Predictive molecular pathology after prolonged fixation: A study on tissue from anatomical body donors.

Histopathological assessment of tissue samples after prolonged formalin fixation has been described previously, but currently there is only limited knowledge regarding the feasibility of molecular pathology on such tissue. In this pilot study, we tested routine molecular pathology methods (DNA isolation, DNA pyrosequencing/next-generation sequencing, DNA methylation analysis, RT-PCR, clonality analysis and fluorescence in situ hybridization) on tissue samples from 11 tumor entities as well as non-neoplastic brain tissue from 43 body donors during the gross anatomy course at Ulm University (winter semester 2019/20 and 2020/21). The mean post mortem interval until fixation was 2.5 ± 1.6 days (range, 1-6 days). Fixation was performed with aqueous formaldehyde solution (formalin, 1.5-2%). The mean storage time of body donors was 12.8 ± 5.6 months (range, 7-25 months). While most diagnostic methods were successful, samples showed significant variability in DNA quality and evaluability. DNA pyrosequencing as well as next-generation sequencing was successful in all investigated samples. Methylation analyses were partially not successful in some extend due to limited intact DNA yield for these analyses. Taken together, the use of prolonged formalin-fixed tissue samples from body donors offers new avenues in research and education, as these samples could be used for morpho-molecular studies and the establishment of biobanks, especially for tissue types that cannot be preserved and studied in vivo. Pathological ward rounds, sample collection, and histopathological and molecular workup have been integrated in the gross anatomy course in Ulm as an integral part of the curriculum, linking anatomy and pathology and providing medical students early insight into the broad field of (molecular) pathology.

How professional and academic pre-qualifications relate to success in medical education: Results of a multicentre study in Germany.

OBJECTIVE: Every year, many applicants want to study medicine. Appropriate selection procedures are needed to identify suitable candidates for the demanding curriculum. Although research on medical school admissions has shown good predictive validity for cognitive selection methods (undergraduate GPA, aptitude tests), the literature on applicants with professional and/or academic experience prior to entering medical school remains slim. In our study, we therefore aimed to examine the association between academic success in medical school and having previously completed vocational training in the medical field, voluntary service (≥11 months) or an academic degree. METHODS: Data were collected in a multicentre, cross-sectional study at five medical schools in Germany (Baden-Wuerttemberg) from students during medical school (i.e. 3rd-, 6th-, and 10th-semester and final-year students). Academic success was assessed according to scores on the first and second state examinations, the total number of examinations repeated and the number of semesters beyond the standard period of study. For the analysis we calculated ordinal logistic regression models for each outcome variable of academic success. RESULTS: A total of N = 2,370 participants (response rate: RR = 47%) participated in the study. Having completed vocational training was associated with a higher amount of repeated examinations (small effect), while having an academic degree was associated with worse scores on the second state examination (medium effect). No significant association emerged between voluntary service and academic success. CONCLUSION: The results indicate that professional and academic pre-qualifications pose no advantage for academic success. Possible associations with the financing of study and living conditions of students with pre-qualifications were analysed and discussed in an exploratory manner. However, the operationalisation of academic success from objective and cognitive data should be critically discussed, as the benefits of prior experience may be captured by personal qualities rather than examination results.

Restoring Axonal Organelle Motility and Regeneration in Cultured FUS-ALS Motoneurons through Magnetic Field Stimulation Suggests an Alternative Therapeutic Approach.

Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by sustained loss of neuromuscular junctions, degenerating corticospinal motoneurons and rapidly progressing muscle paralysis. Motoneurons have unique features, essentially a highly polarized, lengthy architecture of axons, posing a considerable challenge for maintaining long-range trafficking routes for organelles, cargo, mRNA and secretion with a high energy effort to serve crucial neuronal functions. Impaired intracellular pathways implicated in ALS pathology comprise RNA metabolism, cytoplasmic protein aggregation, cytoskeletal integrity for organelle trafficking and maintenance of mitochondrial morphology and function, cumulatively leading to neurodegeneration. Current drug treatments only have marginal effects on survival, thereby calling for alternative ALS therapies. Exposure to magnetic fields, e.g., transcranial magnetic stimulations (TMS) on the central nervous system (CNS), has been broadly explored over the past 20 years to investigate and improve physical and mental activities through stimulated excitability as well as neuronal plasticity. However, studies of magnetic treatments on the peripheral nervous system are still scarce. Thus, we investigated the therapeutic potential of low frequency alternating current magnetic fields on cultured spinal motoneurons derived from induced pluripotent stem cells of FUS-ALS patients and healthy persons. We report a remarkable restoration induced by magnetic stimulation on axonal trafficking of mitochondria and lysosomes and axonal regenerative sprouting after axotomy in FUS-ALS in vitro without obvious harmful effects on diseased and healthy neurons. These beneficial effects seem to derive from improved microtubule integrity. Thus, our study suggests the therapeutic potential of magnetic stimulations in ALS, which awaits further exploration and validation in future long-term in vivo studies.

Poly(I:C)-induced maternal immune activation causes elevated self-grooming in male rat offspring: Involvement of abnormal postpartum static nursing in dam.

Introduction: Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring's development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring. Methods: To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam's postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup's developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups. Results: Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip. Discussion: In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam's postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring.

Downregulation of the Autism Spectrum Disorder Gene Shank2 Decreases Bone Mass in Male Mice.

Mutations of the postsynaptic scaffold protein Shank2 lead to autism spectrum disorders (ASD). These patients frequently suffer from higher fracture risk. Here, we investigated whether Shank2 directly regulates bone mass. We show that Shank2 is expressed in bone and that Shank2 levels are increased during osteoblastogenesis. Knockdown of Shank2 by siRNA targeting the encoding regions for PDZ and SAM domain inhibits osteoblastogenesis of primary murine calvarial osteoblasts. Shank2 knockout mice (Shank2 -/-) have a decreased bone mass due to reduced osteoblastogenesis and bone formation, whereas bone resorption remains unaffected. Induced pluripotent stem cells (iPSCs)-derived osteoblasts from a loss-of-function Shank2 mutation in a patient showed a significantly reduced osteoblast differentiation potential. Moreover, silencing of known Shank2 interacting proteins revealed that a majority of them promote osteoblast differentiation. From this we conclude that Shank2 and interacting proteins known from the central nervous system are decisive regulators in osteoblast differentiation. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fast and efficient synaptosome isolation and post-synaptic density enrichment from hiPSC-motor neurons by biochemical sub-cellular fractionation.

We describe here a time-efficient, in-house protocol for synaptosome isolation and enrichment of the post-synaptic density (PSD) from hiPSC-derived motor neurons. By using biochemical sub-cellular fractionation, the crude synaptosome is first isolated from the cytosol and is then further separated into the synaptic cytosol and the enriched PSD fraction. The protocol can also potentially be adapted to other hiPSC-derived neuronal types, with necessary changes made to cell seeding density and buffer volumes.

The gross anatomy course: SARS-CoV-2 pandemic-related effects on students' learning, interest in peer-teaching, and students' perception of its importance.

The COVID-19 pandemic required adjustments and limitations in university teaching, thereby challenging teaching concepts in anatomy requiring in-person contact, including the gross anatomy course. Therefore, the present study investigates the impact of COVID-19-associated adjustments on students' perception of the gross anatomy course's importance and quality, students' preferred learning setting and outcome, and their motivation to involve themselves in academic activities, including becoming a future peer-teacher of the course. Using paper-based questionnaires in Ulm, Germany, 397 (response rate: 82.3%) students of the winter term of 2020/2021 were surveyed using quantitative and qualitative items, which were compared with cohorts prior to the pandemic. Students reported a higher global rating on course quality during COVID-19 (pre-COVID-19: 5.3 ± 0.9, during-COVID-19: 5.6 ± 0.7, p < 0.001; 1 = very bad, 6 = very good). Students' perceived importance of the gross anatomy course showed a small but significant increase (pre-COVID-19: 4.2 ± 0.6, during-COVID-19: 4.3 ± 0.6, p < 0.001; 1 = strongly disagree, 6 = strongly agree). Students' motivation to apply as a peer-teacher remained stable, nevertheless, they reported less interest in transferring their knowledge to junior students. Finally, students reported that they spent significantly more learning time alone and their examination grades remained unchanged during the pandemic. Astonishingly, despite radical changes of the teaching environment due to COVID-19, students appreciate the offered teaching and highly valued the gross anatomy course.

