radiotherapy permanently alter cellular properties which will adversely affect implant-based reconstruction? If so, is there a benefit in delaying reconstruction after radiotherapy?Our in-vitro model simulates two implant-based mammary reconstruction approaches: the irradiated implant and the delayed implant reconstruction beneath healthy un-irradiated tissue post radiotherapy.

http://ift.tt/2sCOyku

Microneedling: Where do we stand now? A systematic review of the literature

Patients who suffer from scars or wrinkles have several therapeutic options to improve the appearance of their skin. The available treatment modalities that provide desirable results are often overtly invasive and entail a risk of undesirable adverse effects. Microneedling has recently emerged as a non-ablative alternative for treating patients who are concerned with the aesthetic changes that result from injury, disease or aging.

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Pedicled Omental Flaps in the treatment of complex spinal wounds after en-bloc resection of spine tumors

A retrospective study of 5 patients who underwent pedicled omental flap following spine tumor removal.

http://ift.tt/2sCFvAc

Measuring the carbon footprint of Plastic Surgery: a preliminary experience in a Chilean teaching hospital

Global warming is an ongoing phenomenon defined by a steady increase in the Earth temperature. Even though still controversial, evidence suggests that human activity could have an impact on this process by the emission of the so-called greenhouse gases.

http://ift.tt/2tbUVZ7

A prospective randomized study comparing centrifugation and sedimentation for fat grafting in breast reconstruction

Fat grafting is an efficient method to correct large volumetric defects after mastectomy.There is ongoing debate regarding the best method of processing the harvested fat before fat grafting. The aim of this study was to introduce a new MRI-model and to compare two fat processing techniques measuring the gain in soft tissue thickness after fat grafting to the chest wall.

http://ift.tt/2sCFuw8

A 64-bp sequence containing the GAAGA motif is essential for CaMV-35S promoter methylation in gentian

Publication date: Available online 15 June 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Asahi Shimada, Azusa Okumura, Satoshi Yamasaki, Yuji Iwata, Nozomu Koizumi, Masahiro Nishihara, Kei-ichiro Mishiba
This study investigated sequence specificity and perenniality of DNA methylation in the cauliflower mosaic virus (CaMV) 35S promoter of transgenic gentian (Gentiana triflora×G. scabra) plants. Unlike conventional transgene silencing models, 35S promoter hypermethylation in gentian is species-specific and occurs irrespective of the T-DNA copy number and genomic location. Modified 35S promoters were introduced into gentian, and single-copy transgenic lines were selected for methylation analysis. Modified 35S promoter lacking a core (−90) region [35S(Δcore)] in gentian conferred hypermethylation and high levels of de novo methylation of the CpHpH/CpCpG sites in the 35S enhancer regions (−298 to −241 and −148 to −85). Therefore, promoter transcription may not be an absolute requirement for the methylation machinery. In vitro, de novo methylation persisted for more than eight years. In another modified 35S promoter, two "GAAGA" motifs (−268 to −264 and −134 to −131) were replaced by "GTTCA" in the two highly de novo methylated regions. It did not support hypermethylation and showed transgene expression. A 64-bp fragment of the 35S enhancer region (−148 to −85) was introduced into gentian and the resultant transgenic lines analyzed. The 64-bp region exhibited hypermethylation at the CpG/CpWpG sites, but the CpHpH/CpCpG methylation frequency was lower than those of the unmodified 35S- and 35S(Δcore) promoters. Nevertheless, a distinct CpHpH/CpCpG methylation peak was found in the 64-bp region of all single-copy transgenic lines. These results suggest that the 64-bp region may contain an element required for 35S methylation but insufficient for high de novo methylation compared with those in the unmodified 35S and 35S(Δcore) promoters.



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Free Tissue Transfers for Head and Neck Reconstruction in Patients with End-Stage Renal Disease on Dialysis: Analysis of Outcomes Using the Taiwan National Health Insurance Research Database

J reconstr Microsurg
DOI: 10.1055/s-0037-1603739

Background Patients diagnosed with end-stage renal disease (ESRD) are increasing at around 5% annually. Some of these patients will require free tissue transfers to reconstruct their body after trauma or cancer resection. Comorbidities can increase the level of complexity during reconstruction. Aim Our goal is to describe the outcomes of ESRD patients under dialysis who underwent free tissue transfer for head and neck reconstruction. Methods Two cohorts were analyzed: ESRD group on dialysis and a non-ESRD control group after free tissue transfer for head and neck reconstruction. Postoperative complications and mortality were recorded. For coexisting comorbidities, we determine the presence of diabetes mellitus (DM) and peripheral vascular disease (PVD). Results In this study, 85 cases with ESRD on dialysis and 841 controls were analyzed. Most patients were aged ≤ 65 years (82.5%) and nearly 92.9% of them were men. Types of head and neck cancer were neoplasm of other and unspecified parts of the mouth followed by neoplasm of tongue, the gingiva, hypopharynx, and floor of mouth. Patients with ESRD tended to have higher rates of DM and PVD (p < 0.001) and were significantly associated with an increased risk of stroke and increased risk of 30-day mortality. However, there was no significant difference regarding flap failure among groups. Conclusion Despite greater preoperative risk factors, patients with renal failure on hemodialysis do not appear to have a higher rate of free flap failure following head and neck reconstruction. However, other complications can be minimized by optimizing patient's medical condition to succeed with this reconstructive effort.
[...]

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

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Physiological characteristics of Plantago major under SO 2 exposure as affected by foliar iron spray

Abstract

Sulfur dioxide (SO₂) is considered as a main air pollutant in industrialized areas that can damage vegetation. In the present study, we investigated how exposure to SO₂ and foliar application of iron (Fe) would affect certain physiological characteristics of Plantago major. The plant seedlings exposed or unexposed to SO₂ (3900 μg m⁻³) were non-supplemented or supplemented with Fe (3 g L⁻¹) as foliar spray. Plants were exposed to SO₂ for 6 weeks in 100 × 70 × 70 cm chambers. Fumigation of plants with SO₂ was performed for 3 h daily for 3 days per week (alternate day). Lower leaf Fe concentration in the plants exposed to SO₂ at no added Fe treatment was accompanied with incidence of chlorosis symptoms and reduced chlorophyll concentration. No visible chlorotic symptoms were observed on the SO₂-exposed plants supplied with Fe that accumulated higher Fe in their leaves. Both at with and without added Fe treatments, catalase (CAT) and peroxidase (POD) activity was higher in the plants fumigated with SO₂ in comparison with those non-fumigated with SO₂. Foliar application of Fe was also effective in increasing activity of antioxidant enzymes CAT and POD. Exposure to SO₂ led to reduced cellulose but enhanced lignin content of plant leaf cell wall. The results obtained showed that foliar application of Fe was effective in reducing the effects of exposure to SO₂ on cell wall composition. In contrast to SO₂, application of Fe increased cellulose while decreased lignin content of the leaf cell wall. This might be due to reduced oxidative stress induced by SO₂ in plants supplied with Fe compared with those unsupplied with Fe.

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Endoscopic ultrasound-guided fine-needle aspiration and cytology for differentiating benign from malignant lymph nodes

Publication date: Available online 16 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Hussein Okasha, Shaimaa Elkholy, Mohamed Sayed, Ahmed Salman, Yahia Elsherif, Emad El-Gemeie
Background and study aimsIntra-abdominal and mediastinal lymphadenopathy are often difficult to diagnose, particularly in the absence of a primary lesion. Endosonography (EUS)-guided fine-needle aspiration and cytology (FNAC) has provided an easy and safe access to these lymph nodes, sparing the use of invasive and costly interventions. The main aim of this study is to assess the specificity, sensitivity, and predictive value of EUS-guided FNAC in the diagnosis of benign and malignant lymph nodes. In addition, the study aims to determine significant EUS features that could help in predicting lymph node malignancy.Patients and methodsThis prospective study included 142 patients with intra-abdominal or intrathoracic lymphadenopathy who were referred for EUS-guided FNAC because of inaccessibility by other imaging modalities. Ninety (63.3%) patients were found to have malignant lymph nodes, and 52 (36.6%) had lymphadenopathy of benign nature.ResultsEUS-guided FNAC had a sensitivity and specificity of 92% and 100% respectively. It had positive and negative predictive values of 100% and 88% for malignancy, respectively. By logistic regression analysis, EUS features and shortest diameter were found to be potential predictors of malignancy with p-value of <0.0001.ConclusionEUS-guided FNAC is a powerful modality in the diagnosis of benign and malignant lymph nodes. Additional complementary EUS features could be added to this technique for definitive diagnosis.



