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The corona virus outbreak in Wuhan, China, at the end of 2019 has rapidly evolved into a pandemic which is still virulent in many countries. An infection with SARS-CoV-2 can lead to corona virus disease (Covid-19). This paper presents an overview of the knowledge gained so far with regard to histopathological lung lesions in fatal courses of Covid-19. The main findings were diffuse alveolar damage and micro-angiopathies. These included the development of hyaline membranes, thrombi, endothelial inflammation, haemorrhages and angiogenesis. Overall, the vessel lesions seemed to be more lethal than the diffuse alveolar damage. There was obvious hyperreactivity and hyperinflammation of the cellular immune system. An expanded T-cell memory may explain the increased risk of a severe course in the elderly.

Background Lateral mass screws are the most commonly used fixation technique in the Subaxial Cervical Spine (SCS), their main advantages being that they are easy to insert and safe in their application. Pedicle screws are significantly longer, are quite challenging to insert in most settings and are accompanied by the risk of serious complications such as vascular and neural injuries. We have therefore developed a new technique, which permits safe insertion of long screws in the SCS. Methods A radiological evaluation was carried out to determine the maximum possible insertable screw length in the SCS when using the following techniques: pedicle, lateral mass (Magerl’s) and “Attallah” screws. Scans of 66 cervical spines were analyzed to determine the maximum possible screw lengths of all three screw insertion techniques, based on the standard description through the vertebrae from C3 to C7. Results The maximum possible length of the Attallah screw of 20.7 ± 2.5 mm (mean value ± SD) is only 2.4 mm shorter than the pedicle screw (23.1 ± 1.8 mm) along the SCS. The lateral mass screw is with 10.2 ± 1.3 mm full 12.9 mm shorter than the pedicle screw. Conclusions The maximum possible length of the Attallah screw is close to that of the pedicle screw and significantly greater than that of the lateral mass screw. We provide a fixation method comparable to the pedicle screw in its strength and to the lateral mass screw in its safety.

Trauma hemorrhage (TH) and subsequent sepsis are well known to frequently result in severe organ damage. Although macrophage-activating lipopeptide-2 (MALP-2) has been described to exert beneficial effects on organ damage, and further clinical course after both isolated trauma and sepsis, little is known about the impact of MALP-2 in a clinically realistic two-hit scenario of TH and subsequent sepsis. As the liver represents a key organ for the posttraumatic immune response and development of complications, the effects of MALP-2 on the posttraumatic hepatic immunologic response and tissue damage were investigated in a murine “two-hit” model. In C57BL/6 mice, blood pressure-controlled (35 ± 5 mm Hg) TH was induced. Cecal ligation and puncture (CLP) was performed 48 h after TH. Mice were divided into two control groups (control 1, TH and laparotomy without CLP; control 2, TH and CLP) and three experimental groups (TH + CLP) treated with MALP-2 at different timepoints (ETH, end of TH; ECLP, end of CLP; 6CLP, 6 h after CLP). The observation time lasted for 168 h after induction of TH. Kupffer cells (KC) were isolated and cultured, and MPO activity was analyzed. Cell culture supernatants were taken for cytokine analysis (TNF-α, IL-6, MCP-1, GM-CSF, IL-10). Histological analysis was performed using the Hepatic Injury Severity Scoring (HISS). Statistical evaluation was carried out using SPSS (version 24.0.0; IBM, Armonk, NY, USA). MPO activity of control 1 group was lowest compared with all the other groups (p

Pulmonary complications after severe trauma and sepsis remain to be the main cause for adverse outcome. MALP-2 has been described to exert beneficial effects on organ damage and the further course after isolated trauma and sepsis. However, the impact of MALP-2 on a clinically realistic two-hit scenario of trauma and subsequent sepsis remains unknown. We, therefore, investigated if the systemic inflammatory response and pulmonary immune response and damage are beneficially modulated by MALP-2 in a murine two-hit model. Blood pressure-controlled trauma-hemorrhage (TH) and cecal ligation and puncture (CLP) were induced in C57/BL6 mice. Mice were divided into 2 control groups (control 1: TH without CLP; control 2: TH and CLP) and 3 experimental groups treated with MALP-2 at different time points (ETH, end of TH; ECLP, end of CLP; and 6CLP 6 h after CLP). Survival rates were assessed over the observation period of 168 h after the induction of TH. Concentrations of plasma inflammatory cytokines and chemokines (TNF-α, IL-6, MIP-1α, IFN-γ, and IL-10) were assessed, and bacterial clearance of the lungs was determined. Furthermore, pulmonary MPO activity assay to evaluate the infiltration of polymorphonuclear neutrophils (PMN) and histological evaluation were performed. Survival rates were evaluated. Compared with control group 1, the level of TNF-α in the ECLP group showed a significant increase (ECLP, 2.27 pg./ml ± 1.39 vs. control 1: 0.16 pg./ml ± 0.11, p = 0.021). In contrast, levels of IFN-γ were significantly reduced in groups ETH and 6CLP compared with control group 1 (control 1: 8.92 pg./ml ± 4.38 vs. ETH: 1.77 pg./ml ± 4.34, p = 0.026 resp. vs. 6CLP: 1.83 pg./ml ± 4.49, p = 0.014). While systemic concentrations of inflammatory mediators were not affected by MALP-2 treatment, the lung tissue presented with significant alterations. Reduced MPO activity was lowest in group ECLP (ECLP 11,196.77 ± 547.81 vs. ETH 12,773.94 ± 1011.76; p = 0.023 resp. vs. 6CLP 13,155.19 ± 423.99, p = 0.016) in experimental groups. Also, histological damage after MALP-2 application was lowest in ECLP animals (ECLP 0.50 ± 0.08 vs. ETH 0.71 ± 0.05, p = 0.034 resp. vs. 6CLP 0.64 ± 0.08, p = 0.021). Furthermore, MALP-2 treatment was associated with a trend towards improved survival in the ECLP group (ECLP 83.3% vs. ETH 66.7 and 6CLP 58.3%, p > 0.05). Based on our results, MALP-2 might have beneficial effects on the clinical course after hemorrhage and sepsis by reducing pulmonary damage and PMN infiltration. This might also affect survival. According to our data, MALP-2 should be given at the earliest possible time point after the onset of sepsis. However, the optimal dosage and confirmation of our results in larger cohorts need to be the focus of further research.

