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Background: The diagnosis of myocarditis by CMR requires the use of T2 and T1 weighted imaging, ideally incorporating parametric mapping. Current 2D mapping sequences are acquired sequentially and involve multiple breath-holds resulting in prolonged scan times and anisotropic image resolution. We developed an isotropic free-breathing 3D whole-heart sequence which allows simultaneous T1 and T2 mapping and validated it in patients with suspected acute myocarditis., Methods: Eighteen healthy volunteers and 28 patients with suspected myocarditis underwent conventional 2D T1 and T2 mapping with whole heart coverage and 3D joint T1/T2 mapping on a 1.5T scanner. Acquisition time, image quality, and diagnostic performance were compared. Qualitative analysis was performed using a 4-point Likert scale. Bland-Altman plots were used to assess the quantitative agreement between 2D and 3D sequences., Results: The 3D T1/T2 sequence was acquired in 8mins 26s under free breathing, whereas 2D T1 and T2 sequences were acquired with breath holds in 11mins 44s (p=0.0001). All 2D images were diagnostic. For 3D images, 89% of T1 and 96% of T2 images were diagnostic with no significant difference in the proportion of diagnostic images for the 3D and 2D T1 (p=0.2482) and T2 maps (p=1.0000). Systematic bias in T1 was noted with biases of 102ms, 115ms, and 152ms for basal-apical segments, with a larger bias for higher T1 values. Good agreement between T2 values for 3D and 2D techniques was found (bias of 1.8ms, 3.9ms, and 3.6ms for basal-apical segments). The sensitivity and specificity of the 3D sequence for diagnosing acute myocarditis was 74% (95% confidence interval [CI] 49-91%) and 83% (36-100%) respectively, with an estimated c-statistic (95% CI) of 0.85 (0.79-0.91) and no statistically significant difference between the 2D and 3D sequences for the detection of acute myocarditis for T1 (p=0.2207) or T2 (p=1.0000)., Conclusion: Free-breathing whole heart 3D joint T1/T2 mapping was comparable to 2D mapping sequences with respect to diagnostic performance, but with the added advantages of free-breathing, and shorter scan times. Further work is required to address the bias noted at high T1 values, but this did not significantly impact on diagnostic accuracy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Alina Hua reports financial support was provided by British Heart Foundation. Instutition support reports financial support was provided by National Institute for Health Research. Dr Karl P Kunze is an employee of Siemens Healthcare Limited. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests Dr Karl P Kunze is an employee of Siemens Healthcare Limited., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although there is evidence that tailored implementation strategies can be effective, there is little evidence on which methods of tailoring improve the effect. We designed and evaluated five tailored programs (TPs) each consisting of various strategies. The aim of this study was to examine (a) how determinants of practice prioritized in the design phase of the TPs were perceived by health care professionals who had been exposed to the TPs and whether they suggested other important determinants of practice and (b) how professionals used the offered strategies and whether they suggested other strategies that might have been more effective., Methods: We conducted a mixed-method process evaluation linked to five cluster-randomized trials carried out in five European countries to implement recommendations for five chronic conditions in primary care settings. The five TPs used a total of 28 strategies which aimed to address 38 determinants of practice. Interviews of professionals in the intervention groups and a survey of professionals in the intervention and control groups were performed. Data collection was conducted by each research team in the respective national language. The interview data were first analyzed inductively by each research team, and subsequently, a meta-synthesis was conducted. The survey was analyzed descriptively., Results: We conducted 71 interviews; 125 professionals completed the survey. The survey showed that 76 % (n = 29) of targeted determinants of practice were perceived as relevant and 95 % (n = 36) as being modified by the implementation interventions by 66 to 100 % of professionals. On average, 47 % of professionals reported using the strategies and 51 % considered them helpful, albeit with substantial variance between countries and strategies. In the interviews, 89 determinants of practice were identified, of which 70 % (n = 62) had been identified and 45 % (n = 40) had been prioritized in the design phase. The interviewees suggested 65 additional strategies, of which 54 % (n = 35) had been identified and 20 % (n = 13) had been prioritized, but not selected in the final programs., Conclusions: This study largely confirmed the perceived relevance of the targeted determinants of practice. This contrasts with the fact that no impact of the trials on the implementation of the recommendations could be observed. The findings suggest that better methods for prioritization of determinants and strategies are needed., Trial Registration: Each of the five trials was registered separately in recognized trial registries. Details are given in the respective trial outcome papers.

