Hair-thin OLED fibers

Publication date: Available online 19 April 2018
Source:Materials Today
Author(s): David Bradley




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On the role of atmospheric oxygen into mechanical properties and fracture behavior of selective laser melted AlCu5MnCdVA

Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Zhiheng Hu, Haihong Zhu, Xiaojia Nie, Changchun Zhang, Hu Zhang, Xiaoyan Zeng
In this study, the difference in the mechanical properties of AlCu5MnCdVA samples fabricated by selective laser melting (SLM) with different atmospheric oxygen content when it has little effect on the formability has been investigated and the mechanism of the earlier fracture has been proposed. The ultimate tensile strength and elongation of the samples fabricated with the atmospheric oxygen content below 20ppm (LOC samples) are 10.89% and 128.21% higher than those of the samples fabricated with the atmospheric oxygen content below 200ppm (HOC samples), respectively. By comparing the formability, density, microstructure, phase and fracture surface of the HOC samples and the LOC samples, it is found that the earlier fracture is caused by the larger size particles forming during the process. The chemical reaction rate dramatically increases as the atmospheric oxygen content increases. The closer particles and the longer duration of high temperature of the molten pool make the collision of the particles easier, resulting in the formation of the larger particles. These findings indicate the atmospheric oxygen plays a different role when alloys with high oxygen sensitivity are being selective laser melted.

Graphical abstract

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Preface – Virtual Special Issue on Materials and Design for Sports Technology

Publication date: 15 July 2018
Source:Materials & Design, Volume 150
Author(s): Aravind Dasari, Zhong Chen, Wei Min Huang, Alexander M. Korsunsky




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Insights into the degradation of (CF3)2CHOCH3 and its oxidative product (CF3)2CHOCHO & the formation and catalytic degradation of organic nitrates

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Feng-Yang Bai, Zi-Man Jia, Xiu-Mei Pan
In this work, a systematic investigation of the atmospheric oxidation mechanism of (CF3)2CXOCH3 and their oxidative products (CF3)2CXOCHO (X = H, F) initiated by OH radical or Cl atom is performed by density functional theory. This study reveals that the introduction of NO and O2 promotes the formation of organic nitrates, which are hygroscopic and are inclined to form secondary organic aerosols (SOA) and can affect the air quality. The rate constants of the individual reactions are found to be in agreement with the experimental results. One of the intriguing findings of this work is that the peroxynitrite of (CF3)2CHOCH2OONO formed from the subsequent reactions of (CF3)2CHOCH3 is more favorable to isomerize to organic nitrate (CF3)2CHOCH2ONO2 than to dissociate into alkoxy radical (CF3)2CHOCH2O and NO2 because of the lower energy barrier of isomerization. The second significant observation is that the organic nitrate can be degraded more favorably with the presence of NH3, CH3NH2, and CH3NHCH3 than its naked decomposition reaction (CF3)2CHOCH2ONO2→(CF3)2CHOCHO + HONO. The ammonium salt, a vital part of haze, is harmful to human health and can be formed in the existence of the NH3, CH3NH2, and CH3NHCH3. In addition, the toxic substance of peroxyalkyl nitrate (CF3)2CHOC(O)ONO2 which can reduce the visibility of the atmosphere is produced as the primary subsequent oxidation product of (CF3)2CHOCHO in a NO-rich environment. The main species detected experimentally are confirmed by this study. The computational results are crucial to risk assessment and pollution prevention of the volatile organic compounds (VOCs).

Graphical abstract

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New open access no-fee journal on rural neurosciences

Journal of Neurosciences in Rural Practice (https://ift.tt/2HMNOhO) is new semi-annual peer-reviewed open access journal to be published from January 2010 on behalf of the Associacion Ayuda Enfermo Neuroquirurgico. The journal would not charge the authors for submission, processing or publication of manuscripts and would provide immediate free access to all its content.

September-2009

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Editorial Board

Publication date: June 2018
Source:Clinical Immunology, Volume 191





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Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity

Publication date: Available online 18 April 2018
Source:Clinical Immunology
Author(s): Merve Iris, Pei-Suen Tsou, Amr H. Sawalha
Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammatory genes including STAT1, TNF, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted.



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Recasting Human Vδ1 Lymphocytes in an Adaptive Role

Publication date: Available online 18 April 2018
Source:Trends in Immunology
Author(s): Martin S. Davey, Carrie R. Willcox, Alfie T. Baker, Stuart Hunter, Benjamin E. Willcox
γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges.



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Studies on the effects of storage stability of bio-oil obtained from pyrolysis of Calophyllum inophyllum deoiled seed cake on the performance and emission characteristics of a direct-injection diesel engine

Abstract

The highly unbalanced nature of bio-oil composition poses a serious threat in terms of storage and utilization of bio-oil as a viable fuel in engines. So it becomes inevitable to study the variations in physicochemical properties of the bio-oil during storage to value its chemical instability, for designing stabilization methodologies. The present study aims to investigate the effects of storage stability of bio-oil extracted from pyrolyzing Calophyllum inophyllum (CI) deoiled seed cake on the engine operating characteristics. The bio-oil is produced in a fixed bed reactor at 500 °C under the constant heating rate of 30 °C/min. All the stability analysis methods involve an accelerated aging procedure based on standards established by ASTM (D5304 and E2009) and European standard (EN 14112). Gas chromatography-mass spectrometry was employed to analytically characterize the unaged and aged bio-oil samples. The results clearly depict that stabilizing Calophyllum inophyllum bio-oil with 10% (w/w) methanol improved its stability than that of the unstabilized sample thereby reducing the aging rate of bio-oil to 0.04 and 0.13 cst/h for thermal and oxidative aging respectively. Engine testing of the bio-oil sample revealed that aged bio-oil samples deteriorated engine performance and increased emission levels at the exhaust. The oxidatively aged sample showed the lowest BTE (24.41%), the highest BSEC (20.14 MJ/kWh), CO (1.51%), HC (132 ppm), NOx (1098 ppm) and smoke opacity (34.8%).

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Calcified Triticeous Cartilage Detected on Digital Panoramic Radiographs in a Sample of Lebanese Population

Georges Aoun, Ibrahim Nasseh

Journal of Clinical Imaging Science 2018 8(1):16-16

Objective: Triticeous cartilage is a small ovoid structure belonging to the laryngeal skeleton. When calcified, it becomes visible on panoramic radiographs and be mistaken for a carotid artery calcification (CAC) associated with cerebrovascular accidents. This study aimed to estimate the prevalence of calcified triticeous cartilage (CTC) detected by means of digital panoramic radiographs in a sample of Lebanese population. Materials and Methods: Digital panoramic radiographs of 500 Lebanese adult patients (281 females and 219 males) with a mean age of 47.9 years were included in this study and examined for CTC. The IBM® SPSS® for Windows version 20.0 (SPSS, Chicago, IL, USA) was used to carry out statistical analysis of the data collected. Results: Nearly 10.6% (53 out of 500) of the radiographs examined presented CTC. Of all the calcifications, 11 were on the right side, 5 on the left side, and 37 were bilateral. The cases detected belonged to 31 females and 22 males with an average age of 55.6 years (ranging from 24 to 85 years). Chi-square test did not show any statistical connection between gender and CTC, while Spearman's correlation analysis showed low positive correlation with age (r = 0.146). Conclusion: CTC can be detected on panoramic radiographs taken in daily dental practice; its identification is essential to avoid misdiagnosis with other calcifications in the neck region closely related to life-threatening risks such as CAC.

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Herniation of Packing Material into a Bronchopleural Fistula after Right Pneumonectomy and Clagett Window

Iclal Ocak, Gideon Bollino, Diane Strollo

Journal of Clinical Imaging Science 2018 8(1):17-17

Diagnosis of a bronchopleural fistula (BPF) can be challenging in patients after pneumonectomy and Clagett window. Herein, we present a case of pneumonectomy for advanced lung cancer complicated by a BPF. Herniation of packing material from the open-chest cavity into the fistula and airways on computed tomography was an important clue to making the diagnosis.

https://ift.tt/2qK8ui3

Renal Granulomatosis Post Intravesical Bacillus Calmette–Guerin Therapy for Non-muscle-invasive Bladder Cancer

Karen Tran-Harding, Rashmi T Nair, Halemane Ganesh

Journal of Clinical Imaging Science 2018 8(1):18-18

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in <5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

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Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

Clinical Endocrinology, EarlyView.