Cell & tissue research 387(2), 249-260 (2022). doi:10.1007/s00441-021-03553-1, Published by Springer, Berlin ; Heidelberg

Safety is a major issue in the embalming procedures of human cadavers. Reduced application of formaldehyde is often recommended. The aim of this study was to investigate the potency of ultraviolet light (UV-C irradiation) on the bacterial load on the surface of a conserved human cadaver. To test UV-C irradiation, the cadaver was laid out in the dissection hall and, after preparation of the muscles, was covered with linen sheets moistened with water. Swabs of the surface and microbiological analysis revealed sporadic bacterial colonies. The surface area was then spiked with bacteria and irradiated by a UV lamp for 15 or 60 min. Half of the area was covered by aluminum foil to serve as a control. After exposition, swabs were taken and analyzed. The exposition had reduced the number of colonies to one third (15 min exposition) and to one tenth (60 min exposition) of the control area. Thus, UV-C irradiation could be used in the preservation of cadavers without chemical pollution of the environment and without any risk for the employees. Clin. Anat. 32:113-116, 2019. © 2019 Wiley Periodicals, Inc.

Background The aim of this study was to develop two simple positioning devices for anteroposterior pelvis radiographs and to evaluate their effect on accuracy of the radiographs for assessment of the acetabular orientation compared with non-instrumented positioning. Methods The superior anterior iliac spines and the pubic symphysis were used as anatomical landmarks to obtain a horizontal orientation of the pelvis according to the anterior pelvic plane. Anteroposterior pelvis radiographs were taken of 11 human cadaveric pelvic bones with each of the positioning devices and without any device. Defined measurements were carried out to objectify the tilt and rotation of the pelvis and to assess the cross-over sign as well as the presence of the ischial spine sign. Computed tomography scans were performed as a standard of reference. Bland-Altman-Plots were used to compare the continuous measurement values and Cohen’s Kappa was applied for the categorical data. Intra- and inter-observer reliability was determined by the intraclass correlation coefficient and Cohen’s Kappa. Results The mean values of the measurements showed a high variability. A low correlation of the measurement values was found between the radiographs of the different positioning methods and the computed tomography scans. The intra- and inter-observer reliability was good (Cohen’s Kappa 0.78 and 0.69; intraclass correlation coefficient 0.99 and 0.98). Conclusion The use of positioning devices did not lead to more accurate anteroposterior pelvis radiographs compared to non-instrumented positioning. Simple positioning devices do not provide standardized anteroposterior pelvis radiographs for reliable assessment of the acetabular orientation.

Introduction Pending changes regarding the medical curricula in Germany prompted us, members of the Department of Anatomy at the Medical Faculty of Saarland University, to critically evaluate anatomy teaching with special attention to macroscopic anatomy and the dissection class. Aiming at a thorough assessment we were particularly interested to which extend an optional peer-led tutorial (“anatomy boot camp”), which had preceded the dissection class, impacted the outcome in a series of oral exams of those who had participated. Methods We evaluated a student cohort of 307 students in the fall/winter semester 2015/16 at Saarland University, including those enrolled in medicine and dentistry, by implementing a series of questionnaires specifically designed for five mandatory oral exams during the course of the dissection class. The questionnaires contained different exam-relevant questions as well as several demographic items. The evaluation was complemented by interviews with students and examiners. Results Participants of the anatomy boot camp generally performed better in all exams and in three of them statistically significant. Items such as gender, age, and previous experiences in the health care professions contributed marginally – if at all – to the overall students’ performance. Intriguingly, most students welcomed the idea of implementing questionnaire-based oral exams to balance out the different experience level of the respective examiner. Conclusion Our study showed that a comparable minimal timely investment on the part of the students to choose to participate in an optional anatomy boot camp was positively correlated with students’ performance.

