Gekend Talent

Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Experimentele endocrinologie en medisch onderwijs aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 11 mei 2009

Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function

The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHbeta subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases

Regulation of gonadotropin receptor gene expression

The receptors for the gonadotropins differ from the other G protein-coupled receptors by having a large extracellular hormone-binding domain, encoded by nine or ten exons. Alternative splicing of the large pre-mRNA of approximately 100 kb can result in mRNA species that encode truncated receptor proteins. In this review we discuss the regulation of gonadotropin receptor mRNA expression and the possible roles of alternative splicing in gonadotropin receptor function

Regulation of ovarian function: the role of anti-Mullerian hormone

Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance, is a member of the transforming growth factor beta superfamily of growth and differentiation factors. In contrast to other members of the family, which exert a broad range of functions in multiple tissues, the principal function of AMH is to induce regression of the Mullerian ducts during male sex differentiation. However, the patterns of expression of AMH and its type II receptor in the postnatal ovary indicate that AMH may play an important role in ovarian folliculogenesis. This review describes several in vivo and in vitro studies showing that AMH participates in two critical selection points of follicle development: it inhibits the recruitment of primordial follicles into the pool of growing follicles and also decreases the responsiveness of growing follicles to FSH

Ethnic and social disparities in different types of examinations in undergraduate pre-clinical training

Medical schools are increasingly faced with a more diverse student population. Generally, ethnic minority students are reported to underperform compared with those from the ethnic majority. However, there are inconsistencies in findings in different types of examinations. Additionally, little is known about the performance of first-generation university students and about performance differences across ethnic minority groups. This study aimed to investigate underperformance across ethnic minority groups and by first-generation university students in different types of written tests and clinical skills examinations during pre-clinical training. A longitudinal prospective cohort study of progress on a 3-year Dutch Bachelor of Medicine course was conducted. Participants included 2432 students who entered the course over a consecutive 6-year period (2008–2013). Compared with Dutch students, the three non-Western ethnic minority groups (Turkish/Moroccan/African, Surinamese/Antillean and Asian) underperformed in the clinical problem solving tests, the language test and the OSCEs. Findings on the theoretical end-of-block tests and writing skills tests, and results for Western minority students were less consistent. Age, gender, pre-university grade point average and additional socio-demographic variables (including first-generation university student, first language, and medical doctor parent) could explain the ethnicity-related differences in theoretical examinations, but not in language, clinical and writing skills examinations. First-generation university students only underperformed in the language test. Apparently, underperformance differs both across ethnic subgroups and between different types of written and clinical examinations. Medical schools should ensure their assessment strategies create a level playing field for all students and explore reasons for underperformance in the clinical and writing skills examinations

The relationship between extracurricular activities assessed during selection and during medical school and performance

Several medical schools include candidates’ extracurricular activities in their selection procedure, with promising results regarding their predictive value for achievement during the clinical years of medical school. This study aims to reveal whether the better achievement in clinical training of students selected on the basis of their extracurricular activities could be explained by persistent participation in extracurricular activities during medical school (msECAs). Lottery-admitted and selected student admission groups were compared on their participation in three types of msECAs: (1) research master, (2) important board positions or (3) additional degree programme. Logistic regression was used to measure the effect of admission group on participation in any msECA, adjusted for pre-university GPA. Two-way ANCOVA was used to examine the inter-relationships between admission group, participation in msECAs and clerkship grade, with pre-university GPA as covariate. Significantly more selected students compared to lottery-admitted students participated in any msECA. Participation in msECAs was associated with a higher pre-university GPA for lottery-admitted students only, whereas participation in msECAs was associated with higher clerkship grades for selected students only. These results suggest that persistent participation in extracurricular activities of selected students favours better clinical achievement, supporting the inclusion of ECAs in the selection procedure. More insight in the rationale behind participation in extracurricular activities during medical school may explain differences found between lottery-admitted and selected students

Alternative splicing of follicle-stimulating hormone receptor pre-mRNA: cloning and characterization of two alternatively spliced mRNA transcripts

