No abstract available
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Τετάρτη 26 Ιουλίου 2017
Nutritional Deficiency-Related Oral and Cutaneous Lesions in an Obese Patient.
The cutaneous and oral lesions related to nutritional deficiencies are scarcely reported. Micronutrient deficiencies may significantly affect mouth mucosa and skin, causing great morbidity. We report an extraordinary case with detailed clinical and microscopic findings affecting the oral cavity and skin. Physicians must be familiar with these manifestations to suspect the diagnosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2vLteru
Rapid Number Naming and Quantitative Eye Movements May Reflect Contact Sport Exposure in a Collegiate Ice Hockey Cohort.
Detecting masses in dense breast using independent component analysis
Source:Artificial Intelligence in Medicine
Author(s): Luis Claudio de Oliveira Silva, Allan Kardec Barros, Marcus Vinicius Lopes
Breast cancer is the second type of cancer that most affects women in the world, losing only for non-melanoma skin cancer. Breast density can hinder the location of masses, especially in early stages. In this work, the use of independent component analysis for detecting lesions in dense breasts is proposed. Several works suggest the use of computer aided diagnosis (CAD), increasing sensitivity to over 90% in detecting cancer in nondense breasts, however there are few published studies about detecting in dense breasts. To analyse its efficiency in relation to other segmentation techniques, we compare the performance with principal component analysis. To measure the quality of the segmentation obtained by the two methods, an area overlay measure will be used. To verify if there was any difference between the results of the proposed methods in the detection of lesions in nondense breasts and in dense breasts, a statistic test for two proportions was used. Experimental results on the Mini-MIAS and DDSM database showed an accuracy of 92.71% in detecting masses in nondense and 79.17% in dense breasts. All experiments showed that the ICA filters have a better performance for detect lesions in dense breast, compared with PCA. Contrary to previous works, our experiments showed that there is actually a significant difference between the detection of masses in dense and nondense breasts. This study can help specialist to detect lesions in dense breast.
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NO to NO2 conversion rate analysis and implications for dispersion model chemistry methods using Las Vegas, Nevada near-road field measurements
Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Sue Kimbrough, R. Chris Owen, Michelle Snyder, Jennifer Richmond-Bryant
The nitrogen dioxide/oxides of nitrogen (NO2/NOX) ratio is an important surrogate for NO to NO2 chemistry in dispersion models when estimating NOX impacts in a near-road environment. Existing dispersion models use different techniques and assumptions to represent NO to NO2 conversion and do not fully characterize all of the important atmospheric chemical and mechanical processes. Thus, "real-world" ambient measurements must be analyzed to assess the behavior of NO2/NOX ratios near roadways. An examination of NO2/NOX ratio data from a field study conducted in Las Vegas, Nevada (NV), from mid-December, 2008 through mid-December, 2009 provides insights into the appropriateness of assumptions about the NO2/NOX ratio included in dispersion models. Data analysis indicates multiple factors affect the downwind NO2/NOX ratio. These include spatial gradient, background ozone (O3), source emissions of NO and NO2, and background NO2/NOX ratio. Analysis of the NO2/NOX ratio spatial gradient indicates that under high O3 conditions, the change in the ratio is fairly constant once a certain O3 threshold (≥30 ppb) is reached. However, under low O3 conditions (<30 ppb), there are differences between weekdays and weekends, most likely due to a decline in O3 concentrations during the weekday morning hours, reducing the O3 available to titrate the emitted NO, allowing lower NO2/NOX ratios. These results suggest that under high O3 conditions, NOX chemistry is driving the NO2/NOX ratios whereas under low O3 conditions, atmospheric mixing is the driving factor.
Graphical abstract
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The role of the Mt. Merapi eruption in the 2011 Arctic ozone depletion
Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): V.V. Zuev, N.E. Zueva, E.S. Savelieva
One of the strongest ozone depletion events in the Arctic stratosphere was observed in March 2011 due to the strengthening of the polar vortex in February 2011. Earlier, in November 2010, the eruption of Mt. Merapi volcano (Java, Indonesia) with a maximum plume altitude of 18.3 km was recorded. The effect of aerosol heating in the tropical lower stratosphere after the Mt. Merapi eruption on the Arctic polar vortex strengthening in winter–spring 2011 is examined. Based on the ERA-Interim reanalysis temperature data, we show that significant aerosol heating in the lower tropical stratosphere was observed in February–March 2011 and could lead to an increase in the stratospheric equator-to-pole temperature gradient resulting in an enhanced Arctic polar vortex. We also analyze the correlation between large tropical volcanic eruptions occurring in autumn–winter periods and Arctic ozone depletion events observed in the following winter–spring periods.
http://ift.tt/2uZH241
Primary and secondary particulate matter intake fraction from different height emission sources
Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Fatema Parvez, Carmen Lamancusa, Kristina Wagstrom
This study uses intake fraction, the fraction of emissions that are inhaled, to compare potential particulate matter exposure among different height emission sources. We use the Particulate Matter Source Apportionment Technology (PSAT) in the Comprehensive Air Quality Model with Extensions (CAMx) to estimate intake fraction for primary and secondary particulate matter species from different height emission sources. We develop an approach to quantify intake fraction for both primary and secondary particulate matter species emitted from all types of emission sources in the contiguous United States. To compute intake fraction for secondary particulate matter species, we consider the inhalation of the precursor gas and condensed species based on the common atomic unit between the emitted gas and particulate matter product. Our calculated intake fraction varies from 1.0 to 4.9 per million for primary particulate matter, 0.4 to almost 6.0 per million for secondary species, including inhalation of both particulate matter and the relevant precursor species. Intake fraction is consistently higher in the winter than the summer for all species from all emission heights. The shortest height sources, which include area sources, display intake fractions over an order of magnitude greater than more elevated sources.
Graphical abstract
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Experimental and theoretical investigations of the kinetics and mechanism of the Cl + 4-hydroxy-4-methyl-2-pentanone reaction
Source:Atmospheric Environment, Volume 166
Author(s): L. Aslan, A. Mano Priya, C. Sleiman, M.N. Zeineddine, P. Coddeville, C. Fittschen, B. Ballesteros, A. Canosa, L. Senthilkumar, G. El Dib, A. Tomas
The reaction of 4-hydroxy-4-methyl-2-pentanone (4H4M2P) with Cl atoms was studied for the first time experimentally and theoretically. Relative kinetic measurements were carried out at room temperature and 1 bar of synthetic air/N2 in two different environmental chambers: a 300 L Teflon bag and a 16 L borosilicate glass cell. Reactants, reference compounds and products were monitored either by IR absorption or by GC-FID. Theoretical calculations were performed using the density functional theory method at BH&HLYP level of theory for twelve hydrogen abstraction pathways. The individual rate coefficients for the most favorable H-abstraction pathways were calculated by canonical variational theory using small curvature tunneling method at 298 K. An average experimental rate coefficient of (7.4 ± 0.6) × 10−11 cm3 molecule−1 s−1 was obtained at 298 K, in good agreement with the theoretical rate coefficient. The branching ratios for each reaction channel were evaluated theoretically from the individual rate coefficients of the identified channels. The H-atom abstracted on the –CH2 group appeared to be the dominant channel with a small barrier height. Formaldehyde, acetic acid, HCl, CO2 and CO were identified by IR as the major primary products. The obtained results are presented and discussed in terms of structure-reactivity relationships. A mechanism is suggested for the formation of the observed products. The atmospheric implications of the studied reaction are presented and more particularly, the lifetime of 4H4M2P towards Cl atoms is evaluated to be about 3 days.
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Editorial board
Source:Atmospheric Environment, Volume 165
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In vitro fermentation of beta-glucans and other selected carbohydrates by infant fecal inoculum: An evaluation of their potential as prebiotics in infant formula
Publication date: Available online 27 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Ka-Lung Lam, Hoi-Yee Keung, Kin-Chun Ko, Hoi-Shan Kwan, Peter Chi-Keung Cheung
Prebiotics are being added to infant formula in order to mimic the effects of human milk oligosaccharides (HMOs) for the growth of probiotic bacteria especially bifidobacteria and lactobacilli in the infant gut. This preliminary study compares the in vitro fermentation of 13 different carbohydrates including monosaccharides, disaccharides, oligosaccharides and polysaccharides by infant fecal samples collected from 3-month old breast-milk fed babies. The growth of the total anaerobic bacteria and two probiotic bacteria (bifidobacteria and lactobacilli) during the fermentation period was measured by total plate count (TPC) and was expressed as colony forming units (CFUs). Among other things, beta-glucans seem to selectively enhance the growth of lactobacilli for a longer period of fermentation time than most of the carbohydrates tested. The selective enrichment of the probiotic bacteria by these carbohydrates and their potential use as prebiotics in the infant formula are discussed.
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Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells
Publication date: Available online 26 July 2017
Source:Pathology - Research and Practice
Author(s): Hong-Bing Zhao, Xi-Feng Zhang, Xue-Lin Jia, Hong-Bin Wang
Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy.
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Oral bexarotene for post-transplant cutaneous T-cell lymphoma
Abstract
Organ transplant recipients receiving immunosuppression have an increased risk of developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post-transplant T-cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after liver transplantation. The patient was diagnosed with stage IB mycosis fungoides (MF). His lesions were refractory to multiple skin-directed therapies, and so he was given oral bexarotene 150 mg daily and his oral tacrolimus dose was decreased to 2 mg daily. Remarkably, his MF patches have demonstrated a complete response to oral bexarotene 75 mg daily without recurrence over 11 years of follow-up. He developed hypertriglyceridemia with bexarotene 150 mg, so his dose was decreased to 75 mg, without loss of response. Our report is the second to describe PT-CTCL demonstrating a long-term complete response to oral bexarotene. Given its anti-carcinogenic properties and favorable toxicity profile, oral bexarotene represents an appealing treatment option for PT-CTCL refractory to skin-directed therapies.
http://ift.tt/2uDWkJj
Particulate matter (PM's) adheres to human hair exposed to severe aerial pollution: Consequences for certain hair surface properties
Abstract
Background
The deposit and adherence of particulate matter (PM's) from aerial pollution onto the surface of human hair is a poorly studied phenomenon.
