Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Heterogeneity in Response during Multisystemic Therapy: Exploring Subgroups and Predictors

Multiple studies have shown that Multisystemic Therapy (MST) is, at group level, an effective treatment for adolescents showing serious externalizing problem behavior. The current study expands previous research on MST by, first, examining whether subgroups of participants who respond differently to treatment could be identified. Second, we investigated if the different trajectories of change during MST could be predicted by individual (hostile attributions) and contextual (parental sense of parenting competence and deviant and prosocial peer involvement) pre-treatment factors. Participants were 147 adolescents (mean age = 15.91 years, 104 (71%) boys) and their parents who received MST. Pre-treatment assessment of the predictors and 5 monthly assessments of externalizing behavior during treatment took place using both adolescent and parents’ self-reports. Six distinct subgroups, showing different trajectories of change in externalizing problem behavior during MST, were identified. Two of the 6 trajectories of change showed a poor treatment response, as one class did not change in externalizing problem behavior and the other class even increased. The remaining 4 trajectories displayed a positive effect of MST, by showing a decrease in externalizing behavior. Most of these trajectories could be predicted by parental sense of parenting competence. Additionally, lower involvement with prosocial peers was a predictor of the group that appeared to be resistant to MST. Adolescents do respond differently to MST, which indicates the importance of personalizing treatment. Protective factors, such as parental sense of parenting competence and prosocial peers, seem to require additional attention in the first phase of MST

A look under the hood: analyzing engagement and usage data of a smartphone-based intervention

Abstract Background Engagement with smartphone-based interventions stimulates adherence and improves the likelihood of gaining benefits from intervention content. Research often relies on system usage data to capture engagement. However, to what extent usage data reflect engagement is still an open empirical question. We studied how usage data relate to engagement, and how both relate to intervention outcomes. Methods We drew data from a randomized controlled trial (RCT) (N = 86) evaluating a smartphone-based intervention that aims to stimulate future self-identification (i.e., future self vividness, valence, relatedness). General app engagement and feature-specific engagement were retrospectively measured. Usage data (i.e., duration, number of logins, number of days used, exposure to intervention content) were unobtrusively registered. Results Engagement and usage data were not correlated. Multiple linear regression analyses revealed that general app engagement predicted future self vividness (p = .042) and relatedness (p = .004). Furthermore, engagement with several specific features also predicted aspects of future self-identification (p = .005 – .032). For usage data, the number of logins predicted future self vividness (p = .042) and exposure to intervention content predicted future self valence (p = .002). Conclusions Usage data did not reflect engagement and the latter was the better predictor of intervention outcomes. Thus, the relation between usage data and engagement is likely to be intervention-specific and the unqualified use of the former as an indicator of the latter may result in measurement error. We provide recommendations on how to capture engagement and app use in more valid ways

Parallel Changes in Positive Youth Development and Self-awareness: the Role of Emotional Self-regulation, Self-esteem, and Self-reflection

The aim of the present study was to examine whether early adolescents’ positive development (i.e., resilience and psychological wellbeing) could be enhanced by stimulating three dimensions of self-awareness: emotional self-regulation, self-esteem, and self-reflection. An experimental field study (randomized controlled trial) was conducted. Seventh grade students (N = 1299; Mage = 12.38; 54% boys) completed multiple assessments at the beginning, during, and immediately after the intervention or at parallel time points for students in the control condition. Changes in the assessed constructs were examined with parallel process latent growth curve models. The results showed that increases in emotional self-regulation and self-esteem were related to concurrent increases in both resilience and psychological wellbeing. Changes in self-reflection were, however, not related to changes in these outcomes. The trajectories of change and parallel processes were similar in the intervention and control condition. These findings suggest that interventions aiming to stimulate positive youth development might be optimized by also focusing on youth’s self-awareness, though more knowledge about how self-awareness can be stimulated best is needed. This trial was registered in the Dutch Trial Register, number NL6371 (old number: NTR6554), on July 3, 2017

Parallel Changes in Positive Youth Development and Self-awareness: the Role of Emotional Self-regulation, Self-esteem, and Self-reflection

The aim of the present study was to examine whether early adolescents’ positive development (i.e., resilience and psychological wellbeing) could be enhanced by stimulating three dimensions of self-awareness: emotional self-regulation, self-esteem, and self-reflection. An experimental field study (randomized controlled trial) was conducted. Seventh grade students (N = 1299; Mage = 12.38; 54% boys) completed multiple assessments at the beginning, during, and immediately after the intervention or at parallel time points for students in the control condition. Changes in the assessed constructs were examined with parallel process latent growth curve models. The results showed that increases in emotional self-regulation and self-esteem were related to concurrent increases in both resilience and psychological wellbeing. Changes in self-reflection were, however, not related to changes in these outcomes. The trajectories of change and parallel processes were similar in the intervention and control condition. These findings suggest that interventions aiming to stimulate positive youth development might be optimized by also focusing on youth’s self-awareness, though more knowledge about how self-awareness can be stimulated best is needed. This trial was registered in the Dutch Trial Register, number NL6371 (old number: NTR6554), on July 3, 2017

Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events were documented. Seven patients with LoS were treated with MMF. Median age at MMF initiation was 15 years (range 7–74 years). Three patients received MMF due to MTX ineffectiveness and 4 due to MTX intolerance. Disease remission was achieved in 4 patients and maintained in one patient. One patient showed a favourable response, but had to discontinue treatment due to elevated liver enzymes. The remaining patient experienced disease progression. MMF was shown to improve the clinical condition of patients with refractory LoS and may be a relatively safe alternative in patients who are intolerant to MTX

Morphological and phylogenetic data do not support the split of Alexandrium into four genera

A recently published study analyzed the phylogenetic relationship between the genera Centrodinium and Alexandrium, confirming an earlier publication showing the genus Alexandrium as paraphyletic. This most recent manuscript retained the genus Alexandrium, introduced a new genus Episemicolon, resurrected two genera, Gessnerium and Protogonyaulax, and stated that: “The polyphyly [sic] of Alexandrium is solved with the split into four genera”. However, these reintroduced taxa were not based on monophyletic groups. Therefore this work, if accepted, would result in replacing a single paraphyletic taxon with several non-monophyletic ones. The morphological data presented for genus characterization also do not convincingly support taxa delimitations. The combination of weak molecular phylogenetics and the lack of diagnostic traits (i.e., autapomorphies) render the applicability of the concept of limited use. The proposal to split the genus Alexandrium on the basis of our current knowledge is rejected herein. The aim here is not to present an alternative analysis and revision, but to maintain Alexandrium. A better constructed and more phylogenetically accurate revision can and should wait until more complete evidence becomes available and there is a strong reason to revise the genus Alexandrium. The reasons are explained in detail by a review of the available molecular and morphological data for species of the genera Alexandrium and Centrodinium. In addition, cyst morphology and chemotaxonomy are discussed, and the need for integrative taxonomy is highlighted

Galectin-9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation

Objective Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under- and overtreatment of patients. Recently, we identified 2 proteins, galectin-9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin-9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares. Methods Levels of galectin-9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross-sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases. Results Both cross-sectionally and longitudinally, galectin-9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve [AUC] 0.86-0.90 for galectin-9 and CXCL10; AUC 0.66-0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin-9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin-9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin-9 and P <0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin-9 and P <0.0001 for CXCL10). Conclusion In this study, galectin-9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies