New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma

Abstract The use of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro Ki determination, the most promising compound, 2-[18F]-2-fluoroethyl-l-phenylalanine (2-[18F]FELP), was selected for further evaluation and in vitro comparison with [18F]FET. Subsequently, 2-[18F]FELP was assessed in vivo and compared with [18F]FET and [18F]FDG in a F98 glioblastoma rat model. 2-[18F]FELP showed improved in vitro characteristics over [18F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[18F]FELP is a promising new PET tracer for brain tumor imaging

TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS

Veneuze ulcera: verpleegkundige aspecten

status: publishe

Under pressure: effects of standardization of compression therapy in venous leg ulcers in nursing

status: publishe

Under pressure : effects of standardization of compression therapy in venous leg ulcers in nursing

Background: Venous ulcers are the most common chronic wounds in the aging population. Compression therapy forms the cornerstone of venous leg ulcer treatment. There is strong evidence that it enhances leg ulcer healing rates and prevents recurrence. Nevertheless a discrepancy between evidence and practice exists. Literature reveals a lack of knowledge and skills of nurses regarding compression therapy as one of the key reasons. Aim: To examine if a standard education package for community nurses regarding venous ulcer treatment, will lead to a more adequate subbandage pressure, a better performance of the ulcer, pain reduction and longer wearing of compression bandages. Method: Based on literature and international guidelines an evidence-based education package was developed. Experts in wound care, doctors and community nurses were contacted to validate the education package trough a Delphi-procedure. The training focuses both on knowledge and skills related to compression therapy. A group of community nurses will be trained using the standard education package. An other group of home care nurses will receive no additional education. The subbandage pressure, wound evolution, pain and compression wearing time of venous ulcer patients will be compared between both groups. Relevance: Enhancing the knowledge and skills of nurses may result in a better quality of life of patients with a venous ulcer, a faster healing of the ulcer and may reduce the costs of long-term health care treatment

Under pressure: effects of standardization of compression therapy in venous leg ulcers in nursing

UNDER PRESSURE: EFFECTS OF STANDARDIZATION OF COMPRESSION THERAPY IN VENOUS LEG ULCERS IN NURSING Caroline Goeman1, Hilde Boucqué1, Jos Van Der Veken1-2. 1Katholieke Hogeschool Sint-Lieven (Aalst, Belgium) 2Universiteit Gent (Gent, Belgium) Background: Venous ulcers are the most common chronic wounds in the aging population. Compression therapy forms the cornerstone of venous leg ulcer treatment. There is strong evidence that it enhances leg ulcer healing rates and prevents recurrence. Nevertheless a discrepancy between evidence and practice exists. Literature reveals a lack of knowledge and skills of nurses regarding compression therapy as one of the key reasons. Aim: To examine if a standard education package for community nurses regarding venous ulcer treatment, will lead to a more adequate subbandage pressure, a better performance of the ulcer, pain reduction and longer wearing of compression bandages. Method: Based on literature and international guidelines an evidence-based education package was developed. Experts in wound care, doctors and community nurses were contacted to validate the education package trough a Delphi-procedure. The training focuses both on knowledge and skills related to compression therapy. A group of community nurses will be trained using the standard education package. An other group of home care nurses will receive no additional education. The subbandage pressure, wound evolution, pain and compression wearing time of venous ulcer patients will be compared between both groups. Relevance: Enhancing the knowledge and skills of nurses may result in a better quality of life of patients with a venous ulcer, a faster healing of the ulcer and may reduce the costs of long-term health care treatment.status: publishe

Clinical practice guidelines and principles of care for people with dementia: a protocol for undertaking a Delphi technique to identify the recommendations relevant to primary care nurses in the delivery of person-centred dementia care

Introduction Nationally and internationally it is well recognised that dementia is poorly recognised and suboptimally managed in the primary care setting. There are multiple and complex reasons for this gap in care, including a lack of knowledge, high care demands and inadequate time for the general practitioner alone to manage dementia with its multiple physical, psychological and social dimensions. The primary care nurse potentially has a role in assisting the general practitioner in the provision of evidence-based dementia care. Although dementia-care guidelines for general practitioners exist, evidence on resources to support the primary care nurse in dementia care provision is scarce. The ‘Australian Clinical Practice Guidelines and Principles of Care for People with Dementia’ provides 109 recommendations for the diagnosis and management of dementia. This protocol describes a Delphi study to identify which of the 109 recommendations contained in these multidisciplinary guidelines are relevant to the primary care nurse in the delivery of person-centred dementia care in the general practice setting.Methods and analysis Using a Delphi consensus online survey, an expert panel will grade each of the recommendations written in the ‘Clinical Practice Guidelines and Principles of Care for People with Dementia’ as high-to-low relevance with respect to the role of the primary care nurse in general practice. To optimise reliability of results, quality indicators will be used in the data collection and reporting of the study. Invited panel members will include Australian primary care nurses working in general practice, primary care nursing researchers and representatives of the Australian Primary Health Care Nurses Association, the peak professional body for nurses working in primary healthcare.Ethics and dissemination This study has been approved by The University of Newcastle Human Research Ethics Committee (HREC) (H-2019-0029).Findings will be published in a peer-reviewed journal and presented at scientific conferences