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The role of sulfated steroids in reproduction

Publication date: May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 179
Author(s): Joachim Geyer, Martin Bergmann, Stefan A Wudy




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Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6)

Publication date: May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 179
Author(s): Gary Grosser, Josefine Bennien, Alberto Sánchez-Guijo, Katharina Bakhaus, Barbara Döring, Michaela Hartmann, Stefan A. Wudy, Joachim Geyer
The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC–MS/MS analytics of cell lysates. In addition, we aimed to better understand the structural requirements for SOAT substrates and so selected structural pairs varying only at specific positions: 3α/3β-sulfate, 17α/17β-sulfate, mono-sulfate/di-sulfate, and 17α-hydroxylation. We found significant and sodium-dependent SOAT-mediated transport of 17α-hydroxypregnenolone sulfate, 17β-estradiol-17-sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and 5α-dihydrotestosterone sulfate. However, 17β-estradiol-3,17-disulfate was not transported by SOAT.In conclusionSOAT substrates from the group of sulfated steroids are characterized by a planar and lipophilic steroid backbone in trans-trans-trans conformation of the rings and a negatively charged mono-sulfate group at positions 3′ or 17′ with flexibility for α- or β- orientation. Furthermore, 5α-reduction, 16α-hydroxylation, and 17α-hydroxylation are acceptable for SOAT substrate recognition, whereas addition of a second negatively charged sulfate group seems to abolish substrate binding to SOAT, and so 17β-estradiol-3,17-disulfate is not transported by SOAT.



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Editorial Board

Publication date: May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 179





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The polymorphism L204F affects transport and membrane expression of the sodium-dependent organic anion transporter SOAT (SLC10A6)

Publication date: May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 179
Author(s): Katharina Bakhaus, Daniela Fietz, Sabine Kliesch, Wolfgang Weidner, Martin Bergmann, Joachim Geyer
Sodium-dependent organic anion transporter (SOAT) represents a membrane transporter specific for sulfated steroid hormones, which are supposed to participate in the regulation of reproductive processes. In man, SOAT shows predominant mRNA expression in the testis and here was localized to primary spermatocytes. SOAT mRNA expression is significantly downregulated in different disorders of spermatogenesis, including hypospermatogenesis. The resulting decline of SOAT-mediated transport of sulfated steroids may participate in the impairment of functional spermatogenesis. Apart from downregulation of SOAT mRNA expression, genetic polymorphisms affecting the transport function of SOAT may have the same negative effect on spermatogenesis. Therefore, in the present study we searched for functionally relevant SOAT polymorphisms, aiming to comparatively analyze their occurrence in patients with impaired spermatogenesis vs. patients with intact spermatogenesis. We found that the SOAT polymorphism L204F showed a significantly reduced transport function for DHEAS when expressed in HEK293 cells. Although the Km value was identical with that of the SOAT wildtype, the Vmax value dramatically declined for the SOAT-L204F variant (942.5 vs. 313.6pmol×mg protein⁻¹×min⁻¹). Although the same amount of total SOAT-L204F protein was detected in transfected HEK293 cells compared to the SOAT wildtype, plasma membrane expression was significantly reduced, which points to a plasma membrane sorting defect of the SOAT-L204F variant. Groups of 20 subjects with normal spermatogenesis and 26 subjects with hypospermatogenesis were genotyped for this polymorphism. Both groups showed nearly identical distributions of the SOAT-L204F polymorphism (∼10% heterozygous and ∼5% homozygous), indicating that this polymorphism seems not be causative for hypospermatogenesis.



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The art of measuring steroids

Publication date: May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 179
Author(s): S.A. Wudy, G. Schuler, A. Sánchez-Guijo, M.F. Hartmann
Steroids are small and highly important structural or signalling molecules in living organisms and their metabolism is complex. Due to the multiplicity of enzymes involved there are many different steroid related disorders. E.g., an individual enzyme defect is rather rare but can share various clinical symptoms and can thus be hardly diagnosed clinically. Therefore, reliable hormonal determination still presents the most reasonable initial diagnostic approach and helps to avoid uncritical and expensive attempts at molecular diagnostic testing. It also presents a backbone of monitoring these complex patients. In science, reliable hormone measurement is indispensable for the elucidation of new mechanisms of steroid hormone actions.Steroid analytics is highly challenging and should never be considered trivial. Most common methods for steroid determination comprise traditionally immunoassay, or more recently, mass spectrometry based methods. It is absolutely necessary that clinicians and scientists know the methods they are applying by heart. With the introduction of automated direct assays, a loss of quality could be observed over the last two decades in the field of steroid immunoassays.This review wants to meet the need for profound information and orientation in the field of steroid analysis. The pros and cons of the most important methods, such as immunoassays and mass spectrometry based methods will be discussed. The focus of the latter will lie on gas chromatography-mass spectrometry (GC–MS) as well as liquid chromatography-mass spectrometry (LC–MS). Selected analytical applications from our Deutsche Forschungsgemeinschaft Research Group FOR 1369 "Sulfated Steroids in Reproduction" will illustrate the contents.In brief, immunoassays have for long presented the traditional technique for steroid analysis. They are easy to set up. Only one analyte can be measured per immunoassay. Specificity problems can arise and caution has to be exerted especially regarding direct assays lacking purification steps. Mass spectrometry based methods provide structural information on the analyte and thus higher specificity. In combination with chromatographic techniques, they permit the simultaneous determination of a multitude of analytes. Highest specificity can be obtained using GC–MS, a sophisticated but most powerful tool for characterizing steroid metabolomes. LC–MS is a true high throughput technique and highly suited for detecting complex steroids. GC–MS and LC–MS are not competing but complementary techniques.Since reliable steroid determination requires extremely high expertise in the field of analytics as well as steroid biochemistry, it is recommended that collaborations and networking with highly specialized centers of expertise are developed.

Graphical abstract

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Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis

Publication date: Available online 18 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): O. Takaoka, T. Mori, F. Ito, H. Okimura, H. Kataoka, Y. Tanaka, A. Koshiba, I. Kusuki, S. Shigehiro, T. Amami, J. Kitawaki
Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2-20 μM) inhibited the proliferation of OESCs (P<0.05 for 0.2 μM; P<0.01 for 2 and 20 μM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)β by an antagonist, PHTPP, or by ERβ siRNA (P<0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE2 levels (P<0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P<0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis.



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HMGA1a induces alternative splicing of estrogen receptor alpha in MCF-7 human breast cancer cells

Publication date: Available online 17 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Kenji Ohe, Shinsuke Miyajima, Tomoko Tanaka, Yuriko Hamaguchi, Yoshihiro Harada, Yuta Horita, Yuki Beppu, Fumiaki Ito, Takafumi Yamasaki, Hiroki Terai, Masayoshi Mori, Yusuke Murata, Makito Tanabe, Kenji Ashida, Munechika Enjoji, Toshihiko Yanase, Nobuhiro Harada, Toshiaki Utsumi, Akila Mayeda
The high-mobility group A protein 1a (HMGA1a) protein is known as an oncogene whose expression level in cancer tissue correlates with the malignant potential, and known as a component of senescence-related structures connecting it to tumor suppressor networks in fibroblasts. HMGA1 protein binds to DNA, but recent studies have shown it exerts novel functions through RNA-binding. Our previous studies have shown that sequence-specific RNA-binding of HMGA1a induces exon-skipping of Presenilin-2 exon 5 in sporadic Alzheimer disease. Here we show that HMGA1a induced exon-skipping of the estrogen receptor alpha (ERα) gene and increased ERα46 mRNA expression in MCF-7 breast cancer cells. An RNA-decoy of HMGA1a efficiently blocked this event and reduced ERα46 protein expression. Blockage of HMGA1a RNA-binding property consequently induced cell growth through reduced ERα46 expression in MCF-7 cells and increased sensitivity to tamoxifen in the tamoxifen-resistant cell line, MCF-7/TAMR1. Stable expression of an HMGA1a RNA-decoy in MCF-7 cells exhibited decreased ERα46 protein expression and increased estrogen-dependent tumor growth when these cells were implanted in nude mice. These results show HMGA1a is involved in alternative splicing of the ERα gene and related to estrogen-related growth as well as tamoxifen sensitivity in MCF-7 breast cancer cells.



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Analysis and validation of a new extended method for estimating plasma free cortisol including neutrophil elastase and competition from other steroids

Publication date: Available online 17 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Johanne Gudmand-Hoeyer, Johnny T. Ottesen
A non-linear mechanistic model for the distribution of cortisol in plasma on free and bound forms is proposed. The influence of progesterone, testosterone and neutrophil elastase on the cortisol distribution in the blood is investigated.The activity of neutrophil elastase is directly included in the model with the concentration of elastase and the kinetic constants describing the activity of elastase collected in one single input variable. The model is very sensitive towards this input variable and fits data excellently, when it is allowed to be subject specific.The analysis shows that steroids such as testosterone with low affinity for corticosteroid-binding globulin (CBG) do not significantly influence the concentration of free cortisol. Progesterone has a high affinity for CBG, but low plasma concentrations compared to cortisol. Contrary to expectations, progesterone is shown to impact the distribution of cortisol in plasma both under circumstances with high levels as seen in pregnancy and during the normal menstrual cycle of women.Comparing the predictions of our model with predictions made with the equilibrium models by [1], [2] and [3] shows that the models differ considerably not only in their predictions for free cortisol, but also for cortisol on bound forms; i.e. bound to albumin, intact CBG and elastase-cleaved CBG.Disregarding some of the smallest terms of the model equations a reduced version of the model in form of a fourth order polynomial equation is obtained. The reduced version of the model performs almost identically to the full version and serves as a new formula for calculating the plasma free cortisol concentration.



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Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy

Publication date: Available online 17 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Seema Patel
Polycystic ovary syndrome (PCOS) is an endocrine disorder, afflicting females of reproductive age. This syndrome leads to infertility, apart from a gamut of other metabolic co-morbidities such as insulin resistance, obesity, cardiovascular problems, including a litany of other health issues. PCOS is a polygenic, polyfactorial, systemic, inflammatory, dysregulated steroid state, autoimmune disease, manifesting largely due to lifestyle errors. The advent of biochemical tests and ultrasound scanning has enabled the detection of PCOS in the affected females. Subsequently, a huge amount of insight on PCOS has been garnered in recent times. Interventions like oral contraceptive pills, metformin, and hormone therapy have been developed to bypass or reverse the ill effects of PCOS. However, lifestyle correction to prevent aberrant immune activation and to minimize the exposure to inflammatory agents, appears to be the sustainable therapy of PCOS. This holistic review with multiple hypotheses might facilitate to devise better PCOS management approaches.

Graphical abstract

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Regulation and function of runt-related transcription factors (RUNX1 and RUNX2) in goat granulosa cells

Publication date: Available online 4 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Kexin Gao, Peijie Wang, Jiayin Peng, Junjun Xue, Kaiwen Chen, Yuxuan Song, Jiangang Wang, Guang Li, Xiaopeng An, Binyun Cao
Transcription factors, runt-related transcription factor 1 (RUNX1) and 2 (RUNX2), belong to the runt-related (RUNX) gene family and play critical roles in mammalian reproduction processes. However, the regulatory mechanisms of RUNX1 and RUNX2 expression or their functions in goat follicles remain largely unknown. Herein, RUNX1 and RUNX2 proteins were detected in the oocytes and granulosa cells of preantral and antral follicles, as well as corpus luteum by immunohistochemistry. Treatments with human chorionic gonadotropin (hCG) or with the agonists and inhibitors of hCG-induced intracellular signaling pathways in granulosa cells in vitro, we found that hCG increased RUNX1 expression by activating PKC and PI3K signaling molecules, and increased RUNX2 expression by activating adenylate cyclase, PKC, and PI3K signaling molecules. We also demonstrated that miR-181b expression is dependent on the hCG-induced activation of PKC and PKA, and miR-222 expression is dependent on the hCG-induced activation of PI3K and PKC in cultured granulosa cells. Meanwhile, miR-181b and miR-222 suppressed RUNX1 and RUNX2 expression by targeting RUNX1 and RUNX2 3′ untranslated regions (3′UTRs) with or without hCG, respectively. These results suggested that hCG-mediated miR-181b and miR-222 expression are important for the regulation of RUNX1 and RUNX2 expression levels in granulosa cells. To explore the specific functions of RUNX1 and RUNX2, we transfected RUNX1 and RUNX2 small interfering RNAs into primary cultured granulosa cells. Knockdown of RUNX1 and RUNX2 significantly decreased progesterone productions and the mRNA abundance of key steroidogenic enzymes (StAR, CYP11A1 and HSD3B) after hCG treatment. But only miR-222 increased estradiol secretion in goat granulosa cells. In addition, knockdown of RUNX1 and RUNX2 also promoted granulosa cell proliferation. The hormonally regulated expression of RUNX1 and RUNX2 in granulosa cells, their involvement in progesterone production, and promoted granulosa cell proliferation suggest important roles of RUNX1 and RUNX2 in follicular development and luteinization.



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Prevalence, clinical characteristics and long-term outcomes of classical 11 β-hydroxylase deficiency (11BOHD) in Turkish population and novel mutations in CYP11B1 gene

Publication date: Available online 4 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Firdevs Baş, Güven Toksoy, Berrin Ergun-Longmire, Zehra Oya Uyguner, Zehra Yavaş Abalı, Şükran Poyrazoğlu, Volkan Karaman, Şahin Avcı, Umut Altunoğlu, Ruveyde Bundak, Birsen Karaman, Seher Başaran, Feyza Darendeliler
Congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase deficiency (11BOHD) is a rare autosomal recessive disorder and the second most common form of CAH.AimTo investigate genotype-phenotype correlation and to evaluate clinical characteristics and long-term outcomes of patients with 11BOHD.MethodsA total of 28 patients (n = 14, 46,XX; n = 14, 46,XY) with classical 11BOHD from 25 unrelated families were included in this study. Screening of CYP11B1 is performed by Sanger sequencing. Pathogenic features of novel variants are investigated by the use of multiple in silico prediction tools and with family based co-segregation studies. Protein simulations were investigated for two novel coding region alterations.ResultsThe age at diagnosis ranged from 6 days to 12.5 years. Male patients received diagnose at older ages than female patients. The rate of consanguinity was high (71.4%). Five out of nine 46,XX patients were diagnosed late (age 2–8.7 years) and were assigned as male due to severe masculinization. Twenty one patients have reached adult height and sixteen were ultimately short due to delayed diagnosis. Two male patients had testicular microlithiasis and 5 (35.7%) patients had testicular adrenal rest tumor during follow up. Four patients (28.6%) had gynecomastia.Mutation analyses in 25 index patients revealed thirteen different mutations in CYP11B1 gene, 4 of which were novel (c.393 + 3A > G, c.428G > C, c.1398 + 2T > A, c.1449_1451delGGT). The most frequent mutations were c.896T > C with 32%, c.954G > A with 16% and c.1179_1180dupGA with 12% in frequency. There was not a good correlation between genotype and phenotype; phenotypic variability was observed among the patients with same mutation.ConclusionThis study presents the high allelic heterogeneity of CYP11B1 mutations in CAH patients from Turkey. Three dimensional protein simulations may provide additional support for the pathogenicity of the genetic alterations. Our results provide reliable information for genetic counseling, preventive and therapeutic strategies for the families.

Graphical abstract

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Feedstock composition influences vermicomposting performance of Dichogaster annae relative to Eudrilus eugeniae and Perionyx excavatus

Abstract

Carbon to nitrogen (C/N) ratio influences substrate combinations and earthworm performance in vermicomposting systems. To elucidate these factor effects, a comparative evaluation of species, C/N ratio combined with feed rate, was conducted on three local earthworm species: Perionyx excavatus, Eudrilus eugeniae, and Dichogaster annae. Earthworms were stocked at similar densities and fed shredded paper (SP), cattle manure (CM), and lawn clippings (LC) combined to form C/N ratios of 28, 36, and 53. Earthworms were fed at rates of 1, 1.25, and 2 g feed (dry wt.)/g worm/day for a period of 8 weeks. Percent vermiconversion, earthworm adult and juvenile biomass, and vermicast quality were measured. Vermicast production was significantly affected by the combination of C/N ratio and feed rate and varied among species. All treatment combinations resulted in > 70% conversion, except E. eugenaie fed at the medium rate. Vermiconversion increased for P. excavatus and D. annae with increasing C/N ratio but decreased with increasing the feed rate. Vermicast EC, pH, and C/N ratio was strongly affected by species, relative to other experimental factors. D. annae showed the greatest change in biomass, which peaked at the highest feed rate and lowest C/N ratio. Average adult biomass decreased for P. excavatus with increasing feed rate, while differences were nonsignificant for E. eugenaie and D. annae. Significant increases in average juvenile biomass were only evident for D. annae in response to increasing feed rates. Feed rate had a greater influence on earthworm population dynamics and vermicast quality compared to initial feedstock C/N ratio.

