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Insufficient immune tolerance during pregnancy is associated with pathological conditions such as preeclampsia (PE). Soluble fms-like tyrosine kinase-1 (sFLT1), which exerts a role in the late stage of PE, has shown its beneficial anti-inflammatory effects in inflammation-associated diseases. Macrophage migration inhibitory factor (MIF) was reported to upregulate sFLT1 production in experimental congenital diaphragmatic hernia. However, the placental sFLT1 expression in early uncomplicated pregnancy and whether MIF can regulate sFLT1 expression in uncomplicated and preeclamptic pregnancy are unclear. We collected first-trimester placentas and term placentas from uncomplicated and preeclamptic pregnancies to investigate sFLT1 and MIF expression in vivo. Primary cytotrophoblasts (CTBs) and a human trophoblast cell line (Bewo) were used to study the regulation of MIF on sFLT1 expression in vitro. In placentas from first-trimester pregnancy, we observed a high expression of sFLT1, specifically in extravillous trophoblasts (EVTs) and syncytiotrophoblast (STB) cells. MIF mRNA levels strongly correlated with sFLT1 expression in term placentas from preeclamptic pregnancies. In in vitro experiments, sFLT1 and MIF levels increased significantly in CTBs during their differentiation to EVTs and STBs, and MIF inhibitor (ISO-1) significantly reduced sFLT1 expression in a dose-dependent manner during this process. sFLT1 showed significant upregulation with increasing doses of MIF in Bewo cells. Our results show that sFLT1 is highly expressed at the maternal–fetal interface during early pregnancy and that MIF can increase sFLT1 expression in early uncomplicated pregnancy and PE, which suggests that sFLT1 plays an essential role in the modulation of inflammation in pregnancy.

Background: Ligamentous Lisfranc instability is commonly missed on unilateral radiographs. However, measurement protocols for bilateral weightbearing radiographs have not been standardized. The primary aim of this study was to investigate the optimal cut-off values for diagnosing Lisfranc instability by evaluating the side-to-side differences of preoperative bilateral weightbearing radiographs among patients with surgically-confirmed ligamentous Lisfranc instability. A secondary aim was to investigate whether the midfoot measurements for detecting Lisfranc injury could also be used in patients with a pre-existing bilateral Hallux Valgus (HV) deformity by evaluating whether the Lisfranc measurements could be affected by a foot deformity as HV. Patients and methods: Patients who underwent surgical repair of ligamentous Lisfranc instability, as well as a separate cohort with bilateral hallux valgus deformity, were included in this multicenter retrospective cohort study. A standardized radiographic measurement protocol was used to assess the midfoot and a receiver operator correlation (ROC) analysis was used to identify the optimal cut-off value for measurements. Interclass Correlation (ICC) scores were calculated to assess the interrater reliability of the Lisfranc area measurement. Results: Forty-seven patients were included in the Lisfranc group with a mean age of 33 (± 15) years and 25 patients were included in the HV group with a mean age of 51 (± 15) years. For the Lisfranc group, measurements that demonstrated a significant side-to-side difference included; increased C1M2 diastasis of 2.4 mm (± 1.4, P2 (± 15, P2 for the C1M2 surface area. The ICC-score for the second C1M2 area measurement was 0.88. Conclusion: Bilateral foot weightbearing radiographs can effectively diagnose ligamentous Lisfranc instability using a standardized measurement protocol. Malalignment of the medial aspect of the second metatarsal base ≥0.3 mm relatively to the intermediate cuneiform offers a high sensitivity, and distance ≥2.1 mm between the second metatarsal base and the medial cuneiform has a high specificity. Intermetatarsal distance between the first and second metatarsal base has a low sensitivity and specificity and should not be used in solitary for diagnosis. Level of evidence: Level III, retrospective comparative study

This study uses a three-wave prospective longitudinal survey (at 6-month intervals) to test effects of information seeking and scanning on attitudes toward marijuana among college students in Israel (N = 700). We integrate constructs from the elaboration likelihood model to contrast processes of attitude change among individuals who vary in moderators of information processing depth (motivation and ability). In addition, we test whether trust in the information source moderates these processes, and use propensity score matching to reduce bias. Results of autoregressive cross-lagged structural equation models show that scanning from interpersonal sources predicted attitudes toward marijuana among individuals who were low in elaboration motivation or ability. Seeking and scanning information about marijuana from interpersonal sources were positively associated with attitudes toward marijuana among individuals higher in elaboration motivation and ability, who had greater trust in the source. Implications for information processing models, seeking and scanning, and campaigns are discussed.

This study is a qualitative user evaluation of a chatbot designed to promote condom use in young people using motivational interviewing techniques.

Background Most research on web-based help seeking for mental health problems has focused on the antecedents of this behavior. Therefore, little is known about the outcomes of web-based help seeking in general or in specific mental health issues. Objective This study was a systematic review and meta-analysis of the literature on the antecedents and consequences of web-based help-seeking behaviors for depressive symptoms. Methods A systematic literature search was carried out in 6 scientific databases, leading to 48 studies (for a total of 314,921 participants) included in the qualitative synthesis and 19 included in the meta-analysis. Results The results indicated a positive relationship between depressive symptoms and web-based help-seeking behaviors through online support groups (r=0.089; P=.009), and Generation Z (r=0.102; P=.008) tended to participate in support groups more than previous generations. In addition, web-based help seeking was positively related to empowerment (r=0.245; P=.004). Other forms of support reported included the internet and specific self-help tools, but no significant relationships were found with depressive symptoms. Conclusions More studies examining the outcomes are needed, together with a more rigorous assessment of web-based help-seeking behaviors. Ultimately, we propose a summary framework for the literature on this topic, including the antecedents, patterns of use, and outcomes of web-based help seeking in the context of depressive symptoms.

BACKGROUND The question of whether some health information is true or false has gained new momentum since the advent of the Internet. Undoubtedly, more health information is available since it can be retrieved quickly and without much expense. As parties with vested interests may post information filtered through the lenses of their interests, as persons without formal qualifications are allowed to post, and as the identification of a trustworthy source of data is beyond many users, it is very likely that there is misinformation on the web, and that the misinformation in total has increased. OBJECTIVE This study aims to contribute to the knowledge of when and how (and maybe why) there is an input of erroneous information to the mental health discussions in online communities for mental health (OCMH). As the discussions (including original posts, comments, comments to these comments, etc.) have been publicly available (to those participating online groups) for some time, the misinformation remains on the site. During the time the information posted is available, it can spread. This study aims to identify contexts that ease the storing of misinformation or help to find it. METHODS We tested whether differentiation in socio-demographic and communication variables was able to form argumentative contexts (or niches) that made it more likely for interested persons to come across misinformation while looking for correct information. The opposite side of the differentiation would be qualities that impede the spread of erroneous information. The research was a content analysis of 1534 comments (144 first posts) about two Italian-speaking Facebook groups. Two indicators were computed: the prevalence of erroneous content and the failure to attend to errors. RESULTS The study found that about one-third (32.0%. 407/1534) contained medically inaccurate information or challenged medical expertise. However, only a fifth of those (20.6%, 84/407) having at least one misinforming statement were corrected or discussed. We identified data that could be understood as markers of erroneous information. That hope was not often fulfilled. In many cases, the differentiating variable did not differentiate much. However, some differences emerged. Competence-moderation of OCMHs appears to be a stronger impediment to erroneous information than empathy-moderated. Patients searching for psychic causes for physical symptoms behaved differently from others in many respects, as well as those that may support misinformation. Differences between communication variables and misinformation were also found in posts about suicide and anxiety disorders, while there seemed to be no association between depression and Covid-19. Treatment was the primary subject of illness trajectories, with some propensity to help with erroneous information. CONCLUSIONS A crucial question is: Are the error markers or misinformation niches identified indicative of the demands for more patient empowerment in online mental health communities? Demands are often invoked without a guarantee that an empowered person would be capable of taking over the part of a newly autonomous co-determinant of his health. Furthermore, the results evidenced the necessity of experts in these communities. CLINICALTRIAL International registered report identifier (irrid): PRR1-10.2196/35347

Chronic kidney disease (CKD) is a slow-developing, progressive deterioration of renal function. The final common pathway in the pathophysiology of CKD involves glomerular sclerosis, tubular atrophy and interstitial fibrosis. Transforming growth factor-beta (TGF-β) stimulates the differentiation of fibroblasts towards myofibroblasts and the production of extracellular matrix (ECM) molecules, and thereby interstitial fibrosis. It has been shown that endoglin (ENG, CD105), primarily expressed in endothelial cells and fibroblasts, can function as a co-receptor of TGF signaling. In several human organs, endoglin tends to be upregulated when chronic damage and fibrosis is present. We hypothesize that endoglin is upregulated in renal interstitial fibrosis and plays a role in the progression of CKD. We first measured renal endoglin expression in biopsy samples obtained from patients with different types of CKD, i.e., IgA nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN) and patients with chronic allograft dysfunction (CAD). We showed that endoglin is upregulated in CAD patients (p < 0.001) and patients with DN (p < 0.05), compared to control kidneys. Furthermore, the amount of interstitial endoglin expression correlated with eGFR (p < 0.001) and the amount of interstitial fibrosis (p < 0.001), independent of the diagnosis of the biopsies. Finally, we investigated in vitro the effect of endoglin overexpression in TGF-β stimulated human kidney fibroblasts. Overexpression of endoglin resulted in an enhanced ACTA2, CCN2 and SERPINE1 mRNA response (p < 0.05). It also increased the mRNA and protein upregulation of the ECM components collagen type I (COL1A1) and fibronectin (FN1) (p < 0.05). Our results suggest that endoglin is an important mediator in the final common pathway of CKD and could be used as a possible new therapeutic target to counteract the progression towards end-stage renal disease (ESRD).

(1) Background: Soluble Fms-like tyrosine kinase 1 (sFLT1) is an endogenous VEGF inhibitor. sFLT1 has been described as an anti-inflammatory treatment for diabetic nephropathy and heart fibrosis. However, sFLT1 has also been related to peritubular capillary (PTC) loss, which promotes fibrogenesis. Here, we studied whether transfection with sFlt1 aggravates experimental AKI-to-CKD transition and whether sFLT1 is increased in human kidney fibrosis. (2) Methods: Mice were transfected via electroporation with sFlt1. After confirming transfection efficacy, mice underwent unilateral ischemia/reperfusion injury (IRI) and were sacrificed 28 days later. Kidney histology and RNA were analyzed to study renal fibrosis, PTC damage and inflammation. Renal sFLT1 mRNA expression was measured in CKD biopsies and control kidney tissue. (3) Results: sFlt1 transfection did not aggravate renal fibrosis, PTC loss or macrophage recruitment in IRI mice. In contrast, higher transfection efficiency was correlated with reduced expression of pro-fibrotic and pro-inflammatory markers. In the human samples, sFLT1 mRNA levels were similar in CKD and control kidneys and were not correlated with interstitial fibrosis or PTC loss. (4) Conclusion: As we previously found that sFLT1 has therapeutic potential in diabetic nephropathy, our findings indicate that sFLT1 can be administered at a dose that is therapeutically effective in reducing inflammation, without promoting maladaptive kidney damage.

Introduction The podocyte is thought to be the mainly affected cell type in focal segmental glomerulosclerosis (FSGS). However, recent studies have also indicated a role for glomerular endothelial cells and podocyte−endothelial crosstalk in FSGS development. An experimental model for podocyte injury showed that increased endothelin-1 (ET-1) signaling between podocytes and endothelial cells induces endothelial oxidative stress and subsequent podocyte loss. In the current study, we investigated endothelial endothelin receptor A (ETAR) expression in patients with FSGS and its association with podocyte injury and glomerular oxidative stress. Methods We selected 39 biopsy samples of patients with FSGS and 8 healthy control subjects, and stained them for ETAR, nephrin and 8-oxo-guanine, a DNA lesion caused by oxidative damage. Glomeruli with ETAR-positive endothelium and with nephrin loss were scored, and the 8-oxo-guanine−positive glomerular area was measured. Results The mean percentage of glomeruli with ETAR-positive endothelial cells in patients with FSGS was higher compared to that in healthy control subjects (52% vs. 7%; P < 0.001). The presence of glomerular ETAR-positive endothelium was strongly associated with nephrin loss both on the biopsy level (rho = 0.47; P < 0.01), as on the level of individual glomeruli (odds ratio = 2.0; P < 0.001). Moreover, glomeruli with ETAR-positive endothelium showed more 8-oxo-guanine−positive staining (1.9% vs. 2.4%; P = 0.037). Finally, 8-oxo-guanine positivity in glomeruli was associated with increased levels of proteinuria. Conclusion Taking together our findings, we show that ETAR is increased in glomerular endothelial cells of patients with FSGS and associated with podocyte damage and glomerular oxidative stress. These findings support the hypothesis that ET-1 signaling in glomerular endothelial cells contributes to disease development in patients with FSGS., Graphical abstract

BACKGROUND Adults of low socioeconomic position (SEP) are generally less physically active than those who are more socioeconomically advantaged, which increases their cardiovascular disease incidence risk. Moreover, individuals of low SEP are often less easily reached with physical activity (PA) interventions than individuals of higher SEP. Smartphone apps have been presented as a promising platform for delivering PA interventions to difficult-to-reach individuals of low SEP. Although PA apps are widely available, they are rarely based on health behavior theories and most predominantly offer generic PA advice. Consequently, it is unlikely that available apps are the most effective PA intervention tools. OBJECTIVE To respond to these areas for improvement, we developed SNapp, an app-based intervention encouraging adults of low SEP to increase PA by providing tailored coaching messages targeting walking behavior. This study aimed to describe SNapp’s stepwise development and pilot evaluation process. METHODS We applied a stepwise approach: analyzing the health problem, developing a program framework, developing tailoring assessments, writing tailored messages, automating the tailoring process, and implementing and evaluating the program in a qualitative pilot study (11 participants). RESULTS SNapp consisted of several elements. First, an app was developed to collect step count and geolocation data using smartphone sensor functionalities. In addition, a survey measure was created to assess users’ behavior change technique (BCT) preferences. These 3 data types were used to tailor SNapp’s coaching messages to stimulate walking. This allows SNapp to offer feedback on performance levels, contextually tailored prompts when users are near green spaces, and coaching content that aligns with individual BCT preferences. Finally, a server-based Python program that interacts with databases containing user data and tailored messages was built using Microsoft Azure to select and automatically send messages to users through Telegram messenger. Pilot study findings indicated that SNapp was rated positively, with participants reporting that its design, technical functioning, and message content were acceptable. Participants suggested additional functionalities that are worth considering for future updates. CONCLUSIONS SNapp is an app-based intervention that aims to promote walking in adults of low SEP by offering tailored coaching messages. Its development is theory based, and it is among the first to incorporate contextualized feedback and content tailored to individual BCT preferences. The effectiveness of SNapp will be evaluated in a 12-month real-life parallel cluster-randomized controlled trial.

Background: To compare diagnostic parameters for Lisfranc instability on WB and NWB radiographs and to assess the inter-observer reliability of a standardized diagnostic protocol. Patients and methods: Patients who had undergone surgical treatment for subtle, purely ligamentous Lisfranc injury with both WB and NWB post-injury, pre-surgery films (n = 26) were included in this multicentre, retrospective comparative study. Also included was a control group (n = 26) of patients with isolated fifth metatarsal avulsion fractures who similarly had both WB and NWB films. Multiple midfoot distance and alignment measurements were used to evaluate the Lisfranc joint on both WB and NWB views. To evaluate interobserver reliability, measurements were made by two independent observers across a cohort subset. Results: When comparing the NWB views between groups, only C1M2 (medial cuneiform- second metatarsal) distance was found to be significantly larger (∆ = 1.35 mm, p 0. 90 were found when interpreting WB radiographs and ICC's ranging between 0.61 and 0.80 were found when interpreting NWB radiographs. Conclusion: Using WB imaging for diagnosing subtle Lisfranc instability reveals larger diastasis in the tarsometatarsal joint and has a higher interobserver reliability compared to NWB imaging. Clinical concern for subtle or occult Lisfranc instability in any patient should therefore trigger WB radiographic assessment since such injuries may be missed on NWB views.

BACKGROUND Most research on online help-seeking for mental health issues has focused on the antecedents of this behavior. Therefore, little is known about the outcomes of online help-seeking in general or for specific mental health issues. OBJECTIVE This article presents a systematic review of studies on both the antecedents and the consequences of online help-seeking behaviours for depressive symptoms. METHODS After a systematic literature search has been carried out in six scientific databases, 42 studies were included in the qualitative synthesis, of which 18 were considered in the meta-analysis. RESULTS Results indicate that people with depressive symptoms seek help online differently (e.g., using online support groups, the Internet or specific self-help tools). Additionally, people of Generation Z tend to participate in online support groups more than previous generations. According to the meta-analytic findings, online help-seeking was positively related to empowerment. CONCLUSIONS More studies looking at the outcomes are needed together with a more rigorous assessment of online help-seeking behaviours. Ultimately, we propose a summary framework of the literature on this topic, including the antecedents, patterns of use, and outcomes of online help-seeking in the context of depressive symptoms.

