Low blood lead levels and attention-deficit hyperactivity disorder in children: a systematic review and meta-analysis

Abstract

Attention-deficit hyperactivity disorder (ADHD) of children is one of the most common neurodevelopmental diseases; the etiology remains unclear. We reviewed and meta-analyzed case-control studies to assess the effects of blood lead levels in children on ADHD symptoms. Relevant studies were identified by searching electronic databases. A meta-analysis was performed using the fixed model of Review Manager 5.3 software. Seven relevant studies were identified. The case groups exhibited significant increases in ADHD symptoms [mean difference (MD), 0.59; 95% confidence interval (CI), 0.50–0.68; p < 0.0001]. Subgroup assessment showed that even children with blood lead levels <3 μg/dL exhibited significant increases in ADHD symptoms (MD, 0.47; 95% CI, 0.39–0.56; p < 0.0001). Subgroup assessment also showed that children aged 5–12 years exhibited more significant increases in ADHD symptoms (MD, 1.35; 95% CI, 0.28–2.41; p < 0.0001) than children aged >12 years. Our findings suggest that low blood lead levels may be associated with ADHD symptoms in children. However, caution is needed when interpreting the results because among-study heterogeneity was in play. Primary interventions should focus on children with low blood lead levels.

http://ift.tt/2vBHmGV

Level, source identification, and risk analysis of heavy metal in surface sediments from river-lake ecosystems in the Poyang Lake, China

Abstract

The concentrations, sources, and risks of heavy metals (Fe, Al, Mn, Cr, Co, Ni, Cu, Zn, As, Cd, W, Pb, and Tl) in sediments in five river-lake ecosystems in the Poyang Lake region were studied. The concentrations of the heavy metals varied spatially, with most of the highest concentrations in the Raohe river-lake ecosystem (RH). All heavy metals except As, Cd, W, and Tl were enriched in sediments possessing high total organic carbon contents or in finer sediments. Based on enrichment factors and statistical methods, it was found that Cd in sediments in the Xiushui (XS), Ganjiang (GJ), Xinjiang (XJ) river-lake ecosystems, and RH; Mn in the XS, GJ, and RH; and W in the XS and GJ were greatly affected by anthropogenic inputs. Moreover, the origins of Cu, Zn, and As require more attention due to the high concentrations found. The high enrichment factor of Cd in the sediments indicated that this metal might cause significant pollution in the environment. The results of the modified potential ecological risk index revealed that the XS, GJ, RH, and XJ were at considerable ecological risk, while the sediments in the Fuhe river-lake ecosystem (FH) were at moderate ecological risk, with Cd contributing the highest proportion of risk. The hazard score fundamentally validated the modified potential ecological risk analysis and revealed a mean toxicity of 57.80% to the benthic organisms in the RH.

http://ift.tt/2wg9QDl

Reverberatory furnaces in the Puna of Jujuy, Argentina, during colonial times (from the end of the 16th to the beginning of the 19th century A.D.)

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Carlos I. Angiorama, M. Florencia Becerra
This paper presents the study of the extractive metallurgical technology that was employed in four colonial mining-metallurgical sites in the high plateau (Puna) of Jujuy, Argentina, dedicated to silver exploitation during the 17th and 18th centuries. In these archaeological sites, we have identified the presence of reverberatory furnaces. We explore the development of this technology and show the results of the study of the furnaces found in the Puna of Jujuy, their functions and performance, based on our fieldwork and on the results of archaeometric analyses of smelting slag and vitrified clay samples. The excellent conservation of most of the furnaces makes them not only a great source of information for the study of colonial metallurgy in this region, but also a contribution to our understanding of mining and extractive metallurgy in the Andes, of the circulation of workers and technical knowledge and of the changes generated by the Spanish conquest.



http://ift.tt/2v5iHJi

Impact of resistant vs. digested starch on starch energy value in the pig gut

Publication date: Available online 4 August 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Janelle M. Fouhse, Ruurd T. Zijlstra
A major energy substrate for monogastric species such as humans and swine is starch from cereal grains, pulses and tubers. The rate, site and extent of starch digestion in the gastro-intestinal tract are dependent on the intrinsic factors of starch origin and the extrinsic factors such as applied processing methods. In monogastric species, starch escaping small intestinal digestion becomes readily available for microbial fermentation in the hindgut and has been coined resistant starch (RS) accordingly. Host physiological and metabolic responses differ according to the site and rate of starch digestion; however, the quantity of energy derived to the host from fermented vs. digested starch remains debated. A detailed understanding of the underlying mechanisms that cause nutrient flow and substrate availability in the hindgut to alter host energy metabolism and growth potential is lacking. Dietary RS may in fact have nearly equal energetic efficiency as digested starch due adequate provision of short chain fatty acids (SCFAs) and decreased energy loss due to decreased activity. Thus, proper characterization of the energetic efficiency of purified and whole grain starch sources is required for accurate diet formulation. This review will focus on how various methodologies can be used to quantify site, extent and kinetics of starch digestion, illustrating the differences in energetic efficiency between RS vs. digested starch.



http://ift.tt/2v5EUHf

Exceptional Response with Immunotherapy in a Patient with Anaplastic Thyroid Cancer

AbstractChemotherapy with or without radiation is the standard therapy for anaplastic thyroid cancer (ATC), although the response rate is not high and not durable. We describe a 52‐year‐old male who was diagnosed with ATC and initially treated with a thyroidectomy and lymph node dissection, followed by chemotherapy. Next generation sequencing was then performed to guide therapy and the tumor was found to have BRAF and programmed death‐ligand 1 (PD‐L1) positivity that was subsequently treated with vemurafenib and nivolumab. This led to substantial regression of tumor nodules. Genomic sequencing‐based approaches to identify therapeutic targets has potential for improving outcomes. Currently, the patient continues to be in complete radiographic and clinical remission 20 months after beginning treatment with nivolumab.Key Points. Programmed death‐1 (PD‐1)/PD‐L1 immunotherapy has shown evidence of durable responses in certain malignancies such as melanoma, lung cancer, and renal cell carcinoma.PD‐L1 positive tumors promote autoimmunity against the tumor; therefore, PD‐1/PD‐L1 blockade may be beneficial.Molecular profiling could possibly result in improved targeted therapy for certain malignancies.

http://ift.tt/2u9O7eY

Current Treatments for Surgically Resectable, Limited‐Stage, and Extensive‐Stage Small Cell Lung Cancer

AbstractThe prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor‐1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra‐thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited‐stage disease, concurrent platinum‐etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60–70 Gy. For extensive‐stage disease, platinum‐etoposide remains the standard first‐line therapy, and the standard second‐line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10–30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta‐like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first‐line, maintenance, and second‐line settings.Implications for Practice.This review will provide an update on the standard therapies for surgically resected limited‐stage small cell lung cancer and extensive‐stage small cell lung cancer that have been investigated in recent clinical trials.

http://ift.tt/2vyI0UV

Cell‐Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta‐Analysis

AbstractBackground.Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor‐specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor‐specific mutations, whereas the use of total cell‐free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta‐analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.Materials and Methods.A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines were followed, and meta‐analysis applied on both aggregate data extraction and individual patients' data.Results.Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta‐analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03–2.82, p < .0001).Conclusion.The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut‐off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor‐specific mutations was emphasized in a large individual patients' data meta‐analysis.

http://ift.tt/2uaAc8i

Amplification of near-infrared fluorescence in semiconducting polymer nanoprobe for grasping the behaviors of systemically administered endothelial cells in ischemia treatment

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): Duo Mao, Jie Liu, Shenglu Ji, Ting Wang, Yu Hu, Donghui Zheng, Renqiang Yang, Deling Kong, Dan Ding
To date, there have been few studies on using fluorescent cell trackers for non-invasively monitoring the in vivo fate of systemically administered cells. This is because only a relatively small number of cells can reach the disease site post systemic infusion, and thus achieving ideal in vivo cell tracking requires that the fluorescent cell trackers should hold combined merits of ultrahigh near-infrared (NIR) fluorescence, negligible interference on cell behavior and function, excellent retention within cells, as well as accurate long-term cell tracking ability. To address this challenge, we herein developed a highly NIR fluorescent nanoprobe (SPN) based on semiconducting π-conjugated polymers (SPs), by synthesis of a NIR SP-emitter, employment of fluorescence resonance energy transfer (FRET) strategy, and optimization of different FRET donor SPs. Due to the 53.7-fold intra-particle amplification of NIR fluorescence, the SPN could track as few as 2000 endothelial cells (ECs) upon intra-arterial injection into critical limb ischemia (CLI)-bearing mice, showing much higher sensitivity in ECs tracking compared with the most popular commercial cell trackers. What's more, the SPN could provide precise information on the behaviors of systemically injected ECs in CLI treatment including the in vivo fate and regenerative contribution of ECs for at least 21 days.