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Comparative study on the effect of low intensity laser and growth factors on stem cells used in experimentally-induced liver fibrosis in mice

Publication date: Available online 16 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Eman Naguib, Ashraf Kamel, Osama Fekry, Gamal Abdelfattah
Background and study aimsThe therapeutic effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) exposed to diode laser and/or hepatocyte growth factor (HGF) were compared in mice with experimental liver fibrosis induced by carbon tetra chloride (CCl4).Material and methodsAnimal model of liver cirrhosis was induced by intraperitoneal injection of CCl4 in a dose of 0.4ml/kg, twice a week for 6weeks. UC-MSCs were obtained from normal full term placentas and were exposed to diode laser and/or HGF. Before treatment, UC-MSCs were labelled with red fluorescent PKH26. Fifty four male mice weighing 25–35g were randomly divided into four groups control, stem cells, CCl4, and treated groups. After the experimental period, body and liver weights were recorded, and the liver specimens were processed for histological examination using haematoxylin and eosin, Periodic Acid-Schiff (PAS), and Masson's Trichrome staining (MT).ResultsResults showed that administration of UC-MSCs stimulated by diode laser and/or HGF improved body and liver weights, reduced vascular dilatation and congestion, reduced mononuclear cellular infiltration, reduced hepatocyte vacuolation, eosinophilia, and pyknosis. Furthermore, periportal fibrosis was minimized and PAS reaction was increased. These effects were maximum when UC-MSCs were exposed to both diode laser and HGF.ConclusionUC-MSCs stimulated by both diode laser and HGF proved to be an effective therapeutic option in experimental liver fibrosis induced by CCl4 in mice.



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Novel use of fully covered self-expandable metal stent for drainage of perirectal abscess. A case series

Publication date: Available online 16 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Mindy Lee, Manhal Izzy, Sammy Ho




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Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

Publication date: Available online 15 June 2017
Source:Cell Metabolism
Author(s): Thomas Siegmund Postler, Sankar Ghosh
The human gastrointestinal tract is populated by a diverse, highly mutualistic microbial flora, which is known as the microbiome. Disruptions to the microbiome have been shown to be associated with severe pathologies of the host, including metabolic disease, cancer, and inflammatory bowel disease. Mood and behavior are also susceptible to alterations in the gut microbiota. A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior. This includes metabolites that are produced by bacteria from dietary components, metabolites that are produced by the host and biochemically modified by gut bacteria, and metabolites that are synthesized de novo by gut microbes. In this review, we highlight the role of the intestinal microbiome in human metabolic and inflammatory diseases and focus in particular on the molecular mechanisms that govern the gut-immune axis.

Teaser

The bacteria inhabiting the gastrointestinal tract, collectively referred to as the microbiome, have emerged as important regulators of human health. In this review, Postler and Ghosh discuss how the microbiome affects metabolic and inflammatory diseases, with a particular focus on the molecular mechanisms that govern the gut-immune axis.


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Title Page

Publication date: May–June 2017
Source:Current Problems in Cancer, Volume 41, Issue 3





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Information for Readers

Publication date: May–June 2017
Source:Current Problems in Cancer, Volume 41, Issue 3





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Table of Contents

Publication date: May–June 2017
Source:Current Problems in Cancer, Volume 41, Issue 3





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Considerations of developing an NGS assay for clinical applications in precision oncology: The NCI-MATCH NGS assay experience

Publication date: May–June 2017
Source:Current Problems in Cancer, Volume 41, Issue 3
Author(s): Chih-Jian Lih, Naoko Takebe
Next generation sequencing (NGS) technologies have been widely adapted in clinical oncology by utilizing the profiled genetic mutation information to select patients and to guide the choice of target therapy. To fulfill the regulatory compliance, development of an NGS assay that will be used in clinical trials requires an analytical validation to meet its intend clinical use. NCI-MATCH trial is the largest precision oncology basket trial which uses a single NGS assay (NCI-MATHC NGS assay) to screen the actionable mutations in 6000 patients, who have relapsed/refractory solid tumors and lymphomas after standard systemic treatment, and assigns matched treatment. This article reviews on the critical considerations during development and validation of NGS assays as an investigational device for genomic based clinical trials and provides the experiences from the development of NCI-MATCH NGS assay.



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Tooth brushing motion patterns with manual and powered toothbrushes—a randomised video observation study

Abstract

Introduction

Systematic reviews have shown that powered toothbrushes (PTs) are more effective than manual toothbrushes (MTs), but with only minor effect sizes. Whether PTs are used adequately, however, has not been investigated so far. The aim of the present study was therefore to analyse motion habits with PT in comparison to MT toothbrushes by video observation.

Materials and methods

One hundred subjects were enrolled in this observational trial and brushed their teeth in randomised order with a MT and PT while being video-filmed, resulting in 95 analysable sets of recordings. Parameters of interest were brushing duration (s; median (min;max)), type of brushing strokes, area of brushing, changes between areas (n; median (min;max)) and brushing sequence.

Results

Brushing duration was 145 s (60;354) and 135 s (48;271) for PT and MT, respectively (p ≤ 0.001). Subjects brushed vestibular surfaces completely, but reached oral surfaces to a much lesser extent, regardless of the toothbrush type. With both toothbrushes, subjects moved frequently between areas (MT 35 (14;79); PT 33 (14;85); n.s.) and brushed predominantly with circling and horizontal strokes; with the PT, 50.5% of the subjects spent only <10% of the brushing duration with passive brushing (positioning the brush head on the teeth with ≤2 movements/s).

Conclusions

Intra-individual motion patterns were similar with both MT and PT, and most subjects persisted in their habitual motion patterns regardless of the toothbrush type.

Clinical relevance

The use of PT and MT may need intensive training and supervision from oral hygiene educators in order to help subjects taking full advantage from these devices.

http://ift.tt/2roO0e0

Brain-shift compensation using intraoperative ultrasound and constraint-based biomechanical simulation

Publication date: Available online 15 June 2017
Source:Medical Image Analysis
Author(s): Fanny Morin, Hadrien Courtecuisse, Ingerid Reinertsen, Florian Le Lann, Olivier Palombi, Yohan Payan, Matthieu Chabanas
Purpose. During brain tumor surgery, planning and guidance are based on preoperative images which do not account for brain-shift. However, this deformation is a major source of error in image-guided neurosurgery and affects the accuracy of the procedure. In this paper, we present a constraint-based biomechanical simulation method to compensate for craniotomy-induced brain-shift that integrates the deformations of the blood vessels and cortical surface, using a single intraoperative ultrasound acquisition. Methods. Prior to surgery, a patient-specific biomechanical model is built from preoperative images, accounting for the vascular tree in the tumor region and brain soft tissues. Intraoperatively, a navigated ultrasound acquisition is performed directly in contact with the organ. Doppler and B-mode images are recorded simultaneously, enabling the extraction of the blood vessels and probe footprint respectively. A constraint-based simulation is then executed to register the pre- and intraoperative vascular trees as well as the cortical surface with the probe footprint. Finally, preoperative images are updated to provide the surgeon with images corresponding to the current brain shape for navigation. Results. The robustness of our method is first assessed using sparse and noisy synthetic data. In addition, quantitative results for five clinical cases are provided, first using landmarks set on blood vessels, then based on anatomical structures delineated in medical images. The average distances between paired vessels landmarks ranged from 3.51 to 7.32 (in mm) before compensation. With our method, on average 67% of the brain-shift is corrected (range [1.26; 2.33]) against 57% using one of the closest existing works (range [1.71; 2.84]). Finally, our method is proven to be fully compatible with a surgical workflow in terms of execution times and user interactions. Conclusion.In this paper, a new constraint-based biomechanical simulation method is proposed to compensate for craniotomy-induced brain-shift. While being efficient to correct this deformation, the method is fully integrable in a clinical process.

