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Δευτέρα 9 Ιανουαρίου 2017

Characterization and validation of a split belt treadmill for measuring hindlimb ground-reaction forces in able-bodied and spinalized felines

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Publication date: Available online 6 January 2017
Source:Journal of Neuroscience Methods
Author(s): Marko Dimiskovski, Richard Scheinfield, Dwight Higgin, Alexander Krupka, Michel A. Lemay
BACKGROUNDThe measurement of ground reaction forces (GRFs) in animals trained to locomote on a treadmill after spinal cord injury (SCI) could prove valuable for evaluating training outcomes; however, quantitative measures of the GRFs in spinal felines are limited.NEW METHODA split belt treadmill was designed and constructed to measure the GRFs of feline hindlimbs during stepping. The treadmill consists of two independent treadmill assemblies, each mounted on a force plate. The design allows measurements of the vertical (Fz), fore-aft (Fy) and mediolateral (Fx) ground-reaction forces for both hindlimbs while the forelimbs are resting on a platform.RESULTSStatic and dynamic noise tests revealed little to no noise at frequencies below 6Hz. Validation of the force plate measurements with a hand-held force sensor force showed good agreement between the two force readings. Peak normalized (to body mass) vertical GRFs for intact cats were 4.89±0.85N/Kg for the left hindlimb and 4.79±0.97N/Kg for the right. In comparison, trained spinalized cats peak normalized vertical GRFs were 2.20±0.94N/Kg for the left hindlimb and 2.85±0.99N/Kg for the right.COMPARISON WITH OTHER EXISTING METHODSPrevious methods of measuring GRFs used stationary single force plates or treadmill mounted to single force plate. Using independent treadmills for each hindlimb allows measurement of the individual hindlimb's GRFs in spinalized cats following body-weight supported treadmill training.CONCLUSIONSThe split belt force treadmill enables the simultaneous recording of ground-reaction forces for both hindlimbs in cats prior to spinalization, and following spinalization and body-weight-supported treadmill training (BWST).



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Analysis of Longitudinal Diffusion-Weighted Images in Healthy and Pathological Aging: An ADNI Study

Publication date: Available online 3 January 2017
Source:Journal of Neuroscience Methods
Author(s): Frithjof Kruggel, Fumitaro Masaki, Ana Solodkin
Background & New MethodThe widely used framework of voxel-based morphometry for analyzing neuroimages is extended here to model longitudinal imaging data by exchanging the linear model with a linear mixed-effects model. The new approach is employed for analyzing a large longitudinal sample of 756 diffusion-weighted images acquired in 177 subjects of the Alzheimer's Disease Neuroimaging initiative (ADNI).Results and Comparison with Existing MethodsWhile sample- and group-level results from both approaches are equivalent, the mixed-effect model yields information at the single subject level. Interestingly, the neurobiological relevance of the relevant parameter at the individual level describes specific differences associated with aging. In addition, our approach highlights white matter areas that reliably discriminate between patients with Alzheimer's disease and healthy controls with a predictive power of 0.99 and include the hippocampal alveus, the para-hippocampal white matter, the white matter of the posterior cingulate, and optic tracts. In this context, notably the classifier includes a sub-population of patients with minimal cognitive impairment into the pathological domain.ConclusionOur classifier offers promising features for an accessible biomarker that predicts the risk of conversion to Alzheimer's disease.Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://ift.tt/2i3ohpb to apply/ADNI Acknowledgement List.pdf.Significance StatementThis study assesses neuro-degenerative processes in the brain's white matter as revealed by diffusion-weighted imaging, in order to discriminate healthy from pathological aging in a large sample of elderly subjects. The analysis of time-series examinations in a linear mixed effects model allowed the discrimination of population-based aging processes from individual determinants. We demonstrate that a simple classifier based on white matter imaging data is able to predict the conversion to Alzheimer's disease with a high predictive power

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Reduction of carcinomatosis risk using icodextrin as a carrier solution of intraperitoneal oxaliplatin chemotherapy

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Publication date: Available online 9 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Ingrid Jouvin, Haythem Najah, Cynthia Pimpie, C. Canet Jourdan, Rachid Kaci, Massoud Mirshahi, Clarisse Eveno, Marc Pocard
There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumor or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumor cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy.We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI.In the chemo group, PCI was significantly lower than in the control group (3,2 versus 8,4, p = 0,02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1,4 versus 3,2, p = 0,04). There was no morbidity linked to ICDX in toxicity group.Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.



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Wetting and adhesion evaluation of cosmetic ingredients and products: correlation of in vitro – in vivo contact angle measurements

Abstract

Objective

The aim of this work was to use the contact angle measurement in order to predict the behavior of ingredients and finished cosmetic products on skin to improve skin feel and product texture.

Method

Different classes of cosmetic ingredients and formulations were evaluated. The contact angle measurements were carried out by the sessile drop methodusing an apparatus, designed and set up in laboratory. Glass, Teflon and human skin were the reference substrates. In a preliminary phase TEWL parameter, sebum content and hydration of human skin were measured in order to set up method.

Results

Data demonstrated that glass substrate may be used as replacement of the skin:critical surface tension of skin and glass were about of 27 and 31 dyne/cm, respectively. Non ionic surfactant with increasing HLB were evaluated: a correlation between contact angle measured and HLB was not observed because of different and complex molecular structure. In detail, Ethylexylhydroxystearate (θglass = 17,1°) showed lower contact angle value with respect to Polysorbate 20 (θglass = 28.1°). Sodium Laureth Sulfate and Steralkonium Chloride were also evaluated: anionic molecule showed more affinity for glass with respect to Teflon (θglass = 21.7° and θTeflon = 52.3°). Lipids and silicones showed different affinity for substrate according to hydrophilic groups and hydrocarbon chain: contact angles of silicones remained unchanged independently from substrate. Finished cosmetic products (O/W, W/O emulsions, cleansing oil, dry skin oil) showed different profiles according to surfactant and its affinity for continuous phase of the formulation. Comparing the values of the contact angle on skin of non-ionic surfactants, as Ethylexylhydroxystearate and Polysorbate 20, they showed values lower (near to zero) than ones of Sodium Laureth Sulfate and Steralkonium Chloride (21.7° and 66.8°, respectively). Finally, finished cosmetic productstested on human skin, showed different profile: corresponded contact angle values were less than 20°. The product tended to be quickly adsorbed on human skin.

Conclusion

Systematic study carried out by evaluating the wettability of single cosmetic ingredients on different substrates allowed to find correlations between the use of certain ingredients and the final performance of a cosmetic product.

This article is protected by copyright. All rights reserved.



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Significant reductions in heart and lung doses using semi lateral decubitus techniques for left sided breast cancer patients: A comparative dosimetric study with supine techniques

Publication date: Available online 9 January 2017
Source:Alexandria Journal of Medicine
Author(s): Amr Abdul Aziz, Lila Mosa, Mohamed Farouk, Azza Helal, Mahran Abdo
IntroductionVarious treatment techniques as breath hold techniques have been developed to spare the heart and lung in breast cancer patients receiving adjuvant radiotherapy.Purposeto compare the heart and lung dosimetric parameters of semi lateral decubitus technique with and without deep inspiration breath hold with standard supine techniques for left-sided breast cancer patients undergoing breast conservative surgery and adjuvant radiotherapy.MethodsFifty patients with left-sided breast cancer were simulated using standard supine, semi lateral decubitus and semi lateral decubitus and deep inspiration breath hold. The three plans carried out using two tangential opposed photon beams were compared.ResultsThere was a significant reduction in heart V5Gy, V10Gy, V25Gy, V30Gy, mean dose & max dose with semi-lateral decubitus and breath hold technique compared to supine technique & semi-lateral decubitus technique (P<0.001). There was also a significant reduction in the above mentioned heart DVPs with semi-lateral decubitus (P<0.001) compared to supine technique.There was a significant reduction in ipsilateral lung V20Gy and mean dose with semi-lateral decubitus and breath hold technique compared to supine technique (P<0.001) & semi-lateral decubitus technique (P=0.003 & 0.006) respectively. There was also a significant reduction in ipsilateral lung V20Gy and mean dose with semi-lateral decubitus (P<0.001 & 0.007) compared to supine technique.ConclusionSemi-lateral decubitus techniques with and without breath hold for left sided breast cancer patients significantly reduce the dosimetric parameters of the heart and ipsilateral lung compared to supine technique with comparable target dose coverage.



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Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: a histological study of 26 patients

Abstract

Background

Follicular hyperkeratosis along with hyperplasia of the follicular and inter-follicular epithelia are major histopathological characteristics of Hidradenitis Suppurativa (HS). The presence of an occasional thickening of lesional skin in some Folliculitis Decalvans (FD) patients and histological similarities between FD and HS led us to look for epidermal hyperplasia and follicular hyperkeratosis in FD patients.

Patients and method

We performed a retrospective histological analysis of 26 patients with FD.

Objective

We sought to find out whether the presence of hyperplasia of the inter-follicular epidermis and of the follicular epithelia could be verified in FD, with reference to the work of Von Laffert et al. concerning HS.

Results

The main quantitative and qualitative data were: follicular hyperkeratosis (77%), hyperplasia of the inter-follicular epidermis (92%) with a psoriasiform aspect (88%), atrophy of the follicular epithelia (85%), plasma cells in infiltrate (92%) in large quantities (42%), follicular microcysts (60%), atrophy of the sebaceous glands (85%), polytrichia (54%).

Conclusion

Epidermal hyperplasia, sometimes psoriasiform, and follicular microcysts, are significant histological signs of FD, which have been ignored until now although they seem very common.