http://ift.tt/2vpC8he

A novel delocalized lipophilic cation-chlorambucil conjugate inhibits P-glycoprotein in HepG2/ADM cells

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Teng Liu, Yongbo Peng, Xiong Li, Lian Liu, Fang Liu, Leye He
Multidrug resistance (MDR) limits the application of a large number of cancer-fighting agents in clinical therapy. One reason is that P-glycoprotein (Pgp) efflux pumps are usually overexpressed and lead to drug efflux in the cancer cells, which limits the viability of many chemotherapeutics. Current available inhibitors which block the Pgp pump efflux are usually not widely used in clinical practice, because they change other drug pharmacokinetic profiles or increase side effects. Here, through covalent linkage of cancer-targeting delocalized lipophilic cation FF and DNA-damaging drug nitrogen mustard chlorambucil (CLB), we rationally designed and synthesized a tumor-targeting anticancer agent FFCLB. And we found and proved that the FFCLB was capable of reducing the outflow of Pgp substrates efficiently. This conjugate selectively improves adriamycin uptake and toxicity through reducing MDR1 mRNA and Pgp protein expression. Based on molecular targeted strategy, this study can facilitate the discovery of superior MDR reducing agents to provide a more effective and safer way of resensitizing MDR.

Graphical abstract

http://ift.tt/2uahTjs

Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kun Li, Tianyi Ma, Jingjing Cai, Min Huang, Hongye Guo, Di Zhou, Shenglin Luan, Jinyu Yang, Dan Liu, Yongkui Jing, Linxiang Zhao
Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80 μM and 3.52 μM, respectively. The enzyme inhibition ratio of nine compounds at 10 μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.

Graphical abstract

http://ift.tt/2uahSfo

Radiosynthesis and Preclinical PET Evaluation of 89Zr-Nivolumab (BMS-936558) in Healthy Non-Human Primates

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Erin L. Cole, Joonyoung Kim, David J. Donnelly, R. Adam Smith, Daniel Cohen, Virginie Lafont, Paul E. Morin, Richard Y.-C. Huang, Patrick L. Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types. This study reports the preparation and in vivo evaluation of ⁸⁹Zr labeled nivolumab in healthy non-human primates (NHP) as a preliminary study of biodistribution and clearance. The radiochemical and in vivo stabilities of the ⁸⁹Zr complex were shown to be acceptable for imaging. Three naïve NHPs were intravenously injected with tracer only or tracer co-injected with nivolumab followed by co-registered by positron emission tomography (PET) and magnetic resonance imaging (MRI), acquired for eight days following injection. Image-derived standardized uptake values (SUV) were quantified by region of interest (ROI) analysis. Radioactivity in the spleen was significantly reduced by addition of excess nivolumab compared to the tracer only study at all imaging time points. Liver uptake of the radiotracer was consistent as a clearance organ with minimal signal from other tissues: lung, muscle, brain, heart, and kidney. The results indicate specific biodistribution to the spleen, which can be blocked by co-administration of excess nivolumab. Distribution to other organs is consistent with elimination pathways of antibodies, with primary clearance through the liver.

Graphical abstract

http://ift.tt/2u9Ezk5

Biological evaluation of 2-pyrazolinyl-1-carbothioamide derivatives against HCT116 human colorectal cancer cell lines and elucidation on QSAR and molecular binding modes

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Beom Soo Kim, Soon Young Shin, Seunghyun Ahn, Dongsoo Koh, Young Han Lee, Yoongho Lim
In the search of compounds exhibiting anticancer activity, 37 derivatives of 2-pyrazolinyl-1-carbothioamide were designed and synthesized. Clonogenic cell survival assays were adapted to measure the cytotoxicities of the synthetic derivatives against HCT116 human colon cancer cell lines. Half-maximal cell growth inhibitory concentrations (GI50) ranged from 0.49 to 41.22 µM. The compound with the lowest GI50 value, 3-(2-hydroxy-4,5-dimethoxyphenyl)-5-(naphthalen-1-yl)-N-(3,4,5-trimethoxyphenyl)-pyrazolinyl-1-carbothioamide, was subjected to further biological studies, including cell viability and apoptosis assays to examine levels of annexin-V in the outer plasma membrane layer and poly ADP-ribose polymerase cleavage. Additionally, in vitro kinase assays were performed, and Abelson murine leukemia viral oncogene homolog 1 (Abl 1) tyrosine kinase demonstrated good inhibitory activity. The binding mode between the compound of interest and Abl 1 was elucidated using in silico docking. The pharmacophores derived for 2-pyrazolinyl-1-carbothioamides based on their quantitative structure–activity relationships will help us design novel chemotherapeutic agents.

Graphical abstract

http://ift.tt/2ual2Qc

Synthesis and evaluation of analogs of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811, or AbeAdo) – an inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity

Publication date: Available online 3 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anthony J. Brockway, Oleg A. Volkov, Casey C. Cosner, Karen S. MacMillan, Stephen A. Wring, Thomas E. Richardson, Michael Peel, Margaret A. Phillips, Jef K. De Brabander
We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood-brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5'-amine, the ribose, and the purine fragments. Although we gained valuable structure-activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.

Graphical abstract

http://ift.tt/2uaum6S

Lysocardiolipin acyltransferase regulates TGF-β mediated lung fibroblast differentiation

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Long Shuang Huang, Peiyue Jiang, Carol Feghali-Bostwick, Sekhar P. Reddy, Joe G.N. Garcia, Viswanathan Natarajan
Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a key role in mitochondrial function and vascular development. We previously reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells correlated with poor pulmonary function outcomes and decreased survival in IPF patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression and oxidative stress are known to contribute to lung fibroblast differentiation and progression of fibrosis. In this study, we investigated the role of LYCAT in TGF-β mediated differentiation of human lung fibroblasts to myofibroblasts, and whether this occurred through mitochondrial superoxide and NOX4 mediated hydrogen peroxide (H2O2) generation. Our data indicated that LYCAT expression was up-regulated in primary lung fibroblasts isolated from IPF patients and bleomycin-challenged mice, compared to controls. In vitro, siRNA-mediated SMAD3 depletion inhibited TGF-β stimulated LYCAT expression in human lung fibroblasts. ChIP immunoprecipitation assay revealed TGF-β stimulated SMAD2/3 binding to the endogenous LYCAT promoter, and mutation of the SMAD2/3 binding sites (−179/−183 and −540/−544) reduced TGF-β-stimulated LYCAT promoter activity. Overexpression of LYCAT attenuated TGF-β-induced mitochondrial and intracellular oxidative stress, NOX4 expression and differentiation of human lung fibroblasts. Further, pretreatment with Mito-TEMPO, a mitochondrial superoxide scavenger, blocked TGF-β-induced mitochondrial superoxide, NOX4 expression and differentiation of human lung fibroblasts. Treatment of human lung fibroblast with NOX1/NOX4 inhibitor, GKT137831, also attenuated TGF-β induced fibroblast differentiation and mitochondrial oxidative stress. Collectively, these results suggest that LYCAT is a negative regulator of TGF-β-induced lung fibroblast differentiation by modulation of mitochondrial superoxide and NOX4 dependent H2O2 generation, and this may serve as a potential therapeutic target for human lung fibrosis.

Graphical abstract

http://ift.tt/2vyQ1cr

In silico approaches for unveiling novel glycobiomarkers in cancer

Publication date: Available online 4 August 2017
Source:Journal of Proteomics
Author(s): Rita Azevedo, André M.N. Silva, Celso A. Reis, Lúcio Lara Santos, José Alexandre Ferreira
Glycosylation is one of the most common and dynamic post-translational modification of cell surface and secreted proteins. Cancer cells display unique glycosylation patterns that decisively contribute to drive oncogenic behavior, including disease progression and dissemination. Moreover, alterations in glycosylation are often responsible for the creation of protein signatures holding significant biomarker value and potential for targeted therapeutics. Accordingly, many analytical protocols have been outlined for the identification of abnormally glycosylated proteins by mass spectrometry. Nevertheless, very few studies undergo a comprehensive mining of the generated data. Herein, we build on bladder cancer O-glycoproteomics datasets resulting from a hyphenated technique comprising enrichment by Vicia villosa agglutinin (VVA) lectin and nanoLC-ESI-MS/MS to propose an in silico step-by-step tutorial (Panther, NetOGlyc, NetNGlyc, Oncomine, Cytoscape) for biomarker discovery in cancer. We envisage that this approach may be generalized to other mass spectrometry-based analytical approaches, including N-glycoproteomics studies, and different types of cancers.SignificanceThe glycoproteome is an important source of cancer biomarkers holding tremendous potential for targeted therapeutics. We now present an in silico roadmap for comprehensive interpretation of big data generated by mass spectrometry-based glycoproteomics envisaging the identification of clinically relevant glycobiomarkers.



http://ift.tt/2wfXtXU

Effect of ferrate on green algae removal

Abstract

Green algae Cladophora aegagropila, present in cooling water of thermal power plants, causes many problems and complications, especially during summer. However, algae and its metabolites are rarely eliminated by common removal methods. In this work, the elimination efficiency of electrochemically prepared potassium ferrate(VI) on algae from cooling water was investigated. The influence of experimental parameters, such as Fe(VI) dosage, application time, pH of the system, temperature and hydrodynamics of the solution on removal efficiency, was optimized. This study demonstrates that algae C. aegagropila can be effectively removed from cooling water by ferrate. Application of ferrate(VI) at the optimized dosage and under the suitable conditions (temperature, pH) leads to 100% removal of green algae Cladophora from the system. Environmentally friendly reduction products (Fe(III)) and coagulation properties favour the application of ferrate for the treatment of water contaminated with studied microorganisms compared to other methods such as chlorination and use of permanganate, where harmful products are produced.

http://ift.tt/2uctMd2

Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI

Publication date: Available online 4 August 2017
Source:Magnetic Resonance Imaging
Author(s): Prativa Sahoo, Rakesh K. Gupta, Pradeep K. Gupta, Ashish Awasthi, Chandra M. Pandey, Mudit Gupta, Rana Patir, Sandeep Vaishya, Sunita Ahlawat, Indrajit Saha
PurposeAim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI).Material and methodsSixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC).ResultThe diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading.ConclusionIt was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach.



http://ift.tt/2v75Hl1

Copper-tolerant yeasts: Raman spectroscopy in determination of bioaccumulation mechanism

Abstract

Modern, efficient, and cost-effective approach to remediation of heavy metal-contaminated soil is based on the application of microorganisms. In this paper, four isolates from agricultural and urban contaminated soil showed abundant growth in the presence of copper(II) sulfate pentahydrate (CuSO₄·5H₂O) up to 2 mM. Selected yeasts were identified by molecular methods as Candida tropicalis (three isolates) and Schwanniomyces occidentalis (one isolate). C. tropicalis (4TD1101S) showed the highest percentage of bioaccumulation capabilities (94.37%), determined by the inductively coupled plasma optical emission spectrometry (ICP-OES). The Raman spectra of C. tropicalis (4TD1101S) analyzed in a medium with the addition of 2 mM CuSO₄·5H₂O showed certain increase in metallothionein production, which represents a specific response of the yeast species to the stress conditions. These results indicate that soil yeasts represent a potential for practical application in the bioremediation of contaminated environments.

http://ift.tt/2vyzWmX

Comment on: ‘Impact of the method and success of pharyngeal reconstruction on the outcome of treating laryngeal and hypopharyngeal cancers with pharyngolaryngectomy: A national analysis’

Nouraei et al1 present an analysis of 1589 patients undergoing pharyngolaryngectomy in the UK between 2002–2012. This is a very interesting study that provides important information for reflection by specialist head and neck teams. Based upon the study findings, the authors conclude that alimentary conduits worsen short and long-term survival and advocate the centralisation of care within 3-4 specialised centres.

http://ift.tt/2v74utN

Trends in dermatology practices and the implications for the workforce

Publication date: Available online 4 August 2017
Source:Journal of the American Academy of Dermatology
Author(s): Alison Ehrlich, James Kostecki, Helen Olkaba
BackgroundThe American Academy of Dermatology (AAD) practice profile surveys have been conducted for more than a decade to gauge trends in our workforce supply and demand.ObjectiveTo update the trends and current workforce issues for the field of dermatology.MethodsThe AAD Practice Profile Survey is sent by both e-mail and postal mail to a random sample of practicing dermatologists who are AAD members.ResultsShifts are noted in the primary practice setting; fewer dermatologists are in solo practice and more are in group practices than in previous years. Teledermatology use trended upward from 7% to 11% between 2012 and 2014. The implementation of electronic health records increased from 51% in 2011 to 70% in 2014.LimitationsThere is potential for response bias and inaccurate self-reporting. Survey responses collected may not be representative of all geographic areas.ConclusionThe demand for dermatology services remains strong. Shifts in the practice setting may be related to increases in overhead costs that are partially associated with the implementation of technology-based medical records. Integration of electronic health records and utilization of telemedicine are increasing.



http://ift.tt/2wfL1an

Facile synthesis of β-functionalized “push-pull” Zn(II) porphyrins for DSSC applications

Publication date: December 2017
Source:Dyes and Pigments, Volume 147
Author(s): Kamal Prakash, Shweta Manchanda, Vediappan Sudhakar, Nidhi Sharma, Muniappan Sankar, Kothandam Krishnamoorthy
Three new β-substituted "push-pull" Zn(II) porphyrin dyes with various electron donors at meso-positions and cyanoacetic acid as acceptor at β-position have been designed and synthesized. These porphyrins have been characterized by UV-Vis, Fluorescence, ¹H NMR and ¹³C NMR spectroscopic techniques and cyclic voltammetric studies. The Soret and Q band of Zn(II) porphyrin dyes were found to be red-shifted (30–35 nm) as compared to ZnTPP. The fluorescence quenching and the decrement in quantum yield and lifetime suggest intramolecular charge transfer from donor to acceptor. Zn porphyrins exhibited anodic shift in their first redox potentials (0.03–0.11 V) as compared to ZnTPP. The HOMO-LUMO energy levels of Zn porphyrin dyes were compared with the conduction band of TiO2 and the electrolyte I⁻/I3⁻. The HOMO levels of all the dyes are sufficiently higher than the energy level of electrolyte I⁻/I3⁻ and LUMO levels significantly lower than the conduction band of TiO2 which reflect the feasibility of facile electron-transfer. ZnT(Mes)P(CN-COOH) has been co-sensitized with N719 dye to further improve the PCE efficiency. These dyes displayed power conversion efficiency (PCE) of η = 1.72–3.13% where co-sensitized ZnT(Mes)P(CN-COOH) (N719) dye demonstrated maximum PCE efficiency up to 5.35%, with a Jsc of 11.8 mA cm⁻², a Voc of 630 mV and a fill factor (FF) of 72% due to better light harvesting capacity.

Graphical abstract

http://ift.tt/2usuI8f

Newly discovered Neanderthal remains from Shanidar Cave, Iraqi Kurdistan, and their attribution to Shanidar 5

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Emma Pomeroy, Marta Mirazón Lahr, Federica Crivellaro, Lucy Farr, Tim Reynolds, Chris O. Hunt, Graeme Barker
The Neanderthal remains from Shanidar Cave, excavated between 1951 and 1960, have played a central role in debates concerning diverse aspects of Neanderthal morphology and behavior. In 2015 and 2016, renewed excavations at the site uncovered hominin remains from the immediate area where the partial skeleton of Shanidar 5 was found in 1960. Shanidar 5 was a robust adult male estimated to have been aged over 40 years at the time of death. Comparisons of photographs from the previous and recent excavations indicate that the old and new remains were directly adjacent to one another, while the disturbed arrangement and partial crushing of the new fossils is consistent with descriptions and photographs of the older discoveries. The newly discovered bones include fragments of several vertebrae, a left hamate, part of the proximal left femur, a heavily crushed partial pelvis, and the distal half of the right tibia and fibula and associated talus and navicular. All these elements were previously missing from Shanidar 5, and morphological and metric data are consistent with the new elements belonging to this individual. A newly discovered partial left pubic symphysis indicates an age at death of 40–50 years, also consistent with the age of Shanidar 5 estimated previously. Thus, the combined evidence strongly suggests that the new finds can be attributed to Shanidar 5. Ongoing analyses of associated samples, including for sediment morphology, palynology, and dating, will therefore offer new evidence as to how this individual was deposited in the cave and permit new analyses of the skeleton itself and broader discussion of Neanderthal morphology and variation.