What factors motivate male and female Generation Z students to become engaged as peer teachers? A mixed-method study among medical and dental students in the gross anatomy course.

Peer-teaching is widely established in anatomy teaching and offers well-described advantages. Nevertheless, at Ulm University, Germany, a reduction in the number of peer teacher applicants for the dissection course was observed. This study examined factors related to the attractiveness of a position as a peer teacher for Generation Z students. Participants of the gross anatomy course were asked to evaluate factors influencing the attractiveness of a peer teacher position using a six-point Likert scale. Additionally, open-ended questions were analyzed qualitatively. Sex-specific subgroup analysis was performed comparing students of low and high motivation to apply for a tutorship. Of the 374 students who participated in this study (response rate 53%), 38% stated that they were intending to apply as peer teachers. Data indicated that students displayed intrinsic motivation to apply for a tutorship because of the opportunity to improve their anatomy knowledge and/or their pleasure in teaching. In contrast, extrinsic factors like remuneration of the tutorship and its relevance for their curriculum vitae were least important. Anatomy educators underestimated the demotivating factor of the workload associated with the tutorship and encouraged students less frequently to apply than peer teachers. Only minor sex-specific differences could be identified. Nevertheless, female students were encouraged less frequently to apply than their male peers. In summary, Generation Z students apply as peer teachers because they are enthusiastic about the task. To motivate students to commit to extracurricular activities like a tutorship, anatomy educators should actively encourage students-particularly females-more frequently to apply.

Acute TBK1/IKK-ε Inhibition Enhances the Generation of Disease-Associated Microglia-Like Phenotype Upon Cortical Stab-Wound Injury.

Traumatic brain injury has a poorer prognosis in elderly patients, possibly because of the enhanced inflammatory response characteristic of advanced age, known as "inflammaging." Recently, reduced activation of the TANK-Binding-Kinase 1 (Tbk1) pathway has been linked to age-associated neurodegeneration and neuroinflammation. Here we investigated how the blockade of Tbk1 and of the closely related IKK-ε by the small molecule Amlexanox could modify the microglial and immune response to cortical stab-wound injury in mice. We demonstrated that Tbk1/IKK-ε inhibition resulted in a massive expansion of microglial cells characterized by the TMEM119+/CD11c+ phenotype, expressing high levels of CD68 and CD317, and with the upregulation of Cst7a, Prgn and Ccl4 and the decrease in the expression levels of Tmem119 itself and P2yr12, thus a profile close to Disease-Associated Microglia (DAM, a subset of reactive microglia abundant in Alzheimer's Disease and other neurodegenerative conditions). Furthermore, Tbk1/IKK-ε inhibition increased the infiltration of CD3+ lymphocytes, CD169+ macrophages and CD11c+/CD169+ cells. The enhanced immune response was associated with increased expression of Il-33, Ifn-g, Il-17, and Il-19. This upsurge in the response to the stab wound was associated with the expanded astroglial scars and increased deposition of chondroitin-sulfate proteoglycans at 7 days post injury. Thus, Tbk1/IKK-ε blockade results in a massive expansion of microglial cells with a phenotype resembling DAM and with the substantial enhancement of neuroinflammatory responses. In this context, the induction of DAM is associated with a detrimental outcome such as larger injury-related glial scars. Thus, the Tbk1/IKK-ε pathway is critical to repress neuroinflammation upon stab-wound injury and Tbk1/IKK-ε inhibitors may provide an innovative approach to investigate the consequences of DAM induction.

Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients.