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Impact of Intensity-Modulated Radiotherapy with Concurrent Chemotherapy on Survival for Patients with Cervical Esophageal Carcinoma

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Publication date: Available online 9 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Lachlan J. McDowell, Shao Hui Huang, Wei Xu, Jiahua Che, Rebecca K.S. Wong, James Brierley, John Kim, Bernard Cummings, John Waldron, Andrew Bayley, Aaron Hansen, Ian Witterick, Jolie Ringash
Purpose/ObjectivesWe evaluated the impact of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC).Materials/MethodsAll CEC cases treated with definitive radiotherapy (RT) +/- chemotherapy (CTx) from 1997-2013 were reviewed in 3 consecutive protocols: Protocol 1 (P1): two-dimensional radiotherapy (2DRT), 54 Gy/20 fractions [f] with 5-fluorouracil plus either mitomycin C or cisplatin; P2: three-dimensional conformal radiotherapy (3DRT), ≥60 Gy/30f + elective nodal irradiation [ENI]) + cisplatin); P3: intensity-modulated radiotherapy (IMRT), ≥60 Gy/30f + ENI + cisplatin. Multivariable analyses (MVA) assessed the impact of treatment protocol, RT technique and RT dose on OS, separately.ResultsAmong 81 cases (P1: 21; P2: 23; P3: 37), 34 local (P1: 11 [52%]; P2: 12 [52%], P3: 11 [30%]), 16 regional (P1: 6 [29%); P2: 3 [13%]; P3: 7[19%]), and 34 distant (P1: 10 [48%]; P2: 9 [39%]; P3: 15 [41%]) failures were identified. After adjusting for age (p=0.49) and CTx (any vs. none: HR 0.5 [0.3-0.9], p=0.023), MVA showed P3 had improved OS vs. P1 (HR 0.4 [0.2-0.8], p=0.005) and trended to benefit vs. P2 (HR 0.6 [0.3-1.0], p=0.061); P1 and P2 did not differ (p=0.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97 [0.95-1.0], p=0.075). IMRT showed improved OS versus non-IMRT (HR 0.57 [0.3-0.8], p=0.008).ConclusionsThis retrospective consecutive cohort study showed improved OS with our current protocol (high-dose IMRT with concurrent high-dose cisplatin) compared to historical protocols. Outcomes in CEC remain poor and novel approaches to improve the therapeutic ratio are warranted.



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The Risk of Radiation-induced Tumors or Malignant Transformation after Single-Fraction Intracranial Radiosurgery: Results Based on a 25-year Experience

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Publication date: Available online 9 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bruce E. Pollock, Michael J. Link, Scott L. Stafford, Ian F. Parney, Yolanda I. Garces, Robert L. Foote
PurposeTo determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial radiosurgery (SRS).Methods and MaterialsRetrospective review of 1,837 patients having single-fraction SRS for arteriovenous malformation (AVM) or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition for tumor development (n=84), had prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up of the remaining 1,142 patients was 9.0 years (range, 5-24.9).ResultsNo radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of developing a radiation-induced tumor after SRS was 0.0% at 5-years (95% CI 0.0%-0.4%), 0.0% at 10-years (95% CI 0.0%-0.9%), and 0.0% at 15-years (95% CI 0.0%-2.8%). Seven of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) had malignant transformation at a median of 4.9 years (range, 2.8-13.8) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-year, 10-year, and 15-year risk of malignant transformation was 0.5% (95% CI 0.0%-0.9%), 0.8% (95% CI 0.0%-1.8%), and 2.4% (95% CI 0.0%-5.5%), respectively. Patients having prior resection (HR=14.56, 95% CI 1.79-118.33, P=0.01) and meningioma pathology (HR=11.72, 95% CI 1.44-96.15, P=0.02) were at increased risk of malignant transformation.ConclusionsThe risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS for appropriate patients.

Teaser

The risk of radiation-induced tumorigenesis or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS) remains unclear. In this study, we found no cases of radiation-induced tumors and a low rate (0.9%) of malignant transformation after single-fraction SRS. The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS for appropriate patients.


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Are future Radiation Oncologists equipped with the knowledge to manage elderly patients with cancer?

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Publication date: Available online 9 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Lucinda Morris, Niluja Thiruthaneeswaran, Margot Lehman, Gina Hasselburg, Sandra Turner
PurposeTo assess radiation oncology (RO) trainee knowledge, attitudes and clinical practice relating to geriatric oncologyMethods and materialsA custom online survey was anonymously administered on RO trainees across Australia, New Zealand and Singapore. The survey assessed three domains:1. Trainee demographics and prior training in geriatric medicine2. Current clinical practice and attitudes regarding elderly cancer patients and radiation therapy3. Opinions regarding educational opportunities around geriatric oncologyThe survey was developed and reviewed by radiation oncologists with expertise in education and training.ResultsA total of 61 (52%) trainees responded to the survey. Over half had not undertaken a geriatric medicine term prior to RO speciality training. 91.8% of respondents had not received teaching during RO training specifically regarding geriatric oncology.The use of geriatric assessment (GA) tools for determining suitability for radiation therapy was uncommon, with 80.3% of respondents rarely or never using them. Over two thirds of respondents reported not seeking or rarely seeking multidisciplinary input from a geriatrician when assessing suitability for treatment.Trainees had low confidence levels in managing complex issues commonly observed in the elderly. Only 39.3% felt they had the confidence to manage these issues with 31.2% not confident/not at all confident.Respondents reported functional status, assessment of co-morbidity, physiological age and cognition as the major factors applied to treatment decisions. Input from a geriatrician was lowest ranked. Of factors influencing choice of dose/fractionation schedule, physiological age ranked highest, whilst use of GA tool ranked the lowest.The majority of trainees (85.3%) agreed or strongly agreed they would benefit from more training around RO in elderly patients. 65.6% felt the addition of learning objectives to RO curriculum around geriatric oncology would be valuable.ConclusionsRO trainees report inadequate training and experience in geriatric oncology and geriatric medicine. RO trainees rarely use and poorly understand the rationale for GA tools and geriatrician input in clinical practice. Trainees strongly support improved education in geriatric oncology.

Teaser

The education of future radiation oncologists in geriatric oncology is fundamental to ensuring the complex needs of elderly cancer patients are met. This study assesses radiation oncology (RO) trainee knowledge, attitudes and clinical practice in geriatric oncology via a national survey. We conclude that RO trainees receive little education around geriatric oncology, rarely apply appropriate geriatric assessment tools or multidisciplinary input into clinical practice and would benefit from receiving improved training around RO in elderly patients.


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Spectroscopy for Diagnostic Assessment of Oral Mucosal Lesions

Condition:   Oral Cancer
Intervention:   Procedure: Fluorescence Spectroscopy
Sponsor:   M.D. Anderson Cancer Center
Recruiting - verified January 2017

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Role of Nhp6 and Hmo1 in SWI/SNF occupancy and nucleosome landscape at gene regulatory regions

Publication date: Available online 9 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Matias I. Hepp, Michaela Smolle, Cristian Gidi, Roberto Amigo, Nicole Valenzuela, Axel Arriagada, Alejandro Maureira, Madelaine M. Gogol, Marcela Torrejón, Jerry L. Workman, José L. Gutiérrez
Diverse chromatin modifiers are involved in regulation of gene expression at the level of transcriptional regulation. Among these modifiers are ATP-dependent chromatin remodelers, where the SWI/SNF complex is the founding member. It has been observed that High Mobility Group (HMG) proteins can influence the activity of a number of these chromatin remodelers. In this context, we have previously demonstrated that the yeast HMG proteins Nhp6 and Hmo1 can stimulate SWI/SNF activity. Here, we studied the genome-wide binding patterns of Nhp6, Hmo1 and the SWI/SNF complex, finding that most of gene promoters presenting high occupancy of this complex also display high enrichment of these HMG proteins. Using deletion mutant strains we demonstrate that binding of SWI/SNF is significantly reduced at numerous genomic locations by deletion of NHP6 and/or deletion of HMO1. Moreover, alterations in the nucleosome landscape take place at gene promoters undergoing reduced SWI/SNF binding. Additional analyses show that these effects also correlate with alterations in transcriptional activity. Our results suggest that, besides the ability to stimulate SWI/SNF activity, these HMG proteins are able to assist the loading of this complex onto gene regulatory regions.

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Chromatin Dynamics Regulate Mesenchymal Stem Cell Lineage Specification and Differentiation to Osteogenesis

Publication date: Available online 8 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Hai Wu, Jonathan A.R. Gordon, Troy W. Whitfield, Phillip W.L. Tai, Andre J. van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian
Multipotent mesenchymal stromal cells (MSCs) are critical for regeneration of multiple tissues. Epigenetic mechanisms are fundamental regulators of lineage specification and cell fate, and as such, we addressed the question of which epigenetic modifications characterize the transition of nascent MSCs to a tissue specific MSC-derived phenotype. By profiling the temporal changes of seven histone marks correlated to gene expression during proliferation, early commitment, matrix deposition, and mineralization stages, we identified distinct epigenetic mechanisms that regulate transcriptional programs necessary for tissue-specific phenotype development. Patterns of stage-specific enrichment of histone modifications revealed distinct modes of repression and activation of gene expression that would not be detected using single endpoint analysis. We discovered that at commitment, H3K27me3 is removed from genes that are upregulated and is not acquired on downregulated genes. Additionally, we found that the absence of H3K4me3 modification at promoters defined a subset of osteoblast-specific upregulated genes, indicating acquisition of acetyl modifications drive activation of these genes. Significantly, loss or gain of H3K36me3 was the primary predictor of dynamic changes in temporal gene expression. Using unsupervised pattern discovery analysis the signature of osteogenic-related histone modifications identified novel functional cis regulatory modules associated with enhancer regions that control tissue-specific genes. Our work provides a cornerstone to understand the epigenetic regulation of transcriptional programs that are important for MSC lineage commitment and lineage, as well as insights to facilitate MSC-based therapeutic interventions.



