Morphine modulation of pain processing in medial and lateral pain pathways

<p>Abstract</p> <p>Background</p> <p>Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording technique. Pain evoked neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with eight-wire microelectrode arrays in awake rats.</p> <p>Results</p> <p>The results showed that the noxious heat evoked responses of single neurons in all of the four areas were depressed after systemic injection of 5 mg/kg morphine. The depressive effects of morphine included (i) decreasing the neuronal response magnitude; (ii) reducing the fraction of responding neurons, and (iii) shortening the response duration. In addition, the capability of cortical and thalamic neural ensembles to discriminate noxious from innocuous stimuli was decreased by morphine within both pain pathways. Meanwhile, morphine suppressed the pain-evoked changes in the information flow from medial to lateral pathway and from cortex to thalamus. These effects were completely blocked by pre-treatment with the opiate receptor antagonist naloxone.</p> <p>Conclusion</p> <p>These results suggest that morphine exerts analgesic effects through suppressing both sensory and affective dimensions of pain.</p

Isolation of Rhp-PSP, a Member of YER057c/YjgF/UK114 Protein Family with Antiviral Properties, from the Photosynthetic Bacterium \u3cem\u3eRhodopseudomonas palustris\u3c/em\u3e Strain JSC-3b

Rhodopseudomonas palustris strain JSC-3b isolated from a water canal adjacent to a vegetable field produces a protein that was purified by bioactivity-guided fractionation based on ammonium sulfate precipitation, ion-exchange absorption and size exclusion. The protein was further identified as an endoribonuclease L-PSP (Liver-Perchloric acid-soluble protein) by shotgun mass spectrometry analysis and gene identification, and it is member of YER057c/YjgF/UK114 protein family. Herein, this protein is designated Rhp-PSP. Rhp-PSP exhibited significant inhibitory activities against tobacco mosaic virus (TMV) in vivo and in vitro. To our knowledge, this represents the first report on the antiviral activity of a protein of the YER057c/YjgF/UK114 family and also the first antiviral protein isolated from R. palustris. Our research provides insight into the potential of photosynthetic bacterial resources in biological control of plant virus diseases and sustainable agriculture

Clinical spectrum and gene mutations in a Chinese cohort with anoctaminopathy

Recessive mutations in anoctamin-5 (ANO5) are causative for limb-girdle muscular dystrophy (LGMD) 2L and non-dysferlin Miyoshi-like distal myopathy (MMD3). ANDS mutations are highly prevalent in European countries; however it is not common in patients of Asian origin, and there is no data regarding the Chinese population. We retrospectively reviewed the clinical manifestations and gene mutations of Chinese patients with anoctaminopathy. A total of five ANDS mutations including four novel mutations and one reported mutation were found in four patients from three families. No hotspot mutation was found. Three patients presented with presymptomatic hyperCKemia and one patient had limb muscle weakness. Muscle imaging of lower limbs showed preferential adductor magnus and medial gastrocnemius involvement. No hotspot mutation has been identified in Chinese patients to date. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe

Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery

Purpose: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. Methods: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. Results: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p&lt;0.001). Group A had the longest bleb survival time in comparison with other groups (p&lt;0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p&lt;0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 +/- 0.05) ng/ml at day 3 to (7.74 +/- 0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25 +/- 3.24%) compared to other groups (p&lt;0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75 +/- 1.71% and 8.50 +/- 1.92%) compared to the Group B and D (p&lt;0.01). Conclusions: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000295289900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry &amp; Molecular BiologyOphthalmologySCI(E)9ARTICLE270-712495-25061

Social Protection and Child Protection: Two Sides of the Same Coin?