Proteomics / Clinical applications 15(1), 1900143 (2021). doi:10.1002/prca.201900143 special issue: "Special Issue: Cardiovascular and Kidney Health / Issue Edited by: Oliver Klein", Published by Wiley VCH, Weinheim

OBJECTIVES The unicuspid aortic valve (UAV) is a rare cardiac malformation and is associated with the formation of ascending aortic aneurysms. To characterize its associated aortic wall changes, normal and aneurysmatic ascending aortic wall specimens were analysed, focusing on the potential mechanisms of aneurysm formation. Patients with tricuspid aortic valve (TAV) served as controls. METHODS In a retrospective observational study, 74 specimens (dilated and non-dilated aortas; individuals with UAV and TAV) obtained intraoperatively were studied. Standard stains and immunohistochemical labelling of cleaved caspase-3, cluster of differentiation 31 and endothelial nitric oxide synthase (eNOS) were performed to assess the degree of apoptosis, distribution of eNOS within the aortic wall, smooth muscle cell (SMC) nuclei loss and mucoid extracellular matrix accumulation (MEMA). RESULTS Deeper ingrowth of vasa vasorum was found in dilated aortas. Interestingly, eNOS was expressed mostly in vasa vasorum. More apoptosis was seen in UAV aortas compared to TAV aortas (P CONCLUSIONS Aneurysms with UAV show increased apoptosis, the role of which is unclear. Strikingly, more severe MEMA was found in TAV aneurysms compared to UAV aneurysms. Thus, UAV-associated aortic wall changes and resulting aneurysm may be less aggressive than aneurysms with TAV.

Different techniques are available for carpal tunnel release such as classical surgical operations or minimally invasive procedures. A minimally invasive approach and the relevant regional anatomy are reported in this pilot study which was conducted with bodies from a body donation program. The method described here uses a hook knife to cut through the transverse carpal ligament or flexor retinaculum under ultrasound guidance. The results are documented by means of magnetic resonance and ultrasound imaging as well as by anatomical dissection.

Background Pulleys are crucial to convert flexor tendon excursion into angular motion at the metacarpophalangeal and interphalangeal joints. Loss of pulley function can lead to significant impairment of hand function and may require surgical reconstruction. This reconstruction can be achieved using different flexor tendons grafts, such as the intrasynovial flexor digitorum superficialis (FDS) or the extrasynovial palmaris longus (PL). However, there is limited knowledge on the micromorphology of human pulleys and the suitability of flexor tendon grafts for their reconstruction remains elusive. Methods In the present cadaver study A2 and A4 pulleys were compared with FDS and PL tendons by means of scanning electron microscopy (SEM), histology and immunohistochemistry. Surface morphology, core structure and vascularization of the specimens were analyzed. Results SEM imaging of the gliding surfaces revealed morphological differences between tendons and pulleys. Moreover, the core structure of FDS samples was characterized by bundles of individual collagen fibrils whereas PL tendons exhibited a less hierarchical microstructure. In contrast, pulleys consisted of lamellar sheets of densely packed collagen fibrils. Finally, immunohistochemical analyses revealed that the flexor tendons and pulleys contain similar numbers of CD31+ microvessels, indicating a comparable tissue vascularization. Conclusion This study provides novel SEM and immunohistochemical insights into the micromorphology of human pulleys and flexor tendon grafts. Intrasynovial flexor tendons may be particularly suitable for pulley reconstruction and preserving the paratenon may be crucial for graft revascularization.

Background: Chronic respiratory diseases (e.g. cystic fibrosis) are associated with bacterial infections. Toll-like receptor (TLR) ligands recognize bacterial factors, such as flagellin which is expressed by the cystic fibrosis pathogen Pseudomonas aeruginosa. Aim: Here, we aimed to investigate the effect of flagellin on the differentiation of human 3D bronchospheres. Methods: Human primary epithelial cells were differentiated to bronchospheres in Matrigel. Cells were incubated with control media or media containing TLR ligands (100 ng/ml of flagellin, polyI:C, or Pam3CSK4) during the differentiation period. The appearance of lumina and the presence of cilia were determined. Results: Differentiation of bronchospheres associated with the formation of lumina and ciliation within 30 days after seeding. Incubation with flagellin resulted in a delayed formation of lumina and decreased ciliation compared to control bronchospheres. Incubation with polyI:C did not affect these parameters whereas Pam3CSK4 slightly accelerated the differentiation of bronchospheres. Conclusion: Our results indicate that activation of TLR-signaling cascades modifies the differentiation of bronchospheres. Additional analysis will show whether exposure to flagellin induces the expression of mucus and goblet cell metaplasia. Importantly, bronchospheres can be used for mechanistic studies replacing animal experiments.

INTRODUCTION The purpose of this study was to evaluate the effect of posterior septectomy size on surgical exposure and surgical freedom during the endoscopic transsphenoidal approach to the sellar and parasellar region. METHODS A mononostril and binostril approach to the sellar region was performed on 4 formalin-fixed cadaveric heads. Predefined anatomical structures were identified. Additionally, a millimeter gauge was introduced into the surgical site and the extent of dorsal septectomy was analyzed for both approaches. Surgical freedom was defined as the distance between the ipsilateral and contralateral limit of opening of the sphenoid sinus. RESULTS The mean extent of dorsal septectomy was 15.7±5.7mm using a binostril approach to achieve adequate visualization of all relevant anatomical structures. Superior results were obtained via binostril technique with respect to the ability to identify the contralateral internal carotid artery or opticocarotid recessus. No such advantage was found for all other landmarks. Surgical freedom between the ipsilateral and contralateral limit of exposure of the sphenoid sinus was measured with 15±0.8mm in the mononostril and 19.2±0.9mm in the binostril group. CONCLUSIONS The surgical exposure increased significantly with progressively larger posterior septectomy in binostril approaches until a 20-mm posterior septectomy. Bilateral lateral opticocarotid recesses were accessible with a mean of 15mm for posterior septectomy. In the mononostril group no dorsal septectomy was necessary. Thus, the nasal mucosa is more preserved by this technique. However, the lateral exposure is partially limited and the use of angled endoscopes is recommended when adopting a mononostril approach to the sellar region.

