[Mandatory Surgical Subinternship in the Final Year of Medical School - a Stepping Stone to Becoming a Surgeon?] / Chirurgisches Pflichttertial im Praktischen Jahr ­ das Sprungbrett in die chirurgische Weiterbildung?

BACKGROUND: The final year is an important time for a medical student as this is when medical knowledge is transformed into medical responsibilities. The field of surgery is firmly anchored in the educational structure as it is mandatory during the practical year of a medical student. The purpose of this paper is to identify factors that influence medical students to choose surgery after the final year of medical school. MATERIALS AND METHODS: An online survey conducted by the AG DGOU 2012 provided complete data sets from a total of 9079 participants. 184 of these had already completed their PJ compulsory sub-internship (tertiary) surgery. These were divided into four groups for analysis: decision to specialise in surgery prior to the PJ compulsory tertiary ("yes, before", JV), during the PJ compulsory ("yes, during", JW), decision against before the PJ compulsory ("no, before", NV) or during the compulsory ("no, during", NW). The total of 38 survey items were summarised for overall assessment, taking into account the decision on subject specialisation. RESULTS: 57.9% of the respondents were positive regarding the overall impression of the surgical internship during their final year. The respondents of the JW group were especially positive, having made the decision to become a surgeon, based on their internship experience during the final year in comparison to the NW group (decision against surgery). We find significant differences in all analysed items: integration into team JW/NW (p ≤ 0.003), acquisition of expertise (p ≤ 0.014), teachers (p ≤ 0.025), quality and structure of teaching (p ≤ 0.043) and overall satisfaction with the required tertial (p ≤ 0.037). CONCLUSION: In comparison to other specialities, in the field of surgery there is the option of recruiting directly within the framework of the compulsory internship. The results reveal unsatisfactory structures from a student perspective. The lack of medical care/support, the insufficient inclusion in therapeutic considerations, the lack of professional knowledge and lack of contact with the teachers are just a few key points that negatively impact the overall outcome of students' satisfaction with the compulsory tertiary education. The results of the present study should serve as motivation and contribute to the restructuring of the compulsory core of the Practical Year, which the Master Plan 2020 will entail.

Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic cell differentiation.

Two major pathways of human myeloid dendritic cell (DC) subset differentiation have previously been delineated. Langerhans cells (LCs) reside in epithelia in the steady state, whereas monocytes can provide dendritic cells (DCs) on demand in response to inflammatory signals. Both DC subset pathways arise from shared CD14+ monocyte precursors, which in turn develop from myeloid committed progenitor cells. However, the underlying hematopoietic mechanisms still remain poorly defined. Here, we demonstrate that the vitamin D(3) receptor (VDR) is induced by transforming growth factor beta1 during LC lineage commitment and exerts a positive role during LC generation. In contrast, VDR is repressed during interleukin-4 (IL-4)-dependent monocyte-derived DC (moDC) differentiation. We identified GATA-1 as a repressor of VDR. GATA-1 is induced by IL-4 in moDCs. Forced inducible expression of GATA-1 mimics IL-4 in redirecting moDC differentiation and vice versa, GATA-1 knockdown arrests moDC differentiation at the monocyte stage. Moreover, ectopic GATA-1 expression stabilizes the moDC phenotype under monocyte-promoting conditions in the presence of vitamin D3 (VD3). In summary, human myeloid DC subset differentiation is inversely regulated by GATA-1 and VDR. GATA-1 mediates the repression of VDR and enables IL-4-dependent moDC differentiation. Conversely, VDR is induced downstream of transforming growth factor beta1 and is functionally involved in promoting LC differentiation.

Human Langerhans-cell activation triggered in vitro by conditionally expressed MKK6 is counterregulated by the downstream effector RelB.

Environmentally exposed epithelial Langerhans cells (LCs) encounter diverse innate stress signals, which lead to the activation of complex intracellular signaling cascades. Among these, p38 MAPK is consistently phosphorylated. For which aspects of LC activation triggering of p38 signaling is sufficient remains to be elucidated. We show that conditional induction of a dominant active form of MAPK kinase 6 (d.a.MKK6), a direct upstream kinase of p38, in LCs efficiently induces the up-regulation of costimulatory molecules and enhances their T-cell stimulatory capacity. These immediate effects showed no or only a minor requirement for classical NF-kappaB signaling. Concomitant with LC activation, d.a.MKK6 induced the alternative NF-kappaB member RelB, whose nuclear localization marks mature DCs. Specific inhibition of nuclear RelB during d.a.MKK6-induced LC activation further enhanced their maturation state. This observation was validated using the p38 activator anisomycin, thus suggesting a novel LC intrinsic control mechanism regulated by RelB.

Differential involvement of PU.1 and Id2 downstream of TGF-beta1 during Langerhans-cell commitment.

Langerhans cells (LCs) are highly abundant dendritic cells (DCs) in epidermal and mucosal tissues. The transcription factors PU.1 and Id2 have been implicated as positive regulators of LC development from hematopoietic progenitor cells. LC differentiation from progenitors is absolutely dependent on transforming growth factor beta 1 (TGF-beta1) in vitro as well as in vivo; however, downstream mechanisms are poorly defined. We found that both PU.1 and Id2 are induced by TGF-beta1 in human CD34+ monocyte/LC (M/LC) progenitor cells, and that neither ectopic PU.1 or Id2 alone, nor both together, could replace TGF-beta1 in its instructive function on LC commitment. However, both factors critically contributed to LC differentiation by acting at 2 distinct intersection points. Ectopic PU.1 strongly enhanced TGF-beta1-dependent LC development. Additionally, Notch-induced generation of interstitial-type DCs was associated with PU.1 up-regulation. Thus, PU.1 is generally increased during myeloid DC development. Ectopic Id2 inhibits the acquisition of early monocytic characteristics by cells generated in the absence of TGF-beta1 and also inhibits monocyte induction by alternative stimuli. Since TGF-beta1 represses a default monocyte pathway of common progenitor cells, PU.1 and Id2 seem to modulate lineage options of M/LC precursors, downstream of TGF-beta1.