There is widespread recognition that children are a particularly vulnerable group; they have different basic needs than adults do, they are dependent on others for the fulfilment of their needs and the denial of those needs can have far-reaching and long-term adverse consequences (Roelen and Sabates-Wheeler 2012, White, Leavy, and Masters 2003, Sabates-Wheeler, Devereux, and Hodges 2009). The policy areas of social protection and child protection are part and parcel of the response to children and their vulnerabilities. Nevertheless, both policy areas have largely developed in silos (Roelen, Long, and Edstrom 2012). This holds in both academic and policy terms. Whilst issues of child protection are mostly dealt with in disciplines of child psychology and childhood studies, social protection is largely appropriated by economists and social scientists. Similarly, national governments, international organisations and NGOs often deal with issues of child protection and social protection in different departments and through distinct sectoral policies. It is increasingly recognised that this dichotomy is artificial (Shibuya and Taylor 2013), and that it compromises the effectiveness of the response to the wide set of needs of vulnerable children

Ilustrações de cartilhas escolares na Primeira República (1889-1930) : a historiografia da educação no Espírito Santo por entre traços e espaços em branco

Este estudo objetivou investigar significados das ilustrações contidas nas cartilhas utilizadas no ensino primário, no Espírito Santo, na Primeira República, sendo que, nesse recorte temporal, procuramos tomar as duas reformas educacionais capixabas desse período: a Reforma Gomes Cardim (1908-1909) e a Reforma Atílio Vivacqua (1928-1930), como de pontos de referência em nossa investigação. Partindo de uma análise dessas ilustrações no conjunto de projetos políticos, pedagógicos, culturais e estéticos que perpassaram a escolarização no Espírito Santo, procuramos mapear o panorama que contextualizava a produção dessas ilustrações, nas esferas: social, política, econômica, cultural e educacional, procurando compreender suas relações de força e possíveis tensões; investigar se as ilustrações se relacionavam com os métodos de ensino propostos nas cartilhas, procurando estabelecer e compreender a presença ou ausência dessa relação nas práticas pedagógicas propostas para o ensino primário capixaba, nesse período; bem como, verificar quais os possíveis impactos e reflexos das Reformas Educacionais ocorridas na Primeira República, no Espírito Santo, sobre as ilustrações nas cartilhas, procurando identificá-los. Nessa investigação historiográfica, nossa ancoragem teórico-metodológica fundamenta-se em interlocuções com Marc Bloch, em sua perspectiva histórica, onde buscamos compreensão do ofício do historiador, de modo que, privilegiando a multiplicidade das fontes, procuramos tensioná-las a fim de alcançar o seu testemunho histórico; em Ginzburg, construímos fundamentos que nos permitiram tomar o método indiciário como ferramenta de pesquisa, assim como, suas reflexões sobre morfologia das imagens, por meio do método morelliano, e suas aproximações com as teorias warbuguianas, nos embasaram na abordagem histórica e leitura de fontes iconográficas; por fim, em Benjamin, procuramos compreender o contexto de produção das ilustrações, que, pertencendo ao campo de domínio da linguagem da arte, em suas várias formas de expressões, abrangem percepções de mundo, do seu momento histórico. Desse modo, analisando, historicamente, as ilustrações nas cartilhas, percebemos que as mesmas se constituem como indícios que nos oferecem pistas de propostas pedagógicas, tendências metodológicas e políticas públicas, do espaço e tempo de sua produção, circulação e utilização. Portanto, concluímos que as ilustrações têm a potência de narrativas de uma cultura escolar, ao representarem palavras, textos e temas, assim sendo, detêm valores, sentidos e significados. Portanto, enquanto objetos culturais, trazem informações, que registram pontos de vista culturais e escolares das épocas, além dos elementos que desenvolvem habilidades de leitura e escrita. À vista disso, concluímos que as ilustrações e seus significados, que lhe são atribuídos ao longo do tempo nos espaços escolares, se constituem como possibilidades que oportunizam narrativas historiográficas.This study aimed to investigate meanings of the illustrations contained in textbooks used in primary education in Espírito Santo, during the First Republic. Given this time frame, we attempted to take both capixaba educational reformations: Gomes Cardim Reformation (1908-1909) and the Atilio Vivacqua Reformation (1928-1930), as benchmarks in our investigation. Based on an analysis of these illustrations on the set of political, educational, cultural and aesthetic projects that permeated the school in Espírito Santo, we tried to map the landscape that contextualized the production of these illustrations, in the social, political, economic, cultural and educational realms, seeking to understand their power relations and possible tensions; investigating whether the illustrations were related to the teaching methods proposed in the textbooks, and trying to establish and understand the presence or absence of that relationship in the pedagogical practices proposed for the capixaba primary education in this period, as well as check what the possible impacts and outcomes of Educational Reforms occurred in the First Republic, in Espírito Santo on the illustrations in textbooks were, trying to identify them. For this historiographical research, our theoretical and methodological anchoring is based on dialogues with Marc Bloch, in his historical perspective, where we seek understanding of the historian's craft, so that in favoring the multiplicity of sources, we attempt to bend them in order to achieve their historical testimony; in Ginzburg, we build foundations that allowed us to take the evidential method as a research tool, as well as his reflections on the morphology of images, through the Morellian method and its approach to the Warburgian theories, which supported with the historical approach and the "reading" of iconographic sources; Finally, in Benjamin, we tried to understand the context of production of illustrations, which, belonging to the domain of the language of art, in its various forms of expression, encompasses perceptions of the world, and its historical moment. Thus, historically, analyzing the illustrations in textbooks, we realize that they constitute as evidence that give away hints of educational proposals, methodological trends and public policies, about the space and time of its production, circulation and use. We therefore conclude that the illustrations have the narrative power of a school culture, as they represent words, texts and themes, therefore, holding values, senses and meanings. Therefore, as cultural objects, provide information, which record cultural and school views of their times besides the elements meant to develop reading and writing skills. In view of this, we conclude that the illustrations and their meanings, which are assigned over the course of time in school spaces, are constituted as possibilities that allow for historiographical narratives.FAPE