Background Knowledge of the anatomical dimensions of distinct areas of the vertebral bodies and vertebral arches of the subaxial cervical spine are indispensable in the planning of osteosynthesis. The minute dimensions and complex anatomical orientation of the posterior vertebral arch structures in the subaxial spine render the insertion of screws - where needed - a challenging procedure. The pedicle option carries the risk of serious complications while the alternative of lateral mass only permits the insertion of short screws. Objective The transverse process of the subaxial vertebrae offers unique possibilities on all counts and seems quite comparable in its dimensions with the pedicle. To our knowledge it has not been used previously for the insertion of screws in the subaxial spine. Methods Therefore, the scans of 66 cervical spines were analysed for distinct lines of both structures. Results The widths and lengths of the dorsal part of the transverse processes and of the pedicles are similar between both sides. Clear differences between females and males could be observed. The widths of both structures were closer to each other in C3 than in C4 to C7, while the lengths derived the most in C7. Conclusion The dorsal part of the transverse process might be suitable for the insertion of screws to stabilize the vertebral arch of the subaxial cervical spine. Gender adaptation might be required.

Mast cells (MCs) and airway nerves play an important role in allergic asthma. However, little is known about the MCs and their interaction with airway nerves during allergic airway inflammation. This study aims to investigate the distribution and proliferation of MC populations in different lung compartments, along with the association of mast cells with nerve endings, using a house dust mite (HDM) model for allergic airway inflammation. BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. Immunofluorescence and Edu stains were used to examine the colocalisation of MCs and nerves and the proliferation of MCs, respectively. HDM treatment caused an increased migration of MCs into bronchi, alveolar parenchyma and airway vessels. The proportions of tryptase-chymase expressing MC (MCTC) increased significantly in the bronchi and the alveolar parenchyma but not in the vascular tissues, by allergic airway inflammation. The association of MCs with nerves was found only in the bronchi and there were no changes in comparison of controls to HDM-treated animals. The present study shows a strong migration of tryptase expressing MC (MCT) and MCTC into the bronchi and the alveolar parenchyma, as well as of MCT in the vascular compartment under HDM treatment. This supports the hypothesis that these mast cell populations may contribute to allergic airway inflammation.

The anterior abdominal fat pad is associated with the falciform ligament in the upper middle/right abdomen and is frequently seen there in diagnostic imaging. It varies greatly in size and has often been described as an incidental finding in adults and has hitherto rarely been regarded as being illness-relevant. The aim of this study has been to assess whether the dimension of the corpus adiposum may be associated with body mass index. Ultrasound findings of 26 patients from birth until adolescence were analyzed for this purpose. In addition, an example from a recent dissection course has been included. The structure is constantly found with its smallest dimension in newborns, with a slight increase in infancy. The average dimensions were 7.6 by 3.5 by 0.7cm. The cubic volume correlated with age, weight and body mass index, whereas the latter association was strongest. Our data suggest that routinely determined dimension of falciform fat may be a surrogate parameter of relative body weight in childhood.

Impaired phagocytosis of Pseudomonas aeruginosa was found in isolated monocytes of peripheral blood of cystic fibrosis patients, but not in their neutrophils, as reported some years ago. In the present study, we analysed the phagocytic capacity of peripheral blood neutrophils and monocytes of cystic fibrosis patients and of healthy controls. Phagocytosis was determined using a commercial phagocytosis “in whole blood” assay on the basis of fluorescence-labelled opsonized Escherichia coli bacteria and flow cytometry. Venous blood of cystic fibrosis patients and of healthy controls was collected and the phagocytosis assay was performed. No differences in the percentage of phagocytic cells or in the overall phagocytic capacity were found between samples of cystic fibrosis patients and healthy controls either in monocytes or in neutrophils. Thus, our results did not support the hypothesis of a generally reduced phagocytic ability in the peripheral blood immune cells of cystic fibrosis patients.

Only limited data are available on the extent of the vasa vasorum of the human thoracic aorta, although this could be important with regard to certain pathophysiological states, i.e. aortic aneurysm or atherosclerosis. A preliminary investigation shows that the vascularization of the human thoracic aorta reaches deeper layers than generally believed.

Hintergrund: Talusfrakturen sind seltene Verletzungen, die haufig durch axiale Stauchungstraumen verursacht werden. Aufgrund der uberwiegend knorpeligen Oberflache und der eingeschrankten Blutversorgung werden Talusfrakturen zu den schwersten Verletzungen gezahlt, die haufig posttraumatische Spatfolgen nach sich ziehen konnen. Studien deuten darauf hin, dass eine korrekte Klassifikation und dadurch bedingte differenzierte Behandlung das Ausmas der posttraumatischen Arthrose reduzieren konnen. Ziel der vorliegenden Arbeit ist es, die Bedeutung der initialen Frakturklassifikation hinsichtlich des radiologischen Behandlungsergebnisses bei einem grosen Patientenkollektiv zu analysieren. Patienten und Methoden: Uber einen Zeitraum von 12 Jahren wurden an unserer Klinik insgesamt 61 Patienten mit Talusfrakturen behandelt. Bei 45 Patienten wurden retrospektiv die Behandlungsergebnisse analysiert und mit den verschiedenen initialen radiologischen Klassifikationen korreliert. Ergebnisse: Das durchschnittliche Follow-up betrug 17,3 Monate (Range 6–68). Es zeigten sich signifikante Korrelationen zwischen der Marti-Weber-Einteilung und dem Bargon-Score (rs = 0,78; p Schlussfolgerungen: Allein durch die initiale Frakturklassifikation von Talushals- und -korpusfrakturen kann eine prazise Abschatzung des posttraumatischen Arthroserisikos erfolgen. Die Computertomografie hat sich zur Diagnosesicherung und Bestimmung des Ausmases der Verletzung durchgesetzt.