Glycoprotein hormone receptors contain a large extracellular domain that is encoded by multiple exons, facilitating the possibility of expressing alternatively spliced transcripts. We have cloned two new splice variants of the rat follicle-stimulating hormone (FSH) receptor gene: FSH-R1 and FSH-R2. The splice variant FSH-R1 differs from the full-length FSH receptor mRNA by the inclusion of a small extra exon between exons 9 and 10. FSH-R2 lacks the first three base pairs o

Integrity situational judgement test for medical school selection

Context: Despite their widespread use in medical school selection, there remains a lack of clarity on exactly what situational judgement tests (SJTs) measure. Objectives: We aimed to develop an SJT that measures integrity by combining critical incident interviews (inductive approach) with an innovative deductive approach. The deductive approach guided the development of the SJT according to two established theoretical models, of which one was positively related to integrity (honesty–humility [HH]) and one was negatively related to integrity (cognitive distortions [CD]). The Integrity SJT covered desirable (HH-based) and undesirable (CD-based) response options. We examined the convergent and discriminant validity of the Integrity SJT and compared the validity of the HH-based and CD-based subscores. Methods: The Integrity SJT was administered to 402 prospective applicants at a Dutch medical school. The Integrity SJT consisted of 57 scenarios, each followed by four response options, of which two represented HH facets and two represented CD categories. Three SJT scores were computed, including a total, an HH-based and a CD-based score. The validity of these scores was examined according to their relationships with external integrity-related measures (convergent validity) and self-efficacy (discriminant validity). Results: The three SJT scores correlated significantly with all integrity-related measures and not with self-efficacy, indicating convergent and discriminant validity. In addition, the CD-based SJT score correlated significantly more strongly than the HH-based SJT score with two of the four integrity-related measures. Conclusions: An SJT that assesses the ability to correctly recognise CD-based response options as inappropriate (i.e. what one should not do) seems to have stronger convergent validity than an SJT that assesses the ability to correctly recognise HH-based response options as appropriate (i.e. what one should do). This finding might be explained by the larger consensus on what is considered inappropriate than on what is considered appropriate in a challenging situation. It may be promising to focus an SJT on the ability to recognise what one should not do

Academic dismissal policy for medical students:effect on study progress and help-seeking behaviour

CONTEXT Medical students often fail to finish medical school within the designated time. An academic dismissal (AD) policy aims to enforce satisfactory progress and to enable early identification and timely support or referral of struggling students. In this study, we assessed whether the implementation of an AD policy improved study progress in the first 2 years of medical school. Additionally, we analysed its effect on the help-seeking behaviour of struggling students. METHODS We compared two AD cohorts (entering in 2005 and 2006, respectively) and two non-AD cohorts (entering in 2003 and 2004, respectively) on dropout rates, Year 1 curriculum completion rates and the percentage of students with an optimal study rate (i.e. all modules completed) at 1 and 2 years after enrolment. We also measured the effect on study progress of attending the support meetings offered. RESULTS The AD (n = 809) and non-AD cohorts (n = 809) did not differ significantly in dropout rate at 5 months, in Year 1 completion rate at 2 years and in the percentage of optimally performing students at 1 year after enrolment. At 2 years after enrolment, more students from the AD cohorts had left and more non-AD students demonstrated optimal performance, but effect sizes (ESs) for these differences were small. Voluntary support at 4 months was attended by AD students more often than by non-AD students (68.9% versus 39.8%; chi(2)((1)) = 43.95, p <0.001, ES = 0.29). The AD students who attended the support meetings completed the Year 1 curriculum more often than those who did not (73.4% versus 52.5%; chi(2)((1)) = 10.92, p <0.001, ES = 0.20). Attending the obligatory support meeting at 7 months had a similar effect (70.5% versus 33.3%; chi(2)((1)) = 13.60, p <0.001, ES = 0.23). CONCLUSIONS The presence of an AD policy did not lead to earlier dropout, higher completion rates or an improved study rate during the first 2 years at medical school. However, uptake of the support offered increased to almost 70%. Although support participants finished the Year 1 curriculum more often than non-participants, the current support system was not sufficient to improve overall study progress