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Solution to water resource scarcity: water reclamation and reuse



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Resting-state EEG gamma power and theta–gamma coupling enhancement following high-frequency left dorsolateral prefrontal rTMS in patients with depression

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Publication date: Available online 9 January 2017
Source:Clinical Neurophysiology
Author(s): Yoshihiro Noda, Reza Zomorrodi, Takashi Saeki, Tarek K. Rajji, Daniel M. Blumberger, Zafiris J. Daskalakis, Motoaki Nakamura
ObjectiveWe aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression.MethodsThirty one patients diagnosed with depression included in the present study. Resting-state gamma power and theta–gamma coupling (TGC) were calculated before and after a course of rTMS. We explored the relationship among gamma power, TGC, and clinical/cognitive outcomes as measured with the Hamilton Rating Scale for Depression (HAM-D17), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST).ResultsFollowing rTMS, depressed patients demonstrated significant increases of resting gamma power at the F3 and F4 electrode sites and resting TGC at the C3 and T3 electrode sites. Furthermore, the increased gamma power at the F3 electrode site was significantly correlated with improved score on the HAM-D17 and BDI, while the increased TGC at the C3 electrode site was significantly correlated with reduced number of errors on the WCST.ConclusionThus, resting-state gamma power and TGC may represent potential biomarkers of depression associated with therapeutic effects of rTMS.SignificanceResting-state EEG may provide potential biomarkers related to therapeutic effects of rTMS.



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Factors Contributing to Depression and Chronic Pain in Patients with Hidradenitis Suppurativa: Results from a Single-Center Retrospective Review

Background: Hidradenitis suppurativa (HS) is a debilitating chronic disease that leads to inflammation and abscess formation in the involved skin, along with a malodorous discharge. Pain is a considerable aspect of HS and significantly impacts quality of life. In addition, HS is significantly associated with depression. A better understanding of contributing factors to depression and pain in patients with HS can identify opportunities to improve care for patients. Objective: To identify factors that contribute to depression and chronic pain in patients with HS. Methods: This is a retrospective chart review of 283 patients seen at dermatology clinics of an academic health center for HS from July 2012 to December 2015. The association between HS and depression and chronic pain was assessed in multivariate models using logistic regression analyses. Results: Patients with a greater number of areas of involvement were more likely to have both chronic pain and depression. Limitations: This is a single-center retrospective chart review with a limited sample size. Conclusion: This study suggests that the extent of disease rather than severity plays a role in reducing the quality of life in HS patients.
Dermatology

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Micro-endoscopic system for functional assessment of neural circuits in deep brain regions: Simultaneous optical and electrical recordings of auditory responses in mouse’s inferior colliculus

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Publication date: Available online 7 January 2017
Source:Neuroscience Research
Author(s): Hidetaka Yashiro, Ichiro Nakahara, Kazuo Funabiki, Hiroshi Riquimaroux
In vivo Ca2+ imaging is a powerful method for the functional assessment of neural circuits. Although multi-photon excitation fluorescence microscopy has been widely used, observation of circuits in deep brain regions remains challenging. Recently, observing these deep regions has become possible via an endoscope consisting of an optical fiber bundle or gradient-index lens. We have designed a micro-endoscope system that enables simultaneous optical recording of fluorescence and electrical recording of neural activity. Using this system, we recorded auditory responses by simultaneously detecting changes in the fluorescence intensity of a Ca2+ indicator dye, multi-unit activities (MUA), and local field potentials (LFP) in the mouse's inferior colliculus (IC). Such simultaneous optical and electrical recordings enabled detailed comparison of electrically recorded phenomena (MUA and LFP) and optically recorded Ca2+ response. By systematically changing sound frequency and intensity, we determined the frequency tuning of the recording site. The best frequency shifted higher as the probe advanced more deeply, demonstrating that the system is capable of optically measuring the dorso-ventral organization of IC (i.e., tonotopicity). Thus, our new micro-endoscope system will be useful in the neurophysiological studies of a wide range of brain circuits, including those within the auditory system.



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Functional and Quantitative MRI Mapping of Somatomotor Representations of Human Supralaryngeal Vocal Tract

Speech articulation requires precise control of and coordination between the effectors of the vocal tract (e.g., lips, tongue, soft palate, and larynx). However, it is unclear how the cortex represents movements of and contact between these effectors during speech, or how these cortical responses relate to inter-regional anatomical borders. Here, we used phase-encoded fMRI to map somatomotor representations of speech articulations. Phonetically trained participants produced speech phones, progressing from front (bilabial) to back (glottal) place of articulation. Maps of cortical myelin proxies (R1= 1/T1) further allowed us to situate functional maps with respect to anatomical borders of motor and somatosensory regions. Across participants, we found a consistent topological map of place of articulation, spanning the central sulcus and primary motor and somatosensory areas, that moved from lateral to inferior as place of articulation progressed from front to back. Phones produced at velar and glottal places of articulation activated the inferior aspect of the central sulcus, but with considerable across-subject variability. R1 maps for a subset of participants revealed that articulator maps extended posteriorly into secondary somatosensory regions. These results show consistent topological organization of cortical representations of the vocal apparatus in the context of speech behavior.



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Orbitofrontal Cortex Neurons Respond to Sound and Activate Primary Auditory Cortex Neurons

Sensory environments change over a wide dynamic range and sensory processing can change rapidly to facilitate stable perception. While rapid changes may occur throughout the sensory processing pathway, cortical changes are believed to profoundly influence perception. Prior stimulation studies showed that orbitofrontal cortex (OFC) can modify receptive fields and sensory coding in A1, but the engagement of OFC during listening and the pathways mediating OFC influences on A1 are unknown. We show in mice that OFC neurons respond to sounds consistent with a role of OFC in audition. We then show in vitro that OFC axons are present in A1 and excite pyramidal and GABAergic cells in all layers of A1 via glutamatergic synapses. Optogenetic stimulation of OFC terminals in A1 in vivo evokes short-latency neural activity in A1 and pairing activation of OFC projections in A1 with sounds alters sound-evoked A1 responses. Together, our results identify a direct connection from OFC to A1 that can excite A1 neurons at the earliest stage of cortical processing, and thereby sculpt A1 receptive fields. These results are consistent with a role for OFC in adjusting to changing behavioral relevance of sensory inputs and modulating A1 receptive fields to enhance sound processing.



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Axotomized Corticospinal Neurons Increase Supra-Lesional Innervation and Remain Crucial for Skilled Reaching after Bilateral Pyramidotomy

Skilled upper limb function heavily depends on the corticospinal tract. After bilateral lesions to this tract, motor control is disrupted but can be partially substituted by other motor systems to allow functional recovery. However, the remaining roles of motor cortex and especially of axotomized corticospinal neurons (CSNs) are not well understood. Using the single pellet retrieval task in adult rats, we induced significant recovery of skilled reaching after bilateral pyramidotomy by rehabilitative reaching training, and show that reach-related motor cortex activity, recorded in layer V, topographically reappeared shortly after axotomy. Using a chemogenetic neuronal silencing technique, we found that axotomized CSNs retained a crucial role for the recovered pellet retrieval success. The axotomized CSNs sprouted extensively in the red nucleus supplying new innervation to its magnocellular and parvocellular parts. Specific silencing of the rubrospinal tract (RST) also strongly abolished the recovered pellet retrieval success, suggesting a role of this cervically projecting nucleus in relaying cortical motor control. In summary, our results show that after bilateral corticospinal axotomy, motor cortex still actively engages in forelimb motor control and axotomized CSNs are crucially involved in the recovered reaching movement, potentially by relaying motor control via the RST.



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Κυριακή 8 Ιανουαρίου 2017

Consensus on the clinical management, screening-to-treat, and surveillance of Helicobacter pylori infection to improve gastric cancer control on a nationwide scale

Abstract

Background

Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer.

Materials and Methods

This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening-to-treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty-five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting.

Results

There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first-line, second-line, and third-line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost-benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer.

Conclusions

This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer.



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Bioinspired and Biocompatible Carbon Nanotube-Ag Nanohybrid Coatings for Robust Antibacterial Applications

Publication date: Available online 7 January 2017
Source:Acta Biomaterialia
Author(s): Chuanxiong Nie, Ye Yang, Chong Cheng, Lang Ma, Jie Deng, Lingren Wang, Changsheng Zhao
The design of self-sterilizing surfaces with favorable biocompatibility is acknowledged as an effective approach to deal with the bacterial infections of biomedical devices. In this study, we report an intriguing protocol for the large-scale fabrication of self-sterilizing and biocompatible surface film coatings by using polymer shielded silver nanoparticle loaded oxidized carbon nanotube (AgNPs@oCNT) nano-dispersions. To achieve the antibacterial coatings, the bioinspired positively charged and negatively charged AgNPs@oCNTs were alternately deposited onto substrates by spray-coating assisted layer-by-layer assembly. Then the bacterial inhibitory zones, optical density value monitoring, bacterial killing efficiency and adhesion were investigated; and all the results revealed that the AgNPs@oCNTs thin film coatings exhibited robust and long-term antibacterial activity against both Gram negative and Gram positive bacteria. Moreover, due to the shielding effects of polymer layers, the coatings showed extraordinary blood compatibility and limited toxicity against human umbilical vein endothelial cells. It is believed that the proposed large-scale fabrication of bactericidal, blood and cell compatible AgNPs@oCNT based thin film coatings will have great potential to forward novel operational pathogenic inhibition strategies to avoid undesired bacterial contaminations of biomedical implants or biological devices.Statement of SignificanceBacterial infection of medical devices has been considered to be a world-wide clinical threat towards patients' health. In this study, a bioinspired and biocompatible antibacterial coating was prepared via the spray-assisted layer-by-layer (LbL) assembly. The silver nanopartilces loaded oxidized carbon nanotube (AgNPs@oCNT), which were coated by functional polymers (chitosan and synthetic heparin mimicking polymers), were prepared via mussel inspired chemistry; and the spray-assisted assembly process allowed the fast construction on devices. Owing to the antibacterial efficiency of the loaded AgNPs, the coating showed robust bacterial killing activity and resistance towards bacterial adhesion. Moreover, since that the AgNPs were shielded by the polymers, the coating exhibited no clear toxicity at blood or cellular level. Benefiting from the universal and large-scale fabrication advancements of the spray assisted LbL coating; it is believed that the proposed strategy can be applied in designing many other kinds of self-sterilizing biomedical implants and devices.

