Cardiovascular diseases (CVD) are the leading cause of death worldwide, and disturbances in day-night rhythms have recently been implicated as a novel risk factor for CVD. We investigated the... Show moreCardiovascular diseases (CVD) are the leading cause of death worldwide, and disturbances in day-night rhythms have recently been implicated as a novel risk factor for CVD. We investigated the effects of modulating circadian rhythms on energy metabolism using animal models and by studying plasma metaoblites and lipids in humans. Using animal studies we observed that brown adipose tissue (BAT) is strongly regulated by the biological clock, possibly via circadian glucocorticoid rhythms, and attenuated BAT activity through prolonged light exposure increases adiposity. Research focusing on the rhythm in human BAT, and regulation thereof, is necessary to confirm the translational value of our findings. We also observed that mistimed light exposure enhances atherosclerosis development, which may provide a mechanistic link between the known association between shift work and CVD. We anticipate that living according to the natural circadian rhythms presumably contributes to cardiometabolic health. Since disturbances in day-night rhythms are inevitable in modern society, in the future we may advise individuals at risk for development of CVD refrain from shift work and short sleep duration. In addition, data in this thesis may be useful to design strategies to avoid the disadvantageous metabolic effects of shift work. Show less
Spondyloarthritis (SpA) is a heterogeneous group of rheumatic diseases, characterized by sacroiliac-joint inflammation (sacroiliitis), peripheral and extra-articular complaints. The lack of... Show moreSpondyloarthritis (SpA) is a heterogeneous group of rheumatic diseases, characterized by sacroiliac-joint inflammation (sacroiliitis), peripheral and extra-articular complaints. The lack of diagnostic criteria makes diagnosing SpA challenging, yet, classification criteria are available. We tested the performance (sensitivity, specificity) of various classification criteria; the recently developed Assessment of SpondyloArthritis international Society (ASAS) criteria outperformed all other criteria. We investigated the discrepancies in interpretation MRIs and conventional radiographs on the presence of sacroiliitis; agreement on radiographic sacroiliitis between different readers is only moderate, but agreement regarding sacroiliitis on MRI is substantial. Rheumatologists take into account all clinical and laboratory results in addition to the imaging results in the diagnostic process. The diagnostic Berlin algorithm - in which all relevant results are taken into account __ can assist rheumatologists. We proposed a modification of this algorithm, which is accepted by ASAS and also included in the recently published guidelines for the diagnosis and treatment of SpA by the Dutch Society for Rheumatology. Besides, we performed systematic literature reviews, forming the base for the update of the ASAS management recommendations. With these results, SpA-patients can be recognized earlier, offering better treatment options and better outcomes. However, further improvements of care for SpA-patients are necessary. Show less