This mini-review examines the role of the pro-inflammatory cytokine interleukin (IL)-1β in the interaction of Pseudomonas aeruginosa and the host immune system during lung infection. Different studies show that the reduction of the inflammatory response, especially a decrease in IL-1β, leads to a better outcome in acute lung infection with this bacterium. This includes a higher survival rate, reduced damage to the lung tissue and, in particular, a better clearance of the airways and the tissue of the lungs from P. aeruginosa.

Hintergrund: Uber einen langeren Zeitraum wurden in der deutschsprachigen Literatur keine aktuellen Untersuchungen bez. Sageverletzungen mehr veroffentlicht. Sageverletzungen fuhren trotz Aufklarungsmasnahmen und Sicherheitsvorschriften neben den Quetschverletzungen das Spektrum der schweren Handverletzungen an. Circa 12 000 Handkreissageverletzungen ereignen sich jedes Jahr in Deutschland. Zunehmende Energiepreise, verteuerte professionelle Anbieter sowie ein reichhaltiges Angebot an diversen Sagen im Baumarkt fordern eine Verbreitung von Handkreissagen beim Hobbyhandwerker. Patienten und Methoden: In unserer Klinik wurden die Daten von 51 durchweg mannlichen Patienten mit Sageverletzungen ausgewertet. Die vorliegende Studie untersuchte Faktoren, die bei Unfallen mit Sagen eine Rolle spielen konnten. Ergebnisse: 80 % der Unfalle ereigneten sich zu Hause, meist am Wochenende oder nach Feierabend. 51 % der Unfalle ereigneten sich beim Sagen von Kaminholz. In 84 % der Falle wurde eine elektrische Tischkreissage benutzt. Unfalle mit preiswerten Sagen waren insgesamt haufiger. Am haufigsten ereigneten sich Sageverletzungen zwischen 11 und 14 Uhr. Es uberwogen Handteilverletzungen mit Beteiligung von Knochen, Sehnen, Gefasen und Nerven. Replantationswurdige Amputationen oder Teilamputationen traten selten auf. Bei 37 % der Patienten konnte eine erfolgreiche anatomische Rekonstruktion mittels osteosynthetischer und/oder mikrochirurgischer Techniken erreicht werden. Schlussfolgerungen: Sageverletzungen an der Hand betreffen haufig Manner. Uberwiegend Tischkreissagen im Niedrigpreissegment und fehlende Schutzvorrichtungen fuhren zu schwersten Verletzungen. Praventionsmasnahmen sowie verpflichtende Schulungen konnten die Zahl von Sageverletzungen in den kommenden Jahren reduzieren. Unsere Ergebnisse bestatigen weitestgehend die Daten aus vorangegangen Veroffentlichungen.

In this Short Communication, the issue is discussed whether the recently reported anterolateral ligament of the knee is a unique structure or just part of the iliotibial tract. The presented findings from investigations in body donors support the view of a unique structure.

Experimental chest trauma or blunt thoracic trauma using a blast wave mechanism is well established in animal models. The aim of the present study was to establish a complementary, murine experimental chest trauma model precisely defined by physical data and calculations. For this purpose, a device was developed using a dropped weight and physical properties, including velocity, energy and impact, were calculated. The device allowed for the maximum depth of impression to be measured. The device was first tested using blocks of modelling clay and was then applied to mouse cadavers. X-ray and dissection were performed to check for bone fractures and organ injuries following blunt chest traumas of increasing impact. Lesions and hemorrhages were observed in mouse cadavers which sustained a force equivalent to the energy of ~1 J.

Background The anatomy of the anterolateral structures of the knee is complex and still controversial. The aim of our study was to analyze this anatomy by histologic and macroscopic evaluation, with a particular emphasis on the anterolateral ligament (ALL). Material and methods Twenty-three cadaveric knee joints were dissected followed by a qualitative and quantitative anatomic analysis of the anterolateral knee structures. Histology and comparison of different anterolateral structures was performed in addition. Results The ALL was identified in all of the dissected cadaveric knee specimens. It runs in an oblique course from its proximo-dorsal insertion at the distal femur into a ventro-distal direction to the anterolateral tibia. The femoral insertion site was found to be posterior and slightly proximal to the lateral femoral epicondyle and the femoral attachment of the lateral collateral ligament (LCL). The femoral insertion of the ALL overlapped the LCL in all dissected knees. The tibial insertion site was midway between Gerdy's tubercle (GT) and the tip of the fibular head (FH). In 15 of the dissected 23 knee joints, thin attachments to the lateral meniscus were observed. Histology confirmed differences in the composition of the anterolateral knee joint capsule, the ALL and the iliotibial band (ITB). Conclusions The ALL occurs as a regular separate anterolateral ligamentous structure. It is distinguishable from the ITB and the anterolateral joint capsule in both embalmed and non-embalmed specimens. Histology of the ALL indicates typical ligamentous tissue which clearly differs from the anterolateral knee joint capsule and the thicker ITB. Level of evidence Level II, descriptive anatomic study.