Objectives
i) To reproduce in vitro the deposit of known PM's on standardized hair swatches in a closed box, ii) to compare in vitro data with those obtained under "real life" conditions of severe aerial pollution, iii) to assess the changes of the hair surface properties, potentially caused by the adherence of airborne PM's onto the hair.
Methods
In vitro: a PM was sprayed onto untreated or sebum-coated hair swatches.
Real life conditions: other swatches were exposed to a severely polluted environment, for 24 to 72 hours, in Baoding (PR China). In both cases, swatches were examined using Scanning Electron Microscopy. The shine, the frictional properties and the level of metals were measured and compared to those same properties for the unexposed swatches.
Results
The present work clearly indicates that, under real life conditions, a large number of PM's of various sizes are deposited onto the hair surface. This phenomenon is increased by the presence of sebum and longer exposure times. The in vitro level of PMs deposited onto the hair surface is comparable to the in vivo level. The presence of sebum seems to favour the deposit of larger PM's. The shine of the exposed swatches is significantly decreased, whereas their respective friction coefficients are significantly increased. Both the presence of sebum and length of exposure time increased the amount of analysed metals present on the exposed hair surface (Al, Fe, Cu, Ba, Zn).
Conclusion
This work indicates that a very high amount (e.g. billions) of PM's can be deposited on a full head of hair for subjects living in a severely aerially polluted environment. This process can be reproduced in vitro. In real life, pollution has a strong impact on hair surface properties, leading to a modification of the visual aspect (loss of shine) and the alteration of hair surface (increase of friction force). This work may be used to pave the way for prevention and cleansing studies in the field of hair care.
This article is protected by copyright. All rights reserved.
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Hepatoprotective effect of Opuntia microdasys (Lehm.) Pfeiff flowers against diabetes type II induced in rats
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Hassiba Chahdoura, Khawla Adouni, Aida Khlifi, Ichrak Dridi, Zohra Haouas, Fadoua Neffati, Guido Flamini, Habib Mosbah, Lotfi Achour
Opuntia sp. has long been used as a folk medicine to treat hepatitis and diabetes in Sicile (Italy). To extract the polyphenols from the flower of Opuntia microdasys Lehm. at post flowring stage and evaluate the antidiabetic activity in vitro and in vivo. The hepatoprotective activity of Opuntia microdasys aqueous flowers extract at post flowering stage (OFP) has been tested for their antidiabetic activity. On fructose-alloxan induced diabete in rat model, evaluating the inhibitory effects of OFP on some carbohydrate metabolizing enzymes, pancreatic α-amylase and intestinal α-glucosidase activities in vitro. The OFP extract showed inhibitory activity against α-glucosidase (IC50=0.17±0.012mg/ml) and α-amylase (IC50=2.55±0.41mg/ml). The inhibitory potential of OFP extract on these enzymes suggests a positive and probable role of this extract in the management and treatment of diabetes mellitus, particularly, for type 2. Oral administration of the OFP at 200mg/kg to diabetic male rats for 28days demonstrated a significant protective effect by lowering the levels of glucose (123.21±1.38mg/dL) and hepatic marker enzymes (AST, ALT, LDH, γ-GT, BT, PAL, TC, LDL-C, HDL-C and TG). OFP attenuated oxidative stress by decreasing the SOD, CAT, GPX activity and the levels of PC and MDA in the liver and restored the histological architecture of the rat liver. OFP has protective effects on the protection of liver, thereby reducing some of the causes of diabetes in experimental animals.
http://ift.tt/2tFdG78
Flavonoids from Carya cathayensis Sarg. leaves inhibit carotid artery lesion formation induced by low blood flow
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Jin Bo, Ding Zhishan
The aim of the present study was to investigate the protective effect of the total flavonoids (TFs) from the leaves of Carya cathayensis Sarg. against early development of atherosclerosis. An in vivo model of carotid arterial partial ligation was established in mice, and the effects of TFs were investigated by morphometric measurements, Cell proliferation measurement and immunohistochemistry. The results showed that TFs could reduce neointima area by 41%, and the adventitial thickening induced by partial ligation was remarkable inhibited by TFs treatment. medial SMCs proliferation was significantly inhibited in TFs treated group. Immunohistochemistry analyses demonstrated that mice with TFs treatment have significant less macrophages accumulation in adventitia. These findings indicated that TFs have inhibitory effect in early atherosclerosis lesion formation model and strong action on reduce the inflammation in vivo.
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Functional Independence Measure - Minimum Data Set Motor Item Bank: Short Forms Development and Precision Comparison in Veterans
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chih-Ying Li, Sergio Romero, Annie N. Simpson, Heather S. Bonilha, Kit N. Simpson, Ickpyo Hong, Craig A. Velozo
ObjectiveTo improve the practical use of the short forms (SFs) developed from the item bank, we compared the measurement precision of the 4- and 8-item SFs generated from a motor item bank composed of the Functional Independence Measure (FIM™) and the Minimum Data Set (MDS).DesignThe FIM-MDS motor item bank allowed scores generated from different instruments to be co-calibrated. The 4- and 8-item SFs were developed based on Rasch analysis procedures. This paper compared person strata, ceiling/floor effects, test standard error (SE) plots for each administration form and examined 95% confidence interval (CI) error bands of anchored person measures with the corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level of 0.90.SettingVeterans' inpatient rehabilitation facilities and community living centers.Participants2500 Veterans who had both FIM and the MDS data within 6 days during years 2008 through 2010.InterventionsNAMain Outcome Measure(s)4- and 8-item SFs of FIM, MDS and FIM-MDS motor item bank.ResultsSix SFs were generated with 4- and 8-items across a range of difficulty levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher correlations with the item bank (r=0.82∼0.95), higher person strata and less test error than the corresponding 4-item SFs (r=0.80∼ 0.90). The three 4-item SFs did not meet the criteria of SE less than 0.3 for any theta values.Conclusions8-item short forms could improve clinical use of item bank composed of existing instruments across the continuum of care in Veterans. We also found number of items, not test specificity, determines the precision of the instrument.
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Do trials of resistance training to improve mobility after stroke adhere to the American College of Sports Medicine guidelines? A systematic review
Publication date: Available online 26 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Genevieve Hendrey, Anne E. Holland, Benjamin F. Mentiplay, Ross Clark, Gavin Williams
ObjectiveTo determine whether resistance training to improve mobility outcomes after stroke adhere to the ACSM guidelines, and whether adherence was associated with better outcomes.Data sourcesOnline databases searched from 1975 to 30 October 2016.Study SelectionRandomized controlled trials examining the effectiveness of lower limb strength training on mobility outcomes in adult stroke participants.Data Extraction and AnalysisTwo independent reviewers completed data extraction. Quality of trials was determined using the Cochrane Risk of Bias Tool. Trials were scored based on their protocol's adherence to eight ACSM recommendations. To determine if a relationship existed between total adherence score and effect size, Spearman's rho (rs) was calculated and between individual recommendations and effect size, Mann Whitney U or Kruskal Wallis tests were used.ResultsThirty-nine trials met the inclusion criteria and 34 were scored on their adherence to the guidelines. Adherence was high for frequency of training (100% of studies) but few trials adhered to the guidelines for intensity (32%), specificity (24%), and training pattern (3%). Based on the small number of studies that could be included in pooled analysis (n = 12), there was no relationship between overall adherence and effect size (rs = -0.39, p = 0.21).ConclusionsAdherence to the ACSM guidelines for resistance training following stroke varied widely. Future trials should ensure strength training protocols adhere more closely to the guidelines, to ensure their effectiveness in stroke can be accurately determined.
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Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic and periodontal bacterial species?
Source:Dental Materials
Author(s): Suping Wang, Haohao Wang, Biao Ren, Hao Li, Michael D. Weir, Xuedong Zhou, Thomas W. Oates, Lei Cheng, Hockin H.K. Xu
ObjectivesAntibacterial monomers were developed to combat oral biofilm acids and caries; however, little is known on whether quaternary ammonium monomers (QAMs) would induce drug resistance in oral bacteria. The objective of this study was to investigate the effects of new antimicrobial monomers dimethylaminohexadecyl methacrylate (DMAHDM) and dimethylaminododecyl methacrylate (DMADDM) on the induction of drug resistance in eight species of cariogenic, endodontic and periodontal bacteria for the first time.MethodsStreptococcus mutans (S. mutans), Streptococcus sanguis, Streptococcus gordonii, Enterococcus faecalis (E. faecalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), Porphyromonas gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) were tested. Minimum inhibitory concentration (MIC) was assessed using chlorhexidine (CHX) as control. Minimal bactericidal concentration (MBC), bacterial growth and membrane permeability properties were also investigated.ResultsCHX induced drug resistance in four species. DMAHDM did not induce any resistance. DMADDM induced drug resistance in only one benign species S. gordonii. The DMADDM-resistant and CHX-resistant S. gordonii had the same MIC and MBC values as S. gordonii parental strain against DMAHDM (p>0.1), hence DMAHDM effectively inhibited the resistant strains. The resistant strains had slower growth metabolism than parental strain.SignificanceDMAHDM induced no drug resistance, and DMADDM had much less drug resistance than the commonly-used CHX in the eight common oral species. With its potent antimicrobial functions shown previously, the new DMAHDM is promising for applications in restorative, preventive, periodontal and endodontic treatments to combat cariogenic and pathological bacteria with no drug resistance in all tested species.