The effect on the extracellular matrix of the deep fascia in response to leg lengthening

<p>Abstract</p> <p>Background</p> <p>Whereas the alterations of diverse tissues in cellular and molecular levels have been investigated during leg lengthening via microscopy and biochemical studies, little is known about the response of deep fascia. This study aims to investigate the changes of the extracellular matrix in deep fascia in response to leg lengthening.</p> <p>Methods</p> <p>Animal model of leg lengthening was established in New Zealand white rabbits. Distraction was initiated at a rate of 1 mm/day and 2 mm/day in two steps, and preceded until increases of 10% and 20% in the initial length of tibia had been achieved. Alcian blue stain and picrosirius-polarization method were used for the study of the extracellular matrix of deep fascia samples. Leica DM LA image analysis system was used to investigate the quantitative changes of collagen type I and III.</p> <p>Results</p> <p>Alcian blue stain showed that glycosaminoglycans of fascia of each group were composed of chondroitin sulphate and heparin sulphate, but not of keratan sulphate. Under the polarization microscopy, the fascia consisted mainly of collagen type I. After leg lengthening, the percentage of collagen type III increased. The most similar collagen composition of the fascia to that of the normal fascia was detected at a 20% increase in tibia length achieved via a distraction rate of 1 mm/d.</p> <p>Conclusion</p> <p>The changes in collagen distribution and composition occur in deep fascia during leg lengthening. Although different lengthening schemes resulted in varied matrix changes, the most comparable collagen composition to be demonstrated under the scheme of a distraction rate of 1 mm/day and 20% increase in tibia length. Efficient fascia regeneration is initiated only in certain combinations of the leg load parameters including appropriate intensity and duration time, e.g., either low density distraction that persist a relatively short time or high distraction rates.</p

A transcriptome anatomy of human colorectal cancers

BACKGROUND: Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. METHODS: In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. RESULTS: The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. CONCLUSION: Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers