A challenge-based interdisciplinary undergraduate concept fostering translational medicine.

Translational medicine (TM) is an interdisciplinary branch of biomedicine that bridges the gap from bench-to-bedside to improve global health. Fundamental TM skills include interdisciplinary collaboration, communication, critical thinking, and creative problem-solving (4Cs). TM is currently limited in undergraduate biomedical education programs, with little patient contact and opportunities for collaboration between different disciplines. In this study, we developed and evaluated a novel interdisciplinary challenge-based educational concept, grounded in the theoretical framework of experimental research-based education, to implement TM in undergraduate biomedicine and medicine programs. Students were introduced to an authentic clinical problem through an interdisciplinary session with patients, medical doctors, and scientists. Next, students collaborated in groups to design unique laboratory-based research proposals addressing this problem. Stakeholders subsequently rewarded the best proposal with funding to be executed in a consecutive interdisciplinary laboratory course, in which mixed teams of biomedicine and medicine students performed the research in a fully equipped wet laboratory. Written questionnaires and focus groups revealed that students developed 4C skills and acquired a 4C mindset. Working on an authentic patient case and the interdisciplinary setting positively contributed to communication, collaboration, critical thinking, and creative problem-solving skills. Furthermore, students were intrinsically motivated by (i) the relevance of their work that made them feel taken seriously and competent, (ii) the patient involvement that highlighted the societal relevance of their work, and (iii) the acquisition of a realistic view of what doing science in a biomedical research laboratory is. In conclusion, we showcase a widely applicable interdisciplinary challenge-based undergraduate concept fostering TM.

Analysis of C-reactive protein from finger stick dried blood spot to predict high risk of cardiovascular disease.

C-reactive protein (CRP) is an acute-phase protein involved in inflammation. Furthermore, CRP is an important biomarker used in diagnostics to predict risk of cardiovascular disease (CVD) in addition to monitoring bacterial and viral infections. To measure plasma CRP, venipuncture is still necessitated and has to be performed by trained phlebotomists. As a solution, dried blood spots (DBS) are used for minimally invasive at-home sampling of blood and can be send to diagnostic laboratories by regular mail. In this study, we included 53 patients that presented to the outpatient clinic of the University Medical Center Utrecht. Capillary finger stick was used to spot blood on a filter paper card and allowed to dry. After extraction of DBS, CRP was analyzed on an automated high-throughput chemistry analyzer. Additional validation steps regarding stability, effect of hematocrit, precision, and limits of blank and quantitation were conducted according to corresponding Clinical and Laboratory Standards Institute standards. An excellent regression analysis of R2 (95% confidence interval) = 0.986 (0.982-0.989) was found. This enabled correct classification for high CVD risk of all 25 cases with sensitivity (95% CI) of 1.00 (1.00-1.00) and specificity (95% CI) of 0.96 (0.89-1.03) and correct diagnosis of inflammation of 12/13 cases with sensitivity (95% CI) of 0.92 (0.77-1.07) and specificity (95% CI) of 1.00 (1.00-1.00). Furthermore, CRP was found to be stable for 31 days and observed hematocrit variation amongst patients was clinically acceptable. CRP from DBS can be accurately measured on an automated high-throughput chemistry analyzer and used to diagnose inflammation and classify high CVD risk. This method enables individuals to engage in at-home sampling of blood on DBS for (tele)diagnostics, screening programs, patient follow-up, and medication management.

Cellular immunotherapy for medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in children, making up ~20% of all primary pediatric brain tumors. Current therapies consist of maximal surgical resection and aggressive radio- and chemotherapy. A third of the treated patients cannot be cured and survivors are often left with devastating long-term side effects. Novel efficient and targeted treatment is desperately needed for this patient population. Cellular immunotherapy aims to enhance and utilize immune cells to target tumors, and has been proven successful in various cancers. However, for MB, the knowledge and possibilities of cellular immunotherapy are limited. In this review, we provide a comprehensive overview of the current status of cellular immunotherapy for MB, from fundamental in vitro research to in vivo models and (ongoing) clinical trials. In addition, we compare our findings to cellular immunotherapy in glioma, an MB-like intracranial tumor. Finally, future possibilities for MB are discussed to improve efficacy and safety.

A Preliminary Analysis of Thyrotropin Measurement from Finger Stick Dried Blood Spot with an Automated High-Throughput Immunoassay Analyzer.

Background: Hyper- and hypothyroidism are prevalent in Western countries and often go unnoticed for long periods. Thyrotropin (TSH) as a biomarker of thyroid dysfunction is regularly measured in venous plasma/serum. In newborn screening for congenital hypothyroidism, TSH is measured from dried blood spots (DBSs). DBS enables minimally invasive (at-home) sampling of a small blood volume that can be sent to diagnostic laboratories by regular mail. Methods: In this study, we included 109 patients who presented to the outpatient clinic of the University Medical Center Utrecht. Capillary finger stick was used to spot blood on a filter paper card and was dried. After extraction of TSH from DBS, method comparison with venous TSH was performed on an automated high-throughput immunoassay analyzer. Additional validation steps regarding stability, effect of hematocrit (Hct), precision, and limits of blank and quantitation were conducted according to corresponding Clinical and Laboratory Standards Institute evaluation protocol. Results: Method comparison of TSH from venous plasma versus finger stick DBSs showed an R2 [95% confidence interval] = 0.988 [0.986-0.990]. This enabled correct diagnosis of hypothyrotropinemia and hypothyroidism in 12 of 14 and 6 of 7 cases, respectively, with no false positives. Furthermore, TSH from DBS was stable for at least 4 days at temperatures between -20°C and +30°C, and the maximum decrease of eluate TSH was 1.13% for 1% increase in Hct. Conclusions: TSH from DBS may be accurately measured on an automated high-throughput immunoassay analyzer and could be used to diagnose hypothyroidism and, for the first time, hypothyrotropinemia. This method, when confirmed in larger field studies, may enable individuals to engage in (at-home) sampling of blood on DBSs for telediagnostics, screening programs, patient follow-up, and medication management.