Graphical abstract

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Structural Basis for Ribosome Rescue in Bacteria

Publication date: Available online 16 June 2017
Source:Trends in Biochemical Sciences
Author(s): Paul Huter, Claudia Müller, Stefan Arenz, Bertrand Beckert, Daniel N. Wilson
Ribosomes that translate mRNAs lacking stop codons become stalled at the 3′ end of the mRNA. Recycling of these stalled ribosomes is essential for cell viability. In bacteria three ribosome rescue systems have been identified so far, with the most ubiquitous and best characterized being the trans-translation system mediated by transfer–messenger RNA (tmRNA) and small protein B (SmpB). The two additional rescue systems present in some bacteria employ alternative rescue factor (Arf) A and release factor (RF) 2 or ArfB. Recent structures have revealed how ArfA mediates ribosome rescue by recruiting the canonical termination factor RF2 to ribosomes stalled on truncated mRNAs. This now provides us with the opportunity to compare and contrast the available structures of all three bacterial ribosome rescue systems.



http://ift.tt/2sC0TFM

Neurobiological correlates of impulsivity in healthy adults: Lower prefrontal gray matter volume and spontaneous eye-blink rate but greater resting-state functional connectivity in basal ganglia-thalamo-cortical circuitry

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Cole Korponay, Daniela Dentico, Tammi Kral, Martina Ly, Ayla Kruis, Robin Goldman, Antoine Lutz, Richard J. Davidson
Studies consistently implicate aberrance of the brain's reward-processing and decision-making networks in disorders featuring high levels of impulsivity, such as attention-deficit hyperactivity disorder, substance use disorder, and psychopathy. However, less is known about the neurobiological determinants of individual differences in impulsivity in the general population. In this study of 105 healthy adults, we examined relationships between impulsivity and three neurobiological metrics – gray matter volume, resting-state functional connectivity, and spontaneous eye-blink rate, a physiological indicator of central dopaminergic activity. Impulsivity was measured both by performance on a task of behavioral inhibition (go/no-go task) and by self-ratings of attentional, motor, and non-planning impulsivity using the Barratt Impulsiveness Scale (BIS-11). Overall, we found that less gray matter in medial orbitofrontal cortex and paracingulate gyrus, greater resting-state functional connectivity between nodes of the basal ganglia-thalamo-cortical network, and lower spontaneous eye-blink rate were associated with greater impulsivity. Specifically, less prefrontal gray matter was associated with higher BIS-11 motor and non-planning impulsivity scores, but was not related to task performance; greater correlated resting-state functional connectivity between the basal ganglia and thalamus, motor cortices, and prefrontal cortex was associated with worse no-go trial accuracy on the task and with higher BIS-11 motor impulsivity scores; lower spontaneous eye-blink rate was associated with worse no-go trial accuracy and with higher BIS-11 motor impulsivity scores. These data provide evidence that individual differences in impulsivity in the general population are related to variability in multiple neurobiological metrics in the brain's reward-processing and decision-making networks.



http://ift.tt/2tbQlKI

On memories, neural ensembles and mental flexibility

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Dimitris A. Pinotsis, Scott L. Brincat, Earl K. Miller
Memories are assumed to be represented by groups of co-activated neurons, called neural ensembles. Describing ensembles is a challenge: complexity of the underlying micro-circuitry is immense. Current approaches use a piecemeal fashion, focusing on single neurons and employing local measures like pairwise correlations. We introduce an alternative approach that identifies ensembles and describes the effective connectivity between them in a holistic fashion. It also links the oscillatory frequencies observed in ensembles with the spatial scales at which activity is expressed. Using unsupervised learning, biophysical modeling and graph theory, we analyze multi-electrode LFPs from frontal cortex during a spatial delayed response task. We find distinct ensembles for different cues and more parsimonious connectivity for cues on the horizontal axis, which may explain the oblique effect in psychophysics. Our approach paves the way for biophysical models with learned parameters that can guide future Brain Computer Interface development.



http://ift.tt/2sCbMHB

Frontal temporal and parietal systems synchronize within and across brains during live eye-to-eye contact

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Joy Hirsch, Xian Zhang, J. Adam Noah, Yumie Ono
Human eye-to-eye contact is a primary source of social cues and communication. In spite of the biological significance of this interpersonal interaction, the underlying neural processes are not well-understood. This knowledge gap, in part, reflects limitations of conventional neuroimaging methods, including solitary confinement in the bore of a scanner and minimal tolerance of head movement that constrain investigations of natural, two-person interactions. However, these limitations are substantially resolved by recent technical developments in functional near-infrared spectroscopy (fNIRS), a non-invasive spectral absorbance technique that detects changes in blood oxygen levels in the brain by using surface-mounted optical sensors. Functional NIRS is tolerant of limited head motion and enables simultaneous acquisitions of neural signals from two interacting partners in natural conditions. We employ fNIRS to advance a data-driven theoretical framework for two-person neuroscience motivated by the Interactive Brain Hypothesis which proposes that interpersonal interaction between individuals evokes neural mechanisms not engaged during solo, non-interactive, behaviors. Within this context, two specific hypotheses related to eye-to-eye contact, functional specificity and functional synchrony, were tested. The functional specificity hypothesis proposes that eye-to-eye contact engages specialized, within-brain, neural systems; and the functional synchrony hypothesis proposes that eye-to-eye contact engages specialized, across-brain, neural processors that are synchronized between dyads. Signals acquired during eye-to-eye contact between partners (interactive condition) were compared to signals acquired during mutual gaze at the eyes of a picture-face (non-interactive condition). In accordance with the specificity hypothesis, responses during eye-to-eye contact were greater than eye-to-picture gaze for a left frontal cluster that included pars opercularis (associated with canonical language production functions known as Broca's region), pre- and supplementary motor cortices (associated with articulatory systems), as well as the subcentral area. This frontal cluster was also functionally connected to a cluster located in the left superior temporal gyrus (associated with canonical language receptive functions known as Wernicke's region), primary somatosensory cortex, and the subcentral area. In accordance with the functional synchrony hypothesis, cross-brain coherence during eye-to-eye contact relative to eye-to-picture gaze increased for signals originating within left superior temporal, middle temporal, and supramarginal gyri as well as the pre- and supplementary motor cortices of both interacting brains. These synchronous cross-brain regions are also associated with known language functions, and were partner-specific (i.e., disappeared with randomly assigned partners). Together, both within and across-brain neural correlates of eye-to-eye contact included components of previously established productive and receptive language systems. These findings reveal a left frontal, temporal, and parietal long-range network that mediates neural responses during eye-to-eye contact between dyads, and advance insight into elemental mechanisms of social and interpersonal interactions.

Graphical abstract

http://ift.tt/2tbS0jo

On optimal spatial filtering for the detection of phase coupling in multivariate neural recordings

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): G. Waterstraat, G. Curio, V.V. Nikulin
IntroductionNeuronal oscillations synchronize processing in the brain over large spatiotemporal scales and thereby facilitate integration of individual functional modules. Up to now, the relation between the phases of neuronal oscillations and behavior or perception has mainly been analyzed in sensor space of multivariate EEG/MEG recordings. However, sensor-space analysis distorts the topographies of the underlying neuronal sources and suffers from low signal-to-noise ratio. Instead, we propose an optimized source reconstruction approach (Phase Coupling Optimization, PCO).MethodsPCO maximizes the 'mean vector length', calculated from the phases of recovered neuronal sources and a target variable of interest (e.g., experimental performance). As pre-processing, the signal-to-noise ratio in the search-space is maximized by spatio-spectral decomposition. PCO was benchmarked against several competing algorithms and sensor-space analysis using realistic forward model simulations. As a practical example, thirteen 96-channel EEG measurements during a simple reaction time task were analyzed. After time-frequency decomposition, PCO was applied to the EEG to examine the relation between the phases of pre-stimulus EEG activity and reaction times.ResultsIn simulations, PCO outperformed other spatial optimization approaches and sensor-space analysis. Scalp topographies of the underlying source patterns and the relation between the phases of the source activity and the target variable could be reconstructed accurately even for very low SNRs (−10dB). In a simple reaction time experiment, the phases of pre-stimulus delta waves (<0.1Hz) with widely distributed fronto-parietal source topographies were found predictive of the reaction times.Discussion and conclusionsFrom multivariate recordings, PCO can reconstruct neuronal sources that are phase-coupled to a target variable using a data-driven optimization approach. Its superiority has been shown in simulations and in the analysis of a simple reaction time experiment. From this data, we hypothesize that the phase entrainment of slow delta waves (<1Hz) facilitates sensorimotor integration in the brain and that this mechanism underlies the faster processing of anticipated stimuli. We further propose that the examined slow delta waves, observed to be phase-coupled to reaction times, correspond to the compound potentials typically observed in paradigms of stimulus anticipation and motor preparation.



http://ift.tt/2tbICfz

American Thyroid Association Awards Research Grant to to Connie Rhee, MD, MSc, The Regents of the University of California (University of California Irvine)

Supported by the ATA

The American Thyroid Association (ATA) is pleased to announce that it has awarded a 2016 Thyroid Research Grant to Connie Rhee, MD, Assistant Professor, Department of Medicine, Division of Nephrology and Hypertension, University of California Irvine (Orange, CA), for the project entitled "Thyroid Functional Disease, Mental Health, and  Quality of Life in Chronic Kidney Disease Patients." The overall goal of Dr. Rhee's project is to determine whether thyroid functional disorders increase risk of depression and reduced health-related quality of life (QOL) in patients with chronic kidney disease (CKD) and, if so what is the potential to ameliorate these effects using thyroid hormone replacement.

