Clinically relevant variations of the superior thyroid cornu.

PURPOSE: The superior thyroid cornu (STC) of the thyroid cartilage is a variable structure that maybe associated with different clinical symptoms. This study evaluates the three-dimensional anatomy of the STC. METHODS: Measurements were conducted on 97 CT scans (45 male and 52 female). The protocol models a vector from the base to the tip of the STC and references the cornu to the midline. From these data, the length (C), the rotation angle (γ), the inclination angle (ß), and the deviation of STC base (X 2) and tip (X 3) from the midline were measured. An additional measure of the medial inclination quotient (Q = X 3/X 2) was calculated. RESULTS: The STC has a mean length of 13.9 ± 3.26 mm. The male STC is more bent inwards (rotation angle (γ) 60.95° vs. 12.15°; p < 0.001), and the female STC is more steep (inclination angle (ß) 75.44° vs. 73.44°; p < 0.001). The mean Q in men was significantly lower (0.85 ± 0.15 vs. 0.97 ± 0.15; p < 0.001). An extreme medial deformation was found in 13.4 % of the patients. This variation is associated with Q ≤ 0.7, most of the time unilateral and more common in men (86.7 vs. 13.3 %). Furthermore, we can describe STC variations with close proximity to the common carotid artery or the cervical spine. CONCLUSIONS: The clinically most relevant variation of the STC seems to be the extreme medial deviation, which may lead to symptoms described with the superior thyroid cornu syndrome. The evaluation of Q in axial CT scans is easily done and may propose a helpful tool for clinical diagnostics.

Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5.

Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease.

A high-fidelity prototype of a sterile information system for the perioperative area: OR-Pad.

PURPOSE: Supporting the surgeon during surgery is one of the main goals of intelligent ORs. The OR-Pad project aims to optimize the information flow within the perioperative area. A shared information space should enable appropriate preparation and provision of relevant information at any time before, during, and after surgery. METHODS: Based on previous work on an interaction concept and system architecture for the sterile OR-Pad system, we designed a user interface for mobile and intraoperative (stationary) use, focusing on the most important functionalities like clear information provision to reduce information overload. The concepts were transferred into a high-fidelity prototype for demonstration purposes. The prototype was evaluated from different perspectives, including a usability study. RESULTS: The prototype's central element is a timeline displaying all available case information chronologically, like radiological images, labor findings, or notes. This information space can be adapted for individual purposes (e.g., highlighting a tumor, filtering for own material). With the mobile and intraoperative mode of the system, relevant information can be added, preselected, viewed, and extended during the perioperative process. Overall, the evaluation showed good results and confirmed the vision of the information system. CONCLUSION: The high-fidelity prototype of the information system OR-Pad focuses on supporting the surgeon via a timeline making all available case information accessible before, during, and after surgery. The information space can be personalized to enable targeted support. Further development is reasonable to optimize the approach and address missing or insufficient aspects, like the holding arm and sterility concept or new desired features.

[Regenerative medicine in the treatment of sensorineural hearing loss]. / Regenerative Medizin in der Therapie der Innenohrschwerhörigkeit.

Regenerative medicine offers the prospect of causal treatment of sensorineural hearing loss. In humans, the loss of sensory hair cells is irreversible and results in chronic hearing loss. Other vertebrates, particularly birds, have the capability to spontaneously regenerate lost sensory hair cells and restore hearing. In the bird model, regeneration of hair cells is based on the proliferation of supporting cells. In mammals, supporting cells have lost their proliferative capacity and are terminally differentiated. To gain an understanding about regeneration of hair cells in mammals, cell division of supporting cells has to be controlled. Gene disruption of the cell cycle inhibitor p27(Kip1) allows supporting cell proliferation in the organ of Corti in vivo. Furthermore, in vitro studies indicate that newly generated cells may differentiate into hair cells after p27(Kip1) disruption. Other current methods to induce hair cell regeneration include the gene transfer of Math1 and transplantation of stem cells to the inner ear.

