Integrins affecting mechanical strain-induced expression of egr-1 in vascular smooth muscle cells

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 27-29).Integrins are transmembrane proteins that anchor cells to the extracellular matrix, ECM, and they are thought to play a very important role in the transmission of signals between the ECM and the cell. The cells of interest in this study are the vascular smooth muscle (VSM) cells, specifically the mouse aortic VSM cells, which are constantly under cyclic mechanical strain. It has been shown in previous studies that this strain induces proliferation of the cells by autocrine action of platelet derived growth factor (PDGF). The PDGF promoter contains a binding site for the transcription factor, early growth response gene-1 (Egr-1). It was previously shown that when the cell undergoes cyclic mechanical strain, Egr-1 mRNA expression is significantly increased. The scope of this study is to determine the integrins that are involved in the mechanical signaling via cyclic mechanical strain. Introducing neutralizing antibodies that block the function of the integrins and subjecting VSM cells to mechanical strain with the Flexercell strain unit may lead to the deduction of the integrins that are involved in transmitting the signal to increase Egr-1 mRNA expression. Egr-1 expression would be expected to decrease when the integrin that is transducing the strain response is blocked. The RT-PCR procedure was developed and used for determination of Egr- 1 mRNA expression through the course of this study. There are still many problems that must be assessed before the integrin may deduced. Problems in the procedure including antibody concentrations, in the handling of cells and RNA, and in the basal expression of the Egr-1 mRNA arose through the course of the study. From the latest experiment and from previous studies by Wilson et al., it is suggested that the b3 subunit and thus the anb3 integrin may be responsible for transducing the mechanical strain signal and increasing Egr-1 mRNA expression

Challenges Faced by the Biopharmaceutical Industry in the Development and Marketing Authorization of Biosimilar Medicines in BRICS-TM Countries: An Exploratory Study

Abstract: Background: Biosimilars are expected to emerge as a rapidly growing segment of the biopharmaceutical industry. However, the biosimilar industry faces multiple challenges and obstacles in developing and marketing these complex products. Divergent regulatory framework in emerging countries adds to repetitive trials and increased cost of biosimilar development, delaying the approval process. Due to such roadblocks, healthcare systems and patients are yet to realize the full benefits of biosimilars. Objectives: The aim of this exploratory study was to specifically identify the challenges faced by the industry in emerging countries including Brazil, Russia, India, China, South Africa, Turkey and Mexico (BRICS-TM), pertaining to biosimilar development and the regulatory approval process. In particular, this study aims to understand the perceptions of industry on the barriers faced by them in terms of complexity, costs for biosimilar development and time-to-market for biosimilar product. Methods: A semi-quantitative questionnaire was designed based on secondary research. A total of 93 industry personnel and representatives from 14 trade associations from the BRICS-TM countries with 15-year minimum experience were identified and invited to take part in the study and participate in interviews, which were recorded verbatim. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data. Results: Of the 107 biopharmaceutical industry and trade association representatives invited to participate in the study, respondents from 33 biopharmaceutical companies agreed to take part and underwent the interviews. The industry personnel perceived biosimilar guidelines and approval processes as being protracted and in a state of evolution. The absence of an abridged approval pathway limited effectiveness of the regulatory process. The biggest hurdles in the development of biosimilar dossiers were the sourcing of the reference biological product and expectations around confirmatory clinical trials by the agencies. The non-comprehensive implementation of a stepwise approach resulting in unnecessary toxicity studies was also reported as a major challenge. The authors recommend further primary research with BRICS-TM regulatory agencies in order to propose a simplified pathway for development and approval. Conclusions: Lack of standardized biosimilar development criteria and regulatory convergence across BRICS-TM agencies has led to challenges in multi-country development programmes for these medicines, in turn impacting the ability of industry to launch newer and more affordable biosimilars.Peer reviewe

Development of a telehealth monitoring service after colorectal surgery: a feasibility study