BACKGROUND: Increased catabolism has recently been recognized as a clinical manifestation of amyotrophic lateral sclerosis (ALS). The hypothalamic systems have been shown to be involved in the metabolic dysfunction in ALS, but the exact extent of hypothalamic circuit alterations in ALS is yet to be determined. Here we explored the integrity of large-scale cortico-hypothalamic circuits involved in energy homeostasis in murine models and in ALS patients. METHODS: The rAAV2-based large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik software suites were used to identify and quantify projections from the forebrain to the lateral hypothalamus in the SOD1(G93A) ALS mouse model (hypermetabolic) and the FusΔNLS ALS mouse model (normo-metabolic). 3 T diffusion tensor imaging (DTI)-magnetic resonance imaging (MRI) was performed on 83 ALS and 65 control cases to investigate cortical projections to the lateral hypothalamus (LHA) in ALS. RESULTS: Symptomatic SOD1(G93A) mice displayed an expansion of projections from agranular insula, ventrolateral orbitofrontal and secondary motor cortex to the LHA. These findings were reproduced in an independent cohort by using a different analytic approach. In contrast, in the FusΔNLS ALS mouse model hypothalamic inputs from insula and orbitofrontal cortex were maintained while the projections from motor cortex were lost. The DTI-MRI data confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients. CONCLUSION: This study provides converging murine and human data demonstrating the selective structural disruption of hypothalamic inputs in ALS as a promising factor contributing to the origin of the hypermetabolic phenotype.

Synaptic disruption and CREB-regulated transcription are restored by K+ channel blockers in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is still missing effective therapeutic strategies. Although manipulation of neuronal excitability has been tested in murine and human ALS models, it is still under debate whether neuronal activity might represent a valid target for efficient therapies. In this study, we exploited a combination of transcriptomics, proteomics, optogenetics and pharmacological approaches to investigate the activity-related pathological features of iPSC-derived C9orf72-mutant motoneurons (MN). We found that human ALSC9orf72 MN are characterized by accumulation of aberrant aggresomes, reduced expression of synaptic genes, loss of synaptic contacts and a dynamic "malactivation" of the transcription factor CREB. A similar phenotype was also found in TBK1-mutant MN and upon overexpression of poly(GA) aggregates in primary neurons, indicating a strong convergence of pathological phenotypes on synaptic dysregulation. Notably, these alterations, along with neuronal survival, could be rescued by treating ALS-related neurons with the K+ channel blockers Apamin and XE991, which, respectively, target the SK and the Kv7 channels. Thus, our study shows that restoring the activity-dependent transcriptional programme and synaptic composition exerts a neuroprotective effect on ALS disease progression.

A serum microRNA sequence reveals fragile X protein pathology in amyotrophic lateral sclerosis.

Knowledge about converging disease mechanisms in the heterogeneous syndrome amyotrophic lateral sclerosis (ALS) is rare, but may lead to therapies effective in most ALS cases. Previously, we identified serum microRNAs downregulated in familial ALS, the majority of sporadic ALS patients, but also in presymptomatic mutation carriers. A 5-nucleotide sequence motif (GDCGG; D = G, A or U) was strongly enriched in these ALS-related microRNAs. We hypothesized that deregulation of protein(s) binding predominantly to this consensus motif was responsible for the ALS-linked microRNA fingerprint. Using microRNA pull-down assays combined with mass spectrometry followed by extensive biochemical validation, all members of the fragile X protein family, FMR1, FXR1 and FXR2, were identified to directly and predominantly interact with GDCGG microRNAs through their structurally disordered RGG/RG domains. Preferential association of this protein family with ALS-related microRNAs was confirmed by in vitro binding studies on a transcriptome-wide scale. Immunohistochemistry of lumbar spinal cord revealed aberrant expression level and aggregation of FXR1 and FXR2 in C9orf72- and FUS-linked familial ALS, but also patients with sporadic ALS. Further analysis of ALS autopsies and induced pluripotent stem cell-derived motor neurons with FUS mutations showed co-aggregation of FXR1 with FUS. Hence, our translational approach was able to take advantage of blood microRNAs to reveal CNS pathology, and suggests an involvement of the fragile X-related proteins in familial and sporadic ALS already at a presymptomatic stage. The findings may uncover disease mechanisms relevant to many patients with ALS. They furthermore underscore the systemic, extra-CNS aspect of ALS.

Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis.

Intronic hexanucleotide repeat expansions (HREs) in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis, a devastating, incurable motoneuron (MN) disease. The mechanism by which HREs trigger pathogenesis remains elusive. The discovery of repeat-associated non-ATG (RAN) translation of dipeptide repeat proteins (DPRs) from HREs along with reduced exonic C9ORF72 expression suggests gain of toxic functions (GOFs) through DPRs versus loss of C9ORF72 functions (LOFs). Through multiparametric high-content (HC) live profiling in spinal MNs from induced pluripotent stem cells and comparison to mutant FUS and TDP43, we show that HRE C9ORF72 caused a distinct, later spatiotemporal appearance of mainly proximal axonal organelle motility deficits concomitant to augmented DNA double-strand breaks (DSBs), RNA foci, DPRs, and apoptosis. We show that both GOFs and LOFs were necessary to yield the overall C9ORF72 pathology. Increased RNA foci and DPRs concurred with onset of axon trafficking defects, DSBs, and cell death, although DSB induction itself did not phenocopy C9ORF72 mutants. Interestingly, the majority of LOF-specific DEGs were shared with HRE-mediated GOF DEGs. Finally, C9ORF72 LOF was sufficient-albeit to a smaller extent-to induce premature distal axonal trafficking deficits and increased DSBs.

Integration of Scientific Competence into Gross Anatomy Teaching Using Poster Presentations: Feasibility and Perception among Medical Students.

Scientific competences as defined in the German competency framework describes the ability to think independently and act scientifically, and forms a central component of medical education. This report describes its integration into anatomical teaching. On the basis of the findings in dissection courses from two consecutive years, students worked on either a case report (n = 70) or an original work (n=6) in the format of a scientific poster while learning to use primary literature. Posters were evaluated by juror teams using standardized evaluation criteria. Student perception of the project was estimated by quantitative and qualitative data obtained from the faculty´s course evaluation and an online-survey. Overall, students worked collaboratively and invested extra-time (median [MD] 3.0 hours) in poster creation. Primary literature was integrated in 90.8% of the posters. Overall poster quality was satisfactory (46.3 ±8.5 [mean ±standard deviation] out of 72 points), but several insufficiencies were identified. Students integrated information gained from the donor´s death certificate, post-mortem full-body computer tomography (CT) scan (22.4%) and histopathological workup (31.6%) in their case reports. Students were positive about the experience of learning new scientific skills (MD 4 on a six-point Likert scale), but free text answers revealed that some students experienced the project as an extra burden in a demanding course. In summary, it was feasible to introduce students to science during the dissection course and to increase interest in science in approximately a third of the survey respondents. Further adjustments to ensure the posters´ scientific quality might be necessary in the future.

The Use of a Mobile Learning Tool by Medical Students in Undergraduate Anatomy and its Effects on Assessment Outcomes.

Hand-held devices have revolutionized communication and education in the last decade. Consequently, mobile learning (m-learning) has become popular among medical students. Nevertheless, there are relatively few studies assessing students' learning outcomes using m-learning devices. This observational study presents an anatomy m-learning tool (eMed-App), an application developed to accompany an anatomy seminar and support medical students' self-directed learning of the skeletal system. Questionnaire data describe where, how frequently, and why students used the app. Multiple choice examination results were analyzed to evaluate whether usage of the app had an effect on test scores. The eMed-App application was used by 77.5% of the students, mainly accessed by Android smartphones, and at students' homes (62.2%) in order to prepare themselves for seminar sessions (60.8%), or to review learning content (67%). Most commonly, students logged on for less than 15 minutes each time (67.8%). Frequent app users showed better test results on items covering eMed-App learning content. In addition, users also achieved better results on items that were not related to the content of the app and, thus, gained better overall test results and lower failure rates. The top quartile of test performers used the eMed-App more frequently compared to students in lower quartiles. This study demonstrated that many students, especially the high-performing ones, made use of the eMed-App. However, the app itself did not result in better outcomes, suggesting that top students might have been more motivated to use the app than students who were generally weak in anatomy.