Anatomy is a cornerstone of medical undergraduate curricula. Due to increasing changes in various medical fields, a lot of new subjects were introduced in undergraduate curricula, while the teaching areas of basic sciences, i.e. anatomy, were reduced. The introduction of advanced diagnostic and therapeutic devices, i.e. ultrasound and laparoscopy, with outstanding imaging quality will be increasingly introduced in basic sciences. In our project, we examined the effect integrating ultrasound and laparoscopy in an anatomy undergraduate course to illustrate the female pelvis. Anatomy students that completed their practicum and cadaver dissection course were enrolled in our project. They received a theoretical introduction followed by a practical course of ultrasound or laparoscopy in the department of obstetrics and gynaecology. Following the course the students had to answer two questionnaires that evaluated their satisfaction, subjective knowledge-gain, problems and content of the course. At the end, a closing briefing was done to discuss the clinical skills and the course. The answers of the questionnaire were summed up in a Likert scale. 25 students were enrolled in the project. 52% attended laparoscopy operations, while 48% attended ultrasound examinations. After analysing the questionnaires using Likert scales (1=strongly agree, 5=strongly disagree) a general satisfaction of 1.5, a subjective knowledge gain of 2.4 and a thrive to extend these clinical skill programs in gynaecology and other specialities in basic science of 1.5 and 1.2, respectively, was reported. There were no statistically significant differences in the Likert scores between both groups (p>0.05). The introduction of ultrasound and laparoscopy in undergraduate basic science teaching programs is a promising method and should be further evaluated, standardized and expanded.

Here, we report findings in volunteers with bronchial asthma. Biopsies were obtained from the inner bronchial wall before and a short time again after segmental allergen provocation. In most of the baseline biopsies and in all evaluable biopsies after segmental allergen provocation, the follicular lymphoid tissue was detected by immunohistochemistry in the epithelium of these asthmatic patients. The basic occurrence of the tertiary lymphoid tissue in the bronchial mucosa of mild asthmatics was unexpected and may have consequences for the interpretation of pathophysiology, e.g., as a cause or consequence of bronchial asthma.

While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord. We were able to demonstrate that PBN not only significantly prolonged survival but also prevented the progression of clinical symptoms in the EAE model of multiple sclerosis. In addition, we were able to show that PBN reduced inflammation, T cell infiltration and oligodendrocyte cell loss. PBN was previously shown to inhibit – among other targets – pannexin channels. As pannexin channels provide conduits for ATP, are associated with the inflammasome, and act as “find me-signals” in the process of apoptosis, inhibition of pannexins via PBN might contribute to the PBN-effects observed in this study. The beneficial and therapeutic effects of PBN in the context of EAE demonstrate an intriguing link between PBN and neuroinflammation, which might foster translational interest.

Janus kinase (JAK) inhibitors have recently been developed for allergic diseases. We focused on the 2 different JAK inhibitors, tofacitinib (selective for JAK3) and oclacitinib (selective for JAK1 and 2), to clarify the mechanism of anti-inflammatory and anti-itching potency of these drugs. In the process of detecting anti-itching potency, we observed that tofacitinib treated mice showed aggression behaviour. The objective of the study reported here was to investigate the aggressive behaviour induced by tofacitinib by using a mouse model of allergic dermatitis and the resident-intruder test. For the allergic dermatitis model, female BALB/c mice were sensitised and challenged topically with toluene-2,4-diisocyanate (TDI). Vehicle, tofacitinib or oclacitinib, was administered orally 30 min before TDI challenge. Scratching, aggression and standing behaviours were monitored in the 60 min period immediately following challenge of TDI. Another group of male BALB/c mice treated with vehicle, tofacitinib or oclacitinib was evaluated in the resident-intruder test and brains were obtained to determine blood brain barrier penetration. In the allergic dermatitis model, a significant increase in aggression and standing behaviour was only obvious in the tofacitinib treatment group. There was no effect in non-sensitised mice, but similar aggression was also induced by tofacitinib in male resident-intruder test. Penetration of blood-brain barrier was observed both in tofacitinib and oclacitinib treated mice. These results suggest that aggression was induced by tofacitinib under some kind of stressful environment. This study indicates a possible role of the JAK-STAT pathway in modulation of aggression behaviour.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Neurological impairments are caused by axonal damage due to demyelination and neuroinflammation within the central nervous system. T cells mediate the neuroinflammation. The activation of T cells is induced by the release of adenosine triphosphate and involves purinergic receptors as well as pannexin (Panx) proteins. As Panx1 is expressed on T cells, we here propose that application of probenecid, a known Panx inhibitor, will prevent the onset of clinical symptoms in a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE) model. EAE-induced mice received daily injections of probenecid. Disease scores, T cell numbers, and microglia activation were compared between experimental groups. Probenecid treatment resulted in lower disease scores as compared to EAE animals. Probenecid-treated animals also displayed fewer inflammatory lesions. Microglia activation was not altered by treatment. In conclusion, probenecid prevented the onset of EAE.