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“Molecular” MR imaging at high fields

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Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): John C. Gore, Zhongliang Zu, Ping Wang, Hua Li, Junzhong Xu, Richard Dortch, Daniel F. Gochberg
Magnetic resonance imaging (MRI) and spectroscopy (MRS) have contributed considerably to clinical radiology, and a variety of MR techniques have been developed to evaluate pathological processes as well as normal tissue biology at the cellular and molecular level. However, in comparison to nuclear imaging, MRI has relatively poor sensitivity for detecting true molecular changes or for detecting the presence of targeted contrast agents, though these remain under active development. In recent years very high field (7T and above) MRI systems have been developed for human studies and these provide new opportunities and technical challenges for molecular imaging. We identify 5 types of intrinsic contrast mechanisms that do not require the use of exogenous agents but which can provide molecular and cellular information. We can derive information on tissue composition by (i) imaging different nuclei, especially sodium (ii) exploiting chemical shift differences as in MRS (iii) exploiting specific relaxation mechanisms (iv) exploiting tissue differences in the exchange rates of molecular species such as amides or hydroxyls and (v) differences in susceptibility. The increased signal strength at higher fields enables higher resolution images to be acquired, along with increased sensitivity to detecting subtle effects caused by molecular changes in tissues.



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Adipofascial Extension of the Propeller Perforator flap: achieve two things at one stroke

Perforator-Pedicled Propeller(PPP) Flap has been widely accepted for reconstruction of soft tissue defects as it requires a simple operative technique and has a consistent vascular pedicle1. However, according to a systematic review and meta-analysis2, the donor site was only self-closing in 69.7 percent (154 of 221), and covered by a skin graft in 30.3 percent of the cases (67 of 221). Besides, for patients with dead space infection of the defects, the regular PPP flap is difficult to achieve satisfactory results.

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Infratemporal fossa metastasis of colorectal carcinoma

Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eng Haw Lim, Irfan Mohamad, Ramiza Ramza Ramli, Bhavaraju Venkata Murali Krishna
Metastatic disease of colorectal carcinoma can be present at the time of initial diagnosis or develop along the course of the disease. The liver is the most common site of distant metastasis of colorectal carcinoma. Other sites that are frequently involved include lung, peritoneum and bone. Head and neck involvement is extremely rare. We report a case of a middle-aged lady who was treated for colorectal carcinoma presented with infratemporal fossa metastasis 3years after the diagnosis of rectal carcinoma.



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Primary large cell neuroendocrine carcinoma of the larynx

Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): N. Maithrea, Sandie Ewe, K.C. Pua, Irfan Mohamad
Neuroendocrine tumours (NETs) can arise in most organs of the body but are most frequently recorded in the gastrointestinal tract or lungs. They are rarely found in the head and neck region. The commonest site in the head and neck region is in the larynx. NETS in the larynx are almost invariably primary in origin. We describe a case of a middle-aged gentleman, a chronic smoker who was diagnosed with primary large cell neuroendocrine carcinoma of larynx with cervical nodal metastases. Large cell neuroendocrine carcinoma of larynx is a rare subset of NETs with a markedly more aggressive clinical course. He was initially treated with radiotherapy, and subsequently underwent total laryngectomy, total glossectomy. Right radical neck dissection and reconstruction with pectoralis major myocutaneous flap.



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Residual compressive surface stress increases the bending strength of dental zirconia

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Publication date: Available online 8 January 2017
Source:Dental Materials
Author(s): Masanao Inokoshi, Fei Zhang, Kim Vanmeensel, Jan De Munck, Shunsuke Minakuchi, Ignace Naert, Jozef Vleugels, Bart Van Meerbeek
ObjectiveTo assess the influence of surface treatment and thermal annealing on the four-point bending strength of two ground dental zirconia grades.MethodsFully-sintered zirconia specimens (4.0×3.0×45.0mm3) of Y-TZP zirconia (LAVA Plus, 3M ESPE) and Y-TZP/Al2O3 zirconia (ZirTough, Kuraray Noritake) were subjected to four surface treatments: (1) 'GROUND': all surfaces were ground with a diamond-coated grinding wheel on a grinding machine; (2) 'GROUND+HEAT': (1) followed by annealing at 1100°C for 30min; (3) 'GROUND+Al2O3 SANDBLASTED': (1) followed by sandblasting using Al2O3; (4) 'GROUND+CoJet SANDBLASTED': (1) followed by tribochemical silica (CoJet) sandblasting. Micro-Raman spectroscopy was used to assess the zirconia-phase composition and potentially induced residual stress. The four-point bending strength was measured using a universal material-testing machine.ResultsWeibull analysis revealed a substantially higher Weibull modulus and slightly higher characteristic strength for ZirTough (Kuraray Noritake) than for LAVA Plus (3M ESPE). For both zirconia grades, the 'GROUND' zirconia had the lowest Weibull modulus in combination with a high characteristic strength. Sandblasting hardly changed the bending strength but substantially increased the Weibull modulus of the ground zirconia, whereas a thermal treatment increased the Weibull modulus of both zirconia grades but resulted in a significantly lower bending strength. Micro-Raman analysis revealed a higher residual compressive surface stress that correlated with an increased bending strength.SignificanceResidual compressive surface stress increased the bending strength of dental zirconia. Thermal annealing substantially reduced the bending strength but increased the consistency (reliability) of 'GROUND' zirconia.



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One-pot fabrication of fluorescent carbon nitride nanoparticles with high crystallinity as a highly selective and sensitive sensor for free chlorine

Publication date: Available online 8 January 2017
Source:Sensors and Actuators B: Chemical
Author(s): Jiaqing Guo, Yanping Lin, Hao Huang, Shichao Zhang, Tingting Huang, Wen Weng
A facile one-pot solvothermal strategy was used to prepare fluorescent carbon nitride nanoparticles (CNNPs) using tartaric acid and urea as carbon and nitrogen sources at relatively low temperatures. The obtained CNNPs were characterized by multiple analytical techniques. The CNNPs with fluorescence (FL) quantum yield up to 17.9% exhibited excellent selectivity and sensitivity of fluorescence quenching for free chlorine. The quenching rate was quick, and the linear response range of free chlorine was from 0 to 30μM. The limit of detection (LOD) was as low as 13nM, which was much lower than that of the most widely used N,N-diethyl-p-phenylenediamine (DPD) colorimetric method. This sensing system exhibits many advantages, such as short response time (less than 1min), excellent selectivity, high sensitivity, and wide linear response range. The results show that this method has promising potential applications in the detection of free chlorine in real water samples.



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Adenylyl cyclase type 9 gene polymorphisms are associated with asthma and allergy in Brazilian children

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Publication date: February 2017
Source:Molecular Immunology, Volume 82
Author(s): Helena M.P. Teixeira, Neuza M. Alcantara-Neves, Maurício Barreto, Camila A. Figueiredo, Ryan S. Costa
Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders. The aim of this study was to investigate how polymorphisms in the ADCY9 are associated with asthma and allergic markers. The study comprised 1309 subjects from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was accomplished using the Illumina 2.5 Human Omni bead chip. Logistic regression was used to assess the association between allergy markers and ADCY9 variation in PLINK 1.07 software with adjustments for sex, age, helminth infection and ancestry markers. The ADCY9 candidate gene was associated with different phenotypes, such as asthma, specific IgE, skin prick test, and cytokine production. Among 133 markers analyzed, 29 SNPs where associated with asthma and allergic markers in silico analysis revealed the functional impact of the 6 SNPs on ADCY9 expression. It can be concluded that polymorphisms in the ADCY9 gene are significantly associated with asthma and/or allergy markers. We believe that such polymorphisms may lead to increased expression of adenylyl cyclase with a consequent increase in immunoregulatory activity. Therefore, these SNPs may offer an impact on the occurrence of these conditions in admixture population from countries such as Brazil.



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Diethylamino hydroxybenzoyl hexyl benzoate (DHHB) as additive to the UV filter avobenzone in cosmetic sunscreen formulations - Evaluation of the photochemical behavior and photostabilizing effect

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Camila Martins Kawakami, Leandro Nériton Cândido Máximo, Bianca Bueno Fontanezi, Roberto Santana da Silva, Lorena Rigo Gaspar
The aim of the present study was to investigate the photochemical behavior of DHHB and its photostabilizing effect on avobenzone (AVO) in different sunscreen formulations. The formulations were subjected to photostability studies by HPLC and spectrophotometry. In vitro phototoxicity was assessed using 3T3 fibroblast cultures. The mechanism of interaction between DHHB and AVO was investigated by steady state and time-resolved fluorescence spectroscopy. All formulations provided ultra-protection against UVA radiation. HPLC results demonstrated that DHHB did not present a photostabilizing effect on AVO. Fluorescence spectroscopy showed that AVO and DHHB interact by a static quenching mechanism and DHHB did not affect the AVO excited state lifetime. In addition, the energy transfer by Förster mechanism (FRET), which is the most often mechanism responsible for singlet-singlet quenching, is unlikely in this work. These results suggest why DHHB did not work as a photostabilizer on AVO singlet excited state. Phototoxicity results demonstrated that combinations containing DHHB (C2) did not show a phototoxic potential. Finally, although DHHB was considered to be photostable for all formulations studied (F2 and F3) it did not increase the photostability of AVO (F3). Thus, we suggested that formulations containing DHHB (F2) should be considered more advantageous than formulations containing AVO and AVO/DHHB (F1 and F3 respectively).

