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Abstract Objective Callous-unemotional (CU) traits are associated with a more severe and chronic trajectory of antisocial behavior. The present study aimed to identify different classes of CU and anxiety and to compare these classes on overt and covert antisocial behavior and several clinical correlates. Method In a prospective high-risk cohort of adolescents (N = 679; mean age = 14.77, SD = 0.81), latent profile analysis was conducted using CU traits and anxiety symptoms as indicators, and multi-informant aggressive and rule breaking behavior as distal outcomes. Post-hoc analyses with binary logistic regression and a series of ANCOVA were performed on identified classes assessing violent aggression, property offending, and clinical correlates. Results Three classes were found, a reference group (low CU, low anxiety; N = 500), a high CU-low anxiety group (N = 98), and an intermediate CU-high anxious group (N = 81). The high CU-low anxiety group scored highest on property offenses, while the intermediate CU-high anxious group scored highest on aggressive behavior. The intermediate CU-high anxious group scored highest on psychotic experiences, while the high CU group scored highest on internet gaming addiction problems and bullying victimization. Conclusion These findings provide further evidence for diverse variants of CU traits in a high-risk community sample. Future prospective studies should point out whether and to what extent adolescents with CU traits with and without anxiety develop criminal careers and psychiatric disorders in adulthood.

Abstract MRI-detected inflammation around the extensor tendons of metacarpophalangeal (MCP-) joints is prevalent in RA and poses a markedly increased risk of RA development when present in arthralgia patients. Such inflammation is called ‘peritendinitis’ since anatomy literature reports no presence of a tenosynovial sheath at these tendons. However, the presence or absence of tenosynovium at these extensor tendons has never been studied. Therefore, an anatomical and histological study of extensor tendons at the MCP-joints of three embalmed human hands was performed. Immunohistochemical staining showed the presence of markers for synovial macrophages and fibroblast-like synoviocytes bordering a natural dorsal space next to the extensor tendon, suggesting the presence of a synovial lining. This implies that contrast-enhancement on MRI around extensor tendons at MCP-joints observed in early RA and pre-RA likely represents tenosynovitis and that inflammation of this synovial tissue is an early feature of RA.

The human heart has limited regenerative capacity. Therefore, patients often progress to heart failure after ischemic injury, despite advances in reperfusion therapies generally decreasing mortality. Depending on its glycosylation state, Follistatin-like 1 (FSTL1) has been shown to increase cardiomyocyte (CM) proliferation, decrease CM apoptosis, and prevent cardiac rupture in animal models of ischemic heart disease. To explore its therapeutic potential, we used a human in vitro model of cardiac ischemic injury with human induced pluripotent stem cell-derived CMs (iPSC-CMs) and assessed regenerative effects of two differently glycosylated variants of human FSTL1. Furthermore, we investigated the FSTL1-mediated interplay between human cardiac fibroblasts (cFBs) and iPSC-CMs in hypoxia. Both FSTL1 variants increased viability, while only hypo-glycosylated FSTL1 increased CM proliferation post-hypoxia. Human fetal cardiac fibroblasts (fcFBs) expressed and secreted FSTL1 under normoxic conditions, while FSTL1 secretion increased by iPSC-cFBs upon hypoxia but decreased in iPSC-CMs. Co-culture of iPSC-CMs and cFBs increased FSTL1 secretion compared with cFB mono-culture. Taken together, we confirm that FSTL1 induces iPSC-CM proliferation in a human cardiac in vitro hypoxia damage model. Furthermore, we show hypoxia-related FSTL1 secretion by human cFBs and indications for FSTL1-mediated intercellular communication between cardiac cell types in response to hypoxic conditions.