Contains fulltext : 240021.pdf (Publisher’s version ) (Open Access) A promising avenue for health behavior change is to influence conversational valence, that is, the extent to which people talk negatively or positively about health behaviors. However, no research to date has experimentally manipulated conversational valence, thereby inhibiting conclusions about causal inferences. This study aims to fill this gap by investigating the influence of conversational valence instructions on perceived conversational valence and subsequent binge drinking determinants. College students (N = 138) read either negative or positive conversational valence instructions. Subsequently, dyads engaged in a 5-min conversation about drinking, before self-reporting perceived conversational valence and binge drinking determinants (i.e., attitudes, norms, perceived behavioral control, and intentions). Results revealed that valence instructions influenced binge drinking determinants via perceived conversational valence. Those instructed to talk negatively about binge drinking reported healthier binge drinking determinants than those instructed to talk positively. Furthermore, this effect on binge drinking determinants was mediated by perceived conversational valence. These findings demonstrate that conversational valence about health can be manipulated through simple instructions and confirm the idea that conversational valence is causally linked to binge drinking determinants. Thereby, these findings show the potential that interpersonal communication in general, and conversational valence instructions, in particular, have when integrated in health interventions. 7 p.

Biomedical imaging is unequivocally dependent on the ability to reconstruct interpretable and high-quality images from acquired sensor data. This reconstruction process is pivotal across many applications, spanning from magnetic resonance imaging to ultrasound imaging. While advanced data-adaptive reconstruction methods can recover much higher image quality than traditional approaches, their implementation often poses a high computational burden. In ultrasound imaging, this burden is significant, especially when striving for low-cost systems, and has motivated the development of high-resolution and high-contrast adaptive beamforming methods. Here we show that deep neural networks, that adopt the algorithmic structure and constraints of adaptive signal processing techniques, can efficiently learn to perform fast high-quality ultrasound beamforming using very little training data. We apply our technique to two distinct ultrasound acquisition strategies (plane wave, and synthetic aperture), and demonstrate that high image quality can be maintained when measuring at low data-rates, using undersampled array designs. Beyond biomedical imaging, we expect that the proposed deep learning based adaptive processing framework can benefit a variety of array and signal processing applications, in particular when data-efficiency and robustness are of importance.

ObjectiveThe International Society of Nephrology/Renal Pathology Society classification is the gold standard for the characterisation of lupus nephritis (LN) on renal biopsy, with therapeutic repercussions. Its recent revision simplified the current class subdivisions, eliminating the S/G forms of class IV, although data on a possible pathogenetic/clinical value of this subdivision are still contradictory.Methods353 renal biopsies from Belimumab International Study in LN were assessed through central pathology review. Univariate logistic models and a decision tree were performed on 314 adequate biopsies to evaluate the impact of histological features on focal/diffuse classes. Removing class I/II (n=6) and ‘pure’ class V (n=34), principal component analysis (PCA) and heatmap were used to explore similarities among III, IVS and IVG biopsies either incorporating or not the mixed classes (+V, n=274). Finally, a method aimed at partitioning the cases into k clusters based on their similarity (KMeans), was used to study features from the cohort of ‘pure’ class III/IVS/IVG cases (n=214) to determine alternative subdivisions based on phenotypic data.ResultsSegmental endocapillary hypercellularity (EH) was prevalent in class III, global EH, wire loops, hyaline thrombi and double contours were hallmarks of class IVG, with IVS cases showing intermediate characteristics. Heatmap and PCA confirmed the segregation of these features among classes, showing better segregation for focal/diffuse LN as compared with the mixed classes (+V). KMeans revealed the presence of two main clusters, membranoproliferative-like (n=83) or vasculitis-like (n=131).ConclusionsThis study reveals new phenotypic forms of LN surpassing the traditional classes as determined by the current classification. Future validation and confirmation are required to confirm these findings.