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Intracellular signaling modifications involved in the anti-inflammatory effect of 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3-a]quinoxalines on macrophages

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Antonio J. Ruiz-Alcaraz, María Tristán-Manzano, Antonio Guirado, Jesús Gálvez, María Martínez-Esparza, Pilar García-Peñarrubia
Inflammation is part of a complex biological response directed by the immune system to fight pathogens and maintain homeostasis. Dysregulation of the inflammatory process leads to development of chronic inflammatory or autoimmune diseases. Several cell types, such as macrophages, and cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) are involved in the regulation of inflammation. The important role played by these cytokines as mediators of the inflammatory process and the side effects of current therapies have promoted the search of new therapeutic alternatives. Quinoxalines are important compounds allowing a wide range of chemical modifications in order to provide an extensive repertoire of biological activities. We have previously shown that a series of 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3-a]quinoxalines exhibit potent anti-inflammatory activity, inhibiting the production of TNF-α and IL-6. Our aim here was to study the mechanism thereby this series of compounds act upon different intracellular signaling pathways to uncover their potential molecular targets. By using immunoblotting assays, we found that these compounds inhibit ERK 1/2 and JNK/c-Jun cascades, and reduce c-Fos expression, while activate the anti-inflammatory PI3K/Akt route. These results provide further information on their effect upon the intracellular signal transduction mechanisms leading to inhibition of TNF-α and IL-6 secretion. Our results may be of great interest for the pharmaceutical industry, and could be used as a starting point for the development of new and more potent anti-inflammatory drugs derived from the quinoxaline core.

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Efavirenz dissolution enhancement III: Colloid milling, pharmacokinetics and electronic tongue evaluation

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Cristiane R.D. Hoffmeister, Cinira Fandaruff, Maíra A. da Costa, Lucio M. Cabral, Luciana R. Pitta, Stanley E.R. Bilatto, Livia D. Prado, Daniel S. Corrêa, Leandro Tasso, Marcos Antônio S. Silva, Helvécio V.A. Rocha
Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is part of first-line therapy for the treatment of human immunodeficiency virus type 1 infection (HIV-1/AIDS). This drug shows relatively low oral absorption and bioavailability, as well as high intra- and inter-subject variability. Several studies have shown that treatment failure and adverse effects are associated with low and high EFV plasma concentrations, respectively. Some studies suggest different EFV formulations to minimize inter-patient variability and improve its solubility and dissolution; however, all of these formulations are complex, using for instance, cyclodextrins, dendrimers and polymeric nanoparticles, rendering them inviable industrially. The aim of this work was to prepare simple and low-cost suspensions of EFV for improvement of solubility and dissolution rate by using colloid mill, spray or freeze-drying, and characterization of the powders obtained. The results demonstrated an increase in the dissolution rate of EFV, using 0.2% of sodium lauryl sulfate (SLS) and 0.2% of hydroxypropylcellulose (HPC) or hydroxypropylmetilcellulose (HPMC) in both freeze and spray dried powders. The pharmacokinetic studies demonstrated improved pharmacokinetic parameters for the formulation containing SLS and HPC. The powders obtained, which present enhanced dissolution properties, can be incorporated in a solid dosage form for treatment of AIDS in paediatric patients with promising results.

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Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways

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Publication date: Available online 7 January 2017
Source:Trends in Immunology
Author(s): Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected. This review highlights the importance of the crosstalk between retinoic acid inducible gene-I (RIG-I)–mitochondrial antiviral-signaling protein (MAVS) RNA sensing and the cyclic GMP–AMP synthase (cGAS)– stimulator of interferon genes (STING) DNA sensing pathways in potentiating efficient antiviral responses. The potential of cGAS–STING manipulation as a component of cancer immunotherapy is also reviewed.



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What is the most accurate lymph node staging method for perihilar cholangiocarcinoma? Comparison of UICC/AJCC pN stage, number of metastatic lymph nodes, lymph-node ratio, and log odds of metastatic lymph nodes

Publication date: Available online 8 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Simone Conci, Andrea Ruzzenente, Marco Sandri, Francesca Bertuzzo, Tommaso Campagnaro, Fabio Bagante, Paola Capelli, Mirko D'Onofrio, Marco Piccino, Adriano E. Dorna, Corrado Pedrazzani, Calogero Iacono, Alfredo Guglielmi
BackgroundWe compared the prognostic performance of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) 7th edition pN stage, number of metastatic LNs (MLNs), LN ratio (LNR), and log odds of MLNs (LODDS) in patients with perihilar cholangiocarcinoma (PCC) undergoing curative surgery in order to identify the best LN staging method.MethodsNinety-nine patients who underwent surgery with curative intent for PCC in a single tertiary hepatobiliary referral center were included in the study. Two approaches were used to evaluate and compare the predictive power of the different LN staging methods: one based on the estimation of variable importance with prediction error rate and the other based on the calculation of the receiver operating characteristic (ROC) curve.ResultsLN dissection was performed in 92 (92.9%) patients; 49 were UICC/AJCC pN0 (49.5%), 33 pN1 (33.3%), and 10 pN2 (10.1%). The median number of LNs retrieved was 8. The prediction error rate ranged from 42.7% for LODDS to 47.1% for UICC/AJCC pN stage. Moreover, LODDS was the variable with the highest area under the ROC curve (AUC) for prediction of 3-year survival (AUC = 0.71), followed by LNR (AUC = 0.60), number of MLNs (AUC = 0.59), and UICC/AJCC pN stage (AUC = 0.54).ConclusionsThe number of MLNs, LNR, and LODDS appear to better predict survival than the UICC/AJCC pN stage in patients undergoing curative surgery for PCC. Moreover, LODDS seems to be the most accurate and predictive LN staging method.



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Effects of nucleus accumbens amphetamine administration on performance in a delay discounting task

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Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Caitlin A. Orsini, Marci R. Mitchell, Sara C. Heshmati, Kristy G. Shimp, Megan S. Spurrell, Jennifer L. Bizon, Barry Setlow
Chronic administration of cocaine can cause pronounced and enduring cognitive alterations such as increases in impulsive choice. Chronic cocaine can also result in enhanced dopamine (DA) release in the nucleus accumbens (NAc) in response to reward-related cues. It is possible that this enhanced DA release in the NAc is a mechanism by which cocaine increases impulsive choice. To date, however, the specific role of DA in the NAc in impulsive choice is unclear. To begin to address this, rats received acute microinjections of the indirect DA agonist amphetamine directly into the NAc prior to testing in a delay discounting task in which rats chose between a small, immediate and a large, delayed food reward. When delays to the large reward increased within test sessions, amphetamine increased choice of the large reward. When delays decreased within test sessions, however, amphetamine decreased choice of the large reward. These findings suggest that, rather than specifically mediating impulsive choice, DA neurotransmission in the NAc is necessary for flexible adaptation of choice strategies in the presence of shifting reward contingencies. These results further indicate that enhancements in NAc DA release likely do not account for lasting increases in impulsive choice caused by chronic cocaine.



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Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress

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Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): J.J. Herrera-Pérez, L. Martínez-Mota, G. Jiménez-Rubio, L. Ortiz-López, E.A. Cabrera-Muñoz, N. Galindo-Sevilla, E. Zambrano, F. Hernández-Luis, G.B. Ramírez-Rodríguez, M. Flores-Ramos
Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.



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Genetic inhibition of Anaplastic Lymphoma Kinase rescues cognitive impairments in Neurofibromatosis 1 mutant mice

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Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Joseph B. Weiss, Sydney J. Weber, Eileen Ruth S. Torres, Tessa Marzulla, Jacob Raber
Heterozygous Neurofibromatosis 1 (NF1) loss of function mutations occur in approximately 90% of patients with neurofibromatosis. A major, disabling phenotypic consequence of reduced NF1 function is cognitive impairment; a possibly related behavioral phenotype is impaired sleep. Recent results in Drosophila have demonstrated a genetic interaction between Anaplastic Lymphoma Kinase (Alk) and NF1 for both associative learning and sleep. Inhibition of Alk improves associative learning and sleep in heterozygous NF1 mutant flies. The results in Drosophila provide a strong motivation to investigate NF1/Alk genetic interactions in mice. In Drosophila, activation of Alk by its ligand, Jelly belly (Jeb), is the physiologically relevant target of negative regulation by NF1. Therefore, we tested whether genetic inhibition of Alk in heterozygous NF1 mutant mice attenuates or rescues cognitive impairments in mice. Our results are consistent with the hypothesis that NF1 functions in mice biochemically to inhibit signaling from Alk through Ras. The cognitive phenotypes observed in heterozygous NF1 mutant mice are rescued or ameliorated by genetic inhibition of Alk activity. In two tests of hippocampus-dependent learning, the Morris water maze and extinction of contextual fear, mutation of one or both alleles of Alk was sufficient to improve performance to wild type or near wild type levels in NF1−/+ mice. In addition, in NF1 mice genetic inhibition of Alk improves circadian activity levels. These data are intriguing in light of the circadian alterations seen in NF1 patients and indicate that inhibition of Alk activity may cognitively benefit patients with Neurofibromatosis 1.



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Liraglutide prevents cognitive decline in a rat model of streptozotocin-induced diabetes independently from its peripheral metabolic effects

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Caterina Palleria, Antonio Leo, Francesco Andreozzi, Rita Citraro, Michelangelo Iannone, Rosangela Spiga, Giorgio Sesti, Andrew Constanti, Giovambattista De Sarro, Franco Arturi, Emilio Russo
Diabetes has been identified as a risk factor for cognitive dysfunctions. Glucagone like peptide 1 (GLP-1) receptor agonists have neuroprotective effects in preclinical animal models. We evaluated the effects of GLP-1 receptor agonist, liraglutide (LIR), on cognitive decline associated with diabetes. Furthermore, we studied LIR effects against hippocampal neurodegeneration induced by streptozotocin (STZ), a well-validated animal model of diabetes and neurodegeneration associated with cognitive decline. Diabetes and/or cognitive decline were induced in Wistar rats by intraperitoneal or intracerebroventricular injection of STZ and then rats were treated with LIR (300μg/kg daily subcutaneously) for 6 weeks. Rats underwent behavioral tests: Morris water maze, passive avoidance, forced swimming (FST), open field, elevated plus maze, rotarod tests. Furthermore, LIR effects on hippocampal neurodegeneration and mTOR pathway (AKT, AMPK, ERK and p70S6K) were assessed. LIR improved learning and memory only in STZ-treated animals. Anxiolytic effects were observed in all LIR-treated groups but pro-depressant effects in CTRL rats were observed. At a cellular/molecular level, intracerebroventricular STZ induced hippocampal neurodegeneration accompanied by decreased phosphorylation of AMPK, AKT, ERK and p70S6K. LIR reduced hippocampal neuronal death and prevented the decreased phosphorylation of AKT and p70S6K; AMPK was hyper-phosphorylated in comparison to CTRL group, while LIR had no effects on ERK. LIR reduced animal endurance in the rotarod test and this effect might be also linked to a reduction in locomotor activity during only the last two minutes of the FST. LIR had protective effects on cognitive functions in addition to its effects on blood glucose levels. LIR effects in the brain also comprised anxiolytic and pro-depressant actions (although influenced by reduced endurance). Finally, LIR protected from diabetes-dependent hippocampal neurodegeneration likely through an effect on mTOR pathway.

