Biomarker molecules are analyzed in clinical tests to diagnose a disease, but often these test lack sensitivity or specificity. Also, for many diseases there is not even a blood based test... Show moreBiomarker molecules are analyzed in clinical tests to diagnose a disease, but often these test lack sensitivity or specificity. Also, for many diseases there is not even a blood based test available, while blood collection is relatively low invasive. For breast- and pancreatic cancer, there are several proteins that could potentially serve as biomarkers in blood, but these are not yet specific enough to use for diagnostic testing. Further research on other types of biomarkers may therefore be a valuable addition to eventually be able to develop a blood test. Methods for glycosylation profiling from serum and dried bloodspots with mass spectrometry were developed and applied to pancreatic- and breast cancer biomarker studies. Differences were found between profiles of healthy and sick persons for pancreatic cancer, but no clear differences were seen for breast cancer. This is probably due to the many different forms of breast cancer which result in different profiles. In the future, combining different types of markers from serum might ensure that differences between healthy and sick, between different diseases and between types of disease can be identified. This could lead to the development of a blood test for the early detection of cancer and other diseases. Show less
Vreeker, G.C.M.; Bladergroen, M.R.; Nicolardi, S.; Mesker, W.E.; Tollenaar, R.A.E.M.; Burgt, Y.E.M. van der; Wuhrer, M. 2019
Blood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this... Show moreBlood for determining 25-hydroxyvitamin D-3 [25(OH)D-3] is usually obtained through venipuncture although, as an alternative for serum, dried blood spot (DBS) can be considered. The aim of this proof-of-concept study was to investigate levels of agreement between measurements of 25(OH)D-3 obtained with DBS compared with serum. 301 Chinese participants were included who completed 25(OH)D-3 measurement from DBS and from simultaneously collected blood samples obtained by venipuncture. Measurements of both DBS and serum 25(OH)D-3 were performed using liquid chromatography followed by tandem mass spectrometry. Agreement between the two methods was assessed with Passing and Bablok regression analysis and Bland-Altman plot.Measurements showed a good correlation (Pearson's correlation coefficient r = 0.929, P < 0.001) between the two methods. After recalculating for a 13% difference, a regression equation of DBS 25(OH)D-3 = -1.91 + 1.00 serum 25(OH)D-3 was found in Passing and Bablok regression analysis. Bland-Altman analysis showed a fixed bias of 1.7 nmol/L; upper and lower limit of agreement was 24.1 nmol/L and -20.7 nmol/L, respectively.Sensitivity of recalculated DBS for 25(OH)D-3 concentrations < 30 and < 50 nmol/L was 87.8% and 91.1%, respectively, and specificity was 89.2% and 83.1%, respectively.In conclusion, a good agreement was found between the measurement of 25(OH)D-3 obtained with DBS compared with serum. DBS may possibly be used in a future screening program, but it is less suitable for individualized vitamin D status assessment. Show less
Cytomegalovirus (CMV) infection is a worldwide common infection that in a considerable proportion of individuals remains unnoticed. The congenital CMV infection (cCMV) can induce a variety of... Show moreCytomegalovirus (CMV) infection is a worldwide common infection that in a considerable proportion of individuals remains unnoticed. The congenital CMV infection (cCMV) can induce a variety of clinical manifestations at birth (symptoms at birth), and of permanent long-term impairments (LTI). Of the total of infected neonates at birth, 13% are symptomatic at birth, and half of them will develop LTI. However, 13% of the asymptomatic neonates will still develop the same LTI. Therefore, a quite high percentage of neonates will develop LTI. This thesis aimed to identify prognostic markers, for short- and long-term clinical outcome, and correlates of protection, for future vaccine development. In order to identify such biomarkers, a retrospective nationwide cohort of children with (n=125) and without (n=263) cCMV was used. The findings of this thesis allowed us to get more insights into cCMV pathogenesis, and into the potential processes leading to immune dysfunction, and therefore to a worse clinical outcome. Several approaches have been used to explore prognostic markers. The neonatal immune markers, through DNA quantification of the most common TCR and BCR rearrangements from DBS, together with the maternal-child HLA background, through typing DNA from buccal swabs, seemed to be quite promising for prognostic markers. Show less
Schistosomiasis is a helminthic worm infection that affects 260 million people worldwide, 90% of whom live in sub-Saharan Africa. In Tanzania, where the research in this thesis was conducted, two... Show moreSchistosomiasis is a helminthic worm infection that affects 260 million people worldwide, 90% of whom live in sub-Saharan Africa. In Tanzania, where the research in this thesis was conducted, two species of schistosomes are highly endemic (Schistosoma haematobium and S. mansoni), with more than 50% of adults infected with one or both schistosome species in many regions. In and of itself, schistosomiasis causes significant morbidity and mortality, with an estimated 200,000 deaths annually and 3.31 million disability-adjusted life-years. The possibility that it additionally impacts HIV transmission and disease progression render treatment and control of this neglected tropical disease even more urgent. This thesis focuses on HIV prevention and disease management in sub-Saharan Africa. It will first describe population-based epidemiological work in Tanzania associating HIV with S. haematobium and with S. mansoni. Subsequent chapters focus on treatment of S. haematobium infection in women, where it causes genital tract disease, and on the effects of schistosome infection on immunological response to treatment in people living with HIV infection. The final chapter focuses on implementation science work with high potential to improve HIV prevention and early diagnosis in Tanzania. Show less
Downs, J.A.; Corstjens, P.L.A.M.; Mngara, J.; Lutonja, P.; Isingo, R.; Urassa, M.; ... ; Dam, G.J. van 2015