Effects of an Educational Film About Body Donors on Students' Empathy and Anxiety Levels in Gross Anatomy.

While most German anatomy institutes provide only limited information about body donors and their lives, students have expressed a desire to learn more about these individuals, especially about their motivations to donate their bodies for the sake of medical education. In order to gratify this wish, as well as to further humanize body donors, an educational film was compiled, and a study designed to capture the film's effects on medical students. This is the first study using standardized, validated psychological tools to evaluate the impact of an educational film about body donors on students' empathy and psychological stress levels. The study followed a longitudinal, controlled, and cluster randomized design, including 77 (48 females/29 males) participants who watched the video either before, midway, or after the dissection course. Questionnaires were completed at four points in time applying the Jefferson Scale for Empathy (JSPE-S) and the Interpersonal Reactivity Index (IRI) to measure empathy. Psychological stress levels were recorded by the Brief Symptom Inventory (BSI). Overall, students recommended the film to be shown to all students (median 6.0; maximum on the six-point Likert scale). Viewing the film revealed no significant changes between study groups or over time in JSPE-S sum scores. All groups demonstrated a significant reduction of BSI values before the dissection course actually started and increased values during the course, but both developments appeared not to be associated with the intervention. Overall, the educational film did not correlate with any negative effects on students' empathy and psychological stress levels, and it was strongly approved of by students, as it provided more humanizing personal information about body donors without violating their anonymity.

Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism.

Autism spectrum disorder (ASD) is characterized by impaired social communication and repetitive/stereotyped behaviors. The neuropeptide oxytocin (OXT) plays a critical role in regulating social behaviors in the central nervous system, as indicated in both human and animal studies. We hypothesized that central OXT deficit is one of causes of etiology of ASD, which may be responsible for the social impairments. To test our hypothesis, central OXT system was examined in valproic acid (VPA)-induced rat model of autism (VPA rat). Our results showed that adolescent VPA rats exhibited a lower level of OXT mRNA and fewer OXT-ir cells in the hypothalamus than control rats. Additionally, OXT concentration in cerebrospinal fluid (CSF) was reduced. The number of OXT-ir cells in the supraoptic nucleus (SON) of neonatal VPA rats was also lower. Autistic-like behaviors were observed in these animals as well. We found that an acute intranasal administration of exogenous OXT restored the social preference of adolescent VPA rats. Additionally, early postnatal OXT treatment had long-term effects ameliorating the social impairments and repetitive behaviors of VPA rats until adolescence. This was accompanied by an increase in OXT-ir cells. Taken together, we demonstrated there was central OXT deficiency in the VPA-induced rat model of autism, and showed evidence that early postnatal OXT treatment had a long-term therapeutic effect on the autistic-like behaviors in VPA rats.

Anonymous body or first patient? A status report and needs assessment regarding the personalization of donors in dissection courses in German, Austrian, and Swiss Medical Schools.

Many Anglo-American universities have undertaken a paradigm shift in how the dissection of human material is approached, such that students are encouraged to learn about the lives of body donors, and to respectfully "personalize" them as human beings, rather than treating the specimens as anonymous cadavers. For the purposes of this study, this provision of limited personal information regarding the life of a body donor will be referred to as "personalization" of body donors. At this time, it is unknown whether this paradigm shift in the personalization of body donors can be translated into the German-speaking world. A shift from donor anonymity to donor personalization could strengthen students' perception of the donor as a "first patient," and thereby reinforce their ability to empathize with their future patients. Therefore, this study aimed to collect data about the current status of donation practices at German-speaking anatomy departments (n = 44) and to describe the opinions of anatomy departments, students (n = 366), and donors (n = 227) about possible donor personalization in medical education. Anatomy departments in Germany, Austria, and Switzerland were invited to participate in an online questionnaire. One-tenth of registered donors at Ulm University were randomly selected and received a questionnaire (20 items, yes-no questions) by mail. Students at the University of Ulm were also surveyed at the end of the dissection course (31 items, six-point Likert-scale). The majority of students were interested in receiving additional information about their donors (78.1%). A majority of donors also supported the anonymous disclosure of information about their medical history (92.5%). However, this information is only available in about 28% of the departments surveyed and is communicated to the students only irregularly. Overall, 78% of anatomy departments were not in favor of undertaking donor personalization. The results appear to reflect traditional attitudes among anatomy departments. However, since students clearly preferred receiving additional donor information, and most donors expressed a willingness to provide this information, one could argue that a change in attitudes is necessary. To do so, official recommendations for a limited, anonymous personalization of donated cadaveric specimens might be necessary. Anat Sci Educ 11: 282-293. © 2017 American Association of Anatomists.

Neuroprotective effect of acute ethanol intoxication in TBI is associated to the hierarchical modulation of early transcriptional responses.

Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients. We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (-30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs). We demonstrate that ethanol pretreatment before moderate TBI (2cm) significantly reduces neurological impairment and accelerates recovery. In addition, better preservation of neuronal numbers and cFos+cells was observed 7days after TBI. At transcriptional level, ethanol reduced the upregulation of a subset of IEGs encoding for transcription factors such as Atf3, c-Fos, FosB, Egr1, Egr3 and Npas4 but did not affect the upregulation of others (e.g. Gadd45b and Gadd45c). While a subset of IEGs encoding for effector proteins (such as Bdnf, InhbA and Dusp5) were downregulated by ethanol, others (such as Il-6) were unaffected. Notably, the majority of genes were sensitive to ethanol only when administered before TBI and not afterwards (the exceptions being c-Fos, Egr1 and Dusp5). Furthermore, while severe TBI (3cm) induced a qualitatively similar (but quantitatively larger) transcriptional response to moderate TBI, it was no longer sensitive to ethanol pretreatment. Thus, we have shown that a subset of the TBI-induced transcriptional responses were sensitive to ethanol intoxication at the instance of trauma (ultimately resulting in beneficial outcomes) and that the effect of ethanol was restricted to a certain time window (pre TBI treatment) and to TBI severity (moderate). This information could be critical for the translational value of ethanol in TBI and for the design of clinical studies aimed at disentangling the role of ethanol intoxication in TBI.

Implementation and sex-specific analysis of students' attitudes toward a longitudinal, gender-specific medical curriculum - a pilot study.

BACKGROUND: Gender medicine has gained importance over the past 20 years. Nevertheless, the scientific findings concerning gender- and sex-specific patient care have not been sufficiently integrated into the education of physicians. It was therefore our aim, against initial resistance in our school, to integrate clinically relevant aspects of gender medicine into the existing medical curriculum. This paper describes the implementation process of a lecture-based interdisciplinary, longitudinal, basic gender curriculum and evaluates students' attitudes in relation to sex and semester level. METHODS: The curriculum encompasses 15 lecture sessions scheduled in years 1 through 5 of the medical curriculum at Ulm University, Germany. Prospectively gathered evaluation data of two cross-sectional analyses of this basic curriculum in the first and fifth semesters are analyzed by sex. RESULTS: More than 80% of the students have registered for this new curriculum. Evaluation data show a predominantly positive (75.5%) student response; however, only about half of those surveyed indicated that they had learned new material or judged the content on gender to be relevant to their practice of medicine. Students at a more advanced semester level (88.2% vs. 55.2%) and male participants more than female participants (36.7% vs. 62.4%) showed lower acceptance. DISCUSSION: It was possible to integrate gender issues into the existing medical student curriculum. Despite the overall positive rating, our evaluation data identified the aspects of rejection and resistance in some students, particularly male and more advanced students. Further studies on the development of student attitudes toward gender issues are needed.