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Differential effects of bihemispheric and unihemispheric transcranial direct current stimulation in young and elderly adults in verbal learning

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Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Valentina Fiori, Michael Nitsche, Luigi Iasevoli, Gabriella Cucuzza, Carlo Caltagirone, Paola Marangolo
For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. In the language domain, several studies, in healthy and brain-damaged populations, have already shown that tDCS is effective in enhancing naming, repetition and semantic word generation. In those studies, different tDCS electrode configurations have been tested, however, a direct comparison between different montages in verbal learning has never been conducted. In this study, we aimed to explore the impact of bihemispheric and unihemispheric tDCS on verbal learning task performance in two groups (young vs. elderly). Fifteen healthy volunteers participated per group. Each participant received three stimulation conditions: unihemispheric anodal tDCS over the left temporal area, bihemispheric tDCS over the left (anodal) and right (cathodal) temporal areas and a sham condition. During active stimulation, tDCS (20min, 2mA) was applied while each participant learned twenty pseudowords (arbitrarily assigned to corresponding pictures). No significant differences were found between the three conditions for the young group with regard to accuracy and vocal reaction times. In contrast, in the elderly group, real stimulation improved performance compared to sham but bihemispheric tDCS was more efficient than unilateral stimulation. These results suggest that bihemispheric stimulation is more effective in improving language learning but this effect is age-dependent. The hypothesis is advanced that cortical changes in the course of aging might differentially impact on tDCS efficacy on behavioral performance. These data may also have implications for treatment of stroke patients with language impairment.



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High Rates of PTSD Treatment Dropout: A Possible Red Herring?

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Publication date: Available online 8 January 2017
Source:Journal of Anxiety Disorders
Author(s): Derek D. Szafranski, Brian N. Smith, Daniel F. Gros, Patricia A. Resick
Few studies have examined symptom change among dropouts from posttraumatic stress disorder (PTSD) treatment. However, dropout is widely considered a negative event needing to be addressed. The present study investigated PTSD and depression symptom change in patients with PTSD who discontinued psychotherapy. Female civilians (n=321) diagnosed with PTSD participated in two randomized clinical trials examining PTSD treatment outcomes. Of those, 53 were identified as dropouts and included in this study. Symptom change was assessed by clinically significant change (CSC) criteria and symptom end-state criteria. Results demonstrated that considerable proportions of participants (35.85–55.56%) displayed significant improvement and/or met good end-state criteria for PTSD and depression. Results also revealed that participants who displayed symptom improvement were younger, attended more treatment sessions, were married or partnered, and had higher annual household income. Although preliminary, these findings contradict belief that treatment dropouts do not display symptom improvement.



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Self-Disgust as a Potential Mechanism Underlying the Association Between PTSD and Suicide Risk

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Publication date: Available online 8 January 2017
Source:Journal of Anxiety Disorders
Author(s): C. Alex Brake, Sasha M. Rojas, Christal L. Badour, Courtney E. Dutton, Matthew T. Feldner
Suicide risk is highly prevalent among individuals with posttraumatic stress disorder (PTSD). Self-disgust, defined as disgust directed internally and comprised of disgust with oneself (disgusting self) and with one's behaviors (disgusting ways), may impact this increased risk. The present study examined self-disgust as a putative mechanism linking PTSD symptoms with suicide risk. A sample of 347 trauma-exposed undergraduates completed measures of PTSD symptoms, suicide risk, self-disgust, and depressive symptoms. Controlling for depressive symptoms, a process model indicated PTSD symptoms were positively linked to suicide risk via increased disgusting self but not disgusting ways. Process models examining individual PTSD symptom clusters revealed positive, indirect links between all PTSD symptom clusters except alterations in arousal and reactivity and suicide risk via disgusting self. These findings expand on growing literature documenting the importance of self-disgust in trauma-related pathology by identifying connections with suicide risk. Future directions and clinical considerations are discussed.



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In situ effect of enamel salivary exposure time and type of intraoral appliance before an erosive challenge

Abstract

Objectives

This study tested the effect of enamel salivary exposure time prior to an acid challenge (30 min, 1, 2, or 12 h) and type of intraoral appliance (palatal or mandibular) on initial erosion.

Methods

After initial surface hardness evaluation, enamel blocks (n = 340) were randomly divided into groups and volunteers (n = 20). The control group was not exposed to saliva previously to the erosive challenge. The volunteers wore palatal and mandibular appliances simultaneously. After salivary exposure, the blocks were subjected to acid exposure by immersion in hydrochloric acid (0.01 M, pH 2.3) for 30 s. Then, the enamel surface hardness was evaluated. Data were analyzed using ANOVA, Kruskal–Wallis and Tukey's test (p < 0.05).

Results

No difference was observed on percent surface hardness change (% SHC) in the enamel blocks between the types of intraoral appliances. Exposure to saliva for 30 min and 1 h promoted similar enamel resistance to the erosive attack, which was similar to the control group for both appliances. Blocks exposed to saliva for 2 h showed less hardness loss when compared to 30 min. Keeping the blocks in saliva during 12-h overnight resulted in similar percentage of enamel hardness loss compared to 2 h.

Conclusions

A 2-hour in situ exposure to saliva is adequate to promote partial protection against initial erosive lesions, independently of the type of intraoral appliance used.

Clinical significance

This finding will help researchers in the development of erosion studies, which will provide information for dentists to offer a better treatment for erosion.



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Sacrificial photocatalysis: removal of nitrate and hydrogen production by nano-copper-loaded P25 titania. A kinetic and ecotoxicological assessment

Abstract

The photocatalytic removal of nitrate with simultaneous hydrogen generation was demonstrated using zero-valent nano-copper-modified titania (P25) as photocatalyst in the presence of UV-A-Vis radiation. Glycerol, a by-product in biodiesel production, was chosen as a hole scavenger. Under the adopted experimental conditions, a nitrate removal efficiency up to 100% and a simultaneous hydrogen production up to 14 μmol/L of H2 were achieved (catalyst load = 150 mg/L, initial concentration of nitrate = 50 mg/L, initial concentration of glycerol = 0.8 mol/L). The reaction rates were independent of the starting glycerol concentration. This process allows accomplishing nitrate removal, with the additional benefit of producing hydrogen under artificial UV-A radiation. A kinetic model was also developed and it may represent a benchmark for a detailed understanding of the process kinetics. A set of acute and chronic bioassays (Vibrio fischeri, Raphidocelis subcapitata, and Daphnia magna) was performed to evaluate the potential ecotoxicity of the nitrate/by-product mixture formed during the photocatalytic process. The ecotoxicological assessment indicated an ecotoxic effect of oxidation intermediates and by-products produced during the process.



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Does increased salinity influence the competitive outcome of two producer species?

Abstract

Within the context of global climate changes, it is expected that low-lying coastal freshwater ecosystems will face seawater intrusion with concomitant increase in salinity levels. Increased salinity may provoke disruption of competitive relationships among freshwater species. However, species may be capable of acclimating to salinity, which, in turn, may influence the resilience of ecosystems. Accordingly, this work aimed at assessing the effects of multigenerational exposure to low levels of salinity in the competitive outcome of two species of green microalgae: Raphidocelis subcapitata and Chlorella vulgaris. To attain this, three specific objectives were delineated: (1) compare the toxicity of natural seawater (SW) and NaCl (as a surrogate of SW) to the two microalgae, (2) determine the capacity of the two microalgae species to acclimate to low salinity levels, and (3) assess the influence of exposure to low salinity levels in the competitive outcome of the two microalgae. Results revealed SW to be slightly less toxic than NaCl for the two microalgae. The EC25,72 h for growth rate was 4.63 and 10.3 mS cm−1 for R. subcapitata and 6.94 and 15.4 mS cm−1 for C. vulgaris, respectively for NaCl and SW. Both algae were capable of acclimating to low levels of salinity, but C. vulgaris seemed to acclimate faster than R. subcapitata. When exposed in competition, under control conditions, the growth rates of C. vulgaris were lower than those of R. subcapitata. However, C. vulgaris was capable of acquiring competitive advantage equaling or surpassing the growth rate of R. subcapitata with the addition of NaCl or SW, respectively. The multigenerational exposure to low levels of salinity influenced the competitive outcome of the two algae both under control and salinity exposure. These results suggest that long-term exposure to low salinity stress can cause shifts in structure of algae communities and, therefore, should not be neglected since algae are at the basis of food web constituting important energetic resources to higher trophic levels.



