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Objective: The aim of the study was to find out whether it is possible to successfully convert a communication course for around 400 students to a blended-learning format (asynchronous theoretical course/synchronous digital practical course). The main focus thereby was on assessing subjective learning progress and the extent to which the importance of communication and doctor-patient communication can be conveyed online. The study is based on the results of an evaluation of the opinions of both the students and the lecturers that participated in the course.
Methods: The students, who were in their fourth preclinical semester in 2020, were asked to fill in a self-assessment sheet at the beginning of the course, and following its completion. The feedback provided by the lecturers was also assessed. In order to compare the results and identify possible discrepancies, the corresponding self-assessment and evaluation results for the past 10 years (stemming from traditional classroom courses) were also taken into account.
Results: Participants in the online courses reported distinct subjective learning progress, and greater progress than was reported for traditional courses in previous years. The suitability of the online format was viewed critically by both students and lecturers, while the course atmosphere was seen positively. The relevance of doctor-patient communication was assessed particularly highly in the online format.
Conclusion: Based on the results of the evaluation, the experience gained from the blended-learning format will be included into future iterations of the communication course at Goethe University Frankfurt. The results have shown that doctor-patient communication can be learned well online. This format can therefore be recommended for new learning concepts in the future.
The low-threshold L-type calcium channel Cav1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Cav1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Cav1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson's disease.
Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by the accumulation of undifferentiated white blood cells (blasts) in the bone marrow. Valosin-containing protein (VCP) is an abundant molecular chaperone that extracts ubiquitylated substrates from protein complexes and cellular compartments prior to their degradation by the proteasome. We found that treatment of AML cell lines with the VCP inhibitor CB-5083 leads to an accumulation of ubiquitylated proteins, activation of unfolded protein response (UPR) and apoptosis. Using quantitative mass spectrometry-based proteomics we assessed the effects of VCP inhibition on the cellular ubiquitin-modified proteome. We could further show that CB-5083 decreases the survival of the AML cell lines THP-1 and MV4-11 in a concentration-dependent manner, and acts synergistically with the antimetabolite cytarabine and the BH3-mimetic venetoclax. Finally, we showed that prolonged treatment of AML cells with CB-5083 leads to development of resistance mediated by mutations in VCP. Taken together, inhibition of VCP leads to a lethal unfolded protein response in AML cells and might be a relevant therapeutic strategy for treatment of AML, particularly when combined with other drugs. The toxicity and development of resistance possibly limit the utility of VCP inhibitors and have to be further explored in animal models and clinical trials.
Background: Only one previously published study by Nocera et al. addressed the risk of upstaging to ≥pT3 in cT1 clear cell renal cell carcinoma (ccRCC) by using characteristics of the R.E.N.A.L and PADUA score (age, tumor size, rim location, exophytic rate, polar involvement) developing an accurate nomogram. However, this nomogram has never been externally validated yet.
Material and methods: The study cohort consisted of 288 patients with cT1a-b ccRCC, diagnosed between 2008-2021 at the University Hospital Frankfurt, Germany. Analyses addressed clinical, tumor and radiographic characteristics. The external validation of the nomogram relied on accuracy calculations derived from the area under the curve of the receiver operator characteristic analysis.
Results: Overall, 11.8% (n=34) patients harbored ≥pT3 ccRCC. Median radiographic tumor size (3.6 vs. 5.3cm), R.E.N.A.L. (8 vs. 9 points) and PADUA score (9 vs. 11 points), as well as proportions of renal sinus involvement (82.4% vs. 51.6%), renal hilus involvement (44.1 vs. 13.0%), and medial rim location significantly differed between the pT1-2 and ≥pT3 group (all p ≤ 0.01). In subgroup analyses of small renal mass ccRCC patients (<4cm, cT1a), only 3.8% (n=6) patients had ≥pT3 pathology. Upstaged patients were significantly older and more frequently had endophytic tumor than pT1-2 counterparts (p<0.05). The external validation of the Nocera nomogram showed a good accuracy of 76.6%. Using the suggested cut-off of 21%, 26.5% of patients exhibited ≥pT3 ccRCC. Conversely, within patients below cut-off, 5.9% patients exhibited ≥pT3 ccRCC.
Conclusion: We reported the first external validation of the nomogram addressing the risk of ≥pT3 in cT1 ccRCC patients, demonstrating a good accuracy, with a low false-negative rate. Therefore, the nomogram can accurately be used for patients’ counselling and treatment decision making.
Implementation and evaluation of a Tele-OSCE in oral and maxillofacial surgery – a pilot report
(2022)
Background: The ongoing changes in learning and education towards digitalisation have been rapidly accelerated by the COVID-19 pandemic. Especially in dental education where contact to the oral cavity is an integral part of training the chosen digital examination methods and training formats must undergo high requirements to full fill the goal of a real alternative to face-to-face exams. Therefore, this study compared student performance in a newly developed Tele-OSCE with a prior OSCE examinations in presence within an oral- and maxillofacial surgery curriculum.
Methods: Study participants were fourth-year (in a five year curriculum) dental students and board certified maxillofacial surgeons (examiners) that took part in a newly developed Tele-OSCE that comprised three five-minute stations (structured facial examination, management mandibular fracture and squamous cell carcinoma) using the zoom® software. Student performance was measured using validated OSCE-Checklists and compared to a previous OSCE examination from the winter term 2019 with the same OSCE stations that was conducted in presence. Significant differences were tested using the Mann-Whitney U test. Furthermore, the new Tele-OSCE was evaluated by students and examiners using previously developed questionnaires.
Results: Sixty-six dental students (study group: n=34, summer term 2021, control group: n=32 winter term 2019) and nine examiners participated in the study. Compared to previous non-pandemic OSCEs, there were no significant (p=0.53) differences in overall student performance. Evaluation of the Tele-OSCE showed that the demonstration and rating of practical skills was limited due to missing standard patients or phantoms, however, students did not fear to be misjudged. The demonstration and rating of anamnestic and consultation competencies was seen as unproblematic by students and examiners.
Discussion: This pilot-study showed the feasibility of a Tele-OSCE as a formative examination in dental education. However, both students and examiners felt that the demonstration and assessment of practical skills was limited due the new examination format. Nevertheless, Tele-OSCEs might offer an alternative to enable students to complete their dental training.
Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigation. For this endeavor, we used a dopaminergic challenge fMRI study (L-DOPA) in healthy participants who were genotyped for their ADHD, MDD, schizophrenia, and body height polygenic risk score (PRS) and compared results with a study comparing ADHD patients and healthy controls. Our objective was to evaluate how L-DOPA-induced changes of reward-system-related FC are dependent on the individual polygenic risk score. FMRI imaging was used to evaluate resting-state functional connectivity (FC) of targeted subcortical structures in 27 ADHD patients and matched controls. In a second study, we evaluated the effect of ADHD and non-ADHD PRS in a L-DOPA-based pharmaco-fMRI-challenge in 34 healthy volunteers. The functional connectivity between the putamen and parietal lobe was decreased in ADHD patients. In healthy volunteers, the FC between putamen and parietal lobe was lower in ADHD high genetic risk participants. This direction of connectivity was reversed during L-DOPA challenge. Further findings are described for other dopaminergic subcortical structures. The FC between the putamen and the attention network showed the most consistent change in patients as well as in high-risk participants. Our results suggest that FC of the dorsal attention network is altered in adult ADHD as well as in healthy controls with higher genetic risk.
[Congress abstract P-05-09] Calcium, calcium-sensing receptor and its role in leukaemia progression
(2022)
Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital’s databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.