The discovery of erythropoietin (EPO) simplified blood doping in sports, but improved detection methods, for EPO has forced cheating athletes to return to blood transfusion. Autologous blood transfusion with cryopreserved red blood cells (RBCs) is the method of choice, because no valid method exists to accurately detect such event. In endurance sports, it can be estimated that elite athletes improve performance by up to 3% with blood doping, regardless of method. Valid detection methods for autologous blood doping is important to maintain credibility of athletic performances. Recreational male (N = 27) and female (N = 11) athletes served as Transfusion (N = 28) and Control (N = 10) subjects in two different transfusion settings. Hematological variables and physical performance were measured before donation of 450 or 900 mL whole blood, and until four weeks after re-infusion of the cryopreserved RBC fraction. Blood was analyzed for transferrin, iron, Hb, EVF, MCV, MCHC, reticulocytes, leucocytes and EPO. Repeated measures multivariate analysis of variance (MANOVA) and pattern recognition using Principal Component Analysis (PCA) and Orthogonal Projections of Latent Structures (OPLS) discriminant analysis (DA) investigated differences between Control and Transfusion groups over time. Significant increase in performance (15 ± 8%) and VO2max (17 ± 10%) (mean ± SD) could be measured 48 h after RBC re-infusion, and remained increased for up to four weeks in some subjects. In total, 533 blood samples were included in the study (Clean = 220, Transfused = 313). In response to blood transfusion, the largest change in hematological variables occurred 48 h after blood donation, when Control and Transfused groups could be separated with OPLS-DA (R2 = 0.76/Q2 = 0.59). RBC re-infusion resulted in the best model (R2 = 0.40/Q2 = 0.10) at the first sampling point (48 h), predicting one false positive and one false negative. Over all, a 25% and 86% false positives ratio was achieved in two separate trials. In conclusions, autologous re-infusion of RBCs increased VO2max and performance as hypothesized, but hematological profiling by multivariate statistics could not reach the WADA stipulated false positive ratio of <0.001% at any time point investigated. A majority of samples remained within limits of normal individual variation at all times.

Background: Elderly patients with depression are underdiagnosed, undertreated and run a high risk of a chronic course. General practitioners adhere to clinical practice guidelines to a limited degree. In the international research project Tailored Implementation for Chronic Diseases, we tested the effectiveness of tailored interventions to improve care for patients with chronic diseases. In Norway, we examined this approach to improve adherence to six guideline recommendations for elderly patients with depression targeting healthcare professionals, patients and administrators., Methods: We conducted a cluster randomised trial in 80 Norwegian municipalities. We identified determinants of practice for six recommendations and subsequently tailored interventions to address these determinants. The interventions targeted healthcare professionals, administrators and patients and consisted of outreach visits, a website presenting the recommendations and the underlying evidence, tools to manage depression in the elderly and other web-based resources, including a continuous medical education course for general practitioners. The primary outcome was mean adherence to the recommendations. Secondary outcomes were improvement in depression symptoms as measured by patients and general practitioners. We offered outreach visits to all general practitioners and practice staff in the intervention municipalities. We used electronic software that extracted eligible patients from the general practitioners' lists. We collected data by interviewing general practitioners or sending them a questionnaire about their practice for four patients on their list and by sending a questionnaire to the patients., Results: One hundred twenty-four of the 900 general practitioners (14 %) participated in the data collection, 51 in the intervention group and 73 in the control group. We interviewed 77 general practitioners, 47 general practitioners completed the questionnaire, and 134 patients responded to the questionnaire. Amongst the general practitioners who provided data, adherence to the recommendations was 1.6 percentage points higher in the intervention group than in the control group (95 % CI -6 to 9)., Conclusions: The effectiveness of our tailored intervention to implement recommendations for elderly patients with depression in primary care is uncertain, due to the low response rate in the data collection. However, it is unlikely that the effect was large. It remains uncertain how best to improve adherence to evidence-based recommendations and thereby improve the quality of care for these patients., Trial Registration: ClinicalTrials.gov: NCT01913236 .

