455 research outputs found
Critical role of GRP receptor–expressing neurons in the spinal transmission of imiquimod‐induced psoriatic itch
No full textAbstract Aim Ample evidence indicates that gastrin‐releasing peptide receptor (GRPR)–expressing neurons play a critical role in the transmission of acute itch. However, the pathophysiology of spinal mechanisms underlying intractable itch such as psoriasis remains unclear. In this study, we aimed to determine whether itch‐responsive GRPR+ neurons contribute to the spinal transmission of imiquimod (IMQ)‐induced psoriatic itch. Methods To generate a psoriasis model, C57BL/6J mice received a daily topical application of 5% IMQ cream on their shaved back skin for 7‐10 consecutive days. GRP+ neurons were inhibited using Cre‐dependent expression of Gi‐designer receptors exclusively activated by designer drugs (DREADDs), while GRPR+ neurons were ablated by intrathecal administration of bombesin‐saporin. Results Repeated topical application of IMQ elicited psoriasis‐like dermatitis and scratching behaviors. The mRNA expression levels of GRP and GRPR were upregulated in the cervical spinal dorsal horn (SDH) on days 7 and 10 after IMQ application. Either chemogenetic silencing of GRP+ neurons by Gi‐DREADD or ablation of GRPR+ neurons significantly attenuated IMQ‐induced scratching behaviors. Conclusion The GRP‐GRPR system might be enhanced in the SDH, and itch‐responsive GRPR+ neurons largely contribute to intractable itch in a mouse model of psoriasis
JOAO WANDERLEY GERALDI: THE LINGUIST RESEARCHER, TRAINING TEACHER AND UNIQUE BRAZILIAN READER OF BAKHTIN AND HIS STUDY CIRCLE
No full textThis article aims to honor and discuss our meeting with Joao Wanderley Geraldi, the linguist researcher, teacher trainer and unique reader of Bakhtin and his Study circle. Our subject matter in this paper is the meetings we held with the author in his research and teaching activities throughout his years of activism, and in specially during the Linguistics V program taken at Unicamp in 2005. From mediations with Geraldi on language studies, we chose to share our understanding of speech genres - involving life and education - that converge around this construction. Finally, we show how this knowledge guides us to maintain the inseparable relationship between language and literature in dialogue through a poem by Manoel de Barros, a poet who was also introduced to us by Geraldi.Univ Fed Santa Catarina UFSC, Programa Posgrad Linguist PPGL UFSC, Florianopolis, BrazilUniv Fed Santa Catarina, GEBAP Grp Estudos Bakhtinianos Pampa, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilUniv Fed Santa Catarina, NEPALP, Nucleo Estudos & Pesquisas Alfabetizacao & Ensino, Florianopolis, BrazilNELA UFSC, Nucleo Estudos Linguist Aplicada, Florianopolis, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, BrazilUNIPAMPA Univ Fed Pampa, Curso Letras Linguas Adicionais, Campus Bage, RS, BrazilGEBAP Grp Estudos Bakhtinianos Pampa, Bage, BrazilGrp UNESP, Grp Estudos Alfabetizacao Brasil, Sao Paulo, Brazi
Chemogenetic activation of central gastrin‐releasing peptide‐expressing neurons elicits itch‐related scratching behavior in male and female mice
No full textAbstract Several lines of evidence have clarified that the key transmission pathways of itching sensation travel from the periphery to the central nervous system (CNS). Despite the functional significance of gastrin‐releasing peptide (GRP) and its cognate receptor in the itch processing mechanism in the spinal dorsal horn (SDH), the roles of GRP‐expressing (GRP+) neurons in different regions remain unclear. This study aimed to determine whether GRP+ neurons in the CNS directly modulated itch processing. To specifically activate spinal and supraspinal GRP neurons by the designer receptors exclusively activated by designer drugs (DREADDs) system, CAG‐LSL‐Gq‐DREADD mice were crossed with GRP‐Cre mice, resulting in the development of GRP‐hM3Dq mice. Immunohistochemistry showed that hM3Dq was highly expressed in the SDH and brainstem closely related to sensory processing. The intraperitoneal, intrathecal, or intracerebroventricular administration of clozapine‐N‐oxide, an agonist of hM3Dq, strongly elicited dermatome‐dependent itch‐related scratching behavior, but did not change pain sensitivity. Importantly, GRP‐Gq‐DREADD‐mediated scratching behavior in GRP‐hM3Dq mice was not affected by the ablation of transient receptor potential vanilloid 1+ sensory C‐fibers, and it was also observed to a similar degree under chronic itch conditions. Furthermore, there were no significant sex differences in the scratching behavior elicited by GRP‐Gq‐DREADD, suggesting that itch‐dominant roles of central GRP+ neurons might be common in both sexes, at least under normal physiological conditions. These novel findings not only contribute to understanding the functional roles of central GRP+ neurons further, but also propose the development of future effective therapeutics for intractable itching
Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP PATH extension study
