Aryl hydrocarbon receptor activation modulates CD8αα+TCRαβ+ IELs and suppression of colitis manifestations in mice

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Weigang Chen, Aimin Pu, Baifa Sheng, Zhicao Zhang, Liangzi Li, Zhongze Liu, Qimeng Wang, Xiang Li, Yuanhang Ma, Min Yu, Lihua Sun, Yuan Qiu, Hua Yang
BackgroundThis research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis.MethodsColitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration. The mice were weighed and assessed, and colon tissues were measured. Intraepithelial lymphocytes (IELs) were isolated from the colon and examined by flow cytometry and quantitative real-time PCR.ResultsFICZ ameliorated DSS-induced colitis, resulting in a reduced disease activity index and improvement in the histology and length of the colon. Colitis reduced the percentage and number of CD8αα⁺TCRαβ⁺ IELs. FICZ prevented the reduction in the numbers of CD8αα⁺TCRαβ⁺ IELs by upregulating the expression of the IL-15 receptor and the aryl hydrocarbon receptor (AhR), and attenuating the apoptotic rate of CD8αα⁺TCRαβ⁺ IELs. Finally, IL-10 was increased and IFN-γ was decreased in CD8αα⁺TCRαβ⁺ IELs by FICZ administration in DSS-induced colitis.ConclusionsThe results suggest that AhR activation ameliorated DSS-induced acute colitis, in a manner that is associated with the local expansion and functions of CD8αα⁺TCRαβ⁺ IELs in acute colitis. The findings indicate that AhR-related ligands might be targeted as novel drug targets for IBD.



http://ift.tt/2iWuUeC

Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Zahra Mokhtari, Tourandokht Baluchnejadmojarad, Farnaz Nikbakht, Monireh Mansouri, Mehrdad Roghani
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists. Further biochemical analysis showed that riluzole pretreatment of intrahippocampal Aβ-microinjected rats is able to attenuate hippocampal AChE activity and lower some oxidative stress markers, i.e. MDA and nitrite, with no significant change of the defensive enzyme catalase. Furthermore, riluzole prevented hippocampal CA1 neuronal loss and reduced 3-nitrotyrosine immunoreactivity. It is concluded that riluzole could exert a protective effect against memory decline induced by intrahippocampal Aβ25-35 through anti-oxidative, anti-cholinesterase, and neuroprotective potential and its beneficial effect is possibly independent of cholinoceptor activation.



http://ift.tt/2iWEBtA

Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Dan Tang, Qi-Bin Chen, Xue-Lei Xin, Haji-Akber Aisa
Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A–C (compounds A–C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A–C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A–C. The results suggested that compounds A–C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A–C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) were also suppressed by wortmannin. Western blot results indicated that compounds A–C-induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A–C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A–C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.

Graphical abstract

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Interaction of ozone and carbon dioxide with polycrystalline potassium bromide and its atmospheric implication

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Alexander V. Levanov, Oksana Ya. Isaikina, Ivan B. Maksimov, Valerii V. Lunin
It has been discovered for the first time that gaseous ozone in the presence of carbon dioxide and water vapor interacts with crystalline potassium bromide giving gaseous Br2 and solid salts KHCO3 and KBrO3. Molecular bromine and hydrocarbonate ion are the products of one and the same reaction described by the stoichiometric equation 2KBr(cr.) + O3(gas) + 2CO2(gas) + H2O(gas) → 2KHCO3(cr.) + Br2(gas) + O2(gas). The dependencies of Br2, KHCO3 and KBrO3 formation rates on the concentrations of O3 and CO2, humidity of initial gas mixture, and temperature have been investigated. A kinetic scheme has been proposed that explains the experimental regularities found in this work on the quantitative level. According to the scheme, the formation of molecular bromine and hydrocarbonate is due to the reaction between hypobromite BrO⁻, the primary product of bromide oxidation by ozone, with carbon dioxide and water; bromate results from consecutive oxidation of bromide ion by ozone Br−→+O3,−O2BrO−→+O3,−O2BrO2−→+O3,−O2BrO3−.