Patients with CKD, many of whom require dialysis, are more likely to have thyroid functional disease than their peers without CKD. Recent findings indicate that hypothyroidism is associated with a higher risk of death in patients with CKD, but no mechanism to explain this link has been identified. Depression may be an important contributor to this increased mortality risk, as it is a complication of both thyroid dysfunction and CKD.

Dr. Rhee will first examine of thyroid dysfunction on patient-reported mental health and quality of life in a group of patients with CKD undergoing hemodialysis, based on data collected in an NIH-sponsored study. She will then explore the association between hypothyroidism and the development of new-onset depression in pre-dialysis CKD patients and whether the use of thyroid hormone replacement can impact the development of depression and reduced QOL using data from hundreds of thousands of U.S. veterans.

Dr. Motoyasu Saji, Chair, ATA Research Committee says, "The ATA research grant program has been supporting young scientists in various thyroid-related research area, including clinical, translational, and basic areas. Every year we receive over 50 Grant applications from various countries. We excite to see young thyroid researchers, who attack current clinical problems and basic scientific questions using state of art technologies, new ideas, and new views. Many current leaders in the ATA were award recipients and this tells us how this program is important for us. We hope that this grant will be one of gateway to succeed in carrier as thyroid researchers and they will become leaders in next generation in the ATA. Finally, we appreciate all supports from members and various organizations, including cancer survivors, to make us possible creating excellent program."

The American Thyroid Association (ATA) has awarded 85 thyroid research grants totaling over $2.2 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and distribution of over $1.8 million generously donated to the ATA specifically for research grants from ThyCa: Thyroid Cancer Survivors' Association, Inc., Bite Me Cancer and Thyroid Head and Neck Cancer Foundation. For information on other research grants underway and funded by the ATA, see http://ift.tt/2l3TSGC.

ThyCa: Thyroid Cancer Survivors' Association, Inc. (ThyCa) has provided funding in support of 60 special research grants totaling $1,680,000 focused on thyroid cancer and medullary thyroid cancer since 2003. ThyCa is supporting three research grants in 2016 and three renewing grants. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org.

Bite Me Cancer (BMC) is our newest grant funder supporting five thyroid cancer grants since 2014 for a total of $143,750. BMC will be supporting a new thyroid cancer grant in 2016 and one renewing grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org.

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The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts.

Celebrating its 94^th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found at www.thyroid.org.

The post American Thyroid Association Awards Research Grant to to Connie Rhee, MD, MSc, The Regents of the University of California (University of California Irvine) appeared first on American Thyroid Association.

http://ift.tt/2twCQEB

American Thyroid Association Awards Research Grant to David Sharlin, PhD, Minnesota State University, Mankato

Supported by the ATA

The American Thyroid Association has awarded a Research Grant to David Sharlin, Ph.D., Assistant Professor, Department of Biological Sciences, Minnesota State University, Mankato, for his project entitled "Thyroid Hormone and Local Insulin-like Growth Factor Production in Developing Brain." Reduced levels of thyroid hormone (TH) during development put a child at risk of permanent neurological deficits. Dr. Sharlin proposes that these neurological defects result, at least in part, from a significant decrease in the production of insulin-like growth factor (Igf1) in the brain of patients with developmental hypothyroidism. Furthermore, Dr. Sharlin suggests that the reduced levels of brain Igf1 are independent of changes in blood levels of Igf1 in hypothyroidism.  Dr. Sharlin will perform studies in a mouse model to determine in what brain regions Igf1 is reduced following developmental hypothyroidism, to compared the changes in brain and serum Igf1 levels, and to demonstrate that the neurological effects of low TH are a direct result of reduced brain Igf1.

Dr. Motoyasu Saji, Chair, ATA Research Committee says, "The ATA research grant program has been supporting young scientists in various thyroid-related research area, including clinical, translational, and basic areas, over many years. Every year we receive more than 50 Grant applications from various countries around the world. We are excited to see young thyroid researchers, who attack current clinical problems and basic scientific questions using state of art technologies, new ideas, and new views.  Many current leaders in the ATA were award recipients, showing the long-lasting importance of the research grant program. The ATA views the grant program as a gateway to a career in thyroid research and further engagement with the ATA.  Finally, we appreciate the generous support from members and cancer survivors, to make possible the continuation of this excellent program."

The American Thyroid Association (ATA) has awarded 85 thyroid research grants totaling over $2.2 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and distribution of over $1.8 million generously donated to the ATA specifically for research grants from ThyCa: Thyroid Cancer Survivors' Association, Inc., Bite Me Cancer and Thyroid Head and Neck Cancer Foundation. For information on other research grants underway and funded by the ATA, see http://ift.tt/2twzu4r/.

ThyCa: Thyroid Cancer Survivors' Association, Inc. (ThyCa) has provided funding in support of 60 special research grants totaling $1,680,000 focused on thyroid cancer and medullary thyroid cancer since 2003. ThyCa is supporting three research grants in 2016 and three renewing grants. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org

Bite Me Cancer (BMC) is our newest grant funder supporting five thyroid cancer grants since 2014 for a total of $143,750. BMC will be supporting a new thyroid cancer grant in 2016 and one renewing grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org

###

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts.

Celebrating its 94^th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found at www.thyroid.org.

The post American Thyroid Association Awards Research Grant to David Sharlin, PhD, Minnesota State University, Mankato appeared first on American Thyroid Association.

http://ift.tt/2syXCGk

The Performance Gap for Residents in Transfer of Intracorporeal Suturing Skills From Box Trainer to Operating Room

Publication date: Available online 16 June 2017
Source:Journal of Surgical Education
Author(s): Patrice Crochet, Aubert Agostini, Sophie Knight, Noémie Resseguier, Stéphane Berdah, Rajesh Aggarwal
ObjectiveTraining on laparoscopic box trainer (BT) improves suturing skills in the operating room (OR). Optimal laboratory training should provide trainees with an adequate level of skills that can be transferred to the OR with no decline in performances. This study aimed to compare OR intracorporeal suturing performances of residents who trained with a fundamentals of laparoscopic surgery (FLS) BT vs. those of experienced laparoscopists.DesignThis was a prospective observational study. Residents received training with an FLS BT over a period of 4 months. Their performances with the BT and in the OR were then compared with those of experienced senior surgeons. OR assessment took place during a laparoscopic myomectomy. Performance evaluation was based on time taken and 2 validated qualitative assessment tools (GOALS and the Moorthy checklist).SettingsOne academic tertiary care center, La Conception Hospital, Assistance Publique -Hopitaux de Marseille, Marseille, France, was involved.ParticipantsTwelve gynecology residents and 6 experienced laparoscopic surgeons.ResultsFollowing the FLS training period, performances of residents with the BT were equivalent to those of the experienced surgeons. When tested in the OR, the trained residents performed more slowly than experienced surgeons (279.75 vs. 159.75s; p = 0.001), and they obtained lower qualitative outcomes in terms of GOALS (13 vs. 16.75; p = 0.002) and checklist (18.25 vs. 21; p = 0.049). Transfer from the BT to the OR revealed an increase in time taken that was significantly higher for the trained residents' group than for the experienced group (137s vs. 49s; p < 0.001).ConclusionA performance gap emerged between trained residents and experienced surgeons when transferring from the BT to the OR. Finding an intermediate training platform between the BT and independently suturing in the OR is hence warranted.



http://ift.tt/2sC6eNs

Incidental focal uptake in the breast and axilla on FDG PET: Clinical considerations and differential diagnosis

Publication date: Available online 15 June 2017
Source:Clinical Imaging
Author(s): Andrea Magee, Brittany Z. Dashevsky, Kayleen Jahangir, Kirti Kulkarni
Incidental focal FDG uptake in the breast or axilla on PET/CT performed for evaluation of extra-mammary primary disease presents a diagnostic challenge. Radiologists must consider a broad differential diagnosis, assess clinical history, and judiciously employ other imaging modalities such as mammography, ultrasound and MRI in the pursuit of findings which help narrow the differential diagnosis. Tissue sampling may be reserved for nondiagnostic imaging scenarios.



http://ift.tt/2sBRDBD

Progress in hydrogen enriched compressed natural gas (HCNG) internal combustion engines - A comprehensive review