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Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70
Source:DNA Repair
Author(s): Mengtan Xing, Magnar Bjørås, Jeremy A. Daniel, Frederick W. Alt, Valentyn Oksenych
DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3. Genetic inactivation of C-NHEJ factors, such as Ku70, Ku80, XLF, PAXX and DNA-PKcs results in viable mice showing increased levels of genomic instability and sensitivity to DSBs. Knockouts of XRCC4 or Lig4, on the other hand, as well as combined inactivation of XLF and DNA-PKcs, or XLF and PAXX, result in late embryonic lethality in mice, which in most cases correlate with severe apoptosis in the central nervous system. Here, we demonstrate that inactivation of the Ku70 gene rescues the synthetic lethality between XLF and DNA-PKcs, resulting in triple knockout mice that are indistinguishable from Ku70-deficient littermates by size or levels of genomic instability. Moreover, we find that combined inactivation of Ku70 and XLF results in viable mice. Together, these findings suggest that Ku70 is epistatic with XLF and DNA-PKcs and support a model in which inactivation of Ku70 allows DNA lesions to become accessible to alternative DNA repair pathways.
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Comparing manipulation with and without Kinesio Taping® in the treatment of chronic low back pain
Publication date: Available online 26 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Fahimeh Kamali, Ehsan Sinaei, Elham Taherkhani
ObjectivesChronic non-specific low back pain (CNLBP) is a prevalent problem among athletes that can cause long-lasting disability and time lost from sporting activities. Thus far, a variety of methods have been suggested to address this problem, including spinal manipulation (SM) and Kinesio Tape® (KT). The aim of this study was to investigate whether adding KT to SM can provide any extra effect in athletes with CNLBP or not.MethodForty-two athletes (21males, 21females) with CNLBP were randomized into two groups of SM (n = 21) and SM plus KT (n = 21). Pain intensity, functional disability level and trunk flexor-extensor muscles endurance were assessed by Numerical Rating Scale (NRS), Oswestry pain and disability index (ODI), McQuade test, and unsupported trunk holding test, respectively. The tests were done before and immediately, one day, one week, and one month after the interventions and compared between the two groups.ResultsAfter treatments, pain intensity and disability level decreased and endurance of trunk flexor-extensor muscles increased significantly in both groups. Repeated measures analysis, however, showed that there was no significant difference between the groups in any of the evaluations.ConclusionsThe findings of the present study showed that adding KT to SM does not appear to have a significant extra effect on pain, disability and muscle endurance in athletes with CNLBP. However, more studies are needed to examine the therapeutic effects of KT in treating these patients.Clinical trial registry number (irct.ir)IRCT2016020624149N5.
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Simultaneous inhibition of growth and metastasis of hepatocellular carcinoma by co-delivery of ursolic acid and sorafenib using lactobionic acid modified and pH-sensitive chitosan-conjugated mesoporous silica nanocomplex
Source:Biomaterials, Volume 143
Author(s): Ruirui Zhao, Tao Li, Guirong Zheng, Kai Jiang, Lulu Fan, Jingwei Shao
Co-delivery multiple drugs using nanocarriers has been recognized as a promising strategy for cancer treatment to enhance therapeutic efficacy. In this study, a pH sensitive mesoporous silica nanoparticles (MSN) based controlled release nanoparticles for co-delivery of sorafenib (SO), a multi-tyrosine kinase inhibitor, and ursolic acid (UA), a sensitive agent for SO, was developed, which was decorated with pH sensitive chitosan (CS) and lactobionic acid (LA) targeting to asialoglycoprotein receptor (ASGPR) over-expressing hepatocellar carcinoma cells (denoted as USMNs-CL). The nanocomplex enhanced bioavailability of hydrophobic drugs, efficient tumor cell targeting and exhibited pH-responsive function and sustained release profile. USMNs-CL showed synergistic cytotoxicity and could attenuate the adhesion, migration of ASGPR over-expressing liver cancer SMMC-7721 cells at non-toxic concentrations. Moreover, the complex nanoparticles significantly increased the cellular apoptosis and down-regulated the expression of EGFR and VEGFR2 proteins related with cell proliferation and tumor angiogenesis. In vivo, compared with UA or SO alone, the nanocomplex significantly reduced the tumor burden in hepatocellular carcinoma (HCC) H22 tumor-bearing mice model and inhibited the lung metastasis in the H22 lung metastasis models. Overall, co-delivery of UA and SO by MSN-CS-LA nanocarriers could provide a promising strategy for HCC combinational therapy, especially for the HCC metastasis chemoprevention.
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Pharmaceuticals released from senior residences: occurrence and risk evaluation
Abstract
One of the main pursuits, yet most difficult, in monitoring studies is to identify the sources of environmental pollution. In this study, we have identified health-care facilities from south European countries as an important source of pharmaceuticals in the environment. We have estimated that compounds consumed in by the elderly and released from effluents of senior residences can reach river waters at a concentration higher than 0.01 μg/L, which is the European Medicines Agency (EMA) threshold for risk evaluation of pharmaceuticals in surface waters. This study has been based on five health institutions in Portugal, Spain, and France, with 52 to 130 beds. We have compiled the pharmaceuticals dispensed on a daily base and calculated the consumption rates. From 54.9 to 1801 g of pharmaceuticals are consumed daily, with laxatives, analgesics, antiepileptics, antibiotics, and antidiabetic agents being the main drug families administered. According to excretion rates, dilution in the sewerage system, and elimination in wastewater treatment plants, macrogol, metformin, paracetamol, acetylcysteine, amoxicillin, and gabapentin, among others, are expected to reach river waters. Finally, we discuss the risk management actions related to the discharge of pharmaceuticals from senior residences to surface waters.
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Ozone risk assessment in three oak species as affected by soil water availability
Abstract
To derive ozone (O3) dose-response relationships for three European oak species (Quercus ilex, Quercus pubescens, and Quercus robur) under a range of soil water availability, an experiment was carried out with 2-year-old potted seedlings exposed to three levels of water availability in the soil and three levels of O3 pollution for one growing season in an ozone free-air controlled exposure (FACE) facility. Total biomass losses were estimated relative to a hypothetical clean air at the pre-industrial age, i.e., at 10 ppb as daily average (M24). A stomatal conductance model was parameterized with inputs from the three species for calculating the stomatal O3 flux. Exposure-based (M24, W126, and AOT40) and flux-based (phytotoxic O3 dose (POD)0–3) dose-response relationships were estimated and critical levels (CL) were calculated for a 5% decline of total biomass. Results show that water availability can significantly affect O3 risk assessment. In fact, dose-response relationships calculated per individual species at each water availability level resulted in very different CLs and best metrics. In a simplified approach where species were aggregated on the basis of their O3 sensitivity, the best metric was POD0.5, with a CL of 6.8 mmol m−2 for the less O3-sensitive species Q. ilex and Q. pubescens and of 3.5 mmol m−2 for the more O3-sensitive species Q. robur. The performance of POD0, however, was very similar to that of POD0.5, and thus a CL of 6.9 mmol m−2 POD0 and 3.6 mmol m−2 POD0 for the less and more O3-sensitive oak species may be also recommended. These CLs can be applied to oak ecosystems at variable water availability in the soil. We conclude that PODy is able to reconcile the effects of O3 and soil water availability on species-specific oak productivity.
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Examination of pathways involved in leukemia inhibitory factor (LIF)-induced cell growth arrest using label-free proteomics approach
Publication date: Available online 26 July 2017
Source:Journal of Proteomics
Author(s): Syed Azmal Ali, Gurjeet Kaur, Ashok Kumar Mohanty, Sudarshan Kumar
Leukemia inhibitory factor (LIF) is a multifunctional highly glycosylated protein, synthesized and secreted in various body tissues. Besides the abundance in multiple organs, the molecular mechanism underlying the LIF interactions for cell survival and polarity is poorly understood. In the present study, high-resolution LC-MS/MS based LFQ approach identified 2083 proteins with the overall PSM as 16,032. This proteomics data reviles that LIF promotes the AKT-mTOR signaling pathway. It induces cell growth arrest by an intracellular pathways loop to increase the half-life of the cell. Bioinformatics-based enrichment analysis revealed the involvement of LIF interacting partners in cell survival through increasing the cell cycle length. The anti-proliferative effect of LIF was confirmed by BrdU, MTT and Caspase 3/7 assays and further validated by RT-qPCR. Till date to the best of our knowledge, this is the first study that elucidates LIF-mediated cascade of activation of MEK/ERK, Ras, mTOR, Hippo, and RAP1 pathways. This study further expands the repertoire of signaling pathways known to be subject to activation by LIF. These multiple involvements of pathways through autocrine-paracrine mediated cell cycle arrest additionally suggests a novel means for amplification of a growth arrest stimulus from LIF and its homolog's receptors.Biological significanceLeukemia inhibitory factor (LIF) is the polyfunctional cytokine and highly pleiotropic member of the interleukin-6 family. It utilizes a receptor that consists of the LIF receptor b and gp130 and displays diverse effects on target cells. Despite well-known signal transduction mechanisms (JAK/STAT, MAPK, and PI3K) LIF also contains paradoxically opposing influences in several cell types which includes cellular stimulation, inhibition, proliferation, differentiation, and survival. LIF1 is also undergoing clinical trials as a driving force for the embryo implantation in the uterus in women who fail to become pregnant. As LIF can act on the broad spectrum of cell types, it is necessary to understand the basic response mechanism. The available non-canonical regulatory pathways and molecular mechanism associated with LIF are poorly explained. Therefore, we have performed the global proteome analysis of LIF-mediated autocrine-paracrine signaling. The obtained data were examined through advanced bioinformatics tools and LIF inducible changes in terms of pathways were elucidated. The result showed the involvement of cluster of proteins maintaining the Ras/Rap1/STAT3/Hippo pathways which modify the protein component machinery of core histone complexes. This report describes the involvement of proteins responsible for cell growth and progression and defines the LIF-mediated novel autocrine-paracrine signaling loop for cell growth arrest.