Objectives It is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically suspect arthralgia (CSA) to RA. Additionally, we studied whether functional disabilities of hands/feet at CSA onset contribute to predicting RA development.Methods 600 patients with CSA were followed for clinical inflammatory arthritis (IA) during median follow-up of 25 months, during which 99 developed IA. Functional disabilities were measured at baseline/4/12/24 months with the Health Assessment Questionnaire Disability Index (HAQ); HAQ items assessing hand disabilities and foot disabilities were selected. The course of disabilities towards IA development (here considered as t=0) was depicted by increasing incidences and analysed using linear mixed models. To evaluate robustness of findings, tender hand/foot joints and subclinical joint inflammation (measured with CE-1.5TMRI) of hand/foot were additionally studied. Associations between disabilities at CSA presentation (here t=0) and future IA development were studied using Cox regression in the total CSA population.Results During IA development, hand disabilities occurred earlier and more frequently than foot disabilities. Despite both hand disabilities and foot disabilities rose significantly towards IA development, hand disabilities were more severe during this course (mean difference over time: 0.41 units, 95% CI 0.28 to 0.55, p

Anne L Meulenbroek,1 Miriam C Faes,2 Stefanie R van Mil,1 MG Buimer,1 Hans GW de Groot,1 Eelco J Veen,1 Gwan H Ho,1 Leandra JM Boonman-de Winter,3,4 Jolanda de Vries,5,6 Rebecca van Gorkom,1 Fleur Toonders,1 Rene van Alphen,7 Karolien van Overveld,8 Nathalie Verbogt,1 Ewout W Steyerberg,9 Lijckle van der Laan1,10 1Department of Surgery, Amphia Hospital, Breda, the Netherlands; 2Department of Geriatrics, Amphia Hospital, Breda, the Netherlands; 3Department of Scientific Research, Amphia Hospital, Breda, the Netherlands; 4Admiraal de Ruyter Ziekenhuis, Goes, the Netherlands; 5Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands; 6Board, Admiraal de Ruyter Hospital, Goes, the Netherlands; 7Department of Physical Therapy, Amphia Hospital, Breda, the Netherlands; 8Department of Dieticians, Amphia Hospital, Breda, the Netherlands; 9Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, the Netherlands; 10Department of Cardiovascular Science, University Hospitals Leuven, Leuven, BelgiumCorrespondence: Anne L Meulenbroek, Department of Surgery, Amphia Hospital, Molengracht 21, Breda, 4818 CK, the Netherlands, Tel +31 76 595 3157, Fax +31 76 595 3818, Email AMeulenbroek1@amphia.nlObjective: Chronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥ 65 years.Design: A prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program.Methods: Chronic limb threatening ischemia patients ≥ 65 years that require revascularization will participate in the program. This program focuses on optimizing the patient’s overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group.Discussion: This study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient’s preoperative mental and physical condition to prevent postoperative complications, including delirium.Trial: This protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.Keywords: chronic limb threatening ischemia, vascular surgical procedures, delirium, delirium/prevention and control, prehabilitation

Nutrition education is essential for the development of healthy eating behaviours among children. Over the past few years, multiple nutrition education programmes have been implemented in primary schools. In the current study, the long-term effects of the experiential nutrition education programme ‘Learning Street’ are assessed. This 3-week programme comprises a classroom-based introduction lesson, a visit to a fruit or vegetable (FV) farmer, a cooking workshop, and a joint eating moment. The programme is designed for children aged 8–12 years. Questionnaire outcomes of 11-to-12-year-old children (n = 87) who participated in a Learning Street programme two years before were compared to those of a control group (n = 102) with similar demographics. The questionnaire included questions on children’s FV knowledge, liking, intake, and attitude, as well as their general health attitude, cooking self-efficacy, and cooking attitude. There was a significant difference in FV attitude (Cohen’s d = 0.55; 95% CI: −0.69 to −0.21) and general health attitude (Cohen’s d = 0.37; 95% CI: −0.56 to −0.07) between the intervention and the control groups. For general health attitude, the difference was only significant for a subgroup of children (n = 25) who had participated in two Learning Street programmes. The findings suggest that regularly exposing children to experiential nutrition education may have long-term benefits. [ABSTRACT FROM AUTHOR]

Introduction: In the Netherlands, bariatric surgery in adolescents is currently only allowed in the context of scientific research. Besides this, there was no clinical pathway for bariatric surgery in adolescents. In this paper, the development of a comprehensive clinical pathway for bariatric surgery in adolescents with severe obesity in the Netherlands is described. Methods: The clinical pathway for bariatric surgery in adolescents consists of an eligibility assessment as well as comprehensive peri- and postoperative care. Regarding the eligibility assessment, the adolescents need to be identified by their attending pediatricians and afterwards be evaluated by specialized pediatric obesity units. If the provided treatment is considered to be insufficiently effective, the adolescent will anonymously be evaluated by a national board. This is an additional diligence procedure specifically established for bariatric surgery in adolescents. The national board consists of independent experts regarding adolescent bariatric surgery and evaluates whether the adolescents meet the criteria defined by the national professional associations. The final step is an assessment by a multidisciplinary team for adolescent bariatric surgery. The various disciplines (pediatrician, bariatric surgeon, psychologist, dietician) evaluate whether an adolescent is eligible for bariatric surgery. In this decision-making process, it is crucial to assess whether the adolescent is expected to adhere to postoperative behavioral changes and follow-up. When an adolescent is deemed eligible for bariatric surgery, he or she will receive preoperative counseling by a bariatric surgeon to decide on the type of bariatric procedure (Roux-en-Y gastric bypass or sleeve gastrectomy). Postoperative care consists of intensive guidance by the multidisciplinary team for adolescent bariatric surgery. In this guidance, several regular appointments are included and additional care will be provided based on the needs of the adolescent and his or her family. Furthermore, the multidisciplinary lifestyle intervention, in which the adolescents participated before bariatric surgery, continues in coordination with the multidisciplinary team for adolescent bariatric surgery, and this ensures long-term counseling and follow-up. Conclusion: The implementation of bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity requires the development of a clinical pathway with a variety of disciplines. [ABSTRACT FROM AUTHOR]

Helping university students develop productive views of what characterizes good scientific research and scientific knowledge is an important objective of science education. However, many studies show that students' views of the nature of science (NOS) do not become more informed or even become less informed after learning activities that engage students in scientific practice. This could mean that the way we teach students to conduct scientific research might unintentionally strengthen or bring about uninformed views of NOS. In this article, we argue that scientific discourse (how language is used in science) might play a role in this relation between learning scientific inquiry and uninformed views of NOS. We argue that there could be implicit notions relating to NOS underlying scientific discourse that uninformed readers might translate to uninformed views of NOS. We call these implicit notions underlying scientific language use "epistemological notions." In this article, we further define this construct of epistemological notions, contrast it with explicit views of NOS and other related constructs, explain how we think epistemological notions might affect explicit views of NOS, and present a framework we developed to characterize them in scientific language use. It is a descriptive and interpretative analysis framework which combines, optimizes, and extends several text analysis methods, discourse analysis, and reflexive thematic analysis. We provide a guide to use the framework and point out quality criteria. We finish by advocating the framework for educational researchers interested in developing instructional interventions during which learning about science is combined with explicit reflection on NOS. Identifying epistemological notions in scientific language use could provide starting points for these activities by making explicit the translation from NOS understanding to scientific practice and vice versa. [ABSTRACT FROM AUTHOR]