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Chronic obstructive pulmonary diseases related to outdoor PM 10 , O 3 , SO 2 , and NO 2 in a heavily polluted megacity of Iran

Abstract

This study was conducted to quantify, by an approach proposed by the World Health Organization (WHO), the daily hospital admissions for chronic obstructive pulmonary disease (COPD) related to exposure to particulate matter (PM₁₀) and oxidants such as ozone (O₃), sulfur dioxide (SO₂), and nitrogen dioxide (NO₂) in a heavily polluted city in Iran. For the health impact assessment, in terms of COPD, the current published relative risk (RR) and baseline incidence (BI) values, suggested by the WHO, and the 1-h O₃ concentrations and daily PM₁₀, NO₂, and SO₂ concentrations were compiled. The results showed that 5.9, 4.1, 1.2, and 1.9% of the COPD daily hospitalizations in 2011 and 6.6, 1.9, 2.3, and 2.1% in 2012 were attributed to PM₁₀, O₃, SO₂, and NO₂ concentrations exceeding 10 μg/m³, respectively. This study indicates that air quality and the high air pollutant levels have an effect on COPD morbidity. Air pollution is associated with visits to emergency services and hospital admissions. A lower relative risk can be achieved if some stringent control strategies for reducing air pollutants or emission precursors are implemented.

https://ift.tt/2qFlrL8

Interactions between tetrahydroisoindoline-1,3-dione derivatives and human serum albumin via multiple spectroscopy techniques

Abstract

Some tetrahydroisoindoline-1,3-dione derivatives (TDDs) possess potent herbicidal activity. To assess possible impacts of TDDs on humans, the interactions between TDDs and human serum albumin (HSA) were evaluated with steady-state and time-resolved fluorescence spectroscopy, synchronous fluorescence spectroscopy, Fourier transform-infrared spectroscopy, and circular dichroism spectroscopy. The thermodynamic data obtained at temperatures of 298, 307, and 316 K indicate that TDDs spontaneously bind to HSA and thus form a TDD-HSA complex. The conformation and secondary structure of HSA are changed, and the intrinsic fluorescence of HSA is statically quenched by TDDs. Moreover, the TDD-HSA complex is formed primarily through electrostatic interactions and has only one binding site on HSA. A competitive ligand-binding assay revealed that site II (subdomain IIIA) displays the greatest affinity for TDDs. In addition, an acute toxicity bioassay showed no zebrafish mortality upon exposure to 4000 μg L⁻¹ of TDDs. This work is helpful for understanding interactions between TDDs and HSA.

https://ift.tt/2J6wRhr

Polar pesticide contamination of an urban and peri-urban tropical watershed affected by agricultural activities (Yaoundé, Center Region, Cameroon)

Abstract

Urban agriculture is crucial to local populations, but the risk of it contaminating water has rarely been documented. The aim of this study was to assess pesticide contamination of surface waters from the Méfou watershed (Yaoundé, Cameroon) by 32 selected herbicides, fungicides, and insecticides (mainly polar) according to their local application, using both grab sampling and polar organic compounds integrative samplers (POCIS). Three sampling campaigns were conducted in the March/April and October/November 2015 and June/July 2016 rainy seasons in urban and peri-urban areas. The majority of the targeted compounds were detected. The quantification frequencies of eight pesticides were more than 20% with both POCIS and grab sampling, and that of diuron and atrazine reached 100%. Spatial differences in contamination were evidenced with higher contamination in urban than peri-urban rivers. In particular, diuron was identified as an urban contaminant of concern because its concentrations frequently exceeded the European water quality guideline of 0.200 μg/L in freshwater and may thus represent an ecological risk due to a risk quotient > 1 for algae observed in 94% of grab samples. This study raises concerns about the impacts of urban agriculture on the quality of water resources and to a larger extent on the health of the inhabitants of cities in developing countries.

Graphical abstract

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https://ift.tt/2qEDgde

You Can't Fool the Children of the Revolution

Rejuvenation Research, Volume 21, Issue 2, Page 89-90, April 2018.


https://ift.tt/2qGwUKh

Commentary on Some Recent Theses Relevant to Combating Aging: April 2018

Rejuvenation Research, Volume 21, Issue 2, Page 173-177, April 2018.


https://ift.tt/2vruZOo

Telomerase May Paradoxically Accelerate Aging of the DNA Methylome

Rejuvenation Research, Volume 21, Issue 2, Page 168-172, April 2018.


https://ift.tt/2HvFfKh

The Next Generation of Biomedical and Behavioral Sciences Researchers: Breaking Through [Prepublication Draft].

Since the end of the Second World War, the United States has developed the world's preeminent system for biomedical research, one that has given rise to revolutionary medical advances as well as a dynamic and innovative business sector generating high-quality jobs and powering economic output and exports for the U.S. economy. However, there is a growing concern that the biomedical research enterprise is beset by several core challenges that undercut its vitality, promise, and productivity and that could diminish its critical role in the nation's health and innovation in the biomedical industry.

https://ift.tt/2qIyryD

Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Chiara Bulgarelli, Anna Blasi, Simon Arridge, Samuel Powell, Carina C.J.M. de Klerk, Victoria Southgate, Sabrina Brigadoi, William Penny, Sungho Tak, Antonia Hamilton
Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies.fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data. This work opens new avenues for future research on effective connectivity in infancy by contributing a data analysis pipeline and guidance for applying DCM to infant fNIRS data.



https://ift.tt/2H7ww1w

Audio-visual speech processing in age-related hearing loss: Stronger integration and increased frontal lobe recruitment

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Stephanie Rosemann, Christiane M. Thiel
Hearing loss is associated with difficulties in understanding speech, especially under adverse listening conditions. In these situations, seeing the speaker improves speech intelligibility in hearing-impaired participants. On the neuronal level, previous research has shown cross-modal plastic reorganization in the auditory cortex following hearing loss leading to altered processing of auditory, visual and audio-visual information. However, how reduced auditory input effects audio-visual speech perception in hearing-impaired subjects is largely unknown. We here investigated the impact of mild to moderate age-related hearing loss on processing audio-visual speech using functional magnetic resonance imaging. Normal-hearing and hearing-impaired participants performed two audio-visual speech integration tasks: a sentence detection task inside the scanner and the McGurk illusion outside the scanner. Both tasks consisted of congruent and incongruent audio-visual conditions, as well as auditory-only and visual-only conditions. We found a significantly stronger McGurk illusion in the hearing-impaired participants, which indicates stronger audio-visual integration. Neurally, hearing loss was associated with an increased recruitment of frontal brain areas when processing incongruent audio-visual, auditory and also visual speech stimuli, which may reflect the increased effort to perform the task. Hearing loss modulated both the audio-visual integration strength measured with the McGurk illusion and brain activation in frontal areas in the sentence task, showing stronger integration and higher brain activation with increasing hearing loss. Incongruent compared to congruent audio-visual speech revealed an opposite brain activation pattern in left ventral postcentral gyrus in both groups, with higher activation in hearing-impaired participants in the incongruent condition. Our results indicate that already mild to moderate hearing loss impacts audio-visual speech processing accompanied by changes in brain activation particularly involving frontal areas. These changes are modulated by the extent of hearing loss.



https://ift.tt/2qHxk2g

Fehlender Konsens bei Behandlungskonzepten für makroskopische Rezidive nach radikaler Prostatektomie

https://ift.tt/2HzCIyT

Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Marcus T. Wilson, Ben D. Fulcher, Park K. Fung, P.A. Robinson, Alex Fornito, Nigel C. Rogasch
Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity via process of long-term potentiation and depression (LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysical models, which incorporate the physiological properties of TMS-induced plasticity mathematically, provide an excellent framework for reconciling synaptic and macroscopic plasticity. This article overviews the TMS paradigms used to induce plasticity, and their limitations. It then describes the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, it outlines how modeling can complement experimental work to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.



https://ift.tt/2qHq0nb

Investigating the effects of visual distractors on the performance of a motor imagery brain-computer interface

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Zahra Emami, Tom Chau
ObjectivesBrain-computer interfaces (BCIs) allow users to operate a device or application by means of cognitive activity. This technology will ultimately be used in real-world environments which include the presence of distractors. The purpose of the study was to determine the effect of visual distractors on BCI performance.MethodsSixteen able-bodied participants underwent neurofeedback training to achieve motor imagery-guided BCI control in an online paradigm using electroencephalography (EEG) to measure neural signals. Participants then completed two sessions of the motor imagery EEG-BCI protocol in the presence of infrequent, small visual distractors. BCI performance was determined based on classification accuracy.ResultsThe presence of distractors was found to affect motor imagery-specific patterns in mu and beta power. However, the distractors did not significantly affect the BCI classification accuracy; across participants, the mean classification accuracy was 81.5 ± 14% for non-distractor trials, and 78.3 ± 17% for distractor trials.ConclusionThis minimal consequence suggests that the BCI was robust to distractor effects, despite motor imagery-related brain activity being attenuated amid distractors.SignificanceA BCI system that mitigates distraction-related effects may improve the ease of its use and ultimately facilitate the effective translation of the technology from the lab to the home.