Graphical abstract
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iTRAQ proteomic analysis of the interactions between Bombyx mori nuclear polyhedrosis virus and silkworm
Publication date: Available online 26 July 2017
Source:Journal of Proteomics
Author(s): Wei-tao Dong, Long-fei Xiao, Jun-jie Hu, Xin-xu Zhao, Ji-xing Liu, Yong Zhang
The silkworm hemolymph is an important defense system against bacteria and viruses. In this study, silkworms were infected with Bombyx mori nuclear polyhedrosis virus to investigate the subsequent immune response at the protein level. Proteomes were analyzed before and after infection using isobaric tags for relative and absolute quantitation and LC-MS. A total of 456 differentially expressed proteins were identified, of which 179 were upregulated and 193 were downregulated. Changes in expression were validated by western blot for several proteins. Eleven of the differentially expressed proteins were involved in immunity. For example, modular serine protease and cecropin, which were downregulated, facilitate Toll and Imd signaling, while autophagy-related protein 3, which was upregulated, protects cells against oxidative damage. Collectively, the data highlight the unique interactions of baculovirus with the silkworm immune system.Biological significanceThis is the first time isobaric tags for relative and absolute quantitation were used to analyze B. mori proteins mobilized against B. mori nuclear polyhedrosis virus, and to investigate the immunity-associated proteome in B. mori. The results are a significant step towards a deeper understanding of immunoregulation in B. mori.SignificanceThis is the first time isobaric tags for relative and absolute quantitation were used to analyze B. mori proteins mobilized against B. mori nuclear polyhedrosis virus, and to investigate the immunity-associated proteome in B. mori. The results are a significant step towards a deeper understanding of immunoregulation in B. mori.
Graphical abstract
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Comparative proteomics of matrix fractions between pimpled and normal chicken eggshells
Publication date: Available online 26 July 2017
Source:Journal of Proteomics
Author(s): Zhangguo Liu, Lingzi Song, Lizhi Lu, Xianfu Zhang, Fuming Zhang, Kehua Wang, Robert J. Linhardt
Eggshell matrix can be dissociated into three matrix fractions: acid-insoluble matrix (M1), water-insoluble matrix (M2) and acid-water facultative-soluble matrix (M3). Matrix fractions from pimpled and normal eggshells were compared using label-free proteomic method to understand the differences among three matrix fractions and the proteins involved with eggshell quality. A total of 738 and 600 proteins were identified in the pimpled and normal calcified eggshells, respectively. Both eggshells showed a combined proteomic inventory of 769 proteins. In the same type of eggshell, a high similarity was present in the proteomes of three matrix fractions. These triply overlapped common proteins formed the predominant contributor to proteomic abundance in the matrix fractions. In each matrix fraction and between both eggshell models, normal and pimpled eggshells, a majority of the proteomes of the fractions were commonly observed. Forty-two common major proteins (iBAQ-derived abundance ≥0.095% of proteomic abundance) were identified throughout the three matrix fractions and these proteins might act as backbone constituents in chicken eggshell matrix. Finally, using 1.75-fold as up-regulated and using 0.57-fold as down-regulated cutoff values, twenty-five differential major proteins were screened and they all negatively influence and none showed any effect on eggshell quality. Overall, we uncovered the characteristics of proteomics of three eggshell matrix fractions and identified candidate proteins influencing eggshell quality. The next research on differential proteins will uncover the potential mechanisms underlying how proteins affect eggshell quality.Biological significanceIt was reported that the proteins in an eggshell can be divided into insoluble and soluble proteins. The insoluble proteins are thought to be an inter-mineral matrix and acts as a structural framework, while the soluble proteins are thought as intra-mineral matrix that are embedded within the crystal during calcification. However, the difference between matrix fractions is unknown. Cross-analysis of proteomic data of three matrix fractions from the same type of eggshell, uncovered triply overlapped common proteins formed the predominant contributor to proteomic abundance of any matrix fraction, and we suggested that abundance variance of some common proteins between the three matrix fractions might be an important cause of their solubility differences. Moreover, eggshell is formed in hen's uterus, and uterus tend to be considered as unique organ determining eggshell quality. By cross-analysis on proteomic data of three matrix fractions between two eggshell models, normal and pimpled eggshells, the differential proteins were screened as candidates influencing eggshell quality. And we suggested that the liver and spleen or lymphocytes might be the major organs influencing eggshell quality, because the most promising candidates are almost blood and non-collagenous proteins, and originated from above organs.
Graphical abstract
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Autistic traits and internet gaming addiction in Chinese children: The mediating effect of emotion regulation and school connectedness
Source:Research in Developmental Disabilities, Volume 68
Author(s): Sha Liu, Chengfu Yu, Bradley T. Conner, Suiping Wang, Weiping Lai, Wei Zhang
This report details an 18-month longitudinal study designed to investigate the influence of autistic traits' on internet gaming addiction (IGA) in children. A total of 420 Chinese children (220 boys, Mean age=9.74±0.45) participated in the research. Autistic traits were measured in the 4th grade and emotion regulation, school connectedness and IGA measured in both the 4th and 5th grades. After controlling for age, sex, and sensation seeking, results showed that autistic traits were related to decreased emotion regulation, which in turn was related to lower school connectedness, which was related to increased IGA. The results suggest that improving emotion regulation and school connectedness could reduce the risk of IGA. As a result, these findings may inform intervention and prevention programs targeting children with IGA, especially among those with high levels of autistic traits.
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Ketamine changes the local resting-state functional properties of anesthetized-monkey brain
Source:Magnetic Resonance Imaging
Author(s): Jia-Sheng Rao, Zuxiang Liu, Can Zhao, Rui-Han Wei, Wen Zhao, Peng-Yu Tian, Xia Zhou, Zhao-Yang Yang, Xiao-Guang Li
ObjectiveKetamine is a well-known anesthetic. 'Recreational' use of ketamine always induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties.MethodsWe used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions.ResultsResults showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05).ConclusionsThese findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status.
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Fast acceleration of ASL-based time-resolved magnetic resonance angiography by acquisition of control and labeled images in the same shot (fast ACTRESS): An optimization study
Source:Magnetic Resonance Imaging
Author(s): Hiroyuki Sugimori, Noriyuki Fujima, Yuriko Suzuki, Hiroyuki Hamaguchi, Kinya Ishizaka, Kohsuke Kudo
PurposeTo establish an optimized sequence design for fast acceleration of arterial spin labeling (ASL)-based time-resolved magnetic resonance angiography (MRA) by acquisition of control and labeled images in the same shot (fast ACTRESS) and a scan time of <1min, for the evaluation of intracranial vessels.Materials and methodsTen healthy volunteers with no unilateral symptomatic arterial stenosis, who underwent 3-tesla MRI, were investigated. Imaging parameters for the fast ACTRESS sequence were set with an acquisition time of 45s. During post-processing, the first phase in the multi-phase readout, which was defined as the control image, was subtracted from each of the other phases. Thus, four-dimensional (4D)-MRA images of each phase were obtained. The maximum intensity projection was used for the reconstruction of 4D-MRA images and time-to-signal intensity curves (TIC) obtained for each vessel. The area under the curve (AUC), peak time, and maximum signal intensity were obtained from TIC. The different labeling types were broadly divided into six groups: L1, L2, L3, L4, L5, and L6 according to the actual number of labeling pulse.ResultsA total of 5040 regions of interest were evaluated. The peak SI of L3, except for those in the A2 segment of the anterior cerebral artery, was significantly higher than that of L5. However, there were no significant differences between L4 and L5. Although the AUCs of L3 and L4 for anterior circulation were relatively higher than that of the other subgroups, the AUC of L3 was significantly higher than that of L4.ConclusionThe fast ACTRESS was optimized and indicated that the labeling type of L3 was the most appropriate for the well visualization of intracranial arteries. The fast ACTRESS sequence was useful to acquire well-delineated images of intracranial vessels in ˂1min.
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Paediatric Dermatofibrosarcoma Protuberans (DFSP): Evaluation of a Rare Childhood Malignancy, the Welsh Experience
A letter to author regarding paediatric DFSP.
http://ift.tt/2h4mH7T
Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients
Abstract
Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2 months (95% CI [12.1–58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5). Median overall survival was 7.5 years (95% CI [4–NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.
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Jugulodigastric lymph node size by age on CT in an adult cancer-free population
Publication date: Available online 26 July 2017
Source:Clinical Imaging
Author(s): Leticia M.B. Costa e Silva Souza, Katherine J. Leung, Anne O'Neill, Jagadeesan Jayender, Thomas C. Lee
PurposeEvaluate jugulodigastric node size in cancer-free patients.MethodsRetrospective review of 234 neck CT angiograms was performed. Known neoplasm, inflammation or poor imaging were excluded. Maximal diameter of the largest jugulodigastric node in the axial plane bilaterally was measured.Results172 patients (median age=62) were included. Jugulodigastric node size decreased with age and was statistically significant between those above and below 62years. Patients 20–30years had mean 14.4mm (7.5–20.1mm).ConclusionsAlthough 15mm is considered the normal maximum long-axis size of the jugulodigastric node in cancer patients, average size in younger cancer-free patients is commonly above 15mm.
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Complex liver cysts in Autosomal Dominant Polycystic Kidney Disease
Publication date: Available online 25 July 2017
Source:Clinical Imaging
Author(s): Zerwa Farooq, Ashkan Heshmatzadeh Behzadi, Jon D. Blumenfeld, Yize Zhao, Martin R. Prince
PurposeTo determine prevalence of complex liver cysts in Autosomal Dominant Polycystic Kidney Disease (ADPKD).MethodsAbdominal MRI in 186 ADPKD subjects were evaluated by two independent observers to determine prevalence of complex liver cysts.Results23 (12%) of subjects, had at least 1 complex cyst. Only 8 (4%) were reported to have a complex cyst prospectively, representing an under-reporting rate of 65%. Median total cyst volume was 66-times greater for subjects with complex cysts compared to subjects without (p<0.0001).ConclusionComplex hepatic cysts were observed in 12% of ADPKD cases, occurring more frequently in livers with extensive cystic involvement.
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High-dose-rate brachytherapy boost for prostate cancer: Comparison of three different fractionation schemes
Source:Brachytherapy
Author(s): Alexander T. Falk, Sylvain Demontoy, Emmanuel Chamorey, Marie-Eve Chand, Mathieu Gautier, David Azria, Sara Zaki, Daniel Chevallier, Daniel Lam Cham Kee, Jean-Michel Hannoun-Lévi
PurposeDose escalation for prostate cancer can be achieved with a combination of external beam radiotherapy (EBRT) and brachytherapy (BT) boost to increase local control. For high-dose-rate (HDR)-BT, optimal fractionation remains under debate. The objective was to assess the clinical outcome of three schemes of HDR-BT boost.Methods and MaterialsRetrospective single institution data collection was performed. Patients received 46 Gy EBRT then an HDR-BT boost: 3 × 6 Gy, 2 × 9 Gy, or 1 × 14 Gy. HDR needles were placed under general anesthesia with endorectal ultrasonography guidance. CT-scan and treatment were performed postoperatively.ResultsBetween 2009 and 2012, 159 patients were included. Nine patients (5.7%) were low, 32 (20.1%) intermediate, and 118 (74.2%) high risk (D'Amico classification) without significant difference between the three BT schemes. With a median followup of 61 months, 5-year biochemical relapse–free survival, 5-year local relapse–free survival, 5-year metastases-free survival, and 5-year overall survival rates were 86.6% (SE 2.7%), 98.3% (SE 1%), 95.3% (SE 1%), and 96.5% (SE 1.5%), respectively, with no significant difference between the BT schemes. The rates of acute ≥ G2 genitourinary and ≥G2 gastrointestinal toxicities were 11.3% and 6.3%, respectively (p = NS). The rates of late genitourinary ≥ G2 and gastrointestinal ≥ G2 toxicities (at last followup) were 9.4% and 0.6% with, respectively, 0.6% and 0% of G4 (p = NS).ConclusionsHypofractionation up to a single-fraction HDR-BT boost for prostate cancer yields similar results in terms of biochemical control and late toxicity compared with two or three-fraction schemes. Single fraction HDR-BT appears acceptable for boosting prostate cancer after definitive EBRT.
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Serum Glypican 4 Level in Obese Children and Its Relation to Degree of Obesity
Summary
Objective
Previous adult studies have demonstrated associations of serum glypican 4 (Gpc4) and obesity parameters and insulin sensitivity. However, an association of serum Gpc4 and glucose metabolism remains contradictory. Study of serum Gpc4 in obese children has not been conducted. We aimed to determine serum Gpc4 levels in obese children with various degrees of obesity.
Design, Patients and Measurements
Up to 370 overweight and obese children, aged 6–18 years were enrolled in this cross-sectional study. Oral glucose tolerance test (OGTT) was performed with fasting serum Gpc4, lipid profiles, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measured. Insulin sensitivity and β-cell function indices were calculated from plasma glucose and serum insulin levels derived from the OGTT. Bioelectrical impedance analysis was performed for body fat determination. Comparisons of serum Gpc4 levels among the groups of children with various degrees of obesity were performed.
Results
Serum Gpc4 levels progressively increased in children with increasing body mass index standard deviation score (BMI SDS) tertiles [median (interquartile range, IQR): 2.3 (1.8, 3.2), 2.6 (1.9, 3.4) and 3.2 (2.4, 3.8) μg/L, P <0.001]. There were no differences in serum Gpc4 levels among children in the different glucose metabolism categories. Log serum Gpc4 levels were positively correlated with SDSs of weight and BMI, cholesterol, AST and ALT. No associations of log serum Gpc4 and insulin sensitivity and β-cell function indices were demonstrated.
Conclusions
Serum Gpc4 levels were increased with increasing degrees of obesity. There were no differences in serum Gpc4 levels among glucose metabolism categories.
This article is protected by copyright. All rights reserved.
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Outcomes of Patients with Metastatic Phaeochromocytoma and Paraganglioma: a Systematic Review and Meta-analysis
Objective
The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL).
Design
Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016.
Patients
Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow-up data.
Measurements
Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle-Ottawa tool. Random-effects meta-analysis was used to pool event rates across studies.
Results
Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), <comment> Au: Please check numbers: 685+611=1296 not 1338</comment><comment> We would like to clarify – the numbers of PHEO and PGL here are correct – 685 PHEO and 611 PGL. Remaining 42 cases could not be differentiated between PHEO and PGL (they were combined into the same group). </comment>diagnosed at a mean age of 43.9±5.2 years. Mean follow-up was 6.3±3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five-year (7 studies, n=738) and 10-year (2 studies, n=55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24-51%) and 29% (95% CI, 17-42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85).
Conclusions
Available low quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.
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Thyroid disease symptoms during early pregnancy do not identify women with thyroid hypofunction that should be treated
Summary
Objective
to evaluate whether women during early pregnancy with ''hypothyroidism'' symptoms are at risk for biochemical defined hypothyroidism. The 2017 guidelines of the American Thyroid Association (ATA) recommend case finding on the basis of symptoms to identify these women during pregnancy, while evidence is lacking.
Design
Construct validation of a thyroid hypofunction symptom checklist during first trimester of pregnancy comparing high scores with biochemical defined hypothyroidism.
Patients
2,198 healthy pregnant women from an iodine sufficient area in 2013-2014.
Measurements
completion of a draft questionnaire with ''classical'' symptoms of hypothyroidism at 12 weeks gestation. The the 2.5th and 97.5th percentiles of TSH and fT4 during pregnancy in TPO-Ab negative (< 35 kU/l) women were used to define euthyroid women and those with overt (clinical) and sub-clinical hypothyroidism. The prevalence of overt (subclinical) hypothyroidism was compared between women with high symptom scores compared to those with low scores.
Results
According to fT4 and TSH cut-off's (0.23 – 4.0 mIU/L and 11.5 – 18.0 pmol/L, respectively) there were 15 women with ''to treat hypofunction'' (overt hypothyroidism or TSH > 10 mIU/L) and 68 women with subclinical hypothyroidism. Questionnaire construct validation revealed a 12-item hypothyroid checklist with normally distributed scores. The cut-off indicating high scores of OH was set at 1 SD > mean. Women with high symptom scores did not present more often with biochemically defined thyroid hypofunction.
Conclusion
The current study does not support the ATA recommendation that pregnant women who require levothyroxine therapy can be identified by case-based screening of women with symptoms of thyroid disease.
This article is protected by copyright. All rights reserved.
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Letter to the Editor: Reply to “Ultrasonography and cytology as predictors of noninvasive follicular thyroid (NIFTP) neoplasm with papillary-like nuclear features: importance of the differential diagnosis with the invasive encapsulated follicular variant of papillary thyroid cancer”
Abstract
As Dr. Rosario pointed out, it might be more useful to differentiate NIFTP from invasive encapsulated follicular variant of papillary thyroid carcinoma (iE-FVPTC), not from infiltrative FVPTC (I-FVPTC) in clinical setting since infiltrative FVPTCs show overt malignant US features more frequently. However, in the previous study, we attempted to describe the characteristic ultrasound (US) features and diagnostic method of NIFTP specifically.
This article is protected by copyright. All rights reserved.
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A nanoparticle-based method for culture-free bacterial DNA enrichment from whole blood
Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Marwa M. Hassan, Andrea Ranzoni, Matthew A. Cooper
Point-of-care (POC) diagnostics are one of the quick and sensitive detection approaches used in current clinical applications, but always face a performance tradeoff between time-to-result and assay sensitivity. One critical setting where these limitations are evident is the detection of sepsis, where 6–10mL of whole blood may contain as little as one bacterial colony forming unit (cfu). The large sample volume, complex nature of the sample and low analyte concentration necessitates signal enhancement using culture-based or molecular amplification techniques. In the time-critical diagnosis of sepsis, waiting for up to 24h to produce sufficient DNA for analysis is not possible. As a consequence, there is a need for integrated sample preparation methods that could enable shorter detection times, whilst maintaining high analytical performance. We report the development of a culture-free bacterial enrichment method to concentrate bacteria from whole blood in less than 3h. The method relies on triple-enrichment steps to magnetically concentrate bacterial cells and their DNA with a 500-fold reduction in sample volume (from 10 to 0.02mL). Using this sample preparation method, sensitive qPCR detection of the extracted S. aureus bacterial DNA was achieved with a detection limit of 5±0.58cfu/mL within a total elapsed time of 4h; much faster than conventional culture-based approaches. The method could be fully automated for integration into clinical practice for point-of-care or molecular detection of bacterial DNA from whole blood.
Graphical abstract
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Fully disposable microfluidic electrochemical device for detection of estrogen receptor alpha breast cancer biomarker
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Carolina V. Uliana, Camila R. Peverari, André S. Afonso, Marcia R. Cominetti, Ronaldo C. Faria
A novel fully disposable microfluidic electrochemical array device (µFED) was developed and successfully applied for detection of the biomarker estrogen receptor alpha (ERα). The µFED was constructed using low-cost materials and an inexpensive home cutter printer enabled the manufacture of dozens of µFEDs in less than 2h, at a cost of less than US$ 0.20 in material per device. The µFED incorporates counter and reference electrodes and eight carbon-based working electrodes, which were modified with DNA sequences known as estrogen response elements (DNA-ERE), where ERα binds specifically. Paramagnetic particles heavily decorated with anti-ERα antibody and horseradish peroxidase (MP-Ab-HRP) were used to efficiently capture ERα from the sample solution. The ERα-MP-Ab-HRP bioconjugate formed was injected into the µFED and incubated with the DNA-ERE-modified electrodes, followed by amperometric detection with application of −0.2V vs. Ag|AgCl while a mixture of H2O2 and hydroquinone was injected into the microfluidic device. An ultralow limit of detection of 10.0 fg mL−1 was obtained with the proposed method. The performance of the assay, in terms of sensitivity and reproducibility, was studied using undiluted calf serum, and excellent recoveries in the range of 94.7–108% were achieved for the detection of ERα in MCF-7 cell lysate. The µFED system can be easily constructed and applied for multiplex biomarker detection, making the device an excellent cost-effective alternative for cancer diagnosis, especially in developing countries.
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A resettable and reprogrammable keypad lock based on electrochromic Prussian blue films and biocatalysis of immobilized glucose oxidase in a bipolar electrode system
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Xue Yu, Jiying Liang, Tiangang Yang, Mengjie Gong, Dongman Xi, Hongyun Liu
Herein, a resettable and reprogrammable biomolecular keypad lock on the basis of a closed bipolar electrode (BPE) system was established. In this system, one ITO electrode with immobilized chitosan (CS) and glucose oxidase (GOD), designated as CS-GOD, acted as one pole of BPE in the sensing cell; another ITO with electrodeposited Prussian blue (PB) films as the other pole in the reporting cell. The addition of ascorbic acid (AA) in the sensing cell with driving voltage (Vtot) at +2.5V would make the PB films become Prussian white (PW) in the reporting cell, accompanied by the color change from blue to nearly transparent. On the other hand, with the help of oxygen, the addition of glucose in the sensing cell with Vtot at −1.5V would induce PW back to PB. The change of color and the corresponding UV–vis absorbance at 700nm for the PB/PW films in the reporting cell could be reversibly switched by changing the solute in the sensing cell between AA and glucose and then switching Vtot between +2.5 and −1.5V. Based on these, a keypad lock was developed with AA, glucose and Vtot as 3 inputs, and the color change of the PB/PW films as the output. This keypad lock system combined enzymatic catalysis with bipolar electrochemistry, demonstrating some unique advantages such as good reprogrammability, easy resettability and visual readout by naked eye.
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Non-invasive Strategies for Targeting the Posterior Segment of Eye
Publication date: Available online 26 July 2017
Source:International Journal of Pharmaceutics
Author(s): Asadullah Madni, Muhammad Abdur Rahem, Nayab Tahir, Muhammad Sarfraz, Abdul Jabar, Mubashar Rehman, Prince Muhammad Kashif, Syed Faisal Badshah, Kifayat Ullah Khan, Helder A. Santos
The safe and effective treatment of eye diseases has been remained a global myth. Several advancements have been done and various drug delivery and treatment techniques have been suggested. The Posterior segment disorders are the leading cause of visual impairments and blindness. Targeting the therapeutic agents to the anterior and posterior segments of the eye has attracted extensive attention from the scientific community. Significant key factors in the success of ocular therapy are the development of safe, effective, economic and non-invasive novel drug delivery systems. These specialized non-invasive ocular drug delivery systems revolutionized the drug delivery strategies by overcoming the limitations, provided targeted delivery to the ocular tissues by avoiding larger doses, and reducing the toxicity encountered by the conventional approaches. These non-invasive systems are fabricated by ingredients encompassing biodegradability, biocompatibility, mucoadhesion, solubility and permeability enhancement and stimuli responsiveness. The variety of routes are utilized to provide minimally invasive drug delivery to the patients without any discomfort and pain. This review is focused on the brief introduction, types, significance, preparation techniques, components and mechanism of drug release of non-invasive systems, including in situ gelling systems, microspheres, iontophoresis, nanoparticles, nanosuspensions and specialized novel emulsions.
Graphical abstract
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Beneficial metabolic effects of dietary epigallocatechin gallate alone and in combination with exendin-4 in high fat diabetic mice
Publication date: Available online 25 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Nupur M. Pathak, Paul J.B. Millar, Varun Pathak, Peter R. Flatt, Victor A. Gault
ObjectiveSignificant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity.MethodsEGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin. Energy intake, body weight, fat mass, glucose tolerance, insulin sensitivity, lipid profile, biochemical and hormone markers, and islet histology were examined.ResultsAll treatment groups exhibited significantly reduced body weight, fat mass, circulating glucose and insulin concentrations, and HbA1c levels which were independent of changes in energy intake. Similarly, there was marked improvement in glycaemic control, glucose-stimulated insulin release, insulin sensitivity, total cholesterol and triglycerides, with most prominent effects observed following combination therapy. Circulating corticosterone concentrations and 11beta-hydroxysteroid dehydrogenase type1 (11β-HSD1) staining (in pancreas) were beneficially decreased without changes in circulating interleukin 6 (IL-6), alanine transaminase (ALT) and glutathione reductase. Combination therapy resulted in increased islet area and number, beta cell area, and pancreatic insulin content. Generally, metabolic effects were much more pronounced in mice which received combination therapy.ConclusionsEGCG alone and particularly in combination with exendin-4 exerts positive metabolic properties in HF mice. EGCG may be useful dietary adjunct alongside GLP-1 mimetics in treatment of diabetes and related disorders.
http://ift.tt/2uZsEbO
3-Iodothyronamine reduces insulin secretion in vitro via a mitochondrial mechanism
Source:Molecular and Cellular Endocrinology
Author(s): Ina Lehmphul, Carolin S. Hoefig, Josef Köhrle
Purpose3-iodothyronamine (3-T1AM), a decarboxylated and deiodinated thyroid hormone metabolite, leads at pharmacological doses to hypoinsulinemia, hyperglucagonemia and hyperglycemia in vivo. As the pancreatic Langerhans islets express thyroid hormone transmembrane transporters (THTT), we tested the hypothesis that not only plasma membrane-mediated 3-T1AM binding to and activation of G-protein coupled receptors, but also 3-T1AM metabolite(s) generated by 3-T1AM uptake and metabolism might decrease glucose-stimulated insulin secretion (GSIS).MethodsMurine pancreatic β-cells MIN6 were characterized for gene expression of THTT, deiodinases and monoamine oxidases. 3-T1AM uptake and intracellular metabolism to the corresponding 3-iodothyroacetic acid were analysed by liquid-chromatography tandem mass spectrometry (LC-MS/MS) at different time points in cells as well as the conditioned medium. Mitochondrial activity, especially ATP-production, was monitored real-time after 3-T1AM application using Seahorse Bioanalyzer technique. Effect of 3-T1AM on GSIS into the culture medium was assayed by ELISA.ResultsMIN6 cells express classical THTT, proposed to transport 3-T1AM, as well as 3-T1AM metabolizing enzymes comparable to murine primary pancreatic islets. 3-T1AM accumulates in MIN6 cells and is metabolized by intracellular MaoB to 3-iodothyroacetic, which in turn is rapidly exported. 3-T1AM decreases mitochondrial ATP-production concentration dependently. GSIS is diminished by 3-T1AM treatment. Using LC-MS/MS, no further 3-T1AM metabolites except 3-iodothyroacetic were detectable.ConclusionsThis data provides a first link between cellular 3-T1AM uptake and regulation of mitochondrial energy metabolism in ß-cells, resulting in reduced insulin secretion. We conclude that MIN6 is an appropriate cell model to study 3-T1AM-dependent (intra-)cellular biochemical mechanisms affecting insulin production in vitro.
http://ift.tt/2tDZHP4
Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway
Source:Molecular and Cellular Endocrinology
Author(s): Konstanze Zieger, Juliane Weiner, Kerstin Krause, Maximilian Schwarz, Martin Kohn, Michael Stumvoll, Matthias Blüher, John T. Heiker
Vaspin expression is increased in white adipose tissue (WAT) of diet-induced obese mice and rats and is supposed to compensate HFD-induced inflammatory processes and insulin resistance in adipose tissue by counteracting pro-inflammatory gene expression in obesity. Multiple studies have also demonstrated strong anti-inflammatory effects in vascular and skin cells. Here, we used vaspin treated 3T3-L1 murine adipocytes as well as 3T3-L1 cells with stable vaspin expression to investigate the effect of exogenous and endogenous vaspin on inflammatory processes and insulin signaling in adipocytes.Our stably transfected cells secreted significant amounts of vaspin which was in the physiological range of ∼0.5 ng/ml in cell supernatants. Adipocyte differentiation was not affected by vaspin as expression of adipogenic marker genes as well as lipid accumulation after full differentiation was similar to control cells. We found that IL-1β induced expression and secretion of pro-inflammatory cytokines, such as IL-6, MCP1 and TNFα was significantly blunted in vaspin expressing 3T3-L1 cells. Treatment of 3T3-L1 cells with exogenous vaspin resulted in reduced cytokine-induced activation of the intracellular and pro-inflammatory NFκB signaling cascades (IKKα/β, IκB and NFκB). Moreover, endogenous vaspin positively affected insulin signaling by increasing insulin-stimulated phosphorylation of the key mediator protein kinase B (AKT).Together, we demonstrate anti-inflammatory effects of vaspin in 3T3-L1 adipocytes as well as increased insulin signaling by endogenous expression or exogenous treatment. The results provide evidence for potent anti-inflammatory action of vaspin not only in vascular cells but also in adipose tissue.
http://ift.tt/2uZtENb
The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory effect of nicotine on GnRH release: In vitro studies
Source:Molecular and Cellular Endocrinology
Author(s): Elio Messi, Federica Pimpinelli, Valentina Andrè, Chiara Rigobello, Cecilia Gotti, Roberto Maggi
The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity α4β2 and α7 nAchR subtypes. The exposure of GT1-1 cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by K+-induced cell depolarization; these effects were reversed by D-tubocurarine and α-bungarotoxin. In conclusion, the results reported here indicate that: functional nAChRs are present on GT1-1 cells, the activation of the α-bungarotoxin-sensitive subclass (α7) produces an inhibitory effect on the release of GnRH and that the direct action of nicotine on GnRH neurons may be involved in reducing fertility of smokers.
http://ift.tt/2tDDlwZ
Effect of steviol, steviol glycosides and stevia extract on glucocorticoid receptor signaling in normal and cancer blood cells
Source:Molecular and Cellular Endocrinology
Author(s): Christina Panagiotou, Chrysovalantou Mihailidou, George Brauhli, Olga Katsarou, Paraskevi Moutsatsou
The use of steviol glycosides as non-caloric sweeteners has proven to be beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and metabolic syndrome. However, recent data demonstrate that steviol and stevioside might act as glucocorticoid receptor (GR) agonists and thus correlate with adverse effects on metabolism. Herein, we evaluated the impact of steviol, steviol glycosides, and a Greek-derived stevia extract on a number of key steps of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in Jurkat leukemia cells. Our results revealed that none of the tested compounds altered the expression of primary GR-target genes (GILZ, FKPB5), GR protein levels or GR subcellular localization in PBMCs; those compounds increased GILZ and FKPB5 mRNA levels as well as GRE-mediated luciferase activity, inducing in parallel GR nuclear translocation in Jurkat cells. The GR-modulatory activity demonstrated by stevia-compounds in Jurkat cells but not in PBMCs may be due to a cell-type specific effect.
http://ift.tt/2uZt1D8
Improved method for cannula fixation for long-term intracerebral brain infusion
Publication date: Available online 25 July 2017
Source:Journal of Neuroscience Methods
Author(s): Ádám Sike, Jonas Wengenroth, Jolanta Upīte, Thomas Brüning, Iván Eiriz, Petra Sántha, Henrik Biverstål, Baiba Jansone, Håvard Jostein Haugen, Markus Krohn, Jens Pahnke
BackgroundImplanted osmotic minipumps are commonly used for long-term, brain-targeted delivery of a wide range of experimental agents by being connected to a catheter and a cannula. During the stereotactical surgery procedure, the cannula has to be placed correctly in the x-y directions and also with respect to the injection point in the z-direction (deepness). However, the flat fixation base of available cannula holders doesn't allow an easy, secure fixation onto the curve-shaped skull.New methodWe have developed a modified method for a better fixation of the cannula holder by using an easy-to-produce, skull-shaped silicone spacer as fixation adapter.ResultsWe describe the application and its fast and reliable production in the lab.Comparison with existing method(s)Superglue or cement is currently being used as the method of choice. However, the curve-shaped skull surface does not fit well with the flat and rigid cannula adapter which leads to fixation problems over time causing wide infusion channels and often also to leakage problems from intracerebrally applied agents towards the surface meninges. As another consequence of the inappropriate fixation, the cannula may loosen from the skull before the end of the experiment or it causes damage to the brain tissue, harming the animals with leading to a failure of the whole experiment.ConclusionsThe easy-to-produce spacer facilitates the crucial step of long-term, stereotactic brain infusion experiments with intracerebral catheters in a highly secure and reproducible way.
Graphical abstract
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A novel, double intra-carotid cannulation technique to study the effect of central nutrient sensing on glucose metabolism in the rat
Source:Journal of Neuroscience Methods
Author(s): M. Rijnsburger, L. Eggels, J. Castel, C. Cruciani-Guglielmacci, M.T. Ackermans, S. Luquet, S.E. la Fleur
BackgroundThe hypothalamus plays a key role in central nutrient sensing and glucose homeostasis. Due to its position next to the third ventricle, intracerebroventricular (ICV) injections or osmotic minipumps are widely applied techniques in studying effects of hormones and other molecules on the hypothalamus and glucose metabolism.New methodsThe intracarotid catheter technique in which a catheter is placed in the carotid artery, pointing towards the brain, provides a physiological route to centrally infuse blood-borne molecules in an undisturbed animal. To measure effects of central interventions on peripheral glucose metabolism, endogenous glucose production (EGP) and insulin sensitivity can be measured using a stable isotope technique. To combine both techniques, it is necessary to combine different catheters. We here describe a novel cannulation technique for the carotid artery, enabling stress-free infusions towards the brain and blood sampling from the carotid artery concomitantly, and infuse a stable isotope via the jugular vein.ResultsWe showed accurate EGP measurements when intracarotically infusing saline towards the brain. The stress-hormone corticosterone, as well as energy expenditure, did not alter upon central infusion.Comparison existing method(s)ICV infusions bypass the blood-brain-barrier (BBB) and are thus a less physiological approach when studying central effects of blood-borne factors. Furthermore, ICV injections can elicit a stress response which can interfere with outcomes of glucose metabolism. We described a stress-free, physiological method to study effects of central infusions on peripheral parameters.ConclusionsThis technique provides new opportunities for studying central effects of, for instance, hormones and nutrients, on glucose metabolism.
http://ift.tt/2eO0kD2
The 5 Choice Continuous Performance Test (5C-CPT): A novel tool to assess cognitive control across species
Source:Journal of Neuroscience Methods
Author(s): Savita G. Bhakta, Jared W. Young
BackgroundNeurodevelopmental disorders including Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD) are characterized by significant impairment in attention and cognitive control. These cognitive deficits persist throughout development, contribute significantly to socio-occupational impairment, and are relatively impervious to available treatment. A critical challenge in pro-cognitive drug discovery is translatability of findings across species, underscoring the need for developing valid and reliable cross-species cognitive tasks.New MethodHere we describe a cross-species 5 choice continuous performance task that was developed to measure cognitive control processes of attention, vigilance, and response inhibition, enabling the translation of findings for pro-cognitive drug discovery across species and delineate neural mechanisms underlying cognitive control construct.ResultsConstruct validity of 5C-CPT has been verified by multiple cross-species studies. Several lines of evidence report consistent findings across species including, deficits resulting from 36-hour sleep deprivation studies, engagement of parietal cortex in human brain imaging and rodent lesion studies, and vigilance decrements over time.Comparison with existing method: Unlike the widely used rodent 5 choice serial reaction time task (5CSRTT) and the sustained attention task (SAT), the rodent 5C-CPT includes both target and non-target stimuli that allow measuring of cognitive control elements including response inhibition, an ability to inhibit pre-potent response during non-target trials, detect vigilance decrement and calculate signal detection parameters in rodents analogous to human CPT.ConclusionThe cross-species 5C-CPT is a robust translational tool to characterize the neurobiological substrates underlying cognitive control deficits in clinical population including, ADHD and TS and develop targeted pro-cognitive therapeutics.
http://ift.tt/2h3aBvR
Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test
Source:Brain Research Bulletin
Author(s): Sattar Ostadhadi, Abbas Norouzi-Javidan, Mohsen Chamanara, Reyhaneh Akbarian, Muhammad Imran-Khan, Mehdi Ghasemi, Ahmad-Reza Dehpour
Tramadol is an analgesic agent that is mainly used to treat moderate to severe pain. There is evidence that tramadol may have antidepressant property. However, the mechanisms underlying the antidepressant effects of tramadol have not been elucidated yet. Considering that fact that N-methyl-D-aspartate (NMDA) receptor signaling may play an important role in the pathophysiology of depression, the aim of the present study was to investigate the role of NMDA receptor signaling in the possible antidepressant-like effects of tramadol in the mouse forced swimming test (mFST). We found that tramadol exerted antidepressant-like effects at high dose (40mg/kg, intraperitoneally [i.p.]) in the mFST. Co-administration of non-effective doses of NMDA receptor antagonists (ketamine [1mg/kg, i.p.], MK-801 [0.05 mg/kg, i.p.], or magnesium sulfate [10mg/kg, i.p.]) with sub-effective dose of tramadol (20mg/kg, i.p.) exerted significant antidepressant-like effects in the mFST. The antidepressant-like effects of tramadol (40mg/kg) was also inhibited by pre-treatment with non-effective dose of the NMDA receptor agonist NMDA (75mg/kg, i.p.). Our data suggest a role for NMDA receptor signaling in the antidepressant-like effects of tramadol in the mFST.
http://ift.tt/2uC2OZ2
Phenylketonuria Dietary Management and an Emerging Development
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Penelope D. Manta-Vogli, Kleopatra H. Schulpis
http://ift.tt/2w0pGBd
The Struggle Is Real: A Systematic Review of Food Insecurity on Postsecondary Education Campuses
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Meg Bruening, Katy Argo, Devon Payne-Sturges, Melissa N. Laska
BackgroundNumerous international studies have examined cross-sectional correlates of food insecurity (FI) among postsecondary education students. Research is needed to synthesize the findings of this work to support vulnerable students.ObjectiveTo systematically review peer-reviewed and gray literature to assess the prevalence of FI on postsecondary education institutions, as well as factors related to FI among students and suggested/practiced solutions.DesignSystematic literature review. Medline, Web of Science, and PsycINFO databases were searched for peer-reviewed literature for FI research; a Google search (Google Inc) was conducted to obtain gray literature on FI among postsecondary education students.Participants/settingUndergraduate and graduate students at postsecondary institutions of higher education.Main outcome measuresMeasures included prevalence of FI; sociodemographic, health, and academic factors related to FI; and solutions to address FI on postsecondary institutions.ResultsSeventeen peer-reviewed studies and 41 sources of gray literature were identified (out of 11,476 titles). All studies were cross-sectional. Rates of FI were high among students, with average rates across the gray and peer-reviewed literature of 35% and 42%, respectively. FI was consistently associated with financial independence, poor health, and adverse academic outcomes. Suggested solutions to address food security among postsecondary institutions addressed all areas of the socioecologic model, but the solutions most practiced included those in the intrapersonal, interpersonal, and institutional levels.ConclusionsFI is a major public health problem among postsecondary education students. Studies are needed to assess the long-term influence of FI among this vulnerable population. More research is needed on the effectiveness of FI interventions.
