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[english] Objectives: Amended in 2013, the current version of the German Medical Licensure Regulation contains structural specifications that are also required of non-university institutions involved in Practical Year clinical training. The criteria are worded in relatively general terms. Furthermore, not all of the structural specifications can be readily applied to every subject area. In order to ensure commensurability in Practical Year instruction in Germany, not least in light of recently introduced Practical Year mobility, it is necessary to define consistent quality criteria for Practical Year training. The authors therefore propose a catalogue of criteria for the quality management process in Practical Year instruction facilities.Methods: In January 2014, the board of directors of the German Society for Medical Education decided to establish a committee comprised of representatives from various German medical faculties. In a process similar to the Delphi methodology, the group developed criteria for structure, process and outcome quality in Practical Year training in Germany.Results: The criteria developed for structure, process and outcome quality apply to Practical Year training in academic teaching hospitals and university medical centres. Furthermore, modalities for review are proposed. Conclusions: The present catalogue of criteria is intended to contribute to the formation of a basis for the most consistent quality standards possible for Practical Year instruction in Germany.

[english] Aims: Different approaches to performance-oriented allocation of resources according to teaching quality are currently being discussed within German medical schools. The implementation of these programmes is impeded by a lack of valid criteria to measure teaching quality. An assessment of teaching quality should include structural and procedural aspects but focus on learning outcome itself. The aim of this study was to implement a novel, outcome-based evaluation tool within the clinical phase of a medical curriculum and address differences between the novel tool and traditional evaluation methods. Methods: Student self-assessments before and after completion of a teaching module were used to compute performance gains for specific learning objectives. Mean performance gains in each module were compared to student expectations before the module and data derived from a traditional evaluation tool using overall course ratings at the end of the module.Results: A ranking of the 21 modules according to computed performance gains yielded entirely different results than module rankings based on overall course ratings. There was no significant correlation between performance gain and overall ratings. However, the latter were significantly correlated to student expectations before entering the module as well as structural and procedural parameters (Pearson’s r 0.7-0.9).Conclusion: Performance gain computed from comparative self-assessments adds an important new dimension to course evaluation in medical education. In contrast to overall course ratings, the novel tool is less heavily confounded by construct-irrelevant factors. Thus, it appears to be more appropriate than overall course ratings in determining teaching quality and developing algorithms to guide performance-oriented resource allocation in medical education. [german] Zielsetzung: Aktuell werden an den deutschen medizinischen Fakultäten unterschiedliche Konzepte zur leistungsorientierten Mittelvergabe (LOM) in der Lehre diskutiert. Die Umsetzung scheitert mitunter am Mangel valider Messkriterien zur Beurteilung der Lehrqualität. Neben der Struktur und den Prozessen der Lehre sollte das Ergebnis der Lehre im Mittelpunkt der Qualitätsbewertung stehen. Ziele dieser Arbeit waren die Erprobung eines neuen, lernzielbezogenen Evaluationssystems im klinischen Abschnitt des Studiums der Humanmedizin und der Vergleich der Ergebnisse mit den Daten eines traditionellen Evaluationsverfahrens.Methodik: Aus studentischen Selbsteinschätzungen zu Beginn und Ende eines jeden Lehrmoduls wurde nach einer neu entwickelten Formel der lernzielbezogene, prozentuale Lernerfolg berechnet. Die Lernerfolgs-Mittelwerte pro Modul wurden mit traditionellen Evaluationsparametern, insbesondere mit Globalbewertungen, ins Verhältnis gesetzt.Ergebnisse: Der mittels vergleichender Selbsteinschätzungen berechnete Lernerfolg und die Globalbewertungen produzierten deutlich unterschiedliche Rangfolgen der 21 klinischen Module. Zwischen dem Lernerfolg und den Globalbewertungen fand sich keine statistisch signifikante Korrelation. Allerdings korrelierten die Globalbewertungen stark mit den studentischen Erwartungen vor Modulbeginn und mit strukturellen und prozeduralen Parametern der Lehre (Pearson’s r zwischen 0,7 und 0,9). Schlussfolgerung: Die Messung des Lernzuwachses mittels vergleichender studentischer Selbsteinschätzungen kann die traditionelle Evaluation um eine wichtige Dimension erweitern. Im Unterschied zu studentischen Globalbewertungen ist das neue Instrument lernzielbezogen und unabhängiger vom Einfluss Konstrukt-irrelevanter Parameter. Hinsichtlich der Entwicklung eines LOM-Algorithmus eignet sich das neue Instrument gut zur Beurteilung der Lehrqualität.