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Cu(II) adsorption from copper mine water by chitosan films and the matrix effects

Abstract

Adsorption of copper ions onto chitosan films was studied, and the matrix effect was evaluated using a synthetic solution and a real effluent from closed copper mine. Chitosan films were prepared by casting technique and characterized. The adsorption study was carried out by equilibrium isotherms, thermodynamics, and kinetics. The thermodynamic parameters indicated that the copper adsorption onto chitosan film was favorable, spontaneous, and exothermic, suggesting an increased randomness at the solid/solution interface. The matrix effect was evaluated in kinetic assays, where a synthetic solution and a real system were carried out at different stirring rates. The highest values of adsorption capacity reached in all stirring rates were about 20% lower in the real effluent, and this reduction in the competitiveness was due to the presence of other ions in the matrix of the real effluent. The maximum adsorption capacity of copper ions onto chitosan films for the synthetic solution was of 450 mg g−1, and the removal percentage was in the range from 78 to 96%, and these values for the real effluent were of 360 mg g−1 and removal ranging from 62 to 76%. The mapping done of ions present in the water adsorbed of the mine in the films showed that the same was homogeneously distributed in the films' surfaces.



http://ift.tt/2i6NDCL

Efficient removal of amoxicillin and paracetamol from aqueous solutions using magnetic activated carbon

Abstract

Activated carbon (AC)/CoFe2O4 nanocomposites, MAC-1 and MAC-2, were prepared by a simple pyrolytic method using a mixture of iron(III)/cobalt(II) benzoates and iron(III)/cobalt(II) oxalates, respectively, and were used as efficient adsorbents for the removal of amoxicillin (AMX) and paracetamol (PCT) of aqueous effluents. The synthesized nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and transmission electron microscopy (TEM). The sizes of cobalt ferrite nanoparticles formed from benzoates of iron(III)/cobalt(II) and oxalates of iron(III)/cobalt(II) precursors were in the ranges of 5–80 and 6–27 nm, respectively. The saturation magnetization (M s), remanence (M r) and coercivity (H c) of the MAC-2 nanocomposites were found to be 3.07 emu g−1, 1.36 emu g−1 and 762.49 Oe; for MAC-1, they were 0.2989 emu g−1, 0.0466 emu g−1 and 456.82 Oe. The adsorption kinetics and isotherm studies were investigated, and the results showed that the as-prepared nanocomposites MAC-1 and MAC-2 could be utilized as an efficient, magnetically separable adsorbent for environmental cleanup. The maximum sorption capacities obtained were 280.9 and 444.2 mg g−1 of AMX for MAC-1 and MAC-2, respectively, and 215.1 and 399.9 mg g−1 of PCT using MAC-1 and MAC-2, respectively. Both adsorbents were successfully used for simulated hospital effluents, removing at least 93.00 and 96.77% for MAC-1 and MAC-2, respectively, of a mixture of nine pharmaceuticals with high concentrations of sugars, organic components and saline concentrations.



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Chemical composition, structural properties, and source apportionment of organic macromolecules in atmospheric PM 10 in a coastal city of Southeast China

Abstract

Particulate matter (PM10) associated with the fractions of organic macromolecules, including humic acid (HA), kerogen + black carbon (KB), and black carbon (BC), was determined during summer and winter at urban and suburban sites in a coastal city of southeast China. The organic macromolecules were characterized by elemental analysis (EA), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR), and their sources were identified by using stable carbon/nitrogen isotope (δ13C/δ15N) and the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) Model. The results showed that HA, kerogen (K), and BC accounted for the range of 3.89 to 4.55 % in PM10, while they were the dominant fractions of total organic carbon (TOC), ranging from 64.70 to 84.99 %. SEM analysis indicated that BC particles were porous/nonporous and consisted of spherical and non-spherical (i.e., cylindrical and elongate) structures. The FTIR spectra of HA, KB, and BC exhibited similar functional groups, but the difference of various sites and seasons was observed. HA in PM10 contained a higher fraction of aliphatic structures, such as long-chain fatty and carbohydrates with a carboxylic extremity. The C/N ratio, SEM, and δ13C/δ15N values provided reliable indicators of the sources of HA, K, and BC in PM10. The results suggested that HA and K majorly originated from terrestrial plants, and BC came from the mixture of combustion of terrestrial plants, fossil fuel, and charcoal. The air masses in winter originated from Mongolia (4 %), the northern area of China (48 %), and northern adjacent cities (48 %), suggesting the influence of anthropogenic sources through long-range transport, while the air masses for the summer period came from South China Sea (34 %) and Western Pacific Sea (66 %), representing clean marine air masses with low concentrations of organic macromolecules.



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Robustness of 4D-optimized scanned carbon ion beam therapy against interfractional changes in lung cancer

Publication date: Available online 7 January 2017
Source:Radiotherapy and Oncology
Author(s): Christian Graeff
Background and purposeMoving targets could be conformally treated with actively scanned carbon ion beams using 4D-optimization. As this heavily exploits 4D-CTs, an important question is whether the conformity also upholds in the context of interfractional changes, i.e. variable positioning, anatomy and breathing patterns.Materials and methodsIn 4 lung cancer patients, 6 weekly 4D-CTs were available. 4D-CTs and their phases were non-rigidly registered to propagate contours and 4D-doses. On the first 4D-CT, a 4D-optimized plan delivering a uniform dose to each motion phase (total dose 9.4Gy(RBE)) was simulated, as well as an ITV plan for comparison. On the five following 4D-CTs, 4D-dose was forward calculated and evaluated for target coverage and conformity. Variable uniform (3–7mm) and range margins (2mm/%) were investigated.ResultsFor all patients, target coverage (V95>95% accumulated over 5 fractions) could be achieved, but with variable margin size weakly depending on motion amplitude and range changes. The same margins were also necessary for ITV plans, which lead to lower conformity and higher integral doses.Conclusion4D-optimization appears feasible also under interfractional changes and maintains a dosimetric advantage over less conformal ITV irradiations. Further studies are needed to identify patients benefiting most from the technically more complex 4D-optimization.



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Prophylactic cranial irradiation after definitive chemoradiotherapy for limited-stage small cell lung cancer: Do all patients benefit?

Publication date: Available online 7 January 2017
Source:Radiotherapy and Oncology
Author(s): Ahsan S. Farooqi, Emma B. Holliday, Pamela K. Allen, Xiong Wei, James D. Cox, Ritsuko Komaki
PurposeProphylactic cranial irradiation (PCI) can improve overall survival (OS) and suppress brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, PCI can be toxic. We sought to identify characteristics of patients who may not benefit from PCI.MethodsWe identified 658 patients who received chemoradiotherapy at MD Anderson in 1986–2012; 364 received PCI and 294 did not. Median follow-up time was 21.2months (range 1.2–240.8months). Cox proportional hazards regression, competing-risk regression, and Kaplan–Meier analyses were used to identify factors influencing OS and BM.ResultsPCI reduced risks of death [HR 0.73, 95% CI 0.61–0.88, P=0.001] and BM [HR 0.54, 95% CI 0.39–0.76, P<0.001]. Having tumors ⩾5cm increased the risk of BM [HR 1.77, 95% CI 1.22–2.55, P=0.002] but not death [HR 1.16, 95% CI 0.96–1.40, P=0.114]. Among patients ⩾70years with ⩾5-cm tumors, PCI did not improve OS [2-year rates 39.4% vs 40.9%, P=0.739].ConclusionsPCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, older patients may be at risk from comorbidity or extracranial disease. Further work is warranted to identify patients who may not benefit from PCI.



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Clinical factors associated with subclinical spread of in situ melanoma

Publication date: Available online 7 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Thuzar M. Shin, Jeremy R. Etzkorn, Joseph F. Sobanko, David J. Margolis, Joel M. Gelfand, Emily Y. Chu, Rosalie Elenitsas, Waqas R. Shaikh, Christopher J. Miller
BackgroundSubclinical spread of in situ melanoma occurs at a wide frequency, ranging from 12% to 71%.ObjectiveTo identify clinical factors associated with subclinical spread of in situ melanoma.MethodsWe used a retrospective, cross-sectional study of 674 consecutive in situ melanomas to examine 627 patients treated with Mohs surgery and melanoma antigen recognized by T cells 1 immunostaining. The presence of subclinical spread was correlated with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to generate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBoth univariate and multivariate analyses demonstrated significantly increased odds for subclinical spread of in situ melanomas when they were located on the head or neck, at acral sites, or on the pretibial leg (OR 1.97, 95% CI 1.41-3.40); in persons with a history of prior treatment (OR 2.77, 95% CI 1.74-4.420); melanomas of preoperative size >1 cm (OR 1.74, 95% CI 1.23-2.46, P = .002); or in persons ≥60 years old (OR 1.47, 95% CI 1.01-2.13, P = .042). A count prediction model demonstrated that the risk for subclinical spread increased with the number of clinical risk factors.LimitationWe used a single-site, retrospective study design.ConclusionClarifying the risk factors for subclinical spread might help to refine triage of in situ melanomas to the appropriate surgical techniques for margin assessment prior to reconstruction.



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Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan

Publication date: Available online 7 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Chun-Ying Wu, Yun-Ting Chang, Chao-Keui Juan, Jeng-Jer Shieh, Yu-Pu Lin, Han-Nan Liu, Jaw-Town Lin, Yi-Ju Chen
BackgroundA link between rosacea and inflammatory bowel disease (IBD) has been proposed with unknown mechanisms. Epidemiologic evidence of this association needs to be examined.MethodsIn this nationwide cohort study, a total of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 were identified in the Taiwanese National Health Insurance Research Database. Cumulative incidences of IBD were compared between these 2 cohorts. Frailty Cox proportional hazard model was used and subgroup analyses were conducted to examine the risk factors for IBD.ResultsThe 15-year cumulative incidences of IBD were 0.036% (95% confidence interval [CI] 0.00%-1.57%) and 0.019% (95% CI 0.00%-0.83%) in rosacea and nonrosacea cohorts, respectively (P = .05). Rosacea (adjusted hazard ratio 1.94, 95% CI 1.04-3.63, P = .04) and male gender (adjusted hazard ratio 3.52, 95% CI 2.03-6.11, P < .01) were independently associated with IBD, after adjustment for major comorbidities. Multivariate subgroup analyses revealed consistent results. The incidence rates of IBD decreased with increasing antibiotic use in patients with rosacea, but without statistical significance.LimitationInformation related to lifestyle, diet, alcohol, and smoking was not included in the database.ConclusionPatients with rosacea may have an increased risk of IBD.