Anamnese und klinischer Befund: Eine 51-jahrige Patientin mit langjahrigem Drogenabusus wurde mit grosflachigen, strumpfformigen bis in die Leisten reichenden grosen schmerzhaften, nicht wegdruckbaren und konfluierenden Hauteinblutungen in unsere Klinik eingewiesen. Die Hautlasionen waren wenige Stunden nach Beginn einer Antibiotikatherapie aufgetreten. Untersuchungen: Das Notfalllabor zeigte eine Leukopenie, Thrombopenie und Anamie, die erweiterte Gerinnungsdiagnostik einen ausgepragten Protein-C-Mangel. Diagnose, Therapie und Verlauf: Es wurde eine fulminante Purpura fulminans diagnostiziert, die mit Gabe von Protein C initial therapiert wurde. Die Patientin hat uberlebt. Folgerung: Die Purpura fulminans ist ein interdisziplinarer Notfall, der durch eine Verbrauchskoagulopathie zum Schock fuhren kann. Die ernste Prognose kann durch schnelle Therapie mit Protein C verbessert werden.

Acute hemorrhagic hypovolemic shock is caused by a significant high blood loss and leads to hemodynamic instability. The decrease in intravascular volume results in cellular hypoxia and finally in damage to organs such as the liver and the kidney. The liver plays a decisive role in the development or prevention of multiple organ failure after hemorrhagic shock. Despite the large number of experimental studies, the knowledge of pathophysiological mechanisms in the liver after hemorrhagic shock is incomplete. The aim of this mini review was to provide an overview of the pathophysiological changes in liver function after acute hemorrhagic shock and to address treatment options to improve liver perfusion.

Following corneal epithelium scratches, mouse corneas were infected with the multidrug resistant (MDR) P. aeruginosa strain PA54. 24 hours later, 0% (for control group), 0.01%, 0.05% or 0.1% Chlorin e6 (Ce6), a second generation photosensitizer derived from chlorophyll, was combined with red light, for photodynamic inactivation (PDI). 1 hour or 2 days later, entire mouse eyes were enucleated and homogenized for counting colony forming units (CFU) of P. aeruginosa. For comparison, 0.1% Ce6 mediated PDI was started at 12 hours post infection, and 0.005% methylene blue mediated PDI 24 hours post infection. Clinical scores of corneal manifestation were recorded daily. Compared to the control, CFU 1 hour after PDI started 24 hours post infection in the 0.01% Ce6 and 0.05% Ce6 groups were significantly lower (more than one log10 reduction), the CFU 2 days post PDI higher in the 0.1% Ce6 group, clinical score lower in the 0.1% Ce6 group at 1 day post PDI. These findings suggest that PDI with Ce6 and red light has a transient efficacy in killing MDR-PA in vivo, and repetitive PDI treatments are required to fully resolve the infection. Before its clinical application, the paradoxical bacterial regrowth post PDI has to be further studied.

Received 23 October 2012; returned 23 February 2013; revised 17 March 2013; accepted 18 March 2013 Objectives: Pneumonia is associated with a high morbidity and mortality worldwide. Streptococcus pneumoniae remains the most common cause of pneumonia, and pneumococcal antibiotic resistance is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci. We tested the hypothesis that a single dose of recombinant aerosolized Cpl-1 would rescue mice with severe pneumococcal pneumonia. Methods: Female C57Bl/6 mice (aged 8‐12 weeks) were transnasally infected with pneumococci. When severe pneumonia was established 24 h after infection, mice were treated with 25 mL of aerosolized Cpl-1. Survival was monitored for 10 days and the pulmonary and systemic bacterial burdens were assessed. Furthermore, cytokines were quantified in bronchoalveolar lavage fluid, and lung morphology was analysed histologically. Results: The endolysin efficiently reduced pulmonary bacterial counts and averted bacteraemia. Although concentrations of inflammatory cytokines were increased shortly after Cpl-1 inhalation, mice recovered rapidly, as shown by increasing body weight, and inflammatory infiltrates resolved in the lungs, leading to a reduction in mortality of 80%. Conclusions: Administration of Cpl-1 by inhalation may offer a new therapeutic perspective for the treatment of pneumococcal lung infection.

The departments of anatomy in Germany, Austria and the German-speaking part of Switzerland were sent comprehensive (18 items) questionnaires requesting details on memorial ceremonies held at the close of the dissection course in the medical curriculum, including objectives, organization, number of participants and the role of the medical students. The response rate was very high (95%). In more than 95% of instances a ceremony is held, initiated mainly after 1970. The titles of the ceremony range from commemoration ceremony (42%), service of mourning (19%) memorial service (19%) to ceremony of gratitude (7%). The number of participants exceeds 300 in 15% of these ceremonies. The invitation comes mostly from the student group organizing the ceremony (62%). The ceremony is offered mainly for the students of the course (23%), for student tutors (16%), relatives of the body donors (23%) and scientific staff (15%). The students actively participate with musical contributions (19%), gestures such as candles (17%) and flowers (12%), speeches (17%) and readings (12%). The relevance of the practical dissection course and body donation programs is also discussed. The results are compared to ceremonies in various countries with different religious backgrounds. This dissection course is unique among all courses in the medical curriculum as it obviously also has spiritual aspects.

