Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Effect and mechanism of lipopolysaccharide on allergen-induced interleukin-5 and eotaxins production by whole blood cultures of atopic asthmatics

Interleukin (IL)-5 and eotaxin families regulate the development of eosinophilic inflammation of asthma in a co-operative manner. The exposure to airborne lipopolysaccharide (LPS) induces varying degrees of airflow obstruction and neutrophilic airway inflammation. Production of IL-5 and eotaxin subfamily chemokines was analysed in response to Dermatophagoides pteronyssinus allergen (D.p.) according to the presence of specific IgE to D.p., and investigated the mechanism underlying their LPS-mediated regulation of these cytokines in response to the specific allergen. Peripheral blood cells (PBCs) from asthmatics with (group 1) or without (group 2) specific IgE to D.p. and from non-asthmatics with (group 3) or without (group 4) were stimulated with D.p. or LPS. For LPS-mediated inhibition of IL-5 and eotaxin-2 production, LPS-induced cytokines were added to the D.p.-stimulated PBCs. IL-5 and eotaxin-2, but not eotaxin-1 and 3, were significantly increased by D.p.-stimulated-PBCs from group 1, while only eotaxin-2 was elevated in group 3. Eotaxin-2 production was found in monocytes and correlated with the level of specific IgE to D.p. LPS treatment resulted in the decrease in eotaxin-2 and IL-5 production by the D.p.-stimulated PBCs. LPS-induced IL-10 completely inhibited D.p.-stimulated production of eotaxin-2 and IL-5. The differential responses of the eotaxin family to specific antigens suggest that the predominant role of eotaxin-2 and LPS may attenuate eosinophilic inflammation by inhibiting IL-5 and eotaxin-2 synthesis through IL-10 production

Mechanism of Heparin Acceleration of Tissue Inhibitor of Metalloproteases-1 (TIMP-1) Degradation by the Human Neutrophil Elastase

Heparin has been shown to regulate human neutrophil elastase (HNE) activity. We have assessed the regulatory effect of heparin on Tissue Inhibitor of Metalloproteases-1 [TIMP-1] hydrolysis by HNE employing the recombinant form of TIMP-1 and correlated FRET-peptides comprising the TIMP-1 cleavage site. Heparin accelerates 2.5-fold TIMP-1 hydrolysis by HNE. The kinetic parameters of this reaction were monitored with the aid of a FRET-peptide substrate that mimics the TIMP-1 cleavage site in pre-steady-state conditionsby using a stopped-flow fluorescence system. The hydrolysis of the FRET-peptide substrate by HNE exhibits a pre-steady-state burst phase followed by a linear, steady-state pseudo-first-order reaction. The HNE acylation step (k2 = 21±1 s−1) was much higher than the HNE deacylation step (k3 = 0.57±0.05 s−1). The presence of heparin induces a dramatic effect in the pre-steady-state behavior of HNE. Heparin induces transient lag phase kinetics in HNE cleavage of the FRET-peptide substrate. The pre-steady-state analysis revealed that heparin affects all steps of the reaction through enhancing the ES complex concentration, increasing k1 2.4-fold and reducing k−1 3.1-fold. Heparin also promotes a 7.8-fold decrease in the k2 value, whereas the k3 value in the presence of heparin was increased 58-fold. These results clearly show that heparin binding accelerates deacylation and slows down acylation. Heparin shifts the HNE pH activity profile to the right, allowing HNE to be active at alkaline pH. Molecular docking and kinetic analysis suggest that heparin induces conformational changes in HNE structure. Here, we are showing for the first time that heparin is able to accelerate the hydrolysis of TIMP-1 by HNE. The degradation of TIMP-1is associated to important physiopathological states involving excessive activation of MMPs

Soft Skills

Der Begriff Soft Skills wird sehr unterschiedlich verwendet. Wir verstehen darunter überfachliche, nicht berufsspezifische Kompetenzen, welche für den Erfolg in der Arbeitswelt unabdingbar sind. Sie umfassen sowohl die Fähigkeit, mit anderen zu kommunizieren und zusammenzuarbeiten (interpersonell) als auch sich selbst zu organisieren und zu disziplinieren (intrapersonell). Zu den Soft Skills zählen im Wesentlichen die Kommunikations-, Team- und Konfliktlösungs- sowie die Motivationsfähigkeit. Im Gegensatz zu den Hard Skills (berufsspezifische Kompetenzen) können Soft Skills nur indirekt über entsprechende Indikatoren gemessen werden. Der grosse Einfluss der Soft Skills für Erfolg oder Nichterfolg in der Arbeitswelt wurde in verschiedenen Studien für unterschiedliche Berufe und Kulturen nachgewiesen. Kurzum: erfolgreiche Arbeitnehmerinnen und Arbeitnehmer verfügen neben Hard Skills auch über ausgeprägte Soft Skills. Glücklicherweise sind Soft Skills zum Teil erlernbar

The contribution of modern margarine and fat spreads to dietary fat intake

The study of dietary fat consumption and its resultant effects on human health has been one of the most investigated topics in the field of human nutrition. Based on the results obtained from such studies, specific dietary recommendations on fat intake (both in terms of quantity and quality) have been established by health organizations around the globe. Among the various food industry sectors, the margarine manufacturers have also responded to these guidelines and now offer improved formulations with a desirable balance of fat contents and fat types. The main aim of this article is to provide an overview on how these modern margarines can contribute towards reaching the dietary guidelines relating to fat intake. In particular, the dietary recommendations with respect to the specific fatty acid types are comprehensively detailed along with an emphasis on the role of modern margarines in providing balanced fat types (more polyunsaturated fats, less saturated fats and a near-complete absence of trans fats) in the daily diet

The Northern Bald Ibis Geronticus eremitain Morocco since 1900: Analysis of ecological requirements

The Northern Bald Ibis (NBI) Geronticus eremita, is an ‘Endangered’ bird species of which only very few wild breeding colonies have survived along the Atlantic coast of south-west Morocco. This paper analyses ecological conditions of the 72 breeding sites of the NBI that have been known since 1900 in Morocco. Characterisation of breeding sites is based on physical criteria (elevation above sea level, geomorphology, mean annual precipitation and types of landscape) as well as land use, vegetation cover, infrastructure and types of settlement within three perimeters (0–1 km, > 1–5 km and > 5–10(20) km) using Google Earth satellite images. Statistical analyses of the number of breeding pairs, fledglings and rainfall during different quarters of the year from 1994 to 2016 in the two remaining breeding sites in Souss-Massa National Park and Tamri showed expected patterns as well as unexpected differences between the two localities. Based on our findings and indications in the literature, we suggest general and specific recommendations for potential future translocation projects of the NBI. Based on the analysis of the 28 breeding colonies existing after 1977, two elements emerge as the most important prerequisites: a low level of disturbances at the breeding sites and adequate feeding areas at a reasonable distance of 5–15 km