http://ift.tt/2usffVz

Imaging of Intrathoracic Paragangliomas

Publication date: Available online 4 August 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Daniel Ocazionez, Girish S. Shroff, Daniel Vargas, Demetrius Dicks, Abhishek Chaturvedi, Arun Nachiappan, Horacio Murillo, Ameya Baxi, Carlos S. Restrepo
Intrathoracic paragangliomas are uncommon and only represent 1–2% of paragangliomas. They are most commonly found in mediastinal compartments (aortopulmonary (AP) window or posterior mediastinum). Computed tomography, magnetic resonance and specific nuclear medicine radiotracers are routinely used to characterize these lesions and help exclude other more common conditions. Selective angiography is currently used for preoperative embolization and mapping of the vascular supply before surgical resection, rather than for diagnostic purposes alone.



http://ift.tt/2vAZ919

Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer

Publication date: Available online 4 August 2017
Source:Human Pathology
Author(s): Lisha Wang, Zebing Liu, Kurt W. Fisher, Fei Ren, Jiaojie Lv, Darrell D. Davidson, Lee A. Baldridge, Xiang Du, Liang Cheng
Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P=.031), positive p53 expression (P=.031), and negative PD-L1 expression (P=.003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P<.001). In univariate analysis, negative p53 (P=.001), low Ki-67 LI (P=.006), low PD-L1 expression (P=.044), low TNM stage (P<.001), recto-sigmoid location (P=.026), and small size (P=.013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P=.004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P=.027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P<.001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score≥35 and Ki-67 LI≥20% identifies patients with poor clinical outcome.



http://ift.tt/2u9LfhW

The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Publication date: Available online 4 August 2017
Source:Human Pathology
Author(s): Alberto M. Marchevsky, Nolwenn LeStang, Kenzo Hiroshima, Giuseppe Pelosi, Richard Attanoos, Andrew Churg, Lucien Chirieac, Sanja Dacic, Aliya Husain, Andras Khoor, Sonja Klebe, Silvie Lantuejoul, Victor Roggli, Jean-Michel Vignaud, Birgit Weynand, Jennifer Sauter, Douglas Henderson, Kazuki Nabeshima, Francoise Galateau-Salle
Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostast, Englewood N.J.). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best-available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin, mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.



http://ift.tt/2vypXhH

Health Services Research in Rehabilitation and Disability – The Time is Now

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): James E. Graham, Addie Middleton, Janet Prvu Bettger, Trudy Mallinson, Pamela Roberts
Policy drives practice, and health services research (HSR) is at the intersection of policy, practice and patient outcomes. HSR specific to rehabilitation and disability is particularly needed. As rehabilitation researchers and providers, we are uniquely positioned to provide the evidence that guides reforms targeting rehabilitative care. We have the expertise to define the value of rehabilitation in a policy-relevant context. HSR is a powerful tool for providing this evidence. We need to continue building capacity for conducting rigorous, timely rehabilitation-related HSR. Fostering stakeholder engagement in these research efforts will ensure we maintain a patient-centered focus as we address the "Triple Aim" of better care, better health, and better value. In this Special Communication we discuss the role of rehabilitation researchers in HSR. We also provide information on current resources available in our field for conducting HSR and identify gaps for capacity-building and future research. Healthcare reforms are a reality, and through HSR we can give rehabilitation a strong voice during these transformative times.



http://ift.tt/2vxGGl8

Supported Employment for Veterans with Traumatic Brain Injury: Patient Perspectives

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kathleen F. Carlson, Terri K. Pogoda, Tess Gilbert, Sandra G. Resnick, Elizabeth Twamley, Maya E. O'Neil, Nina A. Sayer
ObjectiveTo quantify the need for, and interest in, Supported Employment (SE) among recent military Veterans with traumatic brain injury (TBI), and to examine characteristics associated with Veterans' interest in SE.DesignStratified random sample of Iraq and Afghanistan War Veterans confirmed to have TBI through the Veterans Health Administration (VHA) screening and evaluation system.SettingCommunity-based via mailed survey.ParticipantsWe recruited 1,800 Veterans with clinician-confirmed TBI (1,080 mild TBI; 720 moderate/severe TBI) through multiple mailings. Among 1,451 whose surveys were not returned undeliverable, 616 (42%) responded.InterventionsNot applicable.Main Outcome MeasuresVeterans rated their interest in SE after reading a script describing the program. Additional measures assessed mental health and pain-related comorbidities, employment, financial/housing difficulties, demographics, and military service characteristics. Estimates were weighted to represent the population of Veterans with VHA clinician-confirmed TBI.ResultsUnemployment was reported by 45% (95% confidence interval [CI]: 43, 47) of Veterans with TBI. Although 42% (95% CI: 40, 44) reported they would be interested in using SE if it were offered to them, only 12% had heard of SE (95% CI: 11, 14) and <1% had used it. TBI severity and comorbidities were not associated with Veterans' interest in SE. However, those who were unemployed, looking for work, experiencing financial strain, or at risk for homelessness were more likely to be interested in SE.ConclusionsOur research highlights an important gap between Veterans' vocational needs and interests and their use of SE. Systematically identifying and referring those with employment and financial/housing difficulties may help close this gap.



http://ift.tt/2u90qrR

How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches

Publication date: Available online 4 August 2017
Source:Trends in Biochemical Sciences
Author(s): Kliment A. Verba, David A. Agard
The Hsp90/Cdc37 chaperone system interacts with and supports 60% of the human kinome. Not only are Hsp90 and Cdc37 generally required for initial folding, but many kinases rely on the Hsp90/Cdc37 throughout their lifetimes. A large fraction of these 'client' kinases are key oncoproteins, and their interactions with the Hsp90/Cdc37 machinery are crucial for both their normal and malignant activity. Recently, advances in single-particle cryo-electron microscopy (cryoEM) and biochemical strategies have provided the first key molecular insights into kinase–chaperone interactions. The surprising results suggest a re-evaluation of the role of chaperones in the kinase lifecycle, and suggest that such interactions potentially allow kinases to more rapidly respond to key signals while simultaneously protecting unstable kinases from degradation and suppressing unwanted basal activity.



http://ift.tt/2hvRcUq

Cosmetics, Vol. 4, Pages 26: Cosmeceuticals Properties of Sea Cucumbers: Prospects and Trends

Cosmetics, Vol. 4, Pages 26: Cosmeceuticals Properties of Sea Cucumbers: Prospects and Trends

Cosmetics doi: 10.3390/cosmetics4030026

Authors: Evi Siahaan Ratih Pangestuti Hendra Munandar Se-Kwon Kim

Cosmeceutical, a new term in the cosmetic industry, refers to cosmetic products that contain active ingredients and have medicinal benefits. Cosmeceuticals have attracted increased attention because of their beneficial effects on human health. Sea cucumbers, belonging to the class Holothuroidea, marine invertebrates, are rich in bioactive compounds, including saponin, chondroitin sulphate, collagen, amino acids, and phenols. These bioactive compounds have diverse functional roles as a secondary metabolite and these properties can be applied to the developments of novel cosmeceuticals. This review provides an overview the application of sea cucumber derivatives for cosmeceuticals. Further, prospects and trends of sea cucumber in cosmeceuticals industry were also discussed. The proper development of sea cucumber bioactive compounds will be helpful in cosmeceutical product development and industry.

http://ift.tt/2hunE9X

Pathophysiology and immunological profile of myasthenia gravis and its subgroups

Publication date: December 2017
Source:Current Opinion in Immunology, Volume 49
Author(s): Fredrik Romi, Yu Hong, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present.



http://ift.tt/2u94sAz

Known unknowns: how might the persistent herpesvirome shape immunity and aging?