AIM: To evaluate the feasibility of a text-messaging system to remotely monitor and support patients after discharge following elective colorectal surgery, within an enhanced recovery protocol. METHODS: Florence (FLO) is a National Health Service telehealth solution utilised for monitoring chronic health conditions, such as hypertension, using text-messaging. New algorithms were designed to monitor the well-being, basic physiological observations and any patient-reported symptoms, and provide support messages to patients undergoing colorectal surgery within an enhanced recovery after surgery protocol for 30 d after discharge. All interactions with FLO and physiological readings were recorded and patients were invited to provide feedback. RESULTS: Over a four-week period, 16 out of 17 patients used the FLO telehealth service at home. These patients did not receive telephone follow-up at three days, as per our standard protocol, unless they reported being unwell or did not make use of the technology. Three patients were readmitted within 30 d, and two of these were identified as being unwell by FLO prior to readmission. No adverse events attributable to the use of the technology were encountered. CONCLUSION:The utilisation of telehealth in the early follow-up of patients who have undergone major colorectal surgery after discharge is feasible. The use of this technology may assist in the early recognition and management of complications after discharge

Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care

BACKGROUND: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited. AIMS: To assess the yield of IBD from FC testing in primary care. METHODS: Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed. RESULTS: 410 patients (162 male; median age 42; range 16-91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17-91)) were FC+ (median FC 116.5 µg/g (51-1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC-) patients (FC ≤50 µg/g) (median age 47 (19-76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn's disease, 4 microscopic colitis). 8/11 were FC+ (range 67-1170) and 3 FC-. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%. CONCLUSIONS: FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly

DIVERSIDADE RELIGIOSIDADE E EDUCAÇÃO

Este trabalho integra o Projeto de Pesquisa Formação Continuada e Produção de Metodologias de Ensino Pautadas na Diversidade Cultural, coordenado pela Profª. Drª. Ana Clédina Rodrigues Gomes – professora da Universidade Federal do Sul e Sudeste do Pará (Unifesspa) e contou com o financiamento da Pró-Reitoria de Ensino de Graduação da Unifesspa, através do Programa de Apoio a Projetos de Intervenção Metodológica (PAPIM). O objetivo do referido projeto foi realizar um programa de formação continuada sobre temáticas relacionadas à diversidade cultural e que envolvesse professores (as) que atuam na Educação de Ensino Fundamental em escolas da rede municipal de ensino de Marabá, no estado do Pará. Uma das ações propostas no projeto foi a realização do minicurso “Educação para a Diversidade: Religiosidade e Cultura”, o qual surgiu a partir do relato apresentado pelos (as) professores (as) da Escola participante do projeto. Na apresentação das várias temáticas que envolvem a Diversidade Cultural foi selecionada a temática “Diversidade Religiosa” a ser explorada, tendo em vista a demanda apresentada pela escola nesse campo

DOIS GESTOS DE LEITURA EM HISTÓRIA DAS IDEIAS LINGUÍSTICAS: A ORTOGRAFIA E O DICIONÁRIO EM PAUTA

Neste artigo, apresentamos o objeto de análise da História das Ideias Linguísticas: o saber metalinguístico e o modo como as línguas nacionais se estruturam. Descrevemos as particularidades que possibilitam os aspectos teóricos-metodológicos dessa corrente dos estudos linguísticos, mais especificamente no espaço de produção de conhecimento do território brasileiro. Partindo dessa compreensão, empreendemos dois gestos de leitura bastante particulares que põem em funcionamento um modo de compreensão dos fatos de linguagem pelo itinerário da História das Ideias Linguísticas: a ortografia e o dicionário. Para darmos conta desse objetivo, iniciamos por uma reflexão sobre a gramatização da língua portuguesa do Brasil e o modo como a historicidade dá corpo a esse objeto de conhecimento. DOI: https://doi.org/10.47295/mren.v8i2.196

Correction to: The LUCID study: living with ulcerative colitis; identifying the socioeconomic burden in Europe.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-12-01, epub 2021-12-15Publication status: Publishe