Graphical abstract

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Relative impact of on-road vehicular and point-source industrial emissions of air pollutants in a medium-sized Andean city

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): C.M. González, C.D. Gómez, N.Y. Rojas, H. Acevedo, B.H. Aristizábal
Cities in emerging countries are facing a fast growth and urbanization; however, the study of air pollutant emissions and its dynamics is scarce, making their populations vulnerable to potential effects of air pollution. This situation is critical in medium-sized urban areas built along the tropical Andean mountains. This work assesses the contribution of on-road vehicular and point-source industrial activities in the medium-sized Andean city of Manizales, Colombia. Annual fluxes of criteria pollutants, NMVOC, and greenhouse gases were estimated. Emissions were dominated by vehicular activity, with more than 90% of total estimated releases for the majority of air pollutants. On-road vehicular emissions for CO (43.4 Gg/yr) and NMVOC (9.6 Gg/yr) were mainly associated with the use of motorcycles (50% and 81% of total CO and NMVOC emissions respectively). Public transit buses were the main source of PM10 (47%) and NOx (48%). The per-capita emission index was significantly higher in Manizales than in other medium-sized cities, especially for NMVOC, CO, NOx and CO2. The unique mountainous terrain of Andean cities suggest that a methodology based on VSP model could give more realistic emission estimates, with additional model components that include slope and acceleration. Food and beverage facilities were the main contributors of point-source industrial emissions for PM10 (63%), SOx (55%) and NOx (45%), whereas scrap metal recycling had high emissions of CO (73%) and NMVOC (47%). Results provide the baseline for ongoing research in atmospheric modeling and urban air quality, in order to improve the understanding of air pollutant fluxes, transport and transformation in the atmosphere. In addition, this emission inventory could be used as a tool to identify areas of public health exposure and provide information for future decision makers.



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The impact of atmospheric dust deposition and trace elements levels on the villages surrounding the former mining areas in a semi-arid environment (SE Spain)

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): David Sánchez Bisquert, José Matías Peñas Castejón, Gregorio García Fernández
It is understood that particulate matter in the atmosphere from metallic mining waste has adverse health effects on populations living nearby. Atmospheric deposition is a process connecting the mining wasteswith nearby ecosystems. Unfortunately, very limited information is available about atmospheric deposition surrounding rural metallic mining areas. This article will focus on the deposition from mining areas, combined with its impact on nearby rural built areas and populations. Particle samples were collected between June 2011 and March 2013. They were collected according to Spanish legislation in ten specialised dust collectors. They were located near populations close to a former Mediterranean mining area, plus a control, to assess the impact of mining waste on these villages. This article and its results have been made through an analysis of atmospheric deposition of these trace elements (Mn, Zn, As, Cd and Pb). It also includes an analysis of total dust flux. Within this analysis it has considered the spatial variations of atmospheric deposition flux in these locations. The average annual level of total bulk deposition registered was 42.0 g m-2 per year. This was higher than most of the areas affected by a Mediterranean climate or in semi-arid conditions around the world. Regarding the overall analysis of trace elements, the annual bulk deposition fluxes of total Zn far exceeded the values of other areas. While Mn, Cd and Pb showed similar or lower values, and in part much lower than those described in other Mediterranean mining areas. This study confirmed some spatial variability of dust and trace elements, contained within the atmospheric deposition. From both an environmental and a public health perspective, environmental managers must take into account the cumulative effect of the deposition of trace elements on the soil and air quality around and within the villages surrounding metallic mining areas.

Graphical abstract

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Sulfur, arsenic, fluorine and mercury emissions resulting from coal-washing byproducts: A critical component of China's emission inventory

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Chao Zhao, Kunli Luo
The coal-washing rate in China increased from 1991 to 2014 and shows a particular increase from ∼22% to ∼60% since 2002. However, few studies pay attention to the use and disposal of the coal-washing byproducts (CWBs). A preliminary estimate of the likely S, As, F and Hg contents and emissions from the combustion of CWBs in China was determined in this work. About 632 million tons of CWBs, including middling coal, flotation tailing coal and coal slime, were produced in China in 2014. About 4.03%, 20.80%, 1.48%, and 73.25% CWBs were used for thermal power, industry, domestic and discard. The mean S, As, F and Hg contents of CWBs are 1.52%, 14.04 mg/kg, 216.31 mg/kg and 0.27 mg/kg, respectively. SO2 emissions in 2014 from the combustion of CWBs were ∼5.76 million tons, similar to that released into the atmosphere by China's coal-fired power plants, accounting for ∼29% of the country's total SO2 emissions. Arsenic, F and Hg emissions from CWBs were 1 599.54, 61 575.07 and 77.16 tons, respectively. These emissions have become a critical component of air pollution in China.

Graphical abstract

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Gradenigo syndrome and primitive sphenoid sinus cancer

Publication date: Available online 31 December 2016
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Jbali Souheil, Dhaha Mohamed, Dhambri Sawssen, Kedous Skander, Hedhili Farah, Yazid Delia, Abidi Rim, Attia Zied, Touati Slim, Gritli Said
First described in 1907, Gradenigo's syndrome associates the following triad: acute otitis media as a causative infection of petrous apicitis, ipsilateral abducens nerve palsy and trigeminal neuralgia. This entity is becoming rare because of the wide use of antibiotics. The above definition can be extended as the fifth and sixth cranial nerves are intimately related near the apex of the petrous bone. Thus, any adjacent process may cause petrositis and palsies of these nerves.Paranasal sinus adenocarcinomas are common. But primitive sphenoid bone localization is exceptional and manifest usually with a deep retro orbital headache.¹Gardenigo's syndrome is a rare revelation mode of sphenoid tumors.We report the case of a 55-years old female with a history of Budd Chiari syndrome, who presented with a typical Gradenigo's Syndrome. The imaging showed an invasive process of sphenoid sinus. trans-sphenoidal biopsy concluded to adenocarcinoma. As the patient was inoperable, palliative radiotherapy was indicated.



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Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report

Publication date: February 2017
Source:European Journal of Cancer, Volume 72
Author(s): M.M. de Jonge, A.L. Mooyaart, M.P.G. Vreeswijk, C.D. de Kroon, T. van Wezel, C.J. van Asperen, V.T.H.B.M. Smit, O.M. Dekkers, T. Bosse
BackgroundUterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome.MethodsPubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs. Pooled analysis and comparisons were performed using a random effects logistic model, stratifying for ethnicity (Ashkenazi versus non-Ashkenazi). In addition, tumour tissue from an USC case with a hereditary BRCA1-PM was analysed for loss of heterozygosity at the BRCA1 locus and was functionally analysed for homologous recombination proficiency.ResultsThe search yielded 1893 citations, 10 studies were included describing 345 USC patients. For Ashkenazi Jews, the pooled odds ratio of having a germline BRCA1/2-PM was increased in USC patients compared with the general Ashkenazi population: odds ratio 5.4 (95%confidence interval: 2.2–13.1). In the patient with USC, we identified the known germline BRCA1-PM in the tumour DNA. Furthermore, we showed both loss of heterozygosity of the wild-type allele and a deficiency of homologous recombination.ConclusionThis study suggests that USC may be an overlooked component of BRCA1/2-associated hereditary breast and ovarian cancer syndrome. Screening for germline BRCA1/2-PMs should be considered in patients diagnosed with USC, especially in cases with a positive first-degree family history for breast and/or ovarian cancer.



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Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

Publication date: March 2017
Source:Biomaterials, Volume 120
Author(s): Jaewoo Lee, Jennifer G. Jackman, Jean Kwun, Miriam Manook, Angelo Moreno, Eric A. Elster, Allan D. Kirk, Kam W. Leong, Bruce A. Sullenger
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.



http://ift.tt/2iTA333

The efficacy of Dynorphin fragments at the κ, μ and δ opioid receptor in transfected HEK cells and in an animal model of unilateral peripheral inflammation.

Publication date: Available online 31 December 2016
Source:Peptides
Author(s): M. Morgan, A. Heffernan, F. Benhabib, S. Wagner, A.K. Hewavitharana, P.N. Shaw, P.J. Cabot
BackgroundDynorphin 1-17 is an endogenous peptide that is released at sites of inflammation by leukocytes, binding preferentially to κ-opioid receptors (KOP) to mediate nociception. We have previously shown that dynorphin 1-17 is rapidly biotransformed to smaller peptide fragments in inflamed tissue homogenate. This study aimed to determine the efficacy and potency of selected dynorphin fragments produced in an inflamed environment at the KOP, μ and δ-opioid receptors (MOP and DOP respectively) and in a model of inflammatory pain. Functional activity of Dynorphin 1-17 and fragments (1-6, 1-7 and 1-9) were screened over a range of concentrations against forskolin stimulated human embryonic kidney 293 (HEK) cells stably transfected with one of KOP, MOP or DOP. The analgesic activity of dynorphin 1-7 in a unilateral model of inflammatory pain was subsequently tested. Rats received unilateral intraplantar injections of Freund's Complete Adjuvant to induce inflammation. After six days rats received either dynorphin 1-7, 1-17 or the selective KOP agonist U50488H and mechanical allodynia determined. Dynorphin 1-7 and 1-9 displayed the greatest activity across all receptor subtypes, while dynorphin 1-7, 1-9 and 1-17 displaying a potent activation of both KOP and DOP evidenced by cAMP inihibition. Administration of dynorphin 1-7 and U50488H, but not dynorphin 1-17 resulted in a significant increase in paw pressure threshold at an equimolar dose suggesting the small peptide dynorphin 1-7 mediates analgesia. These results show that dynorphin fragments produced in an inflamed tissue homogenate have changed activity at the opioid receptors and that dynorphin 1-7 mediates analgesia.