https://ift.tt/2H7WT7r

Neural and behavioral changes after the use of hearing aids

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Hanin Karawani, Kimberly A. Jenkins, Samira Anderson
ObjectiveIndividuals with age-related hearing loss (ARHL) can restore some loss of the auditory function with the use of hearing aids (HAs). However, what remains unknown are the physiological mechanisms that underlie how the brain changes with exposure to amplified sounds though the use of HAs. We aimed to examine behavioral and physiological changes induced by HAs.MethodsThirty-five older-adults with moderate ARHL with no history of hearing aid use were fit with HAs tested in aided and unaided conditions, and divided into experimental and control groups. The experimental group used HAs during a period of six months. The control group did not use HAs during this period, but were given the opportunity to use them after the completion of the study. Both groups underwent testing protocols six months apart. Outcome measures included behavioral (speech-in-noise measures, self-assessment questionnaires) and electrophysiological brainstem recordings (frequency-following responses) to the speech syllable /ga/ in two quiet conditions and in six-talker babble noise.ResultsThe experimental group reported subjective benefits on self-assessment questionnaires. Significant physiological changes were observed in the experimental group, specifically a reduction in fundamental frequency magnitude, while no change was observed in controls, yielding a significant time × group interaction. Furthermore, peak latencies remained stable in the experimental group but were significantly delayed in the control group after six months. Significant correlations between behavioral and physiological changes were also observed.ConclusionsThe findings suggest that HAs may alter subcortical processing and offset neural timing delay; however, further investigation is needed to understand cortical changes and HA effects on cognitive processing.SignificanceThe findings of the current study provide evidence for clinicians that the use of HAs may prevent further loss of auditory function resulting from sensory deprivation.



https://ift.tt/2qJ08Yb

Oscillatory local field potentials of the nucleus accumbens and the anterior limb of the internal capsule in heroin addicts

Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Shunnan Ge, Xinyi Geng, Xuelian Wang, Nan Li, Lei Chen, Xinjing Zhang, Yongzhi Huang, Yang Li, Yukun Chen, Shouyan Wang, Guodong Gao
ObjectivesThe nucleus accumbens (NAc) is known to regulate the motivation and underlie addictive behaviors, and the anterior limb of the internal capsule (ALIC) is involved in several psychiatric disorders. Our study aimed to explore the functions of NAc and ALIC electrophysiologically.MethodsThe local field potentials (LFPs) of the NAc and ALIC were recorded from 7 heroin addicts treated with deep brain stimulation. Correlation analysis was made between LFP powers in various frequency bands and the subjects' neuropsychological test scores; coherence was calculated for the LFPs in NAc and ALIC.ResultsBoth the NAc and ALIC exhibited prominent theta and alpha frequency band activity in the LFP power spectra. Additionally, a distinct beta band peak was detected in the power spectra of ALIC LFPs, which may represent the activity of striatal bridge cells. There was a significant negative correlation between the power of the theta frequency band of ALIC LFPs and visual analogue scale (VAS) scores indicative of cravings (Spearman's ρ = −0.758, P = 0.002), and a significant positive correlation was found between the power of the alpha frequency band of NAc LFPs and subjects' scores on the Hamilton depression inventory (ρ = 0.727, P = 0.005). LFPs of the NAc and ALIC exhibited higher coherence values in the theta and alpha frequency bands.ConclusionsThe results suggest that theta power in the ALIC/dorsal striatum and alpha power in the NAc may be associated with drug cravings and depressive symptoms, respectively, in heroin addicts. For these subjects, the neural activities in the dorsal and ventral striatum were mainly coordinated within the low-frequency band.SignificanceThe study illustrates the neurophysiologic characteristics of heroin addiction and its comorbidities, providing a potential theoretical basis for optimizing deep brain stimulation (DBS) therapy.



https://ift.tt/2HdbWg8

Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients

Publication date: Available online 17 April 2018
Source:Journal of Autoimmunity
Author(s): Arsene Mekinian, Mathieu Resche-Rigon, Cloé Comarmond, Alessandra Soriano, Joel Constans, Laurent Alric, Patrick Jego, Florian Busato, Matthieu Cabon, Robin Dhote, Lazaro Estibaliz, Isabelle Kone Pault, Cédric Landron, Christian Lavigne, Bertrand Lioger, Martin Michaud, Marc Ruivard, Karim Sacre, Jacques Eric Gottenberg, Francis Gaches, Tiphaine Goulenok, Carlo Salvarani, Patrice Cacoub, Olivier Fain, David Saadoun
ObjectivesTo assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).MethodsWe conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score).ResultsForty-six patients with TA were included, with a median age of 43 years [29–54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2–3] at baseline to 0 [0–1] and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg [8–19] at baseline to 4 mg [5–21] and 5 mg [4.5–9] at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% [CI 95%; 0.7–0.95], 72% [CI 95%; 0.55–0.95] and 48% [CI 95%; 0.2–0.1] at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 [CI 95%; 1.08–29], p = 0.041), and C-reactive protein level (HR 1.16 [CI 95%; 1.01–1.31], P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02).ConclusionThis large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.



https://ift.tt/2qFjazf

False belief and relative clauses in Autism Spectrum Disorders

Publication date: Available online 17 April 2018
Source:Journal of Communication Disorders
Author(s): Stephanie Durrleman, Wolfram Hinzen, Julie Franck




https://ift.tt/2vpD2Lz

IGEL Laryngeal Mask Airway Device Effectiveness in Irradiated Necks

Condition:   Laryngeal Masks
Intervention:   Device: IGEL Laryngeal mask
Sponsor:   NHS Lothian
Not yet recruiting

https://ift.tt/2JUMF8p

Comparative Study of Robot BABA Approach and Chest Breast Approach for Lateral Neck Dissection

Conditions:   Thyroid Carcinoma;   Robot Surgery;   Endoscopic Surgery
Interventions:   Device: Robot;   Device: Total endoscopic
Sponsor:   Fujian Medical University
Recruiting

https://ift.tt/2J80ZJz

Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml Partially Cystic Thyroid Nodule.

Related Articles

Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml Partially Cystic Thyroid Nodule.

Case Rep Endocrinol. 2018;2018:8046378

Authors: Negro R, Greco G

Abstract
Until nonsurgical techniques like laser ablation (LA) or radiofrequency became available, patients suffering from large nodules with compressive symptoms were addressed to surgery. We describe the case of a 59-year-old woman with a large, partially cystic thyroid nodule having a volume of about 100 ml. As the patient refused surgery, despite her constant local discomfort, such large partially cystic nodule underwent several percutaneous ethanol injections (PEI) and then was submitted to LA. The combination of these two procedures allowed firstly complete disappearance of the cystic component and secondly a significant reduction of thyroid nodule, which finally measured 17 ml in volume (82% reduction compared to baseline). This case demonstrates that even in very large partially cystic nodules LA preceded by PEI represents a valid alternative to surgery.

PMID: 29662707 [PubMed]

https://ift.tt/2J3UV4C

Immunization of BALB/c mice with a combination of four recombinant Brucella abortus proteins, AspC, Dps, InpB and Ndk, confers a marked protection against a virulent strain of Brucella abortus

Publication date: Available online 17 April 2018
Source:Vaccine
Author(s): Huynh Tan Hop, Lauren Togonon Arayan, Tran Xuan Ngoc Huy, Alisha Wehdnesday Bernardo Reyes, WonGi Min, Hu Jang Lee, Soo Jong Park, Hong Hee Chang, Suk Kim
In this study, we assessed the protective efficacy of single subunit vaccines, encoded by the B. abortus 544 genes aspC, dps, yaeC and inpB, against B. abortus infection in mice. First, immunization with these antigens, with the exception of the YaeC protein, was found to elicit both humoral and cellular immune responses with IgG2a being dominant over IgG1. In addition, a massive production of IFN-γ but lower degree of IL-10 was observed, suggesting that all three antigens were able to induce predominantly cell-mediated immunity in response to B. abortus infection. Further investigation of a combined subunit vaccine (CSV) consisting of purified AspC, Dps, InpB and Ndk proteins showed a superior protective effect in mice against brucellosis. The intraperitoneal injection of this combination was shown to induce a remarkable production of IFN-γ and IL-2, which occurred in conjunction with an increase of blood CD4⁺ and CD8⁺ T cell proportions. In addition, the higher titer of IgG2a compared to IgG1 elicited by this CSV was obtained, suggesting that this CSV induced a typical T-helper-1-dominated immune response in vivo. Furthermore, the protection level induced by this combination was significantly higher than that induced by single antigens and was not significantly different compared to a group immunized with a live attenuated vaccine (RB51). Altogether, our findings suggest that the combination of different immunogenic antigens could be a useful approach for the development of a new, effective and safe brucellosis vaccine that can replace current vaccine strains.



https://ift.tt/2J1wox9

Impact of elementary school-located influenza vaccinations: A stepped wedge trial across a community