To give an overview of the basic knowledge of the functional surgical anatomy of the proximal lower leg and the popliteal region relevant to medial high tibial osteotomy (HTO) as key anatomical structures in spatial relation to the popliteal region and the proximal tibiofibular joint are usually not directly visible and thus escape a direct inspection. The surgical anatomy of the human proximal lower leg and its relevance for HTO are illustrated with a special emphasis on the individual steps of the operation involving creation of the osteotomy planes and plate fixation. The posteriorly located popliteal neurovascular bundle, but also lateral structures such as the peroneal nerve, the head of the fibula and the lateral collateral ligament must be protected from the instruments used for osteotomy. Neither positioning the knee joint in flexion, nor the posterior thin muscle layer of the popliteal muscle offers adequate protection of the popliteal neurovascular bundle when performing the osteotomy. Tactile feedback through a loss-of-resistance when the opposite cortex is perforated is only possible when sawing and drilling is performed in a pounding fashion. Kirschner wires with a proximal thread, therefore, always need to be introduced under fluoroscopic control. Due to anatomy of the tibial head, the tibial slope may increase inadvertently. Enhanced surgical knowledge of anatomical structures that are at a potential risk during the different steps of osteotomy or plate fixation will help to avoid possible injuries. Expert opinion, Level V.

Background Phagocytosis activity of peripheral blood leukocytes in smokers or chronic obstructive pulmonary disease patients was found to be controversial and dependent on the phagocytic stimulus. Results We demonstrated that long-term exposure to cigarette smoke in mice clearly suppressed the phagocytosis of granulocytes and monocytes from peripheral blood. Conclusions Impaired phagocytosis activity of peripheral blood leukocytes may have a systemic effect and potentially contribute to smoking-associated diseases such as pneumonia and lung cancer.

OBJECTIVE: The pleiotropic cytokine interleukin (IL)-6 seems to play a pivotal role in sepsis, but contradictory findings in animal models impede a rationale for therapies directed against IL-6. IL-6 signals by two mechanisms via the ubiquitous transmembrane glycoprotein 130 (gp130): "classic" signaling using membrane-bound IL-6 receptor (IL-6R) and trans-signaling using soluble IL-6R (sIL-6R). Trans-signaling is selectively inhibited by soluble gp130 (sgp130). The aim of this study was to systematically compare complete blockade of IL-6 signaling (using a neutralizing anti-IL-6 antibody) and selective blockade of IL-6 trans-signaling (using a fusion protein of sgp130 and the crystallizable fragment of immunoglobulin G1, sgp130Fc) in a standardized cecal ligation and puncture (CLP) sepsis model.DESIGN: Animal study.SETTING: Animal laboratory.SUBJECTS: C57BL/6J mice.INTERVENTIONS: We performed a 96-hr dose-response study and a 24-hr study to investigate short-term mechanisms. In the 96-hr study, CLP was performed in 120 randomized mice (20 mice received vehicle, 10 mice per dose group). Mice were treated with equimolar doses of sgp130Fc (0.01/0.1/1/10 mg/kg) or anti-IL-6 (0.008/0.08/0.8/8 mg/kg) 24 hrs before CLP. Two additional groups received 0.5 mg/kg sgp130Fc 24 hrs before or 1 mg/kg sgp130Fc 24 hrs after CLP. Survival and activity scores were obtained daily until 96 hrs after CLP. In the 24-hr study, mice were randomized into four groups with 10 animals each (sham/vehicle, CLP/vehicle, CLP/anti-IL-6 [0.8 mg/kg], and CLP/sgp130Fc [1 mg/kg]) and killed after 24 hrs.MEASUREMENTS AND MAIN RESULTS: In contrast to anti-IL-6, pretreatment with sgp130Fc significantly and dose-dependently increased survival from 45% to 100%. In addition, 1 mg/kg sgp130Fc administered 24 hrs after CLP increased survival from 45% to 80%. Mechanistically, sgp130Fc efficacy was reflected by complete prevention of epithelial cell apoptosis in the jejunum after CLP, which was not achieved with anti-IL-6.CONCLUSION: Selective inhibition of IL-6 trans-signaling by sgp130Fc has considerable potential for the treatment of sepsis and related disorders.

Background Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro and in vivo. Methods In untreated mice (female C57/Bl6 mice, 11–15 weeks old) and animals treated with adrenomedullin, lung permeability, local and systemic inflammation and markers of distal organ function were assessed following 2 or 6 h of mechanical ventilation with 100% oxygen and protective or moderately injurious ventilator settings, respectively. Results Adrenomedullin dramatically reduced lung permeability in VILI in mice, leading to improved oxygenation. Adrenomedullin treatment reduced myosin light chain phosphorylation, attenuated the accumulation of leucocytes in the lung and prevented the increase in lactate and creatinine levels in mice ventilated with high tidal volumes. Moreover, adrenomedullin protected against VILI even when treatment was initiated 2 h after the beginning of mechanical ventilation in a 6 h VILI mouse model. Conclusion Adjuvant treatment with adrenomedullin may be a promising new pharmacological approach to attenuate VILI.

Preclinical and clinical topics are often separated in medical education. For example, surgery and radiology are often taught much later than anatomy. The aim of this study was to establish and to evaluate an interdisciplinary course combining these closely related subjects to enhance medical comprehension.Two tutorials each lasting one term were offered to second year medical students, in which clinical topics were implemented linking anatomy to surgical and radiological knowledge. A questionnaire was used to evaluate the success of this approach.The motivation of the students was above average and the practical work was done accurately. The students confirmed that the course improved anatomical comprehension (95%) and that the learned matters were relevant for their future (90%). Furthermore, interest in the subjects was higher after the course (85%). Critical suggestions were to extend the course and to include more topics.A mix of surgery, radiology and anatomy is a teaching concept, which leads to high acceptance and interest in medical students.