Publication date: October 2017
Source:Current Opinion in Immunology, Volume 48
Author(s): Janko Nikolich-Zugich, Felicia Goodrum, Kenneth Knox, Megan J Smithey
The microbial community that colonizes all living organisms is gaining appreciation for its contributions to both physiologic and pathogenic processes. The virome, a subset of the overall microbiome, large and diverse, including viruses that persistently inhabit host cells, endogenous viral elements genomically or epigenomically integrated into cells, and viruses that infect the other (bacterial, protozoan, fungal, and archaeal) microbiome phylla. These viruses live in the organism for its life, and therefore are to be considered part of the aging process experienced by the organism. This review considers the impact of the persistent latent virome on immune aging. Specific attention will be devoted to the role of herpesviruses, and within them, the cytomegalovirus, as the key modulators of immune aging.



http://ift.tt/2vxfxig

Satb2 Cre/+ mouse as a tool to investigate cell fate determination in the developing neocortex

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Mateusz Cyryl Ambrozkiewicz, Paraskevi Bessa, Andrea Salazar-Lázaro, Valentina Salina, Victor Tarabykin
BackgroundGeneration of different neuronal subtypes during neocortical development is the most important step in the establishment of cortical cytoarchitecture. The transcription factor Satb2 is expressed in neocortical projection neurons that send their axons intracortically as opposed to Satb2-negative neurons that preferentially project to subcortical targets.New MethodIn this report, we present a novel method to carry out large scale screening for molecules that control cell fate in the developing neocortex. It is based on a Satb2^Cre/+ mouse strain that expresses Cre recombinase from the Satb2 locus.ResultsBy transfecting neuronal progenitors with a Cre-inducible reporter construct by nucleofection or in utero electroporation, we could determine the proportion of cells that become Satb2-positive.Comparison with existing methods Compared to genetic tracing or lineage analysis, this method offers a fast, easy-to-perform and reliable way of determining cell fate of newly born neurons.ConclusionsWe demonstrate that the Satb2^Cre/+ mouse can be applied to study factors, such as small molecule inhibitors, sh-RNAs or overexpression constructs, that can alter the proportion of Satb2-positive cells and thus play key roles in differentiation and acquisition of cell fate.

Graphical abstract

http://ift.tt/2huKBtx

NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Eftychios A. Pnevmatikakis, Andrea Giovannucci
BackgroundMotion correction is a challenging pre-processing problem that arises early in the analysis pipeline of calcium imaging data sequences. The motion artifacts in two-photon microscopy recordings can be non-rigid, arising from the finite time of raster scanning and non-uniform deformations of the brain medium.New methodWe introduce an algorithm for fast Non-Rigid Motion Correction (NoRMCorre) based on template matching. NoRMCorre operates by splitting the field of view (FOV) into overlapping spatial patches along all directions. The patches are registered at a sub-pixel resolution for rigid translation against a continuously updated template. The estimated alignments are subsequently up-sampled to create a smooth motion field for each frame that can efficiently approximate non-rigid artifacts in a piecewise-rigid manner.Existing methodsExisting approaches either do not scale well in terms of computational performance or are targeted to non-rigid artifacts arising just from the finite speed of raster scanning, and thus cannot correct for non-rigid motion observable in datasets from a large FOV.ResultsNoRMCorre can be run in an online mode resulting in comparable to or even faster than real time motion registration of streaming data. We evaluate its performance with simple yet intuitive metrics and compare against other non-rigid registration methods on simulated data and in vivo two-photon calcium imaging datasets. Open source Matlab and Python code is also made available.ConclusionsThe proposed method and accompanying code can be useful for solving large scale image registration problems in calcium imaging, especially in the presence of non-rigid deformations.



http://ift.tt/2huKwpJ

Electrical stimulation of different retinal components and the effect of asymmetric pulses

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Dorit Raz-Prag, Giora Beit-Yaakov, Yael Hanein
BackgroundHigh resolution electrical stimulation of neural tissue is a fundamental challenge in applications such as deep brain stimulation and artificial vision. In artificial vision, achieving and validating local selective epi-retinal stimulation of different layers in the retina is particularly challenging owing to plurality of retinal cell types and delocalized wiring.ResultsStrong selectivity and non-localized responses to epi-retinal stimulation, over a wide range of realistic stimulation parameters, was achieved and validated using asymmetric pulses.New MethodThe reported method consists of multi electrode array (MEA) stimulation and recording from a developing chick retina combined with calcium imaging. Data show direct and indirect neuronal activation in the chick retina model. In particular, axonal activation, orientation and conduction velocity are derived, and the non-local nature of the responses to direct axonal stimulation is demonstrated.Comparison with Existing MethodsSome of the previous research with mammalian retinas demonstrated local responses around the stimulating electrode, revealing little as to axonal activation. Recent studies showed activation along the nerve fibers and studied the effect of pulse duration to improve stimulation localization (Twyford and Fried, 2016; Weitz et al., 2015). The chick retina offers a straight forward mapping of axonal activation. Here we demonstrate that the chick retina, combined with MEA recording and stimulation along with calcium imaging is a powerful tool to study retinal activation and in particular the effect of asymmetry on axonal activation.ConclusionsMEA recording and stimulation from the chick retina is exceptionally powerful in distinguishing between direct and indirect responses. This method facilitates comparison between different stimulation strategies. We show that asymmetric electrical stimulations allow control over the intensity of direct activation.

Graphical abstract

http://ift.tt/2ffnx1i

An Initial Validation of the Virtual of the Virtual Environment Grocery Store

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Thomas D. Parsons, Timothy McMahan
BackgroundVirtual reality-based neuropsychological assessments proffer the potential to address the limited ecological validity of pen-and-paper measures of memory.New MethodTo investigate the construct validity of a newly developed virtual reality-based multiple errands task, the Virtual Environment Grocery Store (VEGS), two studies were performed.Comparison with Existing Method(s)In Study 1, we explored construct validity via comparison of traditional neuropsychological measures of memory and executive functioning with a low distraction condition of the VEGS. In Study 2, a new sample was used to compare traditional neuropsychological measures of memory and executive functioning with a high distraction condition of the VEGS.ResultsPerformances on the VEGS memory tasks (in Study 1: low distraction condition) and the traditional neuropsychological assessments of memory were positively correlated, indicating that memory for VEGS content was similar to memory for traditional paper-and-pencil measures. Again, in Study 2, performances on the VEGS memory tasks correlated with the traditional neuropsychological assessments of memory, indicating that memory for VEGS content was similar to memory for traditional paper-and-pencil measures. As expected, though, the addition of distractors into the virtual environment resulted in significant correlations with traditional measures of inhibitory control.ConclusionsThe VEGS has the advantage over traditional measures of providing objective measurement of individual components of memory in simulations of everyday activities.



http://ift.tt/2ffFhJU

HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Jing Zhang, Lei Zhang, Shu Zhang, Qilin Yu, Fei Xiong, Kun Huang, Cong-Yi Wang, Ping Yang
Obesity has emerged as an imminent global public health concern over the past several decades. It has now become evident that obesity is characterized by the persistent and low-grade inflammation in the adipose tissue, and serves as an independent risk factor for many metabolic disorders such as diabetes and cardiovascular disease. Particularly, adipocytes originated from obese mice and humans likely predominate necrosis upon stressful insults, leading to passive release of cellular contents including the high mobility group box 1 (HMGB1) into the extracellular milieu. Extracellular HMGB1 acts as an innate alarmin to stimulate the activation of resident immune cells in the adipose tissue. Upon activation, those resident immune cells actively secrete additional HMGB1, which in turn activates/recruits additional immune cells, and induces adipocyte death. This review summarizes those novel discoveries in terms of HMGB1 in the initiation and maintenance of chronic inflammatory state in adipose tissue in obesity, and discusses its potential application in clinical settings.



http://ift.tt/2ub0KdN

Corrigendum to “Transplantation of alginate-encapsulated seminiferous tubules and interstitial tissue into adult rats: Leydig stem cell differentiation in vivo?” [Mol. Cell. Endocrinol. 436 (2016) 250–258]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Haolin Chen, Shiying Jin, Shengsong Huang, Janet Folmer, June Liu, Renshan Ge, Barry R. Zirkin




http://ift.tt/2us3wXe

Corrigendum to “Leydig cell stem cells: Identification, proliferation and differentiation” [Mol. Cell. Endocrinol. XXX (2016) 1–9]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Haolin Chen, Yiyan Wang, Renshan Ge, Barry R. Zirkin




http://ift.tt/2uaY4g8

Corrigendum to “A multi-step, allosteric model of testosterone's binding to sex hormone binding globulin” [Mol. Cell. Endocrinol. 399 (2015) 190–200]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Mikhail N. Zakharov, Shalender Bhasin, Thomas G. Travison, Ran Xue, Jagadish Ulloor, Vasan Ramachandran, Emma Carter, Frederick Wu, Ravi Jasuja




http://ift.tt/2urdQPl

A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia

Publication date: Available online 3 August 2017
Source:Cancer Genetics
Author(s): Matthew J. Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia. We describe identification of a FIP1L1-PDGFRA fusion in a 13-year-old boy who presented with T-lymphoblastic leukemia/lymphoma without eosinophilia. Detection of FIP1L1- PDGFRA driven neoplasms at diagnosis is usually critical for proper treatment, since almost all reported cases responded to tyrosine kinase inhibitors. However, our patient's leukemia was refractory to standard chemotherapy, and did not show a meaningful response to tyrosine kinase inhibitor therapy. Testing for a FIP1L1- PDGFRA rearrangement is at present limited to patients with idiopathic hypereosinophilia, and we hypothesize that this abnormality may be under-diagnosed in children with acute leukemias.



http://ift.tt/2husLHc

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55–/– (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at –80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites.

http://ift.tt/2huoG5M

Pituitary stem cell regulation: who is pulling the strings?