No full textObjective To investigate the long-term safety and efficacy of weekly subcutaneous IgPro20 (Hizentra, CSL Behring) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods In a 48-week open-label prospective extension study to the PATH study, patients were initially started on 0.2 g/kg or on 0.4 g/kg weekly and-if clinically stable-switched to 0.2 g/kg weekly after 24 weeks. Upon CIDP relapse on the 0.2 g/kg dose, 0.4 g/kg was (re)initiated. CIDP relapse was defined as a deterioration by at least 1 point in the total adjusted Inflammatory Neuropathy Cause and Treatment score. Results Eighty-two patients were enrolled. Sixty-two patients initially received 0.4 g/kg, 20 patients 0.2 g/kg weekly. Seventy-two received both doses during the study. Sixty-six patients (81%) completed the 48-week study duration. Overall relapse rates were 10% in 0.4 g/kg-treated patients and 48% in 0.2 g/kg-treated patients. After dose reduction from 0.4 to 0.2 g/kg, 51% (27/53) of patients relapsed, of whom 92% (24 of 26) improved after reinitiation of the 0.4 g/kg dose. Two-thirds of patients (19/28) who completed the PATH study without relapse remained relapse-free on the 0.2 g/kg dose after dose reduction in the extension study. Sixty-two patients had adverse events (AEs) (76%), of which most were mild or moderate with no related serious AEs. Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious.Peer reviewe
Accuracy of the Adaptive GRP Scheme and the Simulation of 2-D Riemann Problems for Compressible Euler Equations
No full textThe adaptive generalized Riemann problem (GRP) scheme for 2-D compressible fluid flows has been proposed in [J. Comput. Phys., 229 (2010), 1448-1466] and it displays the capability in overcoming difficulties such as the start-up error for a single shock, and the numerical instability of the almost stationary shock. In this paper, we will provide the accuracy study and particularly show the performance in simulating 2-D complex wave configurations formulated with the 2-D Riemann problems for compressible Euler equations. For this purpose, we will first review the GRP scheme briefly when combined with the adaptive moving mesh technique and consider the accuracy of the adaptive GRP scheme via the comparison with the explicit formulae of analytic solutions of planar rarefaction waves, planar shock waves, the collapse problem of a wedge-shaped dam and the spiral formation problem. Then we simulate the full set of wave configurations in the 2-D four-wave Riemann problems for compressible Euler equations [SIAM J. Math. Anal., 21 (1990), 593-630], including the interactions of strong shocks (shock reflections), vortex-vortex and shock-vortex etc. This study combines the theoretical results with the numerical simulations, and thus demonstrates what Ami Harten observed "for computational scientists there are two kinds of truth: the truth that you prove, and the truth you see when you compute" [J. Sci. Comput., 31 (2007), 185-193].http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000298763800002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Physics, MathematicalSCI(E)16ARTICLE3577-6061
Durability and tolerability of first-line combination including two NRTI and RAL or ATV/r or DRV/r in patients enrolled in the ICONA Foundation cohort
No full textA randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation
No full textInvestigating the effects of recency and size of training text on author recognition problem
No full text19th International Symposium on Computer and Information Sciences (ISCIS 2004) -- OCT 27-29, 2004 -- Kemer Antalya, TURKEYPrediction by partial match (PPM) is an effective tool to address the author recognition problem. In this study, we have successfully applied the trained PPM technique for author recognition on Turkish texts. Furthermore, we have investigated the effects of recency, as well as size of the training text on the performance of the PPM approach. Results show that, more recent and larger training texts help decrease the compression rate, which, in turn, leads to increased success in author recognition. Comparing the effects of the recency and the size of the training text, we see that the size factor plays a more dominant role on the performance.Bilkent Univ, Dept Comp Engn, Inst Elect & Elect Engineers Turkey Sect, Working Grp, Int Federat Informat Proc, Sci & Tech Res Council Turke
[[alternative]]The Study on the Metacognition Performance of Junior High school Students in the Learning of Biology Through Integrated Technology
No full text[[abstract]]The aim of this research is for understanding the metacognition performance of junior high school students in the learning of biology through integrated technology, and comparing the metacognition performance of the student before and after the learning activities. The study is based on the action research, the teacher as the researcher. The research instruments including protofolios, classroom observation, semi-structured interview , questionnaires and other related methods.
Through the study methods of qualitative and quantitative , the results comes to appear the attitude of the students on learning with computer and by peer collaboration to obtain the resources through internet is positive. Among the research activities, the students perform diverse strategies metacognition including planning, monitoring, and assessment. Differences shows between the experimental grp. and the control grp., the former performed more diverse metacognition strategies than the latter. And the study indicated the sexual differentiation among the learning activities, while the students proceeding group study and peer collaboration through the internet, the cooperative attitude and the executive effect of the monitoring strategy of the girls are better than the boys.
According to the results and findings of this study, suggestions for teaching design of 9-integrated science and technology curriculum in junior high school were given. Besides, suggestions for constructing the scientific learning websites and the design of interaction software were given too, those are aimed to promote the study effect for the students in the learning environment through integrated with information technology.
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