Publication date: December 2017
Source:Renewable and Sustainable Energy Reviews, Volume 80
Author(s): Roopesh Kumar Mehra, Hao Duan, Romualdas Juknelevičius, Fanhua Ma, Junyin Li
With the huge growing demand of energy utilization and various threats posed due to the emissions had substantially led the thinkers to put on strategic plans to decrease the usage of energy and reduce the carbon contents of fuels. Moving ahead with these plans hydrogen enriched compressed natural gas (HCNG) engines have emanated as a forthcoming energy carrier for internal-combustion engines. Several nations are endeavoring hard to bring down the pollution level by promoting hydrogen enriched compressed natural gas-fueled vehicles, predominantly by powering medium and heavy transportation vehicles. In general, under precise circumstances the indicated thermal efficiency of the HCNG engine is much better than CNG engines without tolerating the high level of harmful emissions. In spite of that the hydrogen addition to NG provides increased NOx emission because of a great amount of heat generation inside the combustion chamber. However, it can be overcome by some extent of the application of lean burn combustion or with three-way catalyst (TWC). This report presented an encyclopedic overview of hydrogen enriched compressed natural-gas engines. This paper provides a detailed discussion on the hydrogen generation methods, fundamentals of characteristics of HCNG mixture, refinements on different fuel mixture affecting the combustion. For covering the prospects of the HCNG engines, its technical and numerical approaches are discussed. Furthermore, various methods are discussed which increase the power output and thermal efficiency along with a check on the emission parameters. An exploration of HCNG vehicle's demonstration projects worldwide is a key feature of this article.



http://ift.tt/2tbTGJM

Developing a new Bayesian Risk Index for risk evaluation of soil contamination

Publication date: 15 December 2017
Source:Science of The Total Environment, Volumes 603–604
Author(s): M.T.D. Albuquerque, S. Gerassis, C. Sierra, J. Taboada, J.E. Martín, I.M.H.R. Antunes, J.R. Gallego
Industrial and agricultural activities heavily constrain soil quality. Potentially Toxic Elements (PTEs) are a threat to public health and the environment alike. In this regard, the identification of areas that require remediation is crucial. In the herein research a geochemical dataset (230 samples) comprising 14 elements (Cu, Pb, Zn, Ag, Ni, Mn, Fe, As, Cd, V, Cr, Ti, Al and S) was gathered throughout eight different zones distinguished by their main activity, namely, recreational, agriculture/livestock and heavy industry in the Avilés Estuary (North of Spain). Then a stratified systematic sampling method was used at short, medium, and long distances from each zone to obtain a representative picture of the total variability of the selected attributes. The information was then combined in four risk classes (Low, Moderate, High, Remediation) following reference values from several sediment quality guidelines (SQGs). A Bayesian analysis, inferred for each zone, allowed the characterization of PTEs correlations, the unsupervised learning network technique proving to be the best fit. Based on the Bayesian network structure obtained, Pb, As and Mn were selected as key contamination parameters. For these 3 elements, the conditional probability obtained was allocated to each observed point, and a simple, direct index (Bayesian Risk Index-BRI) was constructed as a linear rating of the pre-defined risk classes weighted by the previously obtained probability. Finally, the BRI underwent geostatistical modeling. One hundred Sequential Gaussian Simulations (SGS) were computed. The Mean Image and the Standard Deviation maps were obtained, allowing the definition of High/Low risk clusters (Local G clustering) and the computation of spatial uncertainty. High-risk clusters are mainly distributed within the area with the highest altitude (agriculture/livestock) showing an associated low spatial uncertainty, clearly indicating the need for remediation. Atmospheric emissions, mainly derived from the metallurgical industry, contribute to soil contamination by PTEs.

Graphical abstract

http://ift.tt/2twl6JJ

Intestinal fate of dietary zinc and copper: Postprandial net fluxes of these trace elements in portal vein of pigs

Publication date: December 2017
Source:Journal of Trace Elements in Medicine and Biology, Volume 44
Author(s): J. Jacques Matte, Christiane L. Girard, Frédéric Guay
In pig, the assessment of bioavailability of dietary trace minerals with classical approaches such as relative bioavailability estimates or digestive tract balances have often generated inconsistent responses. In the present study, net portal-drained-viscera fluxes were monitored after a meal to assess intestinal absorption of zinc (Zn) or copper (Cu) according to dietary sources and levels of these trace minerals. Twelve pigs were surgically equipped with portal and carotid catheters and a portal ultrasonic flow probe for 12-h postprandial measurements. In a cross-over design, pigs received boluses of inorganic (I) or organic (O) dietary Cu and Zn at adequate (A, 20 and 200mg, respectively) or high (H, 40 and 400mg, respectively) level just before a 0.8-kg meal (semi-purified diet). Whatever treatments, arterial Zn increased by 72% at 45min postprandial and gradually declined thereafter (P<0.01). Arterial Zn were greater by 11% after O than I (P=0.02) and by 19% after H than A (P<0.01) meals. Net portal-drained-viscera fluxes of Zn during the first 240min postprandial were greater by 44% after O than I (P=0.10) and by 51% after H than A (P=0.07) meals. For Cu, portal-drained-viscera fluxes of Cu up to 240min postprandial were greater (P=0.03) after A than H meals. Those results suggest that Zn is absorbed rapidly, likely in the upper digestive tract of pigs and, whatever dietary levels, more efficiently after O meals. It appears that H levels of both Zn and Cu interfered with intestinal absorption of Cu and/or stimulate post-absorption enterocyte sequestration of this mineral.



http://ift.tt/2twlqI7

Accumulation, spatio-temporal distribution, and risk assessment of heavy metals in the soil-corn system around a polymetallic mining area from the Loess Plateau, northwest China

Publication date: 1 November 2017
Source:Geoderma, Volume 305
Author(s): Fei Zang, Shengli Wang, Zhongren Nan, Jianmin Ma, Qian Zhang, Yazhou Chen, Yepu Li
To investigate the heavy metal concentrations in soil-corn system, 30 pairs of soil (0–20cm) and corn grain samples were collected from Baiyin City, China, a typical industrial oasis in Loess Plateau. The results indicated that the mean concentrations of Cu, Zn, Cd and Pb in agricultural soils from the Dongdagou and Xidagou stream valleys exceeded the soil background concentrations of Gansu Province, China. Correlation analysis showed that the correlation among the total Cu, Zn, Cd and Pb in soils were significant at P<0.01. Results showed that only a fraction of Cd and Pb in the corn grain samples exceeded the limits of eight elements in cereals, legume, tubes and its products and the maximum levels of contaminants in foods in China. The spatial distribution pattern of Cd in corn grains was highly similar to that in sampled soils. Correlation analysis revealed that the main source of Zn, Cd and Pb in corn grains was soils. Temporal distribution of heavy metals showed that heavy metal content in soils was still high, and the Cu, Cd, Pb content in corn grains showed a decreasing trend over 20years. The values of pollution index (PI) and Nemerow integrated pollution index (NIPI) indicated that the heavy metal pollution level was Cd>Zn>Cu>Pb, and Cu, Zn, Cd and Pb belong to safe to heavy pollution. The results of hazard quotient (HQ) indicated that there was no obvious adverse health effect for children and adults.

Graphical abstract

http://ift.tt/2syBZ9n

Noble-metal-free NiO@Ni-ZnO/reduced graphene oxide/CdS heterostructure for efficient photocatalytic hydrogen generation

Publication date: 15 November 2017
Source:Applied Surface Science, Volume 422
Author(s): Fayun Chen, Laijun Zhang, Xuewen Wang, Rongbin Zhang
Noble-metal-free semiconductor materials are widely used for photocatalytic hydrogen generation because of their low cost. ZnO-based heterostructures with synergistic effects exhibit an effective photocatalytic activity. In this work, NiO@Ni-ZnO/reduced graphene oxide (rGO)/CdS heterostructures are synthesized by a multi-step method. rGO nanosheets and CdS nanoparticles were introduced into the heterostructures via a redox reaction and light-assisted growth, respectively. A novel Ni-induced electrochemical growth method was developed to prepare ZnO rods from Zn powder. NiO@Ni-ZnO/rGO/CdS heterostructures with a wide visible-light absorption range exhibited highly photocatalytic hydrogen generation rates under UV–vis and visible light irradiation. The enhanced photocatalytic activity is attributed to the Ni nanoparticles that act as cocatalysts for capturing photoexcited electrons and the improved synergistic effect between ZnO and CdS due to the rGO nanosheets acting as photoexcited carrier transport channels.