The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial–mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

http://ift.tt/2ff2AmV

Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training

Obesity-linked insulin resistance is mainly due to fatty acid overload in non-adipose tissues, particularly skeletal muscle and liver, where it results in high production of reactive oxygen species and mitochondrial dysfunction. Accumulating evidence indicates that resistance and endurance training alone and in combination can counteract the harmful effects of obesity increasing insulin sensitivity, thus preventing diabetes. This review focuses the mechanisms underlying the exercise role in opposing skeletal muscle insulin resistance-linked metabolic dysfunction. It is apparent that exercise acts through two mechanisms: (1) it stimulates glucose transport by activating an insulin-independent pathway and (2) it protects against mitochondrial dysfunction-induced insulin resistance by increasing muscle antioxidant defenses and mitochondrial biogenesis. However, antioxidant supplementation combined with endurance training increases glucose transport in insulin-resistant skeletal muscle in an additive fashion only when antioxidants that are able to increase the expression of antioxidant enzymes and/or the activity of components of the insulin signaling pathway are used.

http://ift.tt/2hv2fNI

Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice

This study assessed the metabolic and neuroprotective actions of the sodium glucose cotransporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high-fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy X-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined. Once-daily administration of DAPA-Lira resulted in significant decreases in body weight, fat mass, glucose and insulin concentrations, despite no change in energy intake. Similar beneficial metabolic improvements were observed regarding glucose tolerance, insulin sensitivity, HOMA-IR, HOMA-β, HbA1c and triglycerides. Plasma glucagon, GLP-1 and IL-6 levels were increased and corticosterone concentrations decreased. DAPA-Lira treatment decreased alpha cell area and increased insulin content compared to dapagliflozin monotherapy. Recognition memory was significantly improved in all treatment groups. Brain histology demonstrated increased staining for doublecortin (number of immature neurons) in dentate gyrus and synaptophysin (synaptic density) in stratum oriens and stratum pyramidale. These data demonstrate that combination therapy of dapagliflozin and liraglutide exerts beneficial metabolic and neuroprotective effects in diet-induced diabetic mice. Our results highlight important personalised approach in utilising liraglutide in combination with dapagliflozin, instead of either agent alone, for further clinical evaluation in treatment of diabetes and associated neurodegenerative disorders.

http://ift.tt/2ffvmEb

Impact of aging immune system on neurodegeneration and potential immunotherapies

Publication date: Available online 4 August 2017
Source:Progress in Neurobiology
Author(s): Zhanfeng Liang, Yang Zhao, Linhui Ruan, Linnan Zhu, Kunlin Jin, Qichuan Zhuge, Dong-Ming Su, Yong Zhao
The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging.



http://ift.tt/2wejVR2

The protective effects of electro-acupuncture in thoracic surgery on trauma stressed rats involve the rostral ventrolateral medulla and supraoptic nucleus

Publication date: Available online 3 August 2017
Source:Brain Research Bulletin
Author(s): Huan-Huan Zhang, Yi-Nan Tao, Mei-Yan Jiang, Jin Wang, Jun Chen, Chun-Mei Xia, Lin-Lin Shen, Meng-Ya Wang, Da-Nian Zhu
The present study was designed to explore whether the rostral ventrolateral medulla (RVLM) and supraoptic nucleus (SON) were involved in the protective effects of electro-acupuncture (EA) on cardiac function in thoracic surgery on trauma-stressed rats. The rats were randomly divided into a non-stressed group (Control), surgical trauma-stressed group (Trauma), and Neiguan EA applied on the surgical trauma-stressed group (Trauma+EA-PC 6). RVLM neuron discharge was observed by using an in vivo electrophysiological method, and micro-dialysis combining high-performance liquid chromatography with fluorometric detection (HPLC-FD) was used to assess expression of amino acids in the RVLM. Immunohistochemical methods were used to assess c-Fos expression in SON neurons. The trauma of surgical stress was shown to dramatically increase the discharge frequency of RVLM neurons and promote the release of glutamate and taurine in the RVLM. The expression of c-Fos was also significantly increased in the SON of traumatized rats. EA application at Neiguan acupoints significantly suppressed trauma-induced increase of discharge frequency of the RVLM neurons, almost completely suppressed the trauma-induced increase of glutamate release but only very slightly reduced the trauma-enhanced taurine release, and inhibited the increase of c-Fos expression in these SON neurons of traumatized rats. These results indicate that Neiguan EA may regulate cardiac function by modulating neurons in the RVLM and the SON in surgically traumatized rats. The taurine-mediated negative feedback may be involved in the protective effect of EA on cardiac function.



http://ift.tt/2v5Gasq

Local protocol variations for Image-Guided Radiotherapy in the multicenter Dutch hypofractionation (HYPRO) trial: impact of rectal balloon and MRI delineation on anorectal dose and gastrointestinal toxicity levels

Publication date: Available online 3 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): R.C. Wortel, W.D. Heemsbergen, R.J. Smeenk, M.G. Witte, A.D.G. Krol, F.J. Pos, L. Incrocci
PurposeThe phase 3 XXX trial randomized intermediate to high-risk localized prostate cancer patients to conventionally fractionated (78Gy/39fr) or hypofractionated radiotherapy (64.6Gy/19fr). Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers.Methods and MaterialsFrom the trial population we selected patients (n=572) from four treatment centers who received image-guided-IMRT (IG-IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5-6mm and was considered the reference center. In center B (n=170, 7mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7mm margins). Center D (n=75) applied the largest PTV-margins of 8mm. The study protocol provided identical anorectal dose constraints and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared applying t-tests. Rectal complaints during follow-up (6 months-4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy.ResultsFavorable anorectal dose distributions were found for center B (MRI delineation) and C (ERB application) as compared to center A and D. This was associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4/day) and mucous loss were observed for center C.ConclusionsDespite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2-3mm difference in PTV-margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.

Teaser

The effects of differences in techniques and treatment protocols on patient-reported rectal toxicity were compared between treatment centers participating in the prospective prostate XXX trial. All included centers applied image-guided-IMRT using identical anorectal dose constraints. As compared to reference center A (5-6mm PTV margins), favorable anorectal dose distributions were found for center B (MRI delineation, 7mm margins) and center C (endorectal balloon application, 7mm margins). This translated into significantly lower incidences of rectal complaints within both centers.


http://ift.tt/2we3LqS

Hypofractionated nodal radiation therapy for breast cancer was not associated with increased patient-reported arm or brachial plexopathy symptoms

Publication date: Available online 3 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nelson Leong, Pauline T. Truong, Keith Tankel, Winkle Kwan, Lorna Weir, Ivo A. Olivotto
PurposeTo determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25-2.5 Gy/fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx.Materials and MethodsTwo cancer registries were used to identify subjects who received CT-planned, nodal RT for pT1-3, pN0-2, M0 breast cancer from 2007-2010 at two cancer institutions. Following ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale (SASS), a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living (ADL). Clinico-pathologic characteristics and SASS scores were compared between HF/CF cohorts using non-parametric analysis, chi-squared analysis and multivariate ordinal regression.Results800/1759 patients returned a completed survey (45.5%). 708 eligible cases formed the study cohort. 406 (57%) received HFRT (40 Gy/16fx, 45 Gy/20fx), and 302 (43%) received CFRT (45-50 Gy/25fx, 50.4 Gy/28fx). Median time interval post-RT was 5.7 years. 43% and 75% of patients received breast conserving surgery and chemotherapy respectively. 22% received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (p<0.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (p=0.44), as were the mean sums of responses in arm symptoms (p=0.17) and ADL (p=0.85). HF patients reported lower rates of shoulder stiffness (p=0.04), trouble moving the arm (p=0.02), and ability to reach overhead (p<0.01) compared to the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy.ConclusionsNodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared to CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Teaser

Among 708 women treated with CT-planned regional nodal radiation therapy (RT) for breast cancer, self-reported arm symptoms were similar or less debilitating following modestly hypofractionated (2.25-2.5 Gy/day) versus conventionally fractionated (≤ 2 Gy/day) RT at a median of 5.7 years after treatment.


http://ift.tt/2v3W5Jk

Keeping Children Safe: a multicentre programme of research to increase the evidence base for preventing unintentional injuries in the home in the under-fives.