Publication date: Available online 17 April 2018
Source:Vaccine
Author(s): Peter G. Szilagyi, Stanley Schaffer, Cynthia M. Rand, Nicolas P.N. Goldstein, A. Dirk Hightower, Mary Younge, Ashley Eagan, Aaron Blumkin, Christina S. Albertin, Kristine DiBitetto, Cathleen Concannon, Phyllis Vincelli, Byung-Kwang Yoo, Sharon G. Humiston
BackgroundInfluenza vaccination rates among children are low and novel strategies are needed to raise coverage. We measured the impact of school-located influenza vaccination (SLIV) on coverage, examined whether SLIV substitutes for practice-based influenza vaccination ("substitution"), and estimated whether a second year of experience with SLIV increases its impact.MethodsWe implemented a stepped wedge study design with schools as clusters. In Year 1, we randomly allocated schools to SLIV or control. In Year 2, all schools performed SLIV. We used emails (suburban schools) or backpack fliers (both urban and suburban schools) to notify parents, and offered web-based (suburban) or paper-based vaccination (urban) consent forms. Local health department nurses administered SLIV vaccinations and billed insurers. We analyzed state immunization registry data to measure influenza vaccination rates.Results42 schools (38,078 children) participated over 2 years. Overall vaccination rates were 5 and 7 percentage points higher among SLIV- school children versus control-school children in suburban (aOR 1.36, 95% CI 1.25–1.49 in Years 1–2 SLIV vs. Year 1 control schools) and urban schools (aOR 1.22, 95% CI 1.10–1.36), respectively, adjusting for prior year's vaccination and other covariates. While no substitution occurred among children attending suburban schools, some substitution occurred among children attending urban schools, although overall vaccination rates were still higher in urban schools due to SLIV. Compared to an initial year of SLIV, more children were vaccinated in a second year of SLIV at urban (8.3% vs. 6.8%, aOR 1.24, 95% CI 1.04–1.47) but not suburban schools (3.5% vs. 2.7%, aOR 1.24, 95% CI 0.98–1.57).ConclusionsIn this stepped wedge trial, SLIV increased overall influenza vaccination rates in suburban and urban schools. Some substitution for primary care vaccination occurred in urban settings. A second year of SLIV expanded its reach slightly in urban schools.



https://ift.tt/2HaPsIV

Sorafenib-induced tumor lysis syndrome in a patient with metastatic hepatocellular carcinoma

Publication date: Available online 17 April 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sardar Zakariya Imam, Mohammad Faizan Zahid, Muhammad Asad Maqbool
Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with metastatic hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following initiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1-2 weeks while being treated.



https://ift.tt/2vokHPc

Vascular-Derived Vegfa Promotes Cortical Interneuron Migration and Proximity to the Vasculature in the Developing Forebrain

Abstract

Vascular endothelial growth factor (Vegfa) is essential for promoting the vascularization of the embryonic murine forebrain. In addition, it directly influences neural development, although its role in the forming forebrain is less well elucidated. It was recently suggested that Vegfa may influence the development of GABAergic interneurons, inhibitory cells with crucial signaling roles in cortical neuronal circuits. However, the mechanism by which it affects interneuron development remains unknown. Here we investigated the developmental processes by which Vegfa may influence cortical interneuron development by analyzing transgenic mice that ubiquitously express the Vegfa120 isoform to perturb its signaling gradient. We found that interneurons reach the dorsal cortex at mid phases of corticogenesis despite an aberrant vascular network. Instead, endothelial ablation of Vegfa alters cortical interneuron numbers, their intracortical distribution and spatial proximity to blood vessels. We show for the first time that vascular-secreted guidance factors promote early-migrating interneurons in the intact forebrain in vivo and identify a novel role for vascular-Vegfa in this process.

https://ift.tt/2EWNMRc

Dysfunctional Autism Risk Genes Cause Circuit-Specific Connectivity Deficits With Distinct Developmental Trajectories

Abstract

Autism spectrum disorders (ASD) are a set of complex neurodevelopmental disorders for which there is currently no targeted therapeutic approach. It is thought that alterations of genes regulating migration and synapse formation during development affect neural circuit formation and result in aberrant connectivity within distinct circuits that underlie abnormal behaviors. However, it is unknown whether deviant developmental trajectories are circuit-specific for a given autism risk-gene. We used MRI to probe changes in functional and structural connectivity from childhood to adulthood in Fragile-X (Fmr1^−/y) and contactin-associated (CNTNAP2^−/−) knockout mice. Young Fmr1^−/y mice (30 days postnatal) presented with a robust hypoconnectivity phenotype in corticocortico and corticostriatal circuits in areas associated with sensory information processing, which was maintained until adulthood. Conversely, only small differences in hippocampal and striatal areas were present during early postnatal development in CNTNAP2^−/− mice, while major connectivity deficits in prefrontal and limbic pathways developed between adolescence and adulthood. These findings are supported by viral tracing and electron micrograph approaches and define 2 clearly distinct connectivity endophenotypes within the autism spectrum. We conclude that the genetic background of ASD strongly influences which circuits are most affected, the nature of the phenotype, and the developmental time course of the associated changes.

https://ift.tt/2HJuoKA

Mapping Cortical Laminar Structure in the 3D BigBrain

Abstract

Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

https://ift.tt/2EWAXWU

Distinct Roles for the Cerebellum, Angular Gyrus, and Middle Temporal Gyrus in Action–Feedback Monitoring

Abstract

Action–feedback monitoring is essential to ensure meaningful interactions with the external world. This process involves generating efference copy-based sensory predictions and comparing these with the actual action-feedback. As neural correlates of comparator processes, previous fMRI studies have provided heterogeneous results, including the cerebellum, angular and middle temporal gyrus. However, these studies usually comprised only self-generated actions. Therefore, they might have induced not only action-based prediction errors, but also general sensory mismatch errors. Here, we aimed to disentangle these processes using a custom-made fMRI-compatible movement device, generating active and passive hand movements with identical sensory feedback. Online visual feedback of the hand was presented with a variable delay. Participants had to judge whether the feedback was delayed. Activity in the right cerebellum correlated more positively with delay in active than in passive trials. Interestingly, we also observed activation in the angular and middle temporal gyri, but across both active and passive conditions. This suggests that the cerebellum is a comparator area specific to voluntary action, whereas angular and middle temporal gyri seem to detect more general intersensory conflict. Correlations with behavior and cerebellar activity nevertheless suggest involvement of these temporoparietal areas in processing and awareness of temporal discrepancies in action-feedback monitoring.

https://ift.tt/2HK7uTs

The Transcription Factor LHX1 Regulates the Survival and Directed Migration of POA-derived Cortical Interneurons

Abstract

The delicate balance of excitation and inhibition is crucial for proper function of the cerebral cortex, relying on the accurate number and subtype composition of inhibitory gamma-aminobutyric (GABA)-expressing interneurons. Various intrinsic and extrinsic factors precisely orchestrate their multifaceted development including the long-range migration from the basal telencephalon to cortical targets as well as interneuron survival throughout the developmental period. Particularly expressed guidance receptors were described to channel the migration of cortical interneurons deriving from the medial ganglionic eminence (MGE) and the preoptic area (POA) along distinct routes. Hence, unveiling the regulatory genetic networks controlling subtype-specific gene expression profiles is key to understand interneuron-specific developmental programs and to reveal causes for associated disorders. In contrast to MGE-derived interneurons, little is known about the transcriptional networks in interneurons born in the POA. Here, we provide first evidence for the LIM-homeobox transcription factor LHX1 as a crucial key player in the post-mitotic development of POA-derived cortical interneurons. By transcriptional regulation of related genes, LHX1 modulates their survival as well as the subtype-specific expression of guidance receptors of the Eph/ephrin family, thereby affecting directional migration and layer distribution in the adult cortex.

https://ift.tt/2EWAJiw

Functional Segregation of the Right Inferior Frontal Gyrus: Evidence From Coactivation-Based Parcellation

Abstract

Previous studies helped unraveling the functional architecture of the human cerebral cortex. However, a comprehensive functional segregation of right lateral prefrontal cortex is missing. Here, we delineated cortical clusters in right area 44 and 45 based on their task-constrained whole-brain activation patterns across neuroimaging experiments obtained from a large database. We identified 5 clusters that differed with respect to their coactivation patterns, which were consistent with resting-state functional connectivity patterns of an independent dataset. Two clusters in the posterior inferior frontal gyrus (IFG) were functionally associated with action inhibition and execution, while two anterior clusters were related to reasoning and social cognitive processes. A fifth cluster was associated with spatial attention. Strikingly, the functional organization of the right IFG can thus be characterized by a posterior-to-anterior axis with action-related functions on the posterior and cognition-related functions on the anterior end. We observed further subdivisions along a dorsal-to-ventral axis in posterior IFG between action execution and inhibition, and in anterior IFG between reasoning and social cognition. The different clusters were integrated in distinct large-scale networks for various cognitive processes. These results provide evidence for a general organization of cognitive processes along axes spanning from more automatic to more complex cognitive processes.