Graphical abstract

http://ift.tt/2syuoHI

Pulvis Fellis Suis extract attenuates ovalbumin-induced airway inflammation in murine model of asthma

Publication date: Available online 15 June 2017
Source:Journal of Ethnopharmacology
Author(s): Jiao He, Le Lv, Ziye Wang, Chuanchuan Huo, Zongwei Zheng, Bing Yin, Peizhi Jiang, Yang Yang, Jing Li, Yuan Gao, Jing Xue
Ethnopharmacological relevancePulvis Fellis Suis (PFS), named with "Zhu Danfen" in China, has been extensively used for the therapy of enteritis, acute pharyngitis, whooping cough and asthma in folk medicine. Although PFS shows anti-inflammatory activities, its effect on airway inflammation in asthma has not been studied.Aim of the studyTo explore the protective effect of PFS ethanol extract against airway inflammation in asthmatic mice.Materials and MethodsAllergic asthma in mice was sensitized and challenged by OVA. Mice were administered in oral with PFS daily at doses of 100, 200 and 400mg/kg on days 21–27. Inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were analysed. Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) and periodic acid-schiff (PAS) staining. The IgE level in serum was measured by using enzyme-linked immunoassay (ELISA). ELISA was also used to detect the levels of Th1/Th2 cytokine and eotaxin in BALF.ResultsHistological results revealed that PFS could ameliorate OVA-induced histological changes by attenuating inflammatory cell infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. Treatment with different doses of PFS significantly decreased the elevated inflammatory cell numbers in BALF and IgE production in serum. PFS treatment reduced the production of Th2 cytokine IL-4, IL-5, IL-13, and promoted Th1 cytokine IFN-γ production in BALF. In addition, PFS also decreased the levels of eotaxin and TNF-α in BALF.ConclusionsThese findings suggest that PFS has a markedly anti-inflammatory effect on OVA-induced allergic asthma in mice, and could be a promising protective agent recommended for allergic asthma patients.

Graphical abstract

http://ift.tt/2rp3Ghn

Consumers’ acceptance of medicinal herbs: an application of the technology acceptance model (TAM)

Publication date: Available online 15 June 2017
Source:Journal of Ethnopharmacology
Author(s): Nargesh Khatun Jokar, Seyyed Ali Noorhosseini, Mohammad Sadegh Allahyari, Christos A. Damalas
Ethnopharmacological relevanceThe shift in consumers' preferences from synthetic to 'natural' products has led to a resurgence of interest in medicinal plants, particularly in developing countries. However, research data about consumers' preferences for particular products is hard to find.Aims and objectivesThe main objective of this study was to contribute to the general understanding of consumers' intention for selecting medicinal herbs for consumption.Materials and methodsFactors underpinning consumers' acceptance of medicinal herbs were studied with the technology acceptance model (TAM) in Rasht City of Iran using a structured questionnaire.ResultsMost respondents had low to moderate familiarity with consumption of medicinal herbs. However, about half of the respondents (47.5%) showed a high level of acceptance of medicinal herbs. Herbs like spearmint (Mentha spicata L.), spinach (Spinacia oleracea L.), basil (Ocimum basilicum L.), Damask rose (Rosa × damascena Herrm.), saffron (Crocus sativus L.), cinnamon (Cinnamomum verum J.Presl), flixweed [Descurainia sophia (L.) Webb ex Prantl], red feathers (Echium amoenum Fisch. & C.A.Mey.), and green tea [Camellia sinensis (L.) Kuntze] had the highest consumption rate among the majority (over 75%) of citizens of Rasht. The highest rate of perceived usefulness of medicinal herbs was related to their perceived role in healing diseases. The variable of importance of use of medicinal herbs had the strongest direct effect and the variables of perceived usefulness and attitude towards use had the second and third strongest direct effect on the acceptance of medicinal herbs' use at p < 0.01.ConclusionsFindings provide a useful evaluation of the acceptance of medicinal herbs and may serve as a benchmark for future research and evaluation concerning the use of medicinal herbs over time. For plant producers, more effective and targeted crop development should be encouraged, whereas for retailers better marketing and delivery strategies should be sought.

Graphical abstract

http://ift.tt/2roNnky

The antinociceptive effects of a standardized ethanol extract of the Bidens odorata Cav (Asteraceae) leaves are mediated by ATP-sensitive K+ channels

Publication date: Available online 16 June 2017
Source:Journal of Ethnopharmacology
Author(s): Juan Ramón Zapata-Morales, Angel Josabad Alonso-Castro, Fabiola Domínguez, Candy Carranza-Álvarez, Mario Isiordia-Espinoza, Alejandro Hernández-Morales, Cesar Solorio-Alvarado
Ethnopharmacological relevanceBidens odorata Cav (Asteraceae)is used for the empirical treatment of inflammation and pain.Aim of the studyThis work evaluatedthein vitro and in vivo toxicity, antioxidant activity, as well as the anti-inflammatory and antinociceptive effects of an ethanol extract from Bidens odorata leaves (BOE).Materials and methodsThe in vitro toxicity of BOE (10–1000µg/ml) was evaluated with the comet assay in PBMC. The in vivo acute toxicity of BOE (500–5000mg/kg) and the effect of BOE (10–1000µg/ml) on the level of ROS in PBMC were determined.The in vivo anti-inflammatory activity of BOE was assessed using the TPA-induced ear edema in mice. The antinociceptive activities of BOE (50–200mg/kg p.o.) were assessed using the acetic acid and formalin tests. The antinociceptive mechanism of BOE was determined using naloxone and glibenclamide.ResultsBOE lacked DNA damage, and showed low in vivo toxicity (LD50>5000mg/kg p.o.). BOE inhibited ROS production (IC50= 252.13 ± 20.54µg/ml), and decreased inflammation by 36.1 ± 3.66%. In both antinociceptive test, BOE (200mg/kg) exerted activity with similar activity than the reference drugs.ConclusionB. odorata exerts low in vitro and in vivo toxicity, antioxidant effects, moderate in vivo anti-inflammatory activity, and antinociceptive effects mediated by ATP-sensitive K⁺ channels.

Graphical abstract

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Brazilian red propolis effects on peritoneal macrophage activity: nitric oxide, cell viability, pro-inflammatory cytokines and gene expression

Publication date: Available online 15 June 2017
Source:Journal of Ethnopharmacology
Author(s): Bruno Bueno-Silva, Dione Kawamoto, Ellen S. Ando-Suguimoto, Renato C.V. Casarin, Severino M. Alencar, Pedro L. Rosalen, Marcia P.A. Mayer
Ethnopharmacological relevancePropolis has been used in folk medicine since ancient times and it presented inhibitory effect on neutrophil recruitment previously. However, its effect on macrophage obtained from mice remains unclear.Aim of the studyto demonstrate BRP effects on LPS activated peritoneal macrophage.Materials and MethodsPeritoneal macrophages, obtained from C57BL6 mice and activated with LPS, were treated with 50 to 80µg/mL of crude extract of Brazilian red propolis (BRP) during 48hours. Cell viability, levels of NO, 20 cytokines and expression of 360 genes were evaluated.ResultsBRP 60µg/ml reduced NO production by 65% without affecting the cell viability and decreased production IL1α, IL1β, IL4, IL6, IL12p40, Il12p70, IL13, MCP1 and GM-CSF. Molecular mechanism beyond the anti-inflammatory activity may be due to BRP-effects on decreasing expression of Mmp7, Egfr, Adm, Gata3, Wnt2b, Txn1, Herpud1, Axin2, Car9, Id1, Vegfa, Hes1, Hes5, Icam1, Wnt3a, Pcna, Wnt5a, Tnfsf10, Ccl5, Il1b, Akt1, Mapk1, Noxa1 and Cdkn1b and increasing expression of Cav1, Wnt6, Calm1, Tnf, Rb1, Socs3 and Dab2.ConclusionsTherefore, BRP has anti-inflammatory effects on macrophage activity by reducing NO levels and diminished release and expression of pro-inflammatory cytokine and genes, respectively.

Graphical abstract

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Superimposable outcomes for sequential and concomitant administration of adjuvant trastuzumab in HER2-positive breast cancer: Results from the SIGNAL/PHARE prospective cohort

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): Xavier Pivot, Pierre Fumoleau, Jean-Yves Pierga, Suzette Delaloge, Hervé Bonnefoi, Thomas Bachelot, Christelle Jouannaud, Hugues Bourgeois, Maria Rios, Patrick Soulié, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Pierre Kerbrat, David Cox, Céline Faure-Mercier, Iris Pauporte, Joseph Gligorov, Elsa Curtit, Julie Henriques, Sophie Paget-Bailly, Gilles Romieu
AimAdjuvant clinical trials in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer have assessed either sequential or concomitant incorporation of trastuzumab with chemotherapy; only the North Central Cancer Treatment Group (NCCTG)-N9831 trial prospectively compared both modalities. In routine trastuzumab has been incorporated into a concurrent regimen with taxane chemotherapy instead of sequential modality on the basis of a positive risk-benefit ratio. This present study assessed sequential versus concomitant administration of adjuvant trastuzumab.MethodsA population combining patients from Protocol for Herceptin^® as Adjuvant therapy with Reduced Exposure (PHARE) a randomised phase III clinical trial (NCT00381901) and SIGNAL (RECF1098) a prospective study specifically designed for Genome-wide Association Studies (GWAS) analyses was studied. In this cohort with 58 months of median follow-up, the comparison in the HER2-positive group of adjuvant trastuzumab and chemotherapy modalities was based on a propensity score methodology. Treatment modalities were based on physician's choice and comparisons adjustment were made by a propensity score methodology. Overall Survival (OS) and Disease-Free Survival (DFS) were estimated using the Kaplan–Meier method, and comparisons between groups were based on the log rank test.ResultsThe SIGNAL/PHARE cohort included 11,728 breast cancer cases treated in adjuvant setting; some 5502 of them with HER2-positive tumour: 34.5% (1897/5502) were treated by sequential and 65.5% (3605/5502) by concomitant modality of administration for taxane-chemotherapy and trastuzumab. The adjusted comparison found similar OS (HR = 1.01; 95% CI: 0.86–1.19) and similar DFS (HR = 1.08; 95% CI: 0.96–1.21).ConclusionThese results suggest that the sequential administration of trastuzumab given after the completion of adjuvant chemotherapy might be as valid as the concomitant administration of trastuzumab and taxane chemotherapy in the adjuvant setting.



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Discrepancy in BRAF status among patients with metastatic malignant melanoma: A meta-analysis

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): Antonis Valachis, Gustav J. Ullenhag
The incidence of malignant melanoma is growing rapidly. Approximately half of the cases are BRAF mutated, making treatment with kinase inhibitors a (MEK and BRAF inhibitors) preferred choice in the advanced setting. The vast majority of these patients will benefit from the treatment. It is therefore of vital importance that the BRAF analysis is reliable and reflects the true nature of the tumour. Intraindividual tumour BRAF heterogeneity may exist, and changes of BRAF status over time might occur.We reviewed the literature by searching the PubMed database and 630 potentially relevant studies were identified. Thereafter, studies that investigated intralesional heterogeneity only, studies with ≤10 patients and studies that did not include adequate data to calculate discrepancy rates were excluded. Twenty-two studies met our inclusion criteria and were included in the meta-analysis.The pooled discrepancy rate between primary and metastatic lesions was 13.4% (95% confidence interval [CI]: 9.2–18.2%) while it was 7.3% (95% CI: 3.3–12.6) between two metastatic lesions. The number of patients whose tumoural BRAF status was changed from mutation to wild type and from wild type to mutation, respectively, was comparable.We conclude that a clinically meaningful discrepancy rate in BRAF status both between primary-metastatic and metastatic–metastatic melanoma lesions exists. Our results support the polyclonal model of melanomas in which subclones with different BRAF status co-exist in the same melanoma lesion. In addition, the results indicate a need for biopsy of a metastatic lesion for subsequent BRAF analysis when treatment with kinase inhibitors is considered.



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Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): Leisha A. Emens, Paolo A. Ascierto, Phillip K. Darcy, Sandra Demaria, Alexander M.M. Eggermont, William L. Redmond, Barbara Seliger, Francesco M. Marincola
Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development. Current challenges facing the field include incorporating immunotherapy into adjuvant and neoadjuvant cancer therapy, refining dose, schedule and duration of treatment and developing novel surrogate endpoints that accurately capture overall survival benefit early in treatment. As the field rapidly evolves, we must prioritise the development of biomarkers to guide the use of immunotherapies in the most appropriate patients. Immunotherapy is already transforming cancer from a death sentence to a chronic disease for some patients. By making smart, evidence-based decisions in developing next generation immunotherapies, cancer should become an imminently treatable, curable and even preventable disease.



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Case series of patients treated with the oral fluoropyrimidine S-1 after capecitabine-induced coronary artery vasospasm

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): Johannes J.M. Kwakman, Arnold Baars, Annette A. van Zweeden, Pieter de Mol, Miriam Koopman, Wouter E.M. Kok, Cornelis J.A. Punt




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Genetic determinants of response to fibroblast growth factor receptor inhibitors in solid tumours

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): Laura Leroy, Sophie Cousin, Antoine Italiano




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First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)

Condition:   Esophageal Neoplasms
Interventions:   Biological: Pembrolizumab;   Drug: Placebo;   Drug: Cisplatin;   Drug: 5-FU
Sponsor:   Merck Sharp & Dohme Corp.
Not yet recruiting - verified June 2017

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Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account

Publication date: August 2017
Source:Cortex, Volume 93
Author(s): Elisa Di Rosa, Lara Bardi, Carlo Umiltà, Fabio Masina, Margherita Forgione, Daniela Mapelli
The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect.



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The timing of spontaneous detection and repair of naming errors in aphasia

Publication date: August 2017
Source:Cortex, Volume 93
Author(s): Julia Schuchard, Erica L. Middleton, Myrna F. Schwartz
This study examined the timing of spontaneous self-monitoring in the naming responses of people with aphasia. Twelve people with aphasia completed a 615-item naming test twice, in separate sessions. Naming attempts were scored for accuracy and error type, and verbalizations indicating detection were coded as negation (e.g., "no, not that") or repair attempts (i.e., a changed naming attempt). Focusing on phonological and semantic errors, we measured the timing of the errors and of the utterances that provided evidence of detection. The effects of error type and detection response type on error-to-detection latencies were analyzed using mixed-effects regression modeling. We first asked whether phonological errors and semantic errors differed in the timing of the detection process or repair planning. Results suggested that the two error types primarily differed with respect to repair planning. Specifically, repair attempts for phonological errors were initiated more quickly than repair attempts for semantic errors. We next asked whether this difference between the error types could be attributed to the tendency for phonological errors to have a high degree of phonological similarity with the subsequent repair attempts, thereby speeding the programming of the repairs. Results showed that greater phonological similarity between the error and the repair was associated with faster repair times for both error types, providing evidence of error-to-repair priming in spontaneous self-monitoring. When controlling for phonological overlap, significant effects of error type and repair accuracy on repair times were also found. These effects indicated that correct repairs of phonological errors were initiated particularly quickly, whereas repairs of semantic errors were initiated relatively slowly, regardless of their accuracy. We discuss the implications of these findings for theoretical accounts of self-monitoring and the role of speech error repair in learning.



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Structure-activity relationship study of tetrapeptide inhibitors of the Vascular Endothelial Growth Factor A binding to Neuropilin-1

Publication date: Available online 13 June 2017
Source:Peptides
Author(s): Dagmara Tymecka, Piotr F.J. Lipiński, Bartłomiej Fedorczyk, Anna Puszko, Beata Wileńska, Gerard Y. Perret, Aleksandra Misicka
Neuropilin-1 is considered as one of the key receptors responsible for signaling pathways involved in pathological angiogenesis necessary for tumor progression, therefore targeting of VEGF165 binding to NRP-1 could be a relevant strategy for antiangiogenic treatment. It was shown before that the VEGF165/NRP-1 interaction can be inhibited by short tetrapeptides with K/RXXR sequence.Here, we present a structure–activity relationship study of the systematic optimization of amino acid residues in positions 1-3 in the above tetrapeptides. All the 13 synthesized analogs possessed C-terminal arginine that is a necessary element for interaction with NRP-1. The obtained results of the inhibitory activity and modeling by molecular dynamics indicate that simultaneous interactions of the basic amino acid residues in position 1 and 4 (Arg) with Neuropilin-1 are crucial and their cooperation strongly affects the inhibitory activity. In addition, the binding strength is modulated by the flexibility of the peptide backbone (in the central part of the peptide), and the nature of the side chain of the amino acids at the second or third position. A dramatic decrease in the activity to the receptor is observed in flexible derivatives that are missing proline residues. The results described in this paper should prove useful for future studies aimed at establishing the best pharmacophore for inhibitors of VEGF165 binding to NRP-1.



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Performance of low-dose cosyntropin stimulation test handled via plastic tube

Abstract

Purpose

Studies on 1 μg low-dose test showed that among 1 μg cosyntropin samples pushed through long IV plastic tubing, some adrenocorticotropic hormone dosage was not recovered, and in healthy volunteers it provided subnormal cortisol responses. The aim of the current study is to assess whether there is any loss in adrenocorticotropic hormone 1–24 concentration when pushed through a short plastic tube, and to assess serum and salivary cortisol responses in low-dose test among healthy volunteers, using a similar short plastic tube vs. direct intravenous consyntropin injection.

Methods

We evaluated in vitro if adrenocorticotropic hormone was absorbed in a 2.5 cm plastic tube by measuring adrenocorticotropic hormone 1–24 concentration in a 1 μg/ml adrenocorticotropic hormone aliquot solution before and after being flushed through the plastic tube. For the in vivo study, we recruited 20 healthy adult volunteers. Each subject underwent low-dose test via 2.5 cm plastic tube via plastic tube and via direct intravenous injection by a metal syringe via direct intravenous injection, and cortisol responses were determined.