Background: To improve adherence to evidence-based recommendations, it is logical to identify determinants of practice and tailor interventions to address these. We have previously prioritised six recommendations to improve treatment of elderly patients with depression, and identified determinants of adherence to these recommendations. The aim of this article is to describe how we tailored interventions to address the determinants for the implementation of the recommendations., Methods: We drafted an intervention plan, based on the determinants we had identified in a previous study. We conducted six group interviews with representatives of health professionals (GPs and nurses), implementation researchers, quality improvement officers, professional and voluntary organisations and relatives of elderly patients with depression. We informed about the gap between evidence and practice for elderly patients with depression and presented the prioritised determinants that applied to each recommendation. Participants brainstormed individually and then in groups, suggesting interventions to address the determinants. We then presented evidence on the effectiveness of strategies for implementing depression guidelines. We asked the groups to prioritise the suggested interventions considering the perceived impact of determinants and of interventions, the research evidence underlying the interventions, feasibility and cost. We audiotaped and transcribed the interviews and applied a five step framework for our analysis. We created a logic model with links between the determinants, the interventions, and the targeted improvements in adherence., Results: Six groups with 29 individuals provided 379 suggestions for interventions. Most suggestions could be fit within the drafted plan, but the groups provided important amendments or additions. We sorted the interventions into six categories: resources for municipalities to develop a collaborative care plan, resources for health professionals, resources for patients and their relatives, outreach visits, educational and web-based tools. Some interventions addressed one determinant, while other interventions addressed several determinants., Conclusions: It was feasible and helpful to use group interviews and combine open and structured approaches to identify interventions that addressed prioritised determinants to adherence to the recommendations. This approach generated a large number of suggested interventions. We had to prioritise to tailor the interventions strategies.

Background: Lignin is a polyphenolic polymer that strengthens and waterproofs the cell wall of specialized plant cell types. Lignification is part of the normal differentiation programme and functioning of specific cell types, but can also be triggered as a response to various biotic and abiotic stresses in cells that would not otherwise be lignifying., Scope: Cell wall lignification exhibits specific characteristics depending on the cell type being considered. These characteristics include the timing of lignification during cell differentiation, the palette of associated enzymes and substrates, the sub-cellular deposition sites, the monomeric composition and the cellular autonomy for lignin monomer production. This review provides an overview of the current understanding of lignin biosynthesis and polymerization at the cell biology level., Conclusions: The lignification process ranges from full autonomy to complete co-operation depending on the cell type. The different roles of lignin for the function of each specific plant cell type are clearly illustrated by the multiple phenotypic defects exhibited by knock-out mutants in lignin synthesis, which may explain why no general mechanism for lignification has yet been defined. The range of phenotypic effects observed include altered xylem sap transport, loss of mechanical support, reduced seed protection and dispersion, and/or increased pest and disease susceptibility., (© The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The prevalence of depression is high and the elderly have an increased risk of developing chronic course. International data suggest that depression in the elderly is under-recognised, the latency before clinicians provide a treatment plan is longer and elderly patients with depression are not offered psychotherapy to the same degree as younger patients. Although recommendations for the treatment of elderly patients with depression exist, health-care professionals adhere to these recommendations to a limited degree only. We conducted a systematic review to identify recommendations for managing depression in the elderly and prioritised six recommendations. We identified and prioritised the determinants of practice related to the implementation of these recommendations in primary care, and subsequently discussed and prioritised interventions to address the identified determinants. The objective of this study is to evaluate the effectiveness of these tailored interventions for the six recommendations for the management of elderly patients with depression in primary care., Methods/design: We will conduct a pragmatic cluster randomised trial comparing the implementation of the six recommendations using tailored interventions with usual care. We will randomise 80 municipalities into one of two groups: an intervention group, to which we will deliver tailored interventions to implement the six recommendations, and a control group, to which we will not deliver any intervention. We will randomise municipalities rather than patients, individual clinicians or practices, because we will deliver the intervention for the first three recommendations at the municipal level and we want to minimise the risk of contamination across GP practices for the other three recommendations. The primary outcome is the proportion of actions taken by GPs that are consistent with the recommendations., Discussion: This trial will investigate whether a tailored implementation approach is an effective strategy for improving collaborative care in the municipalities and health-care professionals' practice towards elderly patients with depression in primary care. The effectiveness evaluation described in this protocol will be accompanied with a process evaluation exploring why and how the interventions were effective or ineffective., Trial Registration: ClinicalTrials.gov: NCT01913236.