The Keeping Children Safe programme produced extensive new evidence on preventing falls, poisonings and thermal injuries in the under-fives, including that an injury prevention briefing did not increase the proportion of families with a fire escape plan, but did improve some secondary outcomes.

http://ift.tt/2vx6Cxe

Clinical Evaluation of the OncAlert RAPID in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making

Conditions:   Palatal Neoplasms;   Lip Neoplasm;   Gingival Neoplasms;   Leukoplakia, Oral;   Tongue Neoplasms;   Oropharyngeal Neoplasms;   Oral Ulcer
Intervention:   Device: OncAlert
Sponsors:   Vigilant Biosciences, Inc.;   Pearl Pathways
Recruiting - verified May 2017

http://ift.tt/2uaQpOP

Dataset on antitumor properties of silver nanoparticles from Gloriosa superba (L.) seed on Dalton Lymphoma Ascites (DLA) tumor: Facile and biocompatible approach

Publication date: Available online 3 August 2017
Source:Data in Brief
Author(s): Muthukirshnan Saradhadevi, Murugesan Gnanadesigan, Gnanajothi Kapildev, Dhakshinamoorthy Vasanth
The dataset depicted in this article related to our earlier article entitled "Phytofabrication and encapsulated of silver nanoparticles from Gloriosa Superba" (Saradha Devi, M., Ashokkumar, K., Annapoorani, S, 2017) [1], which reports the characteristic features (UV Visible spectra, FTIR, SEM, TEM, DLS, Zeta potential and XRD analysis) of the Gloriosa superba biosynthesised silver nanoparticles (AgNPs). In this context, the present dataset was provided to identify the antioxidant, antitumor and apoptotic (in DLA cells) properties with the synthesized AgNPs. The result enlightens the AgNPs exhibits antitumor, apoptotic activity in DLA cells and antioxidant properties. The results of the in vivo experiments increased life span of liver cells in DLA induced tumour mice and not showed any histopathological variations between control and DLA induced mice animals. The HPTLC examination of the Gloriosa superba (L.) seed extract infers the presence of colchicines derivatives as a major alkaloid sources.



http://ift.tt/2v3bdqc

MR-based respiratory and cardiac motion correction for PET imaging

Publication date: Available online 3 August 2017
Source:Medical Image Analysis
Author(s): Thomas Küstner, Martin Schwartz, Petros Martirosian, Sergios Gatidis, Ferdinand Seith, Christopher Gilliam, Thierry Blu, Hadi Fayad, Dimitris Visvikis, F. Schick, B. Yang, H. Schmidt, N.F. Schwenzer
Purpose: To develop a motion correction for Positron-Emission-Tomography (PET) using simultaneously acquired magnetic-resonance (MR) images within 90 seconds.Methods: A 90 seconds MR acquisition allows the generation of a cardiac and respiratory motion model of the body trunk. Thereafter, further diagnostic MR sequences can be recorded during the PET examination without any limitation. To provide full PET scan time coverage, a sensor fusion approach maps external motion signals (respiratory belt, ECG-derived respiration signal) to a complete surrogate signal on which the retrospective data binning is performed. A joint Compressed Sensing reconstruction and motion estimation of the subsampled data provides motion-resolved MR images (respiratory + cardiac). A 1-POINT DIXON method is applied to these MR images to derive a motion-resolved attenuation map. The motion model and the attenuation map are fed to the Customizable and Advanced Software for Tomographic Reconstruction (CASToR) PET reconstruction system in which the motion correction is incorporated. All reconstruction steps are performed online on the scanner via Gadgetron to provide a clinically feasible setup for improved general applicability. The method was evaluated on 36 patients with suspected liver or lung metastasis in terms of lesion quantification (SUVmax, SNR, contrast), delineation (FWHM, slope steepness) and diagnostic confidence level (3-point Likert-scale).Results: A motion correction could be conducted for all patients, however, only in 30 patients moving lesions could be observed. For the examined 134 malignant lesions, an average improvement in lesion quantification of 22%, delineation of 64% and diagnostic confidence level of 23% was achieved.Conclusion: The proposed method provides a clinically feasible setup for respiratory and cardiac motion correction of PET data by simultaneous short-term MRI. The acquisition sequence and all reconstruction steps are publicly available to foster multi-center studies and various motion correction scenarios.

Graphical abstract

http://ift.tt/2wdZx2q

Registration and Fusion Quantification of Augmented Reality based Nasal Endoscopic Surgery

Publication date: Available online 3 August 2017
Source:Medical Image Analysis
Author(s): Yakui CHU, Jian YANG, Danni AI, Wenjie Li, Hong SONG, Liang LI, Shaodong MA, Duanduan CHEN, Lei CHEN, Yongtian WANG
This paper quantifies the registration and fusion display errors of augmented reality-based nasal endoscopic surgery (ARNES). We comparatively investigated the spatial calibration process for front-end endoscopy and redefined the accuracy level of a calibrated endoscope by using a calibration tool with improved structural reliability. We also studied how registration accuracy is combined with the number and distribution of the deployed fiducial points (FPs) for positioning and the measured registration time. A physically integrated ARNES prototype was customarily configured for performance evaluation in skull base tumor resection surgery with an innovative approach of dynamic endoscopic vision expansion. As advised by surgical experts in otolaryngology, we proposed a hierarchical rendering scheme to properly adapt the fused images with the required visual sensation. By constraining the rendered sight in a known depth and radius, the visual focus of the surgeon can be induced only on the anticipated critical anatomies and vessel structures to avoid misguidance. Furthermore, error analysis was conducted to examine the feasibility of hybrid optical tracking based on point cloud, which was proposed in our previous work as an in-surgery registration solution. Measured results indicated that the error of target registration for ARNES can be reduced to 0.77 ± 0.07 mm. For initial registration, our results suggest that a trade-off for a new minimal time of registration can be reached when the distribution of five FPs is considered. For in-surgery registration, our findings revealed that the intrinsic registration error is a major cause of performance loss. Rigid model and cadaver experiments confirmed that the scenic integration and display fluency of ARNES are smooth, as demonstrated by three clinical trials that surpassed practicality.

Graphical abstract

http://ift.tt/2weer98

Stretch-reflex threshold modulation during active elbow movements in post-stroke survivors with spasticity

Publication date: Available online 3 August 2017
Source:Clinical Neurophysiology
Author(s): Nicolas A. Turpin, Anatol G. Feldman, Mindy F. Levin
ObjectivesVoluntary movements post-stroke are affected by abnormal antagonist activation due to exaggerated stretch reflexes (SRs). We examined the ability of post-stroke subjects to regulate SRs in spastic muscles.MethodsElbow flexor and extensor EMGs and angle were recorded in 13 subjects with chronic post-stroke spasticity. Muscles were either stretched passively (relaxed arm) or actively (antagonist contraction) at different velocities. Velocity-dependent SR thresholds were defined as angles where stretched muscle EMG exceeded 3SDs of baseline. Sensitivity of SRs to stretch velocity was defined as µ. The regression through thresholds was interpolated to zero velocity to obtain the tonic SR threshold (TSRT) angle.ResultsCompared to passive stretches, TSRTs during active motion occurred at longer muscle lengths (i.e., increased in flexors and decreased in extensors by 10-40°). Values of μ increased by 1.5-4.0. Changes in flexor TSRTs during active compared to passive stretches were correlated with clinical spasticity (r=-0.68) and arm motor impairment (r=0.81).ConclusionsSpasticity thresholds measured at rest were modulated during active movement. Arm motor impairments were related to the ability to modulate SR thresholds between the two states rather than to passive-state values.Significance. Relationship between spasticity and movement disorders may be explained by deficits in SR threshold range of regulation and modifiability, representing a measure of stroke-related sensorimotor deficits.



http://ift.tt/2hu8sJZ

Cortical involvement in myopathies: insights from transcranial magnetic stimulation

Publication date: Available online 3 August 2017
Source:Clinical Neurophysiology
Author(s): Raffaele Nardone, Viviana Versace, Luca Sebastianelli, Francesco Brigo, Stefan Golaszewski, Monica Christova, Eugen Gallasch, Leopold Saltuari, Eugen Trink
OBJECTIVEThere is increasing evidence that an involvement of central nervous system (CNS) can occur in several myopathies. Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of cortical involvement in neuromuscular disorders. In this review paper we aimed to perform a systematic search of the studies employing TMS techniques in subjects suffering from myopathies.METHODSA literature search was conducted using PubMed and Embase. We identified and reviewed 9 articles matching the inclusion criteria. One hundred twenty patients were included in these studies, which have applied TMS in patients with muscle disorders.RESULTSTo date, a few studies using TMS have been performed in myopathic patients and detected subclinical abnormalities in cortical reactivity and plasticity. The most consistent finding was a decrease in intracortical inhibition, which likely represents a non-specific compensatory mechanism of the CNS in an attempt to overcome the muscle deficit through an increase of the motor cortex output to deficient muscles.CONCLUSIONSApplication of TMS to characterize the pathophysiology of the CNS in these subjects appears to be safe and may lead to the development of valuable biomarkers. Well-defined motor cortical excitability patterns can be identified in the different muscle diseases, even if preliminary findings should be confirmed in future studies in larger cohorts of patients.SIGNIFICANCETMS studies may shed new light on the physiological and pathophysiological mechanisms underlying the cortical involvement in muscle disorders.



http://ift.tt/2fffdhX

Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing

Publication date: Available online 4 August 2017
Source:Advanced Drug Delivery Reviews
Author(s): Mirza Ali Mofazzal Jahromi, Parham Sahandi Zangabad, Seyed Masoud Moosavi Basri, Keyvan Sahandi Zangabad, Ameneh Ghamarypour, Amir R. Aref, Mahdi Karimi, Michael R. Hamblin
According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D–printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.

Graphical abstract

http://ift.tt/2vwN7ow

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria

Publication date: Available online 4 August 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Anna Kiersztan, Nina Trojan, Aleksandra Tempes, Paweł Nalepa, Joanna Sitek, Katarzyna Winiarska, Michał Usarek
Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits.Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria.Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio.As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes.



http://ift.tt/2wdtlfT

Looking for the origins of anorexia nervosa in adolescence - A new treatment approach

Publication date: Available online 3 August 2017
Source:Aggression and Violent Behavior
Author(s): S. Matt Lacoste
Anorexia nervosa is an eating disorder, which affects particularly adolescents. The media coverage of feminine thinness is demonstrated as a token of beauty, with diet as a tool to achieve this. However, diets are not enough to explain the numerous cases. This disease is the symptom of a psychological disorder and looking for the origin must coincide with psychotherapeutic treatment. Multifactorial explanations seem dominate within our female patients. For most female patients, family problems and past experience with sexual assault explain this transition to anorexia. It is demonstrated throughout this paper how and why anorexia nervosa is used as a tool for identification and personalization in the assumption of autonomy and independence, and how and why anorexia becomes a defensive response to aggression. We give a clinical confirmation of the diverse origins of anorexia nervosa and of the impact of sexual abuse. This paper proposes a new therapeutic approach to patients with anorexia nervosa, in which the eating disorder is a symptom of an emotional disorder, often triggered by sexual assault or emotional deprivation.



http://ift.tt/2wdjhTX

Yongdamsagan-tang, a traditional herbal formula, inhibits cell growth through the suppression of proliferation and inflammation in benign prostatic hyperplasia epithelial-1 cells

Publication date: Available online 4 August 2017
Source:Journal of Ethnopharmacology
Author(s): Eunsook Park, Mee-Young Lee, Chang-Seob Seo, Woo-Young Jeon, Hyeun-Kyoo Shin
Ethnopharmacological relevanceBenign prostatic hyperplasia (BPH), also called benign enlargement of the prostate, is a progressive disease that is observed in most elderly men. Yongdamsagan-tang, a traditional herbal formula, is used commonly for the treatment of inflammation-related diseases. Although the therapeutic efficacy of Yongdamsagan-tang against BPH in vivo was reported previously, its underlying mechanisms are not clearly understood.Aim of the studyIn this study, we investigated the effect of Yongdamsagan-tang water extract (YSTE) and its mechanism on the growth of human BPH epithelial BPH-1 cells.Materials and methodsYSTE was extracted from 11 herbaceous plants and its chemical composition was analyzed by High-performance liquid chromatography (HPLC). YSTE was treated in the epithelial BPH-1 cell line and then cell lysates or supernant were used to evaluate cell viability, cell cycle, proliferation and cytokine production.ResultsHPLC revealed that Baicalin and gentiopicroside were involved as the major compounds of YSTE. YSTE treatment in BPH-1 cells repressed cell viability in a dose-dependent manner. Regarding the inhibitory mechanisms of YSTE on cell growth, YSTE inhibited cell proliferation via a decrease in endogenous cyclin D1 protein levels and arrest at the S phase during cell-cycle progression. Furthermore, YSTE treatment in BPH-1 cells suppressed prostaglandin E2 production and cyclooxygenase-2 (COX-2) protein levels. The secretion of the proinflammatory cytokines, interleukin-8 and interleukin-6, was also reduced by YSTE treatment.ConclusionsYSTE in BPH-1 cells showed antiproliferative and anti-inflammatory activities via cell-cycle arrest and downregulation of COX-2 expression, respectively. Taken together, the results of the present study will enhance our understanding of the mechanisms underlying the effect of YSTE in BPH.

Graphical abstract

http://ift.tt/2u7ZXG5

Anti-inflammatory effect of Cortex Eucommiae via modulation of the Toll-like receptor 4 pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages

Publication date: Available online 3 August 2017
Source:Journal of Ethnopharmacology
Author(s): Wonil Koh, Joon-Shik Shin, Jinho Lee, In-Hee Lee, Sang Kook Lee, In-Hyuk Ha, Hwa-Jin Chung
Ethnopharmocological relevanceCortex Eucommiae (CE), the bark of Eucommia ulmoides Oliv., has been traditionally used for its kidney-tonifying and bone- and tendon-enhancing properties in Korea, China, and Japan. CE has been historically prescribed for inflammatory conditions such as arthritis of the knee and ankle.Aim of the studyAlthough CE has recently been shown to suppress inflammation in scientific studies, whether this effect involves modulation of the toll-like receptor 4 (TLR-4) pathway is currently unknown.Materials and MethodsThe modulatory effect of CE on the TLR-4 pathway, both myeloid differentiation primary response gene 88 (Myd88)-dependent and independent, was investigated through real-time reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, and a reporter gene assay in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages.ResultsCE dose-dependently inhibited nitric oxide production without significant cytotoxicity with an IC50 of 356.23 μg/mL. In addition, CE down-regulated both LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in a dose-dependent manner. CE suppressed LPS-induced activation of nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathways, which together comprise the Myd88-dependent TLR-4 pathway. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also down-regulated by CE in a dose-dependent manner. CE additionally suppressed LPS-induced activation of interferon-β (IFN-β) and signal transducer and activator of transcription (STAT) pathway, which is associated with the Myd88-independent TLR-4 pathway.ConclusionsCE down-regulated both Myd88-dependent and independent TLR-4 pathways, thus exerting anti-inflammatory effects. These results suggest that CE may be used as a potential therapeutic agent against chronic inflammatory diseases.

Graphical abstract

http://ift.tt/2u7zEQt

Ancient Roots – Modern Applications: Mindfulness As A Novel Intervention For Cardiovascular Disease

Publication date: Available online 4 August 2017
Source:Medical Hypotheses
Author(s): Gabriel Zieff
Cardiovascular disease (CVD) has been associated with chronic psychological stress. Unremittent psychological stress causes dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis, which collectively promotes inflammation, atherosclerosis, and subsequent CVD risk. Stress reduction techniques, such as mindfulness meditation, have been shown to improve some markers of HPA and SNS function at rest and in response to acute stressors, suggesting that such techniques, over time, may be cardioprotective. Therefore, it may be hypothesized that eight weeks of daily mindfulness meditation, compared to a non-mindful relaxation control, may provide a novel strategy to buffer stress responses in healthy and at-risk populations, thereby lowering the risk of chronic psychological stress and the associated CVD risk as measured by arterial stiffness. The current paper outlines methodological considerations for testing this hypothesis, including appropriate acute stressors, and measurement of SNS, HPA axis and cardiovascular function. If the hypothesis is correct, mindfulness meditation would complement healthy lifestyle techniques such as exercise and diet to prevent CVD risk.



http://ift.tt/2feWSl1