Results

Mean adrenocorticotropic hormone 1–24 concentration did not differ significantly when flushed via plastic tube or measured in the aliquot solution (P = 0.25). In vivo, mean 30-min serum cortisol concentrations were 20.47 ± 2.87 and 21.62 ± 3.89 μg/dl in via plastic tube and in via direct intravenous injection tests, respectively, and did not show a significant difference (P = 0.16).

Conclusions

In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.

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“Slow and steady wins the race”: the importance of perseverance in the management of oncogenic osteomalacia

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Effects of cigarette smoke exposure during suckling on food intake, fat mass, hormones, and biochemical profile of young and adult female rats

Abstract

Purpose

Children from smoking mothers have a higher risk of developing obesity and associated comorbidities later in life. Different experimental models have been used to assess the mechanisms involved with this increased risk. Using a rat model of neonatal nicotine exposure via implantation of osmotic minipumps in lactating dams, we have previously shown marked sexual dimorphisms regarding metabolic and endocrine outcomes in the adult progeny. Considering that more than four thousand substances are found in tobacco smoke besides nicotine, we then studied a rat model of neonatal tobacco smoke exposure: adult male offspring had hyperphagia, obesity, hyperglycemia, hypertriglyceridemia, secondary hyperthyroidism and lower adrenal hormones. Since litters were culled to include only males and since sexual dimorphisms had already been identified in the nicotine exposure model, here we also evaluated the effects of tobacco smoke exposure during lactation on females.

Methods

Wistar rat dams and their pups were separated into two groups of 8 litters each: SMOKE (4 cigarettes per day, from postnatal day 3 to 21) and CONTROL (filtered air). Offspring of both sexes were euthanized at PN21 and PN180.

Results

Changes in male offspring corroborated previous data. At weaning, females showed lower body mass gain and serum triglycerides, but no alterations in visceral fat and hormones. At adulthood, females had higher body mass, hyperphagia, central obesity, hyperleptinemia, hypercholesterolemia, hypercorticosteronemia, but no change in serum TSH and T3, and adrenal catecholamine

Conclusions

Sexual dimorphisms were observed in several parameters, thus indicating that metabolic and hormonal changes due to smoke exposure during development are sex-dependent.

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Erratum to: CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves’ disease and modulates clinical phenotype of disease

http://ift.tt/2roNE76

Circulating microRNA-1a is a biomarker of Graves’ disease patients with atrial fibrillation

Abstract

Purpose

It has been increasingly suggested that specific microRNAs expression profiles in the circulation and atrial tissue are associated with the susceptibility to atrial fibrillation. Nonetheless, the role of circulating microRNAs in Graves' disease patients with atrial fibrillation has not yet been well described. The objective of the study was to identify the role of circulating microRNAs as specific biomarkers for the diagnosis of Graves' disease with atrial fibrillation.

Methods

The expression profiles of eight serum microRNAs, which are found to be critical in the pathogenesis of atrial fibrillation, were determined in patients with Graves' disease with or without atrial fibrillation. MicroRNA expression analysis was performed by real-time PCR in normal control subjects (NC; n = 17), patients with Graves' disease without atrial fibrillation (GD; n = 29), patients with Graves' disease with atrial fibrillation (GD + AF; n = 14), and euthyroid patients with atrial fibrillation (AF; n = 22).

Results

Three of the eight serum microRNAs,i.e., miR-1a, miR-26a, and miR-133, had significantly different expression profiles among the four groups. Spearman's correlation analysis showed that the relative expression level of miR-1a was positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively related to thyroid stimulating hormone. Spearman's correlations analysis also revealed that the level of miR-1a was negatively correlated with a critical echocardiographic parameter (left atrial diameter), which was dramatically increased in GD + AF group compared to GD group. Furthermore, the receiver-operating characteristic curve analysis indicated that, among the eight microRNAs, miR-1a had the largest area under the receiver-operating characteristic curves not only for discriminating between individuals with and without Graves' disease, but also for predicting the presence of atrial fibrillation in patients with Graves' disease.

Conclusions

Our findings showed that the levels of serum miR-1a were significantly decreased in GD + AF group compared with GD group, suggesting that serum miR-1a might serve as a novel biomarker for diagnosis of atrial fibrillation in patients with Graves' disease.

http://ift.tt/2sHaLh8

Androgenetic alopecia: a review

Abstract

Purpose

Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia.

Methods

Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016.

Results

The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome AR⁄EDA2R locus and the chromosome 20p11 locus.

Conclusions

Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.

http://ift.tt/2roLTXq

Effectiveness of vitamin K2 on osteoporosis in adults with cerebral palsy

Publication date: Available online 16 June 2017
Source:Brain and Development
Author(s): Yuichi Kodama, Yasuhiro Okamoto, Tomohiro Kubota, Yoshifumi Hiroyama, Hiroshi Fukami, Kensuke Matsushita, Yoshifumi Kawano
BackgroundOsteoporosis can lead to spontaneous fractures in adults with cerebral palsy (CP). Undercarboxylated osteocalcin (ucOC) is a useful marker for vitamin K insufficiency in osteoporosis. The primary objective of this study was to determine the effect of vitamin K2 on bone mineral density (BMD) in adults with CP and vitamin K insufficiency.MethodsSixteen adults, median age of 56years, with CP and osteoporosis in whom the serum ucOC concentration exceeded 4.5ng/mL were included. All patients received 45mg of vitamin K2 per day. BMD was measured and presented as a percentage of the young adult mean (%YAM). Serum levels of ucOC and BMD were measured at baseline and after 6 and 12months.ResultsSerum levels of ucOC decreased from 7.8ng/mL (range, 4.9–32) at baseline to 3.9ng/mL (range, 1.9–6.8) after 6months (P=0.001). BMD increased from 59%YAM (range, 45–67) at baseline to 68%YAM (range, 50–79) after 12months (P=0.003).ConclusionsVitamin K2 had a positive effect on BMD in osteoporotic adults with CP and high serum concentrations of ucOC, and might be useful as a first line treatment for osteoporotic adults with CP and vitamin K insufficiency.



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American Thyroid Association Awards Research Grant to Kristen R. Vella, Ph.D., Beth Israel Deaconess Medical Center and Harvard Medical School

Supported by ATA

The ATA is pleased to present a 2016 Research Grant to Kristen Vella, PhD, to support her project entitled "Neuronal Regulation of Hepatic Thyroid Hormone Clearance." Dr. Vella is an Instructor in the Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.

Dr. Vella presents a research study intended to identify the subset of neurons that activate thyroid hormone (TH) clearance in the liver during fasting and with weight loss, leading to decreased energy expenditure. These regulatory mechanisms work against efforts to maintain weight loss. A better understanding of the mechanisms and of how certain neurons activate or inhibit hepatic TH clearance could lead to the discovery of novel therapeutic targets to treat metabolic disorders and aid in weight loss maintenance.

Dr. Vella and colleagues have previously identified specific genes that suppress TH levels during fasting and regulate hepatic TH clearance. She has hypothesized that these genes are express by neurons in the hypothalamus. Through her research project, Dr. Vella will explore the neuronal and downstream signaling pathways that link the hypothalamus and the liver and how those connections may become altered during metabolic disease and weight loss maintenance.

Dr. Motoyasu Saji, Chair, ATA Research Committee says, "The ATA research grant program has been supporting young scientists in various thyroid-related research area, including clinical, translational, and basic areas. Every year we receive over 50 Grant applications from various countries. We excite to see young thyroid researchers, who attack current clinical problems and basic scientific questions using state of art technologies, new ideas, and new views. Many current leaders in the ATA were award recipients and this tells us how this program is important for us. We hope that this grant will be one of gateway to succeed in carrier as thyroid researchers and they will become leaders in next generation in the ATA. Finally, we appreciate all supports from members and various organizations, including cancer survivors, to make us possible creating excellent program."

The American Thyroid Association (ATA) has awarded 85 thyroid research grants totaling over $2.2 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and distribution of over $1.8 million generously donated to the ATA specifically for research grants from ThyCa: Thyroid Cancer Survivors' Association, Inc., Bite Me Cancer and Thyroid Head and Neck Cancer Foundation. For information on other research grants underway and funded by the ATA, see http://ift.tt/2l3TSGC.

ThyCa: Thyroid Cancer Survivors' Association, Inc. (ThyCa) has provided funding in support of 60 special research grants totaling $1,680,000 focused on thyroid cancer and medullary thyroid cancer since 2003. ThyCa is supporting three research grants in 2016 and three renewing grants. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org.

Bite Me Cancer (BMC) is our newest grant funder supporting five thyroid cancer grants since 2014 for a total of $143,750. BMC will be supporting a new thyroid cancer grant in 2016 and one renewing grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org.

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The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts.

Celebrating its 94^th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found at www.thyroid.org.

 

 

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