Retro-inversion of certain cell-penetrating peptides causes severe cellular toxicity

AbstractCell-penetrating peptides (CPPs) are a promising group of delivery vectors for various therapeutic agents but their application is often hampered by poor stability in the presence of serum. Different strategies to improve peptide stability have been exploited, one of them being “retro-inversion” (RI) of natural peptides. With this approach the stability of CPPs has been increased, thereby making them more efficient transporters. Several RI-CPPs were here assessed and compared to the corresponding parent peptides in different cell-lines. Surprisingly, treatment of cells with these peptides induced trypsin insensitivity and rapid severe toxicity in contrast to l-peptides. This was measured as reduced metabolic activity and condensed cell nuclei, in parity with the apoptosis inducing agent staurosporine. Furthermore, effects on mitochondrial network, focal adhesions, actin cytoskeleton and caspase-3 activation were analyzed and adverse effects were evident at 20μM peptide concentration within 4h while parent l-peptides had negligible effects. To our knowledge this is the first time RI peptides are reported to cause cellular toxicity, displayed by decreased metabolic activity, morphological changes and induction of apoptosis. Considering the wide range of research areas that involves the use of RI-peptides, this finding is of major importance and needs to be taken under consideration in applications of RI-peptides

Retro-inversion of certain cell-penetrating peptides causes severe cellular toxicity

AbstractCell-penetrating peptides (CPPs) are a promising group of delivery vectors for various therapeutic agents but their application is often hampered by poor stability in the presence of serum. Different strategies to improve peptide stability have been exploited, one of them being “retro-inversion” (RI) of natural peptides. With this approach the stability of CPPs has been increased, thereby making them more efficient transporters. Several RI-CPPs were here assessed and compared to the corresponding parent peptides in different cell-lines. Surprisingly, treatment of cells with these peptides induced trypsin insensitivity and rapid severe toxicity in contrast to l-peptides. This was measured as reduced metabolic activity and condensed cell nuclei, in parity with the apoptosis inducing agent staurosporine. Furthermore, effects on mitochondrial network, focal adhesions, actin cytoskeleton and caspase-3 activation were analyzed and adverse effects were evident at 20μM peptide concentration within 4h while parent l-peptides had negligible effects. To our knowledge this is the first time RI peptides are reported to cause cellular toxicity, displayed by decreased metabolic activity, morphological changes and induction of apoptosis. Considering the wide range of research areas that involves the use of RI-peptides, this finding is of major importance and needs to be taken under consideration in applications of RI-peptides

SOBcows - Specialized organic breeding goals and breeding schemes within dairy production

This presentation provides an overview of the results from the projects "The optimal cow" and "SOBcows". The aim of "The optimal cow" is to derive economic values for breeding goal traits in four different production systems, among them an organic production system. The aim of "SOBcows" is to enhance the size and the profitability of the organic dairy production by adapting the breeding material to organic production circumstances and by indicating sustainable methods for sustainable niche production based on animals with specific genetic characteristic

A comparison between medication reconciliation by a pharmacy technician and the use of an online personal health record by patients for identifying medication discrepancies in patients' drug lists prior to elective admissions

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Barriers and facilitators for the usage of a personal health record for medication reconciliation: a qualitative study among patients

AIM: Personal health records (PHRs) are more often used for medication reconciliation (MR). However, patients' adoption rate is low. We aimed to provide insight into patients' barriers and facilitators for the usage of a PHR for MR prior to an in- or outpatient visit. METHODS: A qualitative study was conducted among PHR users and non-users who had a planned visit at the outpatient rheumatology department or the inpatient cardiology or neurology department. About one week after the hospital visit, patients were interviewed about barriers and facilitators for the usage of a PHR for MR using a semi-structured interview guide based on the theoretical domains framework. Afterwards, data were analysed following thematic analysis. RESULTS: Ten PHR users and non-users were interviewed. Barriers and facilitators were classified in four domains: patient, application, process and context. We identified fourteen barriers like limited (health) literacy and/or computer skills, practical and technical issues, ambiguity about who is responsible (the patient or the healthcare provider) and lack of data exchange and connectivity between applications. Besides that, ten facilitators were identified like place and time independent, improve usability, target patients who benefit most and/or have sufficient skills and integration of different applications. CONCLUSION: Barriers and facilitators identified at the patient, application, process and context level, need to be addressed to effectively develop and implement PHRs for MR

Barriers and facilitators for the usage of a personal health record for medication reconciliation:a qualitative study among patients

AIMS: Personal health records (PHRs) are more often used for medication reconciliation (MR). However, patients' adoption rate is low. We aimed to provide insight into patients' barriers and facilitators for the usage of a PHR for MR prior to an in- or outpatient visit. METHODS: A qualitative study was conducted among PHR users and non-users who had a planned visit at the outpatient rheumatology department or the inpatient cardiology or neurology department. About 1 week after the hospital visit, patients were interviewed about barriers and facilitators for the usage of a PHR for MR using a semi-structured interview guide based on the theoretical domains framework. Afterwards, data were analysed following thematic analysis. RESULTS: Ten PHR users and non-users were interviewed. Barriers and facilitators were classified in four domains: patient, application, process and context. We identified 14 barriers including limited (health) literacy and/or computer skills, practical and technical issues, ambiguity about who is responsible (the patient or the healthcare provider) and lack of data exchange and connectivity between applications. Besides that, ten facilitators were identified including being place and time independent, improve usability, target patients who benefit most and/or have sufficient skills, and integration of different applications. CONCLUSION: Barriers and facilitators identified at the patient, application, process and context level, need to be addressed to effectively develop and implement PHRs for MR

Shellfish bed restoration pilots Voordelta, Netherlands : Annual report 2018

The general objectives of the shellfish bed restoration pilots in the Voordelta are: to select suitable locations for shellfish bed restoration, identify critical factors for shellfish bed development, develop methods for shellfish bed restoration and explore the implications of this project for shellfish bed restoration in the wider North Sea area