http://ift.tt/2iV3zcD

pH–value-controlled assembly of photoluminescent zinc coordination polymers in the mixed-ligand system

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Kang Liu, Hanbin Hu, Jing Sun, Yiheng Zhang, Jishu Han, Lei Wang
Three novel coordination polymers, [Zn(sdi)2(NO3)(H2O)]·NO3 (1), [Zn(sdi)2(H2O)2]·2NO3 (2) and [Zn(sdi)0.5(H2C3O4)(H2O)] (3), (sdi = N,N′-sulfuryldiimidazole) have been synthesized and characterized by elemental analysis, IR spectroscopy, single crystal X-ray diffraction, powder X-ray diffraction and thermogravimetric analyses. These compounds have abundant structural chemistry ranging from zero-dimensional (0D) (1), one-dimensional (1D) (2), to three-dimensional (3D) (3) networks. Compound 1 displays a 0D structure which formed by [Zn(sdi)2]2 dimers. Compound 2 possesses 1D chain with closed loops. Notably, compound 3 exhibits a 3D (3,4)-connected net with a (6³)(6⁵·8) topology. Interestingly, compounds 1–3 were obtained under similar reaction conditions and the structural diversity of these coordination polymers illustrate the remarkable effect of pH on the self-assembling process. Moreover, the fluorescent properties of these compounds have been investigated.

Graphical abstract

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Eradication ofPseudomonas aeruginosacells by cathodic electrochemical currents delivered with graphite electrodes

Publication date: Available online 31 December 2016
Source:Acta Biomaterialia
Author(s): Tagbo H.R. Niepa, Hao Wang, Jeremy L. Gilbert, Dacheng Ren
Antibiotic resistance is a major challenge to the treatment of bacterial infections associated with medical devices and biomaterials. One important intrinsic mechanism of such resistance is the formation of persister cells that are phenotypic variants of microorganisms and highly tolerant to antibiotics. Recently, we reported a new approach to eradicating persister cells of Pseudomonas aeruginosa using low-level direct electrochemical current (DC) and synergy with the antibiotic tobramycin. To further understand the underlying mechanism and develop this technology toward possible medical applications, we investigated the electricidal activities of non-metallic biomaterial on persister and biofilm cells of P. aeruginosa using graphite-based TGON™ 805 electrodes. We employed both single and dual chamber systems to compare electrochemical factors of TGON and stainless steel 304 electrodes. The results revealed that TGON-based treatments were highly effective against P. aeruginosa persister cells. In the single chamber system, complete eradication of planktonic persister cells (corresponding to a 7-log killing) was achieved with 70 μA/cm² DC using TGON electrodes within 40 min of treatment, while cell viability in biofilms was reduced by 2 logs within 1 h. The killing effects were dose and time dependent with higher current densities requiring less time. Moreover, reduction reactions were found more effective than oxidation reactions, confirming that metal cations are not indispensable, although they may facilitate cell killing. The findings of this study can help develop electrochemical technologies to eradicate persister and biofilm cells for more effective treatment of medical device and biomaterial related infections.[Significance Statement]Infections associated with medical devices and biomaterials present a major challenge due to high-level tolerance of microbes to conventional antibiotics. It is well established that such tolerance is due to the formation of dormant persister cells and multicellular structures known as biofilms. Recent studies have demonstrated electrochemical treatment as a promising alternative to eradicate bacterial infections, since the killing mechanism is independent of the growth phase of bacterial cells, but relies on the various electrochemical species interplaying during the treatment. The current study investigated major bactericidal properties of the electrochemical currents mediated via TGON, a carbon-based electrode material. Up to total eradication of Pseudomonas aeruginosa persister cells was achieved. The new knowledge of electrochemical properties and the bioactivity of TGON may help develop new methods/devices to eradicate bacterial infections by delivering safe levels of electrochemical currents.



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Adaptation is mandatory for intensity modulated proton therapy of advanced lung cancer to ensure target coverage

Publication date: Available online 31 December 2016
Source:Radiotherapy and Oncology
Author(s): Lone Hoffmann, Markus Alber, Maria Fuglsang Jensen, Marianne Ingerslev Holt, Ditte Sloth Møller
Background and purposeLarge anatomical changes during radiotherapy are seen for a large proportion of lung cancer patients. We investigate the applicability of a decision support protocol for photon therapy in a proton therapy setting.Material and methodsTwenty-three consecutive NSCLC patients treated with adaptive photon therapy were retrospectively planned using IMPT. The adaptive protocol was based on geometrical measures of target positioning and large anatomical changes as shown on daily CBCT scans. Two surveillance CT-scans were acquired during the treatment course. The consequences of anatomical changes were evaluated by recalculating the proton plans on the surveillance scans. The CTV receiving 95% of the prescribed dose was analysed.ResultsFourteen (61%) patients needed adaptations when treated with protons, given that 95% of the CTV must be covered by 95% of the dose. In comparison, no patients needed adaptation when treated with photons using this criterion. The adaptive protocol was found to identify patients with large target under-dosage for proton therapy (six patients). Additionally, target under-dosage was observed for eight patients with non-rigid changes up to 15mm in the positioning of the bones.ConclusionsProton therapy for loco-regional lung cancer demands daily imaging and therapy adaptation for a high proportion of patients.



http://ift.tt/2ivROZH

QuEChERS extraction for multi-residue analysis of PCBs, PAHs, PBDEs and PCDD/Fs in biological samples

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Pierre-Luc Cloutier, Frédérik Fortin, Paule Emilie Groleau, Pauline Brousseau, Michel Fournier, Mélanie Desrosiers
In this study, a fast and rugged method is presented for the analysis of PCBs, PAHs, PBDEs and PCDD/Fs in biological tissues using a simple Quick, Easy, Cheap, Efficient, Rugged and Safe (QuEChERS) extraction and a clean-up by Gel Permeation Chromatography (GPC) and silica Solid Phase Extraction (SPE). Development was performed on blue mussels (Mytilus edulis) and Atlantic salmon (Salmo salar) for evaluation of two ranges of lipid and water content of biological tissues. Statistical validation was performed with Atlantic salmon samples. Forty-five PAHs were analyzed including the priority list of the US EPA and the European Union with 41 PCBs, 24 PBDEs and 17 PCDD/Fs. Instrumental analyses were performed on Gas Chromatography – High Resolution Mass Spectrometry (GC-HRMS). Accuracy was evaluated for PCBs and PCDD/Fs with a certified reference material furnished by the National Research Council Canada (NRCC) and also compared with results obtained by the conventional Soxhlet extraction. Statistical validation showed recoveries for PCBs, PAHs, PBDEs and PCDD/Fs close to 100% with average Relative Standard Deviation (RSD) lower than 10% and internal standard recoveries in the range of 70% with average RSD ranging from 5–15%. Average calculated Method Detection Limits (MDLs) were lower than 0.05μg/Kg for PCBs, 0.2μg/Kg for PAHs and PBDEs and 1ng/Kg for PCDD/Fs. The method is a faster and cheaper alternative to the time-consuming conventional method that has been used in most environmental laboratories.

Graphical abstract

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Shared orthographic neuronal representations for spelling and reading

Publication date: 15 February 2017
Source:NeuroImage, Volume 147
Author(s): Jeremy J. Purcell, Xiong Jiang, Guinevere F. Eden
A central question in the study of the neural basis of written language is whether reading and spelling utilize shared orthographic representations. While recent studies employing fMRI to test this question report that the left inferior frontal gyrus (IFG) and ventral occipitotemporal cortex (vOTC) are active during both spelling and reading in the same subjects (Purcell et al., 2011a; Rapp and Lipka, 2011), the spatial resolution of fMRI limits the interpretation of these findings. Specifically, it is unknown if the neurons which encode orthography for reading are also involved in spelling of the same words. Here we address this question by employing an event-related functional magnetic resonance imaging-adaptation (fMRI-A) paradigm designed to examine shared orthographic representations across spelling and reading. First, we identified areas that independently showed adaptation to reading, and adaptation to spelling. Then we identified spatial convergence for these two separate maps via a conjunction analysis. Consistent with previous studies (Purcell et al., 2011a; Rapp and Lipka, 2011), this analysis revealed the left dorsal IFG, vOTC and supplementary motor area. To further validate these observations, we then interrogated these regions using an across-task adaptation technique, and found adaptation across reading and spelling in the left dorsal IFG (BA 44/9). Our final analysis focused specifically on the Visual Word Form Area (VWFA) in the vOTC, whose variability in location among subjects requires the use of subject-specific identification mechanisms (Glezer and Riesenhuber, 2013). Using a functional localizer for reading, we defined the VWFA in each subject, and found adaptation effects for both within the spelling and reading conditions, respectively, as well as across spelling and reading. Because none of these effects were observed during a phonological/semantic control condition, we conclude that the left dorsal IFG and VWFA are involved in accessing the same orthography-specific representations for spelling and reading.