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Seromucinous ovarian tumor A comparison with the rest of ovarian epithelial tumors

Publication date: Available online 7 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Georgia Karpathiou, Celine Chauleur, Thomas Corsini, Melany Venet, Cyril Habougit, Freschia Honeyman, Fabien Forest, Michel Peoc'h
BackgroundSeromucinous ovarian tumors are rare and not adequately described in the literature and this is especially true for seromucinous carcinomas.Aim of the studyTo describe histological and clinical features of these tumors in comparison with the rest of ovarian epithelial tumors.Materials and MethodsTwo hundred and forty one (241) ovarian tumors, borderline (n=92) or malignant (n=149), treated surgically without neoadjuvant chemotherapy, were examined.ResultsSeromucinous borderline (SMBT) and malignant tumors (SMC) comprised 7.8% (n=7) and 4% (n=6) of all borderline tumors and carcinomas, respectively, studied. Mean age of diagnosis was 63.2 and 68.3 years and mean size was 6.4 cm and 12 cm for SMBT and SMC, respectively. Seromucinous tumors were associated with endometriosis in 23.1% of the cases and they were bilateral in 30.8%. Microscopically, variety in cellular composition, papillary architecture and development into thick walled, occasionally muscular, cysts were the main findings. Medullary/paraovarian/tubal or deeply cortical localization was also characteristic. Stage predicted overall and progression-free survival (p<0.0001 and p=0.03, respectively). Five-year survival was 62% for patients with high grade serous carcinoma, 55% for seromucinous carcinoma, 100% for endometrioid carcinoma, 75% for clear cell carcinoma, and 80% for patients with mucinous carcinoma. Differences were not however statistically significant.ConclusionSeromucinous tumors have unique features that support their classification as a different entity. Their localization and their often thick fibrous or/and muscular wall provides further evidence for an histogenesis from the secondary müllerian system or vestigial structures.



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Brainstem auditory responses to predict literacy

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Publication date: Available online 8 January 2017
Source:Clinical Neurophysiology
Author(s): Jenin El-Sayes, Aimee J. Nelson




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Using transcranial direct current stimulation to enhance performance in balance tasks

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Publication date: Available online 7 January 2017
Source:Clinical Neurophysiology
Author(s): Hanna Pohjola, Tommi Tolmunen, Tuukka Kotilainen, Soili M. Lehto




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Corrigendum to “Intracortical inhibition abnormality during the remission phase of multiple sclerosis is related to upper limb dexterity and lesions” [Clin. Neurophysiol. 127 (2016) 1503–1511]

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Publication date: Available online 7 January 2017
Source:Clinical Neurophysiology
Author(s): Julia C. Nantes, Jidan Zhong, Scott A. Holmes, Benjamin Whatley, Sridar Narayanan, Yves Lapierre, Douglas L. Arnold, Lisa Koski




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Reply to “Using transcranial direct current stimulation to enhance performance in balance tasks”

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Publication date: Available online 7 January 2017
Source:Clinical Neurophysiology
Author(s): Elisabeth Kaminski, Patrick Ragert




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Golden root: A wholesome treat of immunity

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Kunjan Khanna, K.P. Mishra, Lilly Ganju, Shashi Bala Singh
Rhodiola is native to the high altitude regions of Asia, Europe and Northern Hemisphere. It has a long history of use as a medicinal plant in various ailments, boosting immunity, increasing energy and mental capacity. It is also known as "Adaptogen" to help the body to adapt and resist stress. The part of the plant, which is used for medicinal values, is rhizome, which is an underground stem. The rhizome contains mainly salidroside, rosin, rosavin and p-tyrosol. There are many studies, which have reported the effects of Rhodiola spp. on different organs and health conditions. In this review, we have selected the articles from Pubmed and Google Scholar from year 1992–2016 to report the effects of Rhodiola spp. and their role in curtailing various diseases and stress. The present review emphasizes the medicinal and therapeutic applications of Rhodiola spp. on different experimental models. Overall conclusion is that Rhodiola spp. has immense therapeutic potential and hence, this review would give impetus to new research for the development of Rhodiola based herbal nutraceuticals as well as pharmaceuticals.



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Allergen aerosol from pollen-nucleated precipitation: A novel thunderstorm asthma trigger

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Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Paul John Beggs




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Salt-marsh plants as potential sources of Hg0 into the atmosphere

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Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): João Canário, Laurier Poissant, Martin Pilote, Miguel Caetano, Holger Hintelmann, Nelson J. O'Driscoll
To assess the role of salt-marsh plants on the vegetation-atmospheric Hg0 fluxes, three salt marsh plant species, Halimione portulacoides, Sarcocornia fruticosa and Spartina maritima were selected from a moderately contaminated site in the Tagus estuary during May 2012. Total mercury in stems and leaves for each plant as well as total gaseous mercury and vegetation-air Hg0 fluxes were measured over two continuous days. Mercury fluxes were estimated with a dynamic flux Tedlar® bag coupled to a high-resolution automated mercury analyzer (Tekran 2537A). Other environmental parameters such as air temperature, relative humidity and net solar radiation were also measured aside. H. portulacoides showed the highest total mercury concentrations in stems and leaves and the highest average vegetation-air Hg0 flux (0.48 ± 0.40 ng Hg m−2 h−1). The continuous measurements converged to a daily pattern for all plants, with enhanced fluxes during daylight and lower flux during the night. It is noteworthy that throughout the measurements a negative flux (air-vegetation) was never observed, suggesting the absence of net Hg0 deposition. Based on the above fluxes and the total area occupied by each species we have estimated the total amount of Hg0 emitted from this salt-marsh plants. A daily emission of 1.19 mg Hg d−1 was predicted for the Alcochete marsh and 175 mg Hg d−1 for the entire salt marsh area of the Tagus estuary.



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Spastic diplegia in preterm-born children: Executive function impairment and neuroanatomical correlates

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Maria Chiara Di Lieto, Paola Brovedani, Chiara Pecini, Anna Maria Chilosi, Vittorio Belmonti, Franco Fabbro, Cosimo Urgesi, Simona Fiori, Andrea Guzzetta, Silvia Perazza, Elisa Sicola, Giovanni Cioni
BackgroundThe neuropsychological literature on preterm-born children with spastic diplegia due to periventricular leukomalacia is convergent in reporting deficits in non-verbal intelligence and in visuo-spatial abilities. Nevertheless, other cognitive functions have found to be impaired, but data are scant and not correlated with neuroimaging findings.AimsThis study analyzes the neuropsychological strengths and weaknesses in preterm-born children with spastic diplegia (pSD) and their relationships with neuroanatomical findings, investigated by a novel scale for MRI classification.Methods and proceduresNineteen children with pSD, mild to moderate upper limb impairment and Verbal IQ>80, and 38 normal controls were evaluated with a comprehensive neuropsychological battery (NEPSY-II), assessing Attention/Executive Functioning, Language, Memory, Sensorimotor, Social Perception and Visuospatial Processing domains. The MRIs were quantitatively scored for lesion severity.Outcomes and resultsThe results showed that, beyond core visuo-spatial and sensory-motor deficits, impairments in attention and executive functions were present in more than half of the sample, particularly in children with damage to the anterior corpus callosum.Conclusions and implicationsThe findings are discussed in terms of clinical and rehabilitative implications tailored for pSD subgroups diversified for neuropsychological and neuroanatomical characteristics.



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Hypertext comprehension of deaf and hard-of-hearing students and students with specific language impairment

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Helen Blom, Eliane Segers, Daan Hermans, Harry Knoors, Ludo Verhoeven
This paper provides insight into the reading comprehension of hierarchically structured hypertexts within D/HH students and students with SLI. To our knowledge, it is the first study on hypertext comprehension in D/HH students and students with SLI, and it also considers the role of working memory. We compared hypertext versus linear text comprehension in D/HH students and students with SLI versus younger students without language problems who had a similar level of decoding and vocabulary. The results demonstrated no difference in text comprehension between the hierarchically structured hypertext and the linear text. Text comprehension of D/HH students and students with SLI was comparable to that of the students without language problems. In addition, there was a similar positive predictive value of visuospatial and not verbal working memory on hypertext comprehension for all three groups. The findings implicate that educational settings can make use of hierarchically structured hypertexts as well as linear texts and that children can navigate in the digital world from young age on, even if language or working memory problems are present.



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Σάββατο 7 Ιανουαρίου 2017

Recent advancements of high efficient donor–acceptor type blue small molecule applied for OLEDs

Publication date: Available online 7 January 2017
Source:Materials Today
Author(s): Yunchuan Li, Ji-Yan Liu, Yuan-Di Zhao, Yuan-Cheng Cao
Although the organic light-emitting devices (OLEDs) encompassing TVs, smartphones, and wearable devices, etc. already have been commercialized, there is still room to pursue material improvements in efficiency and cost-effectiveness. Organic light-emitting materials have experienced the development of the three generation system, it is timely to summary the recent advances and the remaining challenges of the materials as well as their corresponding devices. Special attention is mainly concentrated on describing the blue material structures and related electroluminescence (EL) device performances (the maximum EQE data, Commission Internationale de l'Eclairage (CIE) coordinates, and efficiency roll-off). This short review will show the current governing hotspots concerning OLEDs in academic fields, which may pave the way for next step of industrial application.



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On Maxwell's displacement current for energy and sensors: the origin of nanogenerators

Publication date: Available online 7 January 2017
Source:Materials Today
Author(s): Zhong Lin Wang
Self-powered system is a system that can sustainably operate without an external power supply for sensing, detection, data processing and data transmission. Nanogenerators were first developed for self-powered systems based on piezoelectric effect and triboelectrification effect for converting tiny mechanical energy into electricity, which have applications in internet of things, environmental/infrastructural monitoring, medical science and security. In this paper, we present the fundamental theory of the nanogenerators starting from the Maxwell equations. In the Maxwell's displacement current, the first term ε0∂E∂t gives the birth of electromagnetic wave, which is the foundation of wireless communication, radar and later the information technology. Our study indicates that the second term ∂P∂t in the Maxwell's displacement current is directly related to the output electric current of the nanogenerator, meaning that our nanogenerators are the applications of Maxwell's displacement current in energy and sensors. By contrast, electromagnetic generators are built based on Lorentz force driven flow of free electrons in a conductor. This study presents the similarity and differences between pieozoelectric nanogenerator and triboelectric nanogenerator, as well as the classical electromagnetic generator, so that the impact and uniqueness of the nanogenerators can be clearly understood. We also present the three major applications of nanogenerators as micro/nano-power source, self-powered sensors and blue energy.



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