https://ift.tt/2HK7uCW

Modality-specific Subpopulations of Place Fields Coexist in the Hippocampus

Abstract

Hippocampal place cells integrate signals from multiple sensory modalities. However, it is unclear how these different inputs are combined to generate place fields. We investigated how visual spatial cues and an animal's locomotion are integrated by CA3 place cells of Mongolian gerbils. While the animals moved on a virtual linear track, we adapted the gain between the visually projected environment and the treadmill movement. Place cells responded differently to this manipulation. In a subset, place fields were kept in accord with salient visual cues in the virtual environment or reward location, whereas in another subset, place fields were strongly influenced by locomotion. Theta phase precession was present and indistinguishable between the place field types. Theta compression remained intact under gain changes and extended over both types of place field. Hippocampal place cells thus retain strong influence from distinct input streams suggesting a role of the hippocampus CA3 as a multimodal associator on the theta time scale.

https://ift.tt/2EWAwvK

Somatotopic Mapping of the Developing Sensorimotor Cortex in the Preterm Human Brain

Abstract

In the mature mammalian brain, the primary somatosensory and motor cortices are known to be spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical "homunculus". This organization creates an internal body representation which is fundamental for precise motor control, spatial awareness and social interaction. Although it is unknown when this organization develops in humans, animal studies suggest that it may emerge even before the time of normal birth. We therefore characterized the somatotopic organization of the primary sensorimotor cortices using functional MRI and a set of custom-made robotic tools in 35 healthy preterm infants aged from 31 + 6 to 36 + 3 weeks postmenstrual age. Functional responses induced by somatosensory stimulation of the wrists, ankles, and mouth had a distinct spatial organization as seen in the characteristic mature homunculus map. In comparison to the ankle, activation related to wrist stimulation was significantly larger and more commonly involved additional areas including the supplementary motor area and ipsilateral sensorimotor cortex. These results are in keeping with early intrinsic determination of a somatotopic map within the primary sensorimotor cortices. This may explain why acquired brain injury in this region during the preterm period cannot be compensated for by cortical reorganization and therefore can lead to long-lasting motor and sensory impairment.

https://ift.tt/2HIpsFP

Intracortical Myelination of Heschl’s Gyrus and the Planum Temporale Varies With Heschl’s Duplication Pattern and Rhyming Performance: An Investigation of 440 Healthy Volunteers

Abstract

We investigated, in 445 healthy adults whose Heschl's gyrus (HG) gyrification patterns had been previously identified, how an in vivo MRI marker of intracortical myelination of HG and the planum temporale (PT) varied as a function of HG gyrification pattern and, in cases of duplication, of anatomical characteristics of the second HG (H2). By measuring the MRI T1/T2 ratio in regions of interest covering the first HG (H1), H2 in cases of common stem (H2CSD), or complete posterior duplication (H2CPD) and the PT, we showed that H1 had the highest T1/T2 values, while the PT had the lowest. The major impact of duplication was a decrease in both H1 and PT T1/T2 values in cases of left CPD. Concerning H2, the right and left T1/T2 values of right H2CSD were closer to those of H1, and those of left H2CPD were closer to those of PT. After adjusting for verbal skills, rhyming performance was not associated with T1/T2 values in left regions, but it decreased with increasing right PT T1/T2 values. These results reveal the existence of hemispheric differences in H2 myelination and underline the importance of neuroimaging markers of intracortical myelination for investigating brain structure–function relationships.

https://ift.tt/2vpqDXZ

Foxg1 Regulates the Postnatal Development of Cortical Interneurons

Abstract

Abnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion of Foxg1, which was achieved by crossing Foxg1^fl/fl with the Gad2-Cre^ER line, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity of Foxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4. Overexpression of Dlx1 or knock down its downstream Pak3 rescued the differentiation detects, demonstrated that Foxg1 functioned upstream of Dlx1-Pak3 signal pathway to regulate the postnatal development of cortical interneurons. Due to the imbalanced neural circuit, Foxg1 mutants showed increased seizure susceptibility. These findings will improve our understanding of the postnatal development of interneurons and help to elucidate the mechanisms underlying seizure in patients carrying Foxg1 mutations.

https://ift.tt/2HGY4ry

Ventromedial Prefrontal Volume in Adolescence Predicts Hyperactive/Inattentive Symptoms in Adulthood

Abstract

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = −0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.

https://ift.tt/2vlYj97

Duality of Function: Activation for Meaningless Nonwords and Semantic Codes in the Same Brain Areas

Abstract

Studies of the neural substrates of semantic (word meaning) processing have typically focused on semantic manipulations, with less consideration for potential differences in difficulty across conditions. While the idea that particular brain regions can support multiple functions is widely accepted, studies of specific cognitive domains rarely test for co-location with other functions. Here we start with standard univariate analyses comparing words to meaningless nonwords, replicating our recent finding that this contrast can activate task-positive regions for words, and default-mode regions in the putative semantic network for nonwords, pointing to difficulty effects. Critically, this was followed up with a multivariate analysis to test whether the same areas activated for meaningless nonwords contained semantic information sufficient to distinguish high- from low-imageability words. Indeed, this classification was performed reliably better than chance at 75% accuracy. This is compatible with two non-exclusive interpretations. Numerous areas in the default-mode network are task-negative in the sense of activating for less demanding conditions, and the same areas contain information supporting semantic cognition. Therefore, while areas of the default mode network have been hypothesized to support semantic cognition, we offer evidence that these areas can respond to both domain-general difficulty effects, and to specific aspects of semantics.

https://ift.tt/2HLhwDu

Cross-Task Contributions of Frontobasal Ganglia Circuitry in Response Inhibition and Conflict-Induced Slowing

Abstract

Why are we so slow in choosing the lesser of 2 evils? We considered whether such slowing relates to uncertainty about the value of these options, which arises from the tendency to avoid them during learning, and whether such slowing relates to frontosubthalamic inhibitory control mechanisms. In total, 49 participants performed a reinforcement-learning task and a stop-signal task while fMRI was recorded. A reinforcement-learning model was used to quantify learning strategies. Individual differences in lose–lose slowing related to information uncertainty due to sampling, and independently, to less efficient response inhibition in the stop-signal task. Neuroimaging analysis revealed an analogous dissociation: subthalamic nucleus (STN) BOLD activity related to variability in stopping latencies, whereas weaker frontosubthalamic connectivity related to slowing and information sampling. Across tasks, fast inhibitors increased STN activity for successfully canceled responses in the stop task, but decreased activity for lose–lose choices. These data support the notion that fronto-STN communication implements a rapid but transient brake on response execution, and that slowing due to decision uncertainty could result from an inefficient release of this "hold your horses" mechanism.

https://ift.tt/2EY0QWy

Cocaine Decreases Spontaneous Neuronal Activity and Increases Low-Frequency Neuronal and Hemodynamic Cortical Oscillations

Abstract

Low-frequency oscillations (LFOs) in hemodynamics assessed by fMRI reflect synchronized neuronal activities and are the basis for mapping brain function and its disruption by drugs and disease. Here we assess if cocaine disrupts coupling between neuronal and vascular LFOs by simultaneously measuring cortical field potentials (FP) and cerebral blood flow (CBF) regarding their LFOs (0–1 Hz) spectral bandwidths in the somatosensory cortex of naïve and chronic cocaine-exposed rats at baseline and during cocaine intoxication. While across all conditions the dominant oscillation frequencies for FP and CBF LFOs were ~0.1 Hz, the bandwidth of FP LFOs was about 4.8 ± 0.67 times broader than that of CBF LFOs. Acute cocaine depressed high-frequency FP events but increased the relative intensity of neuronal and hemodynamic LFOs, an effect that was markedly accentuated in magnitude and duration in chronic cocaine-exposed animals. Neuronal LFOs were correlated with CBF LFOs in control animals but not in chronically cocaine-exposed animals, which suggests neurovascular uncoupling. The marked increases in neuronal LFOs with chronic cocaine, which we interpret to reflect increases in neuronal synchronization in the LFOs, and the uncoupling of hemodynamics with resting neuronal activities could contribute to brain dysfunction in cocaine abusers and confound the interpretation of fMRI studies.

https://ift.tt/2HHZiD8

Constitutive Inactivation of the PRRT2 Gene Alters Short-Term Synaptic Plasticity and Promotes Network Hyperexcitability in Hippocampal Neurons

