👤 Janna Keulen

Transitional-age youth (TAY; 15 to 25 years old) are more likely to experience psychological problems compared to other age groups. This study aimed to identify the most relevant transdiagnostic factors underlying internalizing and externalizing symptoms in TAY, including perfectionism, perceived stress, self-compassion, psychological flexibility, adaptive and maladaptive emotion regulation, self-esteem, and autonomy. The sample consisted of 87 TAY from a clinical and 649 from a community sample (M = 20.71, 64.1% female). Confidence Interval Based Estimation of Relevance (CIBER) was used to detect the most relevant transdiagnostic factors, and Latent Profile Analyses (LPA) were used to identify groups of TAY sharing similar patterns of transdiagnostic factors. CIBER showed that all transdiagnostic factors were associated with both internalizing and externalizing symptoms, with most factors being more strongly associated with internalizing symptoms. LPA identified six groups of TAY: low resilience (6.5%), moderate low resilience (20.5%), average resilience (29.3%), moderate high resilience (26.8%), moderate high resilience - high perfectionism and autonomy (1.8%) and high resilience (15.1%). Generally, TAY in the lower resilience groups were more likely to be in the clinical sample than in the community sample and showed more symptoms compared to TAY in the higher resilience groups. Conversely, TAY in the moderate high resilience - high perfectionism and autonomy group were most likely to be in the community sample. The study highlights the importance of focusing on transdiagnostic factors in research and clinical practice for TAY. Show less

Disrupted diurnal rest-activity rhythms (RAR), that is, daily 24-h patterns of rest and activity, have been associated with fatigue and decreased quality of life among survivors of colorectal cancer (CRC). To identify potential targets for interventions to improve RAR, we investigated longitudinal associations of time spent in sedentary behavior and physical activity with RAR parameters after CRC treatment. In a prospective cohort study, repeated measurements were performed among 268 survivors of stage I-III CRC at 6 weeks, 6 months, and 1, 2, and 5 years after treatment. Thigh-worn accelerometers were used to determine hours/day spent in sedentary behavior, standing, and total physical activity during waking time, as well as RAR parameters including mesor, amplitude, circadian quotient (CQ), dichotomy index (I < O) and 24 h-autocorrelation (R24). Self-reported light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were determined via the validated SQUASH questionnaire. Longitudinal associations were analyzed using confounder-adjusted linear mixed models. More sedentary time was statistically significantly associated with a lower mesor, amplitude, I < O and R24 over the 5-year post-treatment period. More standing time was associated with a higher mesor, amplitude, CQ, and I < O but not with R24. Higher levels of objectively assessed total physical activity as well as self-reported MVPA were associated with higher values for all RAR parameters. LPA was not associated with any of the RAR parameters. In the years after CRC treatment, less sedentary behavior and more standing and physical activity were generally associated with higher RAR parameters indicating a more robust rhythm. Future studies should provide more insight into causality of these associations as RAR may be a potential new target for interventions to reduce fatigue after CRC.Trial registration: EnCoRe study NL6904 (https://www.Onderzoekmetmensen.nl/). Show less

Previous studies indicate a role for Oncostatin M (OSM) in atherosclerosis and other chronic inflammatory diseases for which inhibitory antibodies are in development. However, to date no intervention studies with OSM have been performed, and its relation to coronary heart disease (CHD) has not been studied. Gene expression analysis on human normal arteries (n = 10) and late stage/advanced carotid atherosclerotic arteries (n = 127) and in situ hybridization on early human plaques (n = 9) showed that OSM, and its receptors, OSM receptor (OSMR) and Leukemia Inhibitory Factor Receptor (LIFR) are expressed in normal arteries and atherosclerotic plaques. Chronic OSM administration in APOE*3Leiden.CETP mice (n = 15/group) increased plasma E-selectin levels and monocyte adhesion to the activated endothelium independently of cholesterol but reduced the amount of inflammatory Ly-6CHigh monocytes and atherosclerotic lesion size and severity. Using aptamer-based proteomics profiling assays high circulating OSM levels were shown to correlate with post incident CHD survival probability in the AGES-Reykjavik study (n = 5457). Chronic OSM administration in APOE*3Leiden.CETP mice reduced atherosclerosis development. In line, higher serum OSM levels were correlated with improved post incident CHD survival probability in patients, suggesting a protective cardiovascular effect. Show less

Endothelial activation is involved in many chronic inflammatory diseases, such as atherosclerosis, and is often initiated by cytokines. Oncostatin M (OSM) is a relatively unknown cytokine that has been suggested to play a role in both endothelial activation and atherosclerosis. We comprehensively investigated the effect of OSM on endothelial cell activation from different vascular beds and in APOE*3Leiden.CETP mice. Human umbilical vein endothelial cells, human aortic endothelial cells and human microvascular endothelial cells cultured in the presence of OSM express elevated MCP-1, IL-6 and ICAM-1 mRNA levels. Human umbilical vein endothelial cells and human aortic endothelial cells additionally expressed increased VCAM-1 and E-selectin mRNA levels. Moreover, ICAM-1 membrane expression is increased as well as MCP-1, IL-6 and E-selectin protein release. A marked increase was observed in STAT1 and STAT3 phosphorylation indicating that the JAK/STAT pathway is involved in OSM signaling. OSM signals through the LIF receptor alfa (LIFR) and the OSM receptor (OSMR). siRNA knockdown of the LIFR and the OSMR revealed that simultaneous knockdown is necessary to significantly reduce MCP-1 and IL-6 secretion, VCAM-1 and E-selectin shedding and STAT1 and STAT3 phosphorylation after OSM stimulation. Moreover, OSM administration to APOE*3Leiden.CETP mice enhances plasma E-selectin levels and increases ICAM-1 expression and monocyte adhesion in the aortic root area. Furthermore, Il-6 mRNA expression was elevated in the aorta of OSM treated mice. OSM induces endothelial activation in vitro in endothelial cells from different vascular beds through activation of the JAK/STAT cascade and in vivo in APOE*3Leiden.CETP mice. Since endothelial activation is an initial step in atherosclerosis development, OSM may play a role in the initiation of atherosclerotic lesion formation. Show less