Human organic anion transporter 4 (hOAT4) was recently cloned and reported to be functionally expressed in the placenta and on the apical side of the proximal tubule cells of the kidneys. hOAT4 mediates the transport of estrone sulfate (ES) and dehydroepiandrosterone-sulfate (DHEA-S) with high affinity, and possesses affinity for a variety of organic anions including drugs and xenobiotics. Consequently, it is involved in the excretion of potentially harmful metabolites as well as in the uptake of nephrotoxic substances such as the mycotoxin ochratoxin A. The transport mode and driving forces of this transporter are still controversial. To address this question, we used HEK 293 cells stably transfected with hOAT4, and performed uptake studies using 6- carboxyfluorescein (6-CF) showing a Km of 253 µM. 6-CF and [³H]ES accumulation by hOAT4 was almost abolished by 0.5mM each of ES, DHEA-S and probenecid, whereas p-aminohippurate (PAH), lactate, pyrazinoate and glutarate showed no effect. Urate reduced 6-CF uptake significantly by 40%, and exhibited an IC50 value determined with [³H]ES of 1,026 µM, suggesting urate to be a substrate of hOAT4. In chloride-free medium the [³H]ES uptake was substantially higher indicating chloride as a potential exchange anion. Trans-stimulation experiments revealed significant elevations of 6-CF uptake for PAH and glutarate, and also a significant trans-inhibition for lactate documenting asymmetrical interaction of hOAT4 with some of these substrates. Changes of the pH-value to 5.5 in the medium increased the 6-CF uptake by 3.5 fold and ES uptake by 1.6 fold, whereas an outside alkaline pH reduced 6-CF and ES accumulation significantly. Acidification of intracellular pH by NH4Cl- pulse resulted in a reduction of ES uptake, while intracellular alkalinization increased the ES uptake. This observation is consistent with the idea of an exchange of organic anions against OH- ions. In conclusion, we provide evidence that OAT4 is an asymmetrical exchanger taking several substrates only from one side of the cell consistent with a physiological role in secretion. hOAT4 interacts with urate, and it exchanges organic anions against OH- or Cl- ions. We assume that this transporter is the low affinity urate exchanger of the luminal membrane, which was postulated from the studies with human brush-border membrane vesicles. [ABSTRACT FROM AUTHOR]

Objective: Kidney proximal tubule cells take up Krebs cycle intermediates for metabolic purposes and for secretion of organic anions through dicarboxylate/organic anion exchange. Sodium-dependent dicarboxylate cotransporters (NaDCs) are located at either side of the proximal tubule cell. They accept dicarboxylates with a chain length of 4 and 5 carbon atoms and substitutions at the C2-carbon position. Folate contains a nonionoized substitution at the C2-carbon atom and a backbone of 5 carbons. Thus folate might possess the structural features of a substrate for hNaDC-3. Methods: Substrate-associated currents in Xenopus laevis oocytes injected with cRNA coding for hNaDC-3 were investigated three days post injection using a two-electrode voltage clamp device. Results: The currents increased in magnitude with increasing concentrations of succinate. Whereas the maximal inducible current increased with hyperpolarization, Km (30 micromolar, n = 4) stayed fairly constant within the potential range between -90 and 0mV. hNaDC-3 was rather insensitive against lithium: Therapeutic lithium concentrations of 1 or 2.5mM inhibited currents evoked by 1mM succinate by only 8.1 ± 7.2 and 20 ± % (n = 6), respectively, at all testing membrane potentials. Folate in concentrations up to 10mM did not induce sodium- and lithium-sensitive currents comparable in magnitude to those evoked by succinate (n = 4-6). Conclusions: As opposed to NaDC-3 from other species, hNaDC-3 is rather insensitive to lithium. Moreover, the dicarboxylate folate is not a substrate for hNaDC-3. [ABSTRACT FROM AUTHOR]

Objective: The immunosuppressant mycophenolic acid (MPA) is predominantly (>90%) eliminated via the kidneys, mostly as the 7-O-glucuronide (MPAG), a pharmacologically inactive metabolite. In addition to MPAG, a pharmacologically active acylglucuronide (AcMPAG) metabolite of MPA is also formed in humans. The cellular mechanisms of the excretion of MPA and its metabolites have not been elucidated. However, the structure of MPA as well as the observed increases in plasma levels of coadministered antiviral drugs point to an interaction with the organic anion transporters 1 (OAT1) and/or 3 (OAT3), which are involved in renal organic anion secretion. Methods: hOAT1 and hOAT3 were expressed from in vitro synthesized cRNA (20 ng/ oocyte) in collagenase-defolliculated oocytes. On day 3 post injection, uptake of 10 µM [⊃3H] p-aminohippurate (PAH) or 50 nM estrone sulfate (ES) was assayed in the absence or presence of either MPA, MPAG, or AcMPAG. Results: The parent compound MPA inhibited both hOAT1 and hOAT3 with similar potency (57 and 77% at 10 µM, 91 and 88% at 100 µM, respectively). An initial experiment with hOAT3 yielded an IC50 value below 1 µM. In contrast, both glucuronidated metabolites significantly inhibited hOAT3 (89 and 67% at 100 µM for AcMPAG and MPAG, respectively), but had little effect on hOAT1. For AcMPAG, the IC50 averaged about 3 micro;M (n = 3). Experiments to test whether MPA or its metabolites are actually translocated by OAT1 or OAT3 are under way. Conclusions: Our results prove that MPA and its metabolites strongly interact with hOAT1 and/or hOAT3. Therefore, they may interfere with coadministered drugs eliminated via the renal organic anion secretory pathway, e.g. virustatics, causing potentially harmful elevations in their serum levels. [ABSTRACT FROM AUTHOR]