Abstract

Mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function, emphasizing the pathogenic role of the PRRT2 deficiency. In this work, we investigated the phenotype of primary hippocampal neurons obtained from mouse embryos in which the PRRT2 gene was constitutively inactivated. Although PRRT2 is expressed by both excitatory and inhibitory neurons, its deletion decreases the number of excitatory synapses without significantly affecting the number of inhibitory synapses or the nerve terminal ultrastructure. Analysis of synaptic function in primary PRRT2 knockout excitatory neurons by live imaging and electrophysiology showed slowdown of the kinetics of exocytosis, weakened spontaneous and evoked synaptic transmission and markedly increased facilitation. Inhibitory neurons showed strengthening of basal synaptic transmission, accompanied by faster depression. At the network level these complex synaptic effects resulted in a state of heightened spontaneous and evoked activity that was associated with increased excitability of excitatory neurons in both PRRT2 knockout primary cultures and acute hippocampal slices. The data indicate the existence of network instability/hyperexcitability as the possible basis of the paroxysmal phenotypes associated with PRRT2 mutations.

https://ift.tt/2vqwHQ3

Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction

Abstract

Individuals differ in how they perceive, remember, and think. There is evidence for the existence of distinct subgroups that differ in cognitive performance within the older population. However, it is less clear how individual differences in cognition in old age are linked to differences in brain-based measures. We used latent-profile analysis on n-back working-memory (WM) performance to identify subgroups in a large sample of older adults (n = 181; age = 64–68 years). Our analysis identified one larger normal subgroup with higher performance (n = 113; 63%), and a second smaller subgroup (n = 55; 31%) with lower performance. The low-performing subgroup showed weaker load-dependent BOLD modulation and lower connectivity within the fronto-parietal network (FPN) as well as between FPN and striatum during n-back, along with lower FPN connectivity at rest. This group also exhibited lower FPN structural integrity, lower frontal dopamine D2 binding potential, inferior performance on offline WM tests, and a trend-level genetic predisposition for lower dopamine-system efficiency. By contrast, this group exhibited relatively intact episodic memory and associated brain measures (i.e., hippocampal volume, structural, and functional connectivity within the default-mode network). Collectively, these data provide converging evidence for the existence of a group of older adults with impaired WM functioning characterized by reduced cortico-striatal coupling and aberrant cortico-cortical integrity within FPN.

https://ift.tt/2HHytib

Editorial Board

Publication date: 15 June 2018
Source:European Journal of Pharmaceutical Sciences, Volume 118





https://ift.tt/2HKnh4y

The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

Abstract

Mature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids.

https://ift.tt/2vwUoGL

Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults

Abstract

Tau is associated with hypometabolism in patients with Alzheimer's disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [¹⁸F] AV-1451, [¹⁸F] Fluorodeoxyglucose, and [¹¹C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.

https://ift.tt/2HHqTnM

Protein network module-based identification of key pharmacological pathways of Curcuma phaeocaulis Val. acting on hepatitis

Publication date: 15 July 2018
Source:Journal of Ethnopharmacology, Volume 221
Author(s): Yanxiong Gan, Shichao Zheng, Jiaqi Zhao, Chen Zhang, Tianhui Gao, Wan Liao, Qiang Fu, Chaomei Fu
Ethnopharmacological relevanceCurcuma phaeocaulis Val. (CP), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study.Materials and methodsFirstly, the content of active components of CP was detected based on HPLC-DAD. Then the liver protection of CP on Con A-induced hepatitis was validated via the analysis of serum levels of ALT, AST and LDH and histological findings. Next, the targets of CP components obtained from TCMD database were predicted by STITCH and ChEMBL retrieval. In addition, the protein interaction network (PIN) of CP was constructed by Cytoscape based on protein-protein interaction of targets obtained from STRING database. Following the topological analysis of CP PIN, it showed to exhibit the properties of scale-free, small world, and modularity matched with the property of complex biological networks. Finally, the functional modules were identified by gene ontology enrichment analysis based on Molecular Complex Detection algorithm.ResultsThe functional modules indicated that the mechanism of CP acting on the hepatitis is significantly associated with NF-κB and TGF-β signaling pathway. More interestingly, curcumin, demethoxycurcumin and bisdemethoxycurcumin were the main active components of CP acting on the hepatitis, which were demonstrated to be associated with the inflammatory process that occurs during the progression of hepatitis.ConclusionThe protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP.

Graphical abstract

https://ift.tt/2HGO3e1

Effects of anthraquinones from Cassia occidentalis L. on ovalbumin-induced airways inflammation in a mouse model of allergic asthma

Publication date: 15 July 2018
Source:Journal of Ethnopharmacology, Volume 221
Author(s): Wenhao Xu, Meiqun Hu, Qihong Zhang, Jingbo Yu, Weike Su
Ethnopharmacological relevanceCassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough ('pertussis') and inflammatory diseases. Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma.Aim of the studyTo explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma.Materials and methodsExtraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN-γ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2^-ΔΔCt method.ResultsTreatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN-γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung.ConclusionsThese findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.

Graphical abstract

https://ift.tt/2EXRMRl

Editorial Board

Publication date: May 2018
Source:DNA Repair, Volume 65





https://ift.tt/2HGSa9S

Swiss (German) Version of the Actinic Keratosis Quality of Life questionnaire

Background: Actinic keratosis (AK) is a sun-induced skin lesion that may progress to invasive squamous cell carcinoma of the skin. Recently, the Actinic Keratosis Quality of Life questionnaire (AKQoL) was designed for patients with AK in Denmark as a specific quality of life instrument for AK patients. Objective: The objective of this study was to adapt the AKQoL for the German language region of Switzerland and to evaluate its psychometric properties (validity, reliability). Methods: Translation and cultural adaptation of the questionnaire were assessed by using the technique of cognitive interviewing. During the translation process, 34 patients with AK from the Department of Dermatology, University Hospital Zurich, were interviewed in 3 sessions of cognitive interviewing. The translated questionnaire was then distributed together with the Dermatology Life Quality Index (DLQI) to a second group of 113 patients for validation and reliability testing. Within this group, we measured the internal consistency by the Cronbach coefficient α and Spearman correlation coefficient between the AKQoL and the DLQI. Results: The problems encountered during the translation process led to changes in 5 categories as described by Epstein: stylistic changes, change in breadth, change in actual meaning, change in frequency and time frame, change in intensity. We found a Cronbach α of 0.82, an acceptable internal consistency. The Spearman correlation coefficient between total scores of AKQoL and DLQI was 0.57. Conclusion: We culturally adapted and validated a Swiss (German) version of the AKQoL questionnaire applicable for the population of a university center in Switzerland to measure and monitor the quality of life in patients with AK.
Dermatology

https://ift.tt/2JTieiO

Acetylation of Oxidized Base Repair-Initiating NEIL1 DNA Glycosylase Required for Chromatin Bound Repair Complex Formation in Human Genome Increases Cellular Resistance to Oxidative Stress

Publication date: Available online 17 April 2018
Source:DNA Repair
Author(s): Shiladitya Sengupta, Chunying Yang, Muralidhar L. Hegde, Pavana M. Hegde, Joy Mitra, Arvind Pandey, Arijit Dutta, Abdul Tayyeb Datarwala, Kishor K. Bhakat, Sankar Mitra
Posttranslational modifications of DNA repair proteins have been linked to their function. However, it is not clear if posttranslational acetylation affects subcellular localization of these enzymes. Here, we show that the human DNA glycosylase NEIL1, which is involved in repair of both endo- and exogenously generated oxidized bases via the base excision repair (BER) pathway, is acetylated by histone acetyltransferase p300. Acetylation occurs predominantly at Lys residues 296, 297 and 298 located in NEIL1's disordered C-terminal domain. NEIL1 mutant having the substitution of Lys 296–298 with neutral Ala lost nuclear localization, whereas Lys > Arg substitution (in 3KR mutant) at the same sites did not affect NEIL1's nuclear localization or chromatin binding, presumably due to retention of the positive charge. Although non-acetylated NEIL1 can bind to chromatin, acetylated NEIL1 is exclusively chromatin-bound. NEIL1 acetylation while dispensable for its glycosylase activity enhances it due to increased product release. The acetylation-defective 3KR mutant forms less stable complexes with various chromatin proteins, including histone chaperones and BER/single-strand break repair partners, than the wild-type (WT) NEIL1. We also showed that the repair complex with WT NEIL1 has significantly higher BER activity than the 3KR mutant complex. This is consistent with reduced resistance of non-acetylable mutant NEIL1 expressing cells to oxidative stress relative to cells expressing acetylable WT enzyme. We thus conclude that the major role of acetylable Lys residues in NEIL1 is to stabilize the formation of chromatin-bound repair complexes which protect cells from oxidative stress.



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Scholar : These new articles for Canadian Water Resources Journal / Revue canadienne des ressources hydriques are available online

The online platform for Taylor & Francis Online content New for Canadian Water Resources Journal / Revue canadienne des ressources hydriques and online now on Taylor & Francis Online: Original Articles Bringing twentieth-century water projects into the twenty-first century: The case for revisiting dam operations in Alberta Reed D. Benson & Stewart B. Rood Pages: 1-12 | DOI: 10.1080/07011784.2018.1455539 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.