It is an established fact that allelic variation and post-translational modifications create different variants of proteins, which are observed as isoelectric and size subspecies in two-dimensional gel based proteomics. Here we explore the stromal proteome of spinach and Arabidopsis chloroplast and show that clustering of mass spectra is a useful tool for investigating such variants and detecting modified peptides with amino acid substitutions or post-translational modifications. This study employs data mining by hierarchical clustering of MALDI-MS spectra, using the web version of the SPECLUST program (http://bioinfo.thep.lu.se/speclust.html). The tool can also be used to remove peaks of contaminating proteins and to improve protein identification, especially for species without a fully sequenced genome. Mutually exclusive peptide peaks within a cluster provide a good starting point for MS/MS investigation of modified peptides, here exemplified by the identification of an A to E substitution that accounts for the isoelectric heterogeneity in protein isoforms., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The TL29 protein is one of the more abundant proteins in the thylakoid lumen of plant chloroplasts. Based on its sequence homology to ascorbate peroxidases, but without any supporting biochemical evidence, TL29 was suggested to be involved in the plant defense system against reactive oxygen species and consequently renamed to APX4. Our in vivo and in vitro analyses failed to show any peroxidase activity associated with TL29; it bound neither heme nor ascorbate. Recombinant overexpressed TL29 had no ascorbate-dependent peroxidase activity, and various mutational analyses aiming to convert TL29 into an ascorbate peroxidase failed. Furthermore, in the thylakoid lumen no such activity could be associated with TL29 and, additionally, TL29 knock-out mutants did not show any decreased peroxidase activity or increased content of radical oxygen species when grown under light stress. Instead we could show that TL29 is a lumen-located component associated with PSII.

In plants oxygenic photosynthesis is performed by large protein complexes found in the thylakoid membranes of chloroplasts. The soluble thylakoid lumen space is a narrow and compressed region within the thylakoid membrane which contains 80-200 proteins. Because the thylakoid lumen proteins are in close proximity to the protein complexes of photosynthesis, it is reasonable to assume that the lumen proteins are highly influenced by the presence of light. To identify light regulated proteins in the thylakoid lumen of Arabidopsis thaliana we developed a faster thylakoid preparation and combined this with difference gel electrophoresis (DIGE) of dark-adapted and light-adapted lumen proteomes. The DIGE experiments revealed that 19 lumen proteins exhibit increased relative protein levels after eight hour light exposure. Among the proteins showing increased abundance were the PsbP and PsbQ subunits of Photosystem II, major plastocyanin and several other proteins of known or unknown function. In addition, co-expression analysis of publicly available transcriptomic data showed that the co-regulation of lumen protein expression is not limited to light but rather that lumen protein genes exhibit a high uniformity of expression. The large proportion of thylakoid lumen proteins displaying increased abundance in light-adapted plants, taken together with the observed uniform regulation of transcription, implies that the majority of thylakoid lumen proteins have functions that are related to photosynthetic activity. This is the first time that an analysis of the differences in protein level during a normal day/night cycle has been performed and it shows that even a normal cycle of light significantly influences the thylakoid lumen proteome. In this study we also show for the first time, using co-expression analysis, that the prevalent lumenal chloroplast proteins are very similarly regulated at the level of transcription.

Two homologous plastocyanin isoforms are encoded by the genes PETE1 and PETE2 in the nuclear genome of Arabidopsis thaliana. The PETE2 transcript is expressed at considerably higher levels and the PETE2 protein is the more abundant isoform. Null mutations in the PETE genes resulted in plants, designated pete1 and pete2, with decreased plastocyanin contents. However, despite reducing plastocyanin levels by over approximately 90%, a pete2 null mutation on its own affects rates of photosynthesis and growth only slightly, whereas pete1 knockout plants, with about 60-80% of the wild-type plastocyanin level, did not show any alteration. Hence, plastocyanin concentration is not limiting for photosynthetic electron flow under optimal growth conditions, perhaps implying other possible physiological roles for the protein. Indeed, plastocyanin has been proposed previously to cooperate with cytochrome c(6A) (Cyt c(6A)) in thylakoid redox reactions, but we find no evidence for a physical interaction between the two proteins, using interaction assays in yeast. We observed homodimerization of Cyt c(6A) in yeast interaction assays, but also Cyt c(6A) homodimers failed to interact with plastocyanin. Moreover, phenotypic analysis of atc6-1 pete1 and atc6-1 pete2 double mutants, each lacking Cyt c(6A) and one of the two plastocyanin-encoding genes, failed to reveal any genetic interaction. Overexpression of either PETE1 or PETE2 in the pete1 pete2 double knockout mutant background results in essentially wild-type photosynthetic performance, excluding the possibility that the two plastocyanin isoforms could have distinct functions in thylakoid electron flow.