http://ift.tt/2v89h16
Loperamide-Induced Torsades de Pointes: A Case Series
Source:The Journal of Emergency Medicine
Author(s): Kenneth D. Katz, Robert D. Cannon, Matthew D. Cook, Alexandra Amaducci, Ryan Day, Joshua Enyart, Glenn Burket, Lauren Porter, Timothy Roach, Jennifer Janssen, Karl E. Williams
BackgroundLoperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations.Case Report 1A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered intravenous sodium bicarbonate and magnesium sulfate and admitted to the intensive care unit, eventually developing Torsades de Pointes (TdP). He was given lidocaine and isoproterenol infusions, and an external pacemaker was placed. He was discharged in stable condition on hospital day (HD) 16.Case Report 2A 39-year-old woman with a history of hepatitis C, depression, and SUD was transported to the ED after reported seizure-like activity. The patient experienced TdP in the ED and admitted to ingesting large amount of loperamide daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208 ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit admission, the patient experienced no further TdP and was discharged on HD 6.Why Should an Emergency Physician Be Aware of This?Emergency physicians should proceed with caution when treating patients with loperamide toxicity. Even in asymptomatic patients and drug discontinuance, obtain consultation with a medical toxicologist, promptly treat ECG abnormalities aggressively, and admit all patients for further monitoring.
http://ift.tt/2tK6ue3
Measurements of Argon-39 at the U20az underground nuclear explosion site
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): J.I. McIntyre, C.E. Aalseth, T.R. Alexander, H.O. Back, B.J. Bellgraph, T.W. Bowyer, V. Chipman, M.W. Cooper, A.R. Day, S. Drellack, M.P. Foxe, B.G. Fritz, J.C. Hayes, P. Humble, M.E. Keillor, R.R. Kirkham, E.J. Krogstad, J.D. Lowrey, E.K. Mace, M.F. Mayer, B.D. Milbrath, A. Misner, S.M. Morley, M.E. Panisko, K.B. Olsen, M.D. Ripplinger, A. Seifert, R. Suarez
Pacific Northwest National Laboratory reports on the detection of 39Ar at the location of an underground nuclear explosion on the Nevada Nuclear Security Site. The presence of 39Ar was not anticipated at the outset of the experimental campaign but results from this work demonstrated that it is present, along with 37Ar and 85Kr in the subsurface at the site of an underground nuclear explosion. Our analysis showed that by using state-of-the-art technology optimized for radioargon measurements, it was difficult to distinguish 39Ar from the fission product 85Kr. Proportional counters are currently used for high-sensitivity measurement of 37Ar and 39Ar. Physical and chemical separation processes are used to separate argon from air or soil gas, yielding pure argon with contaminant gases reduced to the parts-per-million level or below. However, even with purification at these levels, the beta decay signature of 85Kr can be mistaken for that of 39Ar, and the presence of either isotope increases the measurement background level for the measurement of 37Ar. Measured values for the 39Ar measured at the site ranged from 36,000 milli- Becquerel/standard-cubic-meter-of-air (mBq/SCM) for shallow bore holes to 997,000 mBq/SCM from the rubble chimney from the underground nuclear explosion.
http://ift.tt/2tJQF7a
Efficient and Robust Cell Detection: A Structured Regression Approach
Publication date: Available online 26 July 2017
Source:Medical Image Analysis
Author(s): Yuanpu Xie, Fuyong Xing, Xiaoshuang Shi, Xiangfei Kong, Hai Su, Lin Yang
Efficient and robust cell detection serves as a critical prerequisite for many subsequent biomedical image analysis methods and computer-aided diagnosis (CAD). It remains a challenging task due to touching cells, inhomogeneous background noise, and large variations in cell sizes and shapes. In addition, the ever-increasing amount of available datasets and the high resolution of whole-slice scanned images pose a further demand for efficient processing algorithms. In this paper, we present a novel structured regression model based on a proposed fully residual convolutional neural network for efficient cell detection. For each testing image, our model learns to produce a dense proximity map that exhibits higher responses at locations near cell centers. Our method only requires a few training images with weak annotations (just one dot indicating the cell centroids). We have extensively evaluated our method using four different datasets, covering different microscopy staining methods (e.g., H & E or Ki-67 staining) or image acquisition techniques (e.g., bright-filed image or phase contrast). Experimental results demonstrate the superiority of our method over existing state of the art methods in terms of both detection accuracy and running time.
Graphical abstract
http://ift.tt/2eOpRMC
Bioaccessibility assessment of toxic and essential elements in produced pulses, Bahia, Brazil
Publication date: 1 February 2018
Source:Food Chemistry, Volume 240
Author(s): Wagna Piler Carvalho Santos, Nubia Moura Ribeiro, Daniele Cristina Muniz Batista Santos, Maria Graças Andrade Korn, Mariângela Vieira Lopes
The objective of this study was to analyze the effect of heat treatment on the bioaccessibility of major (K, Ca, Mg, P) and trace elements (As, Ba, Cu, Fe, Mn, Cd, Cr, Hg, Mo, Ni, Pb, Se, Sb, Sn, and Zn) in three different pulse species: Vigna unguiculata L. Walp (cowpea beans), Cajanus cajan L. (pigeon pea) and Lablab purpureus L. Sweet (mangalo). Analyte concentrations were determined in the samples by inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. The results showed that thermal processing can affect the concentrations of the elements investigated in pulse samples. The influence of the heat treatment can range between legume species and chemical elements, as well as with the type of heat treatment, dry, wet, conductive heating and using microwaves.
http://ift.tt/2vHTV0a
Environmental footprints of brick kiln bottom ashes: Geostatistical approach for assessment of metal toxicity
Publication date: 31 December 2017
Source:Science of The Total Environment, Volume 609
Author(s): Ananya Mondal, Subhasish Das, Rajesh Kumar Sah, Pradip Bhattacharyya, Satya Sundar Bhattacharya
Coal fired brick kiln factories generate significant of brick kiln bottom ash (BKBA) that contaminate soil and water environments of areas near the dumping sites through leaching of toxic metals (Pb, Cr, Cd, Zn, Mn, and Cu). However, characteristics and environmental effects of BKBAs are yet unknown. We collected BKBA samples from 32 strategic locations of two rapidly developing States (West Bengal and Assam) of India. Scanning electron microscope images indicated spherical and granular structures of BKBAs produced in West Bengal (WBKBA) and Assam (ABKBA) respectively; while energy dispersive spectroscopy and analytical assessments confirmed substantial occurrence of total organic C and nutrient elements (N, P, K, Ca, Mg, and S) in both the BKBAs. FTIR analysis revealed greater predominance of organic matter in ABKBAs than WBKBAs. Occurrence of toxic metals (Cd, Cr, Pb, Zn, Mn, and Cu) was higher in ABKBAs than in WBKBAs; while organic and residual fractions of metals were highly predominant in most of the BKBAs. Principal component analysis showed that metal contents and pH were the major distinguishing characteristics of the BKBAs generated in the two different environmental locations. Human health risk associated with BKBAs generated in Assam is of significant concern. Finally, geo-statistical tools enabled to predict the spatial distribution patterns of toxic metals contributed by the BKBAs in Assam and West Bengal respectively. Assessment of contamination index, geo-accumulation index, and ecological risk index revealed some BKBAs to be more toxic than others.
Graphical abstract
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The end of the line: antagonistic attentional weightings in unilateral neglect
Source:Cortex
Author(s): Robert D. McIntosh
The line bisection task is widely used in the study of neglect. Some years ago, McIntosh, Schindler, Birchall, & Milner (2005) proposed a radical reframing of this ubiquitous task. Rather than using the traditional measure of directional bisection error, they quantified the sensitivities of the response to the changing locations of the left and right endpoints of the line, expressing these as 'endpoint weightings'. A novel prediction generated from their analysis was that manipulations increasing attention to the left end of the line should cause an increase in the left endpoint weighting and a corresponding reduction in the right endpoint weighting. The present study fulfilled this prediction, using a forced-report cueing method in a group of 12 patients with left neglect. The data confirm an antagonistic relationship between endpoint weightings, consistent with the idea that they represent the sharing of a finite resource. It is argued that the endpoint weightings model of line bisection offers a sensitive and uniquely useful framework for studying competitive lateral biases of attention in neglect, and may also provide insight into non-lateralised attentional impairments.
http://ift.tt/2eNhS2l
Normal Contractile Algorithm of Swallowing Related Muscles Revealed by Needle EMG and its Comparison to Videofluoroscopic Swallowing Study and High Resolution Manometry Studies: A Preliminary Study
Publication date: Available online 25 July 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Donghwi Park, Hyun Haeng Lee, Seok Tae Lee, Yoongul Oh, Jun Chang Lee, Kyoung Won Nam, Ju Seok Ryu
The purpose of this study was to investigate the function and importance of infrahyoid muscles with the suprahyoid muscles during swallowing, and to investigate swallowing sequences using kinematic analysis, high-resolution manometry (HRM) and electromyography (EMG). As a preliminary study, ten healthy subjects were prospectively enrolled. A needle EMG evaluated the onset latency, peak latency and duration of the suprahyoid and infrahyoid muscles. HRM measured the time intervals among the velopharynx, tongue base, and upper esophageal sphincter. We also evaluated hyoid motion using an automated kinematic analysis software® (AKAS). All of these parameters were synchronized with a tilting motion of the epiglottis. In the EMG analysis, the activations of the suprahyoid muscles developed about 300ms earlier than that of the infrahyoid muscles. There was a significant relationship between the differences of suprahyoid and infrahyoid muscles' latency and total duration of the hyoid motion. (p<0.05) The interval time of anterior hyoid motion has a significant correlation in the upper esophageal sphincter (UES) opening time. In conclusions, the functions of the infrahyoid muscles are also as important as that of the suprahyoid muscles for prolonged laryngeal elevation and UES opening. Moreover, kinematic analysis of videofluoroscopic swallowing study (VFSS) and HRM studies could reflect results of needle EMG study and replace EMG study.
http://ift.tt/2vIXq6x
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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