Abstract Background Rheumatoid arthritis (RA) is a heterogeneous disease, as evidenced by the differences in long-term outcomes. This applies especially to anti-citrullinated protein antibodies (ACPA)-negative RA, where a proportion achieves sustained DMARD-free remission (SDFR; sustained absence of synovitis after DMARD cessation). Differentiation of RA patients who will achieve SDFR can guide personalized treatment/tapering strategies. Although this subgroup remains scarcely discerned, previous research demonstrated that these RA patients are characterized by an early clinical response (DAS remission after 4 months) after DMARD start. We studied whether, in addition to this clinical response, a specific biomarker response can further distinguish the subgroup of RA patients most likely to achieve SDFR. Methods In 266 RA patients, levels of 12 biomarkers (SAA/CRP/MMP-1/MMP-3/resistin/leptin/IL-6/TNF-R1/YKL-40/EGF/VEGF/VCAM-1), in the first 2 years after diagnosis, were studied in relation to SDFR, stratified for ACPA status. Subsequently, biomarkers associated with SDFR development were combined with early DAS remission to study its additional value in defining subgroups. Since most biomarker levels are not routinely measured in clinical practice, we explored how this subgroup can be clinically recognized. Results ACPA-negative RA patients achieving SDFR were characterized by high baseline levels and stronger decline in MMP-1/MMP-3/SAA/CRP after DMARD-start, respectively 1.30×/1.44×/2.12×/2.24× stronger. This effect was absent in ACPA-positive RA. In ACPA-negative RA, a strong biomarker decline is associated with early DAS remission. The combination of both declines (clinical, biomarker) was present in a subgroup of ACPA-negative RA patients achieving SDFR. This subgroup can be clinically recognized by the combination of high baseline CRP levels (≥ 3 times ULN), and early DAS remission (DAS4 months < 1.6). This latter was replicated in independent ACPA-negative RA patients. Conclusions ACPA-negative RA patients with early DAS remission and a strong biomarker response (or baseline CRP levels ≥ 3× ULN) are most likely to achieve SDFR later on. This could guide personalized decisions on DMARD tapering/cessation in ACPA-negative RA.

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

Background Clinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown if the function of the hands is already affected and what mechanisms underlie impaired hand-function in CSA.Methods We studied various measures of hand function in two CSA populations. CSA patients in the TREAT EARLIER-trial (n=236) were evaluated at baseline for: grip strength on a dynamometer (GS), patient-reported difficulties in the grip domain of the Health Assessment Questionnaire (HAQ) questionnaire and incomplete fist closure at physical examination. Findings were validated in an independent CSA cohort (n=600) where hand function was measured as: GS evaluated by squeezing the examiner’s fingers, grip domain of the HAQ questionnaire and fist closure. Contrast-enhanced MRI of the hands measured synovitis, tenosynovitis and bone marrow oedema (summed as subclinical inflammation) in both cohorts.Results GS (on a dynamometer) was reduced in 75% compared with reference values in healthy controls, 60% reported grip difficulties and 13% had incomplete fist closure. Reduced GS was associated with subclinical inflammation (−0.38 kg/point inflammation, 95% CI −0.68 to −0.08). Studying separate MRI features, GS reduction was independently associated with tenosynovitis, decreasing with −2.63 kg (95% CI −2.26 to −0.33)/point tenosynovitis (range observed tenosynovitis scores: 0–20). Similar relations with tenosynovitis were seen for patient-reported grip difficulties (OR 1.12/point, 95% CI 1.07 to 1.42) and incomplete fist closure (OR 1.36/point, 95% CI 1.03 to 1.79). In the validation cohort, 36% had decreased examiner-assessed GS, 51% reported grip difficulties and 14% incomplete fist closure: all were associated with tenosynovitis. Decreased dynamometer-measured GS was most sensitive for detecting tenosynovitis (75%), while incomplete fist closure was most specific (88%–90%).Conclusion Hand function is already often affected before RA development. These limitations are related to subclinical inflammation and tenosynovitis in particular.

Centuries of trade have left their traces in the culture and society of port cities. This paper explores the usefulness of the concept “maritime mindset” to recognize these traces, and analyses it from different disciplinary perspectives. In the second part, it proposes the practice of “deep mapping” as a methodology of identifying and documenting expressions of maritime culture and trade in public space. In conclusion, it addresses some questions that are crucial when addressing a maritime mindset, such as whether it is a top-down or bottom-up mindset, which spatial scale it entails, and whose values and interests the mindset represents. Ultimately, we argue that (deep) mapping can play a role in producing a more layered spatial, social and cultural understanding of the complex nature of port cities.