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The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus

Publication date: Available online 31 December 2016
Source:Clinical Immunology
Author(s): Robert J. Ragotte, Anita Dhanrajani, Julian Pleydell-Pearce, Kate L. Del Bel, Maja Tarailo-Graovac, Clara van Karnebeek, Jefferson Terry, Christof Senger, Margaret L. McKinnon, Michael Seear, Julie S. Prendiville, Lori B. Tucker, Kristin Houghton, David A. Cabral, Jaime Guzman, Ross E. Petty, Kelly L. Brown, Jenny Tekano, John Wu, Kimberly A. Morishita, Stuart E. Turvey
ObjectivesClinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.Methods and resultsBy harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosis (SLE).ConclusionsThis case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.



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Effect of full helmet systems on human head responses under blast loading

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): M. Rodríguez-Millán, L.B Tan, K.M. Tse, H.P. Lee, M.H Miguélez
This paper focuses on helmet design for head protection under blast threats. It is presented a numerical investigation of the head response accruing to blast loads on helmet protective systems. Various combinations of the helmet, visor and mandible guard were numerically analyzed for a given mass of TNT at a distance to the target representing an anti-vehicle buried mine threat. Limited published articles on the subject are available in the scientific literature. In this paper, a 3D head–helmet numerical model for blast analyses is developed in the finite element code ABAQUS/Explicit. The results showed that individual protective systems are not effective enough to mitigate the damage caused by blast loading. The complete protective equipment reduces the pressures on the brain by up to 5 times and ensures that no fracture in the skull appears. This numerical study aims to provide helmet manufacturers and users with some insight in what possible brain injuries are to be expected in various blast scenarios so as to help in better diagnosis of unsuspected brain injury.

Graphical abstract

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Global Updates on the Future Directions of Neurotoxins and Fillers

Summary: Neurotoxins and fillers continue to remain in high demand, comprising a large part of the growing business of cosmetic minimally invasive procedures. Multiple Food and Drug Administration-approved safe yet different products exist within each category, and the role of each product continues to expand. The authors review the literature to provide an overview of the use of neurotoxins and fillers and their future directions. Copyright (C) 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

http://ift.tt/2iD7g3p

Technical Considerations for Filler and Neuromodulator Refinements

Background: The toolbox for cosmetic practitioners is growing at an unprecedented rate. There are novel products every year and expanding off-label indications for neurotoxin and soft-tissue filler applications. Consequently, aesthetic physicians are increasingly challenged by the task of selecting the most appropriate products and techniques to achieve optimal patient outcomes. Methods: We employed a PubMed literature search of facial injectables from the past 10 years (2005-2015), with emphasis on those articles embracing evidence-based medicine. We evaluated the scientific background of every product and the physicochemical properties that make each one ideal for specific indications. The 2 senior authors provide commentary regarding their clinical experience with specific technical refinements of neuromodulators and soft-tissue fillers. Results: Neurotoxins and fillers are characterized by unique physical characteristics that distinguish each product. This results in subtle but important differences in their clinical applications. Specific indications and recommendations for the use of the various neurotoxins and soft-tissue fillers are reviewed. The discussion highlights refinements in combination treatments and product physical modifications, according to specific treatment zones. Conclusions: The field of facial aesthetics has evolved dramatically, mostly secondary to our increased understanding of 3-dimensional structural volume restoration. Our work reviews Food and Drug Administration-approved injectables. In addition, we describe how to modify products to fulfill specific indications such as treatment of the mid face, decolletage, hands, and periorbital regions. Although we cannot directly evaluate the duration or exact physical properties of blended products, we argue that "product customization" is safe and provides natural results with excellent patient outcomes. Copyright (C) 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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