Recent detailed genomic analysis of mycosis fungoides (MF) identified suppressor of cytokine signaling 1 (SOCS1), an inhibitor of JAK/STAT signaling, as one of the frequently deleted tumor...Show moreRecent detailed genomic analysis of mycosis fungoides (MF) identified suppressor of cytokine signaling 1 (SOCS1), an inhibitor of JAK/STAT signaling, as one of the frequently deleted tumor suppressors in MF, and one-copy deletion of SOCS1 was confirmed in early-stage MF lesions. To better understand the functional role of SOCS1 in the genesis of MF, we used a genetically engineered mouse model emulating heterozygous SOCS1 loss in skin resident CD4+ T cells. In these mice an experimentally induced contact-allergic reaction was maintained for 20 weeks. Ten weeks after discontinuing contact-allergic challenges, only the skin with locally one-copy deletion of Socs1 in CD4+ T cells still showed high numbers of CD3+/CD4+ Socs1 k.o. cells in the dermis (p ＜ 0.0001) with prevalent Stat3 activation (p ＜0.001). And in one out of 9 mice, this had progressed to far more dramatic increases, including the thickened epidermis, and with an explosive growth of Socs1 k.o. T cells in circulation; indicative of cutaneous lymphoma. Hence, we show that Socs1 mono-allelic loss in CD4+ T cells locally in protractedly inflamed skin results in autonomous skin inflammation with features of early-stage MF. Show less
Rostamian, S.; Haan, S. de; Grond, J. van der; Buchem, M.A. van; Ford, I.; Jukema, J.W.; Sabayan, B. 2019
BackgroundImpairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the... Show moreBackgroundImpairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the risk of long-term mortality in dementia-free older subjects. Moreover, we investigated the role of structural brain abnormalities in this association.MethodsWe included 547 dementia-free participants (mean age 78 years, 56.5% male) from the nested magnetic resonance imaging sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were used to model 10-year risk of all-cause, cardiovascular, and noncardiovascular mortality in relation to performance in executive function and memory. Moreover, we evaluated the role of total brain parenchymal volume, cerebral blood flow, white matter hyperintensity, and the presence of microbleeds and infarcts in the link between cognitive function and mortality.ResultsIn the multivariable model, lower performance in executive function was associated with greater risk of all-cause (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.31-1.70), cardiovascular (HR 1.69; 95% CI, 1.36-2.11), and noncardiovascular (HR 1.36; 95% CI, 1.15-1.62) mortality. Similarly, poorer performance in memory tests associated with higher risk of all-cause (HR 1.47; 95% CI, 1.29-1.68), cardiovascular (HR 1.45; 95% CI, 1.15-1.83), and noncardiovascular (HR 1.49; 95% CI, 1.27-1.76) mortality. The associations were similar in subjects with various levels of brain structural abnormalities and cerebral blood flow (all P for interaction ≫ .05).ConclusionsPoorer performance in both executive function and memory tests associates with all-cause, cardiovascular, and noncardiovascular mortality in elderly individuals. This association is independent of cardiovascular risk factors and diseases, brain structural abnormalities, and cerebral blood flow. Show less
Luigjes, J.; Lorenzetti, V.; Haan, S. de; Youssef, G.J.; Murawski, C.; Sjoerds, Z.; ... ; Yücel, M. 2019
Compulsive tendencies are a central feature of problematic human behavior and thereby are of great interest to the scientific and clinical community. However, no consensus exists about the precise... Show moreCompulsive tendencies are a central feature of problematic human behavior and thereby are of great interest to the scientific and clinical community. However, no consensus exists about the precise meaning of ‘compulsivity,’ creating confusion in the field and hampering comparison across psychiatric disorders. A vague conceptualization makes compulsivity a moving target encompassing a fluctuating variety of behaviors, which is unlikely to improve the new dimension-based psychiatric or psychopathology approach. This article aims to help progress the definition of what constitutes compulsive behavior, cross-diagnostically, by analyzing different definitions in the psychiatric literature. We searched PubMed for articles in human psychiatric research with ‘compulsive behavior’ or ‘compulsivity’ in the title that focused on the broader concept of compulsivity—returning 28 articles with nine original definitions. Within the definitions, we separated three types of descriptive elements: phenomenological, observational and explanatory. The elements most applicable, cross-diagnostically, resulted in this definition: Compulsive behavior consists of repetitive acts that are characterized by the feeling that one ‘has to’ perform them while one is aware that these acts are not in line with one’s overall goal. Having a more unified definition for compulsive behavior will make its meaning precise and explicit, and therefore more transferable and testable across clinical and non-clinical populations. Show less