This study analyzes news media coverage about cancer screening in the Netherlands. We investigate the volume, tone and content of news media reports, how media coverage may have changed over time (2010 to 2022), how it may differ for different cancer types, and how information about cancer screening in news media reports is contextualized. The tone and content of news media reports will be analyzed in a two-step approach. First, we will manually (double-)code a subset of the corpus. Next, we will develop machine learning classifiers using traditional models and state-of-the-art models to investigate whether they can reliably classify the full corpus. This preregistration describes the analysis plan based on the manually coded dataset. The analyses will be only applied on the full corpus if the machine learning classifiers can reliably classify the content of news reports.

Item does not contain fulltext Digital health interventions for sexual health promotion have evolved considerably alongside innovations in technology. Despite these efforts, studies have shown that they do not consistently result in the desired sexual health outcomes. This could be attributed to low levels of user engagement, which can hinder digital health intervention effectiveness, as users do not engage with the system enough to be exposed to the intervention components. It has been suggested that conversational agents (automated two-way communication systems e.g. Alexa) have the potential to overcome the limitations of prior systems and promote user engagement through the increased interactivity offered by bidirectional, natural language-based interactions. The present review, therefore, provides an overview of the effectiveness and user acceptability of conversational agents for sexual health promotion. A systematic search of seven databases provided 4534 records, and after screening, 31 articles were included in this review. A narrative synthesis of results was conducted for effectiveness and acceptability outcomes, with the former supplemented by a meta-analysis conducted on a subset of studies. Findings provide preliminary support for the effectiveness of conversational agents for promoting sexual health, particularly treatment adherence. These conversational agents were found to be easy to use and useful, and importantly, resulted in high levels of satisfaction, use and intentions to reuse, whereas user evaluations regarding the quality of information left room for improvement. The results can inform subsequent efforts to design and evaluate these interventions, and offer insight into additional user experience constructs identified outside of current technology acceptance models, which can be incorporated into future theoretical developments. 15 p.

People making food choices are often exposed to different cues that can activate relevant goals that influence the choice outcome. Hedonic goals are frequently primed by advertising while health policy enlists primes that activate health goals in the moment of food decision-making – e.g., healthy food labels. However, little is known about the effect of such goal-priming cues on the population level and how people respond when exposed to both types of primes simultaneously. The results of this study, based on a large, representative sample (N = 1200), show no effect of health-goal priming on healthy food choices. Being exposed to a sole hedonic prime, however, reduces healthy choices by 3%. This effect completely disappeared when both primes were presented at the same time. All effects remained insensitive to people’s gender, hunger status, level of dietary restraint, and BMI. These findings cast doubt over the effectiveness of health goal primes as a tool to increase healthy food choices but suggest a protective effect against competing hedonic primes and could thereby prevent less healthy choices.

BackgroundA medication-related Clinical Decision Support System (CDSS) is an application that analyzes patient data to provide assistance in medication-related care processes. Despite its potential to improve the clinical decision-making process, evidence shows that clinicians do not always use CDSSs in such a way that their potential can be fully realized. This systematic literature review provides an overview of frequently-reported barriers and facilitators for acceptance of medication-related CDSS.Materials and methodsSearch terms and MeSH headings were developed in collaboration with a librarian, and database searches were conducted in Medline, Scopus, Embase and Web of Science Conference Proceedings. After screening 5404 records and 140 full papers, 63 articles were included in this review. Quality assessment was performed for all 63 included articles. The identified barriers and facilitators are categorized within the Human, Organization, Technology fit (HOT-fit) model.ResultsA total of 327 barriers and 291 facilitators were identified. Results show that factors most often reported were related to (a lack of) usefulness and relevance of information, and ease of use and efficiency of the system.DiscussionThis review provides a valuable insight into a broad range of barriers and facilitators for using a medication-related CDSS as perceived by clinicians. The results can be used as a stepping stone in future studies developing medication-related CDSSs.

Complement factor C4d was recently observed in renal biopsies from patients who had IgA nephropathy and a poor prognosis. We previously reported that C4d is a common denominator in microangiopathies. In this retrospective cohort study, we investigated whether C4d is a marker of microangiopathy in both IgA nephropathy and IgA vasculitis with nephritis, and whether patients with C4d and microangiopathy have poor renal outcome. We examined 128 renal biopsies from adult and pediatric patients, including normotensive and hypertensive patients, who presented with IgA nephropathy or IgA vasculitis with nephritis. Biopsies were re-evaluated in accordance with the Oxford classification, scored for additional lesions, and stained for complement proteins using immunohistochemistry, including C4d and C5b-9. Clinical data were collected with a mean (±SD) follow-up period of 51 ± 39 months. Changes in estimated glomerular filtration rate over time were compared using linear mixed-effects models. Renal survival was analyzed using multivariable Cox regression. Microangiopathic lesions were present in 20% of all biopsies (23% and 9% of patients with IgA nephropathy and IgA vasculitis with nephritis, respectively). Microangiopathy was associated with C4d and C5b-9 deposits, a higher number of chronic lesions, and hypertension (all p

Background Physical activity (PA) can increase mental and physical health in adults aged 50 years and older. However, it has been shown that PA guidelines are often not met within this population. Therefore, our research group developed 2 computer-tailored intervention programs in the last decade to stimulate PA: Active Plus and I Move. Although these programs were proven effective, positive effects diminished over time and attrition rates were relatively high. To respond to this, we will integrate 3 interactive mobile elements into the existing programs: activity tracker, ecological momentary intervention program, and virtual coach app. Objective The goal of the research is to define systematic and evidence-based steps for extending our online computer-based PA intervention programs with 3 interactive mobile elements. Methods Components often included in other (eHealth) design models were identified as key components and served as a base for the definition of systematic steps: exploration of context, involvement of the target population, prototype and intervention testing, and implementation. Based on these key components, 10 systematic steps were defined. The initial step is a literature search, with the results serving as a base for development of the low-fidelity prototypes in step 2. The pilot phase comprises the 3rd to 6th steps and includes semistructured interviews, pilot tests, and adaptations of the prototypes with intensive involvement of the target population of adults aged 50 years and older, where particular attention will be paid to lower educated persons. The 7th step is an effect evaluation in the form of a randomized controlled trial. During the 8th step, the most effective intervention programs will be selected and reinforced. These reinforced intervention programs will be used during the design of an implementation plan in the 9th step and the subsequent field study in the 10th step. Results The project will be executed from December 2019 to December 2023. During this period, the systematic approach presented will be practically executed according to the methodological procedures described. Conclusions Based on the 4 identified key components, we were able to design an evidence-based systematic design approach for separately adding 3 mobile elements to our existing online PA intervention programs. The 10 steps are presented as a useful approach to guide future eHealth design studies. International Registered Report Identifier (IRRID) DERR1-10.2196/31677

BACKGROUND Physical activity (PA) can increase mental and physical health in adults aged 50 years and older. However, it has been shown that PA guidelines are often not met within this population. Therefore, our research group developed 2 computer-tailored intervention programs in the last decade to stimulate PA: Active Plus and I Move. Although these programs were proven effective, positive effects diminished over time and attrition rates were relatively high. To respond to this, we will integrate 3 interactive mobile elements into the existing programs: activity tracker, ecological momentary intervention program, and virtual coach app. OBJECTIVE The goal of the research is to define systematic and evidence-based steps for extending our online computer-based PA intervention programs with 3 interactive mobile elements. METHODS Components often included in other (eHealth) design models were identified as key components and served as a base for the definition of systematic steps: exploration of context, involvement of the target population, prototype and intervention testing, and implementation. Based on these key components, 10 systematic steps were defined. The initial step is a literature search, with the results serving as a base for development of the low-fidelity prototypes in step 2. The pilot phase comprises the 3rd to 6th steps and includes semistructured interviews, pilot tests, and adaptations of the prototypes with intensive involvement of the target population of adults aged 50 years and older, where particular attention will be paid to lower educated persons. The 7th step is an effect evaluation in the form of a randomized controlled trial. During the 8th step, the most effective intervention programs will be selected and reinforced. These reinforced intervention programs will be used during the design of an implementation plan in the 9th step and the subsequent field study in the 10th step. RESULTS The project will be executed from December 2019 to December 2023. During this period, the systematic approach presented will be practically executed according to the methodological procedures described. CONCLUSIONS Based on the 4 identified key components, we were able to design an evidence-based systematic design approach for separately adding 3 mobile elements to our existing online PA intervention programs. The 10 steps are presented as a useful approach to guide future eHealth design studies. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/31677