Posterior translacrimal approach to the maxillary sinus.

BACKGROUND: This study aimed to compare the view into the maxillary sinus using the posterior translacrimal approach compared with grade 3 antrostomy. METHODS: Grade 3 antrostomy followed by a posterior translacrimal approach was performed on four cadavers. The maximum intramaxillary view was documented endoscopically guided by electromagnetic navigation. Representative screenshots were evaluated in a blinded manner by three independent sinus surgeons. In addition, a prospective investigation of specific complications in the post-operative course of consecutive patients was performed. RESULTS: In the cadaver study, the posterior translacrimal approach provided a significantly better view into the maxillary sinus compared with grade 3 antrostomy. In the clinical study, only 1 out of 20 patients reported on a minor problem with lacrimal drainage at 6 months. CONCLUSION: The posterior translacrimal approach to visualising the maxillary sinus should be considered a strong alternative to more radical techniques.

The influence of tutor training for peer tutors in the dissection course on the learning behavior of students.

INTRODUCTION: Student tutors in the dissection course are expected to meet high demands in their job, to fulfill these expectations they receive training. Combined tutor training is well accepted by tutors and tutees, however, it is not known how tutor training influences student learning. Deduced from the learning goals of the tutor training, a randomized, controlled, single-blinded study was set up with a quantitative cross-sectional analysis to compare student learning behavior. METHODS: A total of 197 medical students, coached either by ten trained or ten untrained tutors, were enlisted in the study. To assess the students' learning behavior we employed the LIST questionnaire. A common factor analysis was calculated to extract dimensions. Factor scores of the extracted dimensions were calculated for both groups to estimate differences in learning behavior. RESULTS: Factor analysis of the LIST questionnaire revealed eight factors explaining 47.57% of the overall variance. The eight factors comprise: deep learning, attention, learning organization, cooperative learning, time management, learning effort, superficial learning and learning environment. Comparing the factor scores of the extracted dimensions, students coached by trained tutors learned significantly more with their fellow students (factor score in cooperative learning 0.194 vs. -0.205, p<0.05), than students trained by untrained tutors. Students coached by trained tutors also tend to be better organized in their learning (factor score in learning organization 0.115 vs. -0.122, p=0.16). CONCLUSION: The learning behavior of students coached by trained tutors differs from the learning behavior of students coached by untrained tutors. Students coached by trained tutors learn significantly more often in teams than their colleagues and are better organized.

Development of a seminar on medical professionalism accompanying the dissection course.

INTRODUCTION: Medical professionalism is an increasingly important issue in medical education. The dissection course represents a profound experience for undergraduate medical students, which may be suitable to address competencies such as self-reflection and professional behavior. MATERIAL AND METHODS: Based on a needs assessment, a seminar on medical professionalism was developed to parallel the dissection course. The conceptual framework for the teaching intervention is experiential learning. Specific learning goals and an interview guideline were formulated. After a pilot run, peer-teaching was introduced. RESULTS: Over three terms (winter 2012/13, 2013/14, 2014/15), an average of 129 students voluntarily participated in the seminar, corresponding to 40% of the student cohort. The evaluation (n=38) shows a majority of students agreeing that the seminar offers support with this extraordinary situation in general and also that the seminar helps them to become first impressions on how to cope with death and dying in their later professional life as a doctor, and, that it also provides them the means to reflect upon their own coping mechanisms. CONCLUSION: Although not yet implemented as an obligatory course, the seminar is appreciated and positively evaluated. Medical professionalism is an implicit aspect of the dissection course. To emphasize its importance, a teaching intervention to explicitly discuss this topic is advisable.

Transorbital transnasal endoscopic combined approach to the anterior and middle skull base: a laboratory investigation.

Orbital approaches provide significant trajectory to the skull base and are used with differently designed pathways. The aim of this study is to investigate the feasibility of a combined transorbital and transnasal approach to the anterior and middle cranial fossa. Cadaveric dissection of five silicon-injected heads was used. A total of 10 bilateral transorbital approaches and 5 extended endonasal approaches were performed. Identification of surgical landmarks, main anatomical structures, feasibility of a combined approach and reconstruction of the superior orbital defect were examined. Rod lens endoscope (with 0° and 45° lenses) and endoscopic instruments were used to complete the dissection. The transorbital approach showed good versatility and provides the surgeon with a direct route to the anterior and middle cranial fossa. The transorbital avascular plane showed no conflict with major nerves or vessels. Large exposure area from crista galli to the third ventricle was demonstrated with significant control of different neurovascular structures. A combined transorbital transnasal approach provides considerable value in terms of extent of exposure and free hand movement of the two surgeons, and allows better visualisation and control of the ventral skull base, thus overcoming the current surgical limits of a single approach. Combination of these two minimally invasive approaches should reduce overall morbidity. Clinical trials are needed to evaluate the virtual applications of this approach.

Control region of SV40 minichromosomes is preferentially cleaved by single-strand specific S1 nuclease.

We have analysed S1 sensitivity of SV40 minichromosomes isolated from the nuclei of infected cells at the late stage of infection. We show that a fraction of purified minichromosomes is sensitive towards double-strand cleavage by S1 nuclease. The pattern of specific cleavage reminiscent of that found for subcloned fragment under supercoiling is superimposed upon apparently random double-strand cuts along the entire regulatory region. Therefore, the cleavage sites are not exclusively confined to the regions with the reported alternate DNA conformation.

All functional aquaporin-4 isoforms are expressed in the rat cochlea and contribute to the formation of orthogonal arrays of particles.

The water channel aquaporin-4 (AQP4) is expressed in the cochlea and is essential for normal hearing. Unlike other AQPs, multiple isoforms of AQP4 have been reported in diverse tissues, three of which, M1, M23, and Mz, function as water channels. In addition, these protein isoforms are found in higher order complexes. Morphologically these higher order complexes correspond to orthogonal arrays of particles (OAPs) that are found in cell membranes by freeze fracture analysis. Using RT-PCR, quantitative PCR and blue-native PAGE immunoblots we identified all functional AQP4 isoforms -M1, M23, and Mz- and the formation of higher-order complexes in the organ of Corti of the rat. Complementary freeze-fracture studies revealed OAPs distributed in the lateral and basal membrane domains of the cochlear duct supporting cells, specifically Hensen's cells and outer sulcus cells. The unique inter- and intracellular heterogeneity in size, density and shape of OAPs suggests exceptional physiological requirements for the maintenance of water homeostasis during auditory sensory transduction in the cochlea.

Surgical prosection in a traditional anatomical curriculum-Tübingens' Sectio chirurgica.

Despite the rapid rise of integrated curricula, the teaching of gross anatomy by traditional dissection remains a central element in most medical programs worldwide. However, modern didactic concepts demand the integration of clinical content in preclinical settings. The implementation of interdisciplinary tools often leads to a reduction in teaching of comprehensive anatomy. 'Tübingen's Sectio chirurgica' (TSC) introduces a concept of a teaching activity in which surgical prosection is performed in addition to the traditional dissection course. TSC is designed to integrate clinical and preclinical content in a traditional medical curriculum without affecting the systematic presentation of anatomical content. In the past 2 years, about 10,000 medical students have participated in the use of telemedical transmissions of 'live surgery' in a total of 25 sessions of TSC. Here we describe the organisational plan of TSC and the results of an evaluation which was performed to monitor the influence of TSC on student motivation for surgical disciplines as well as for the learning of anatomical factual content. We demonstrate that additional surgical prosection is a valuable tool in increasing the coherence between preclinical and clinical parts of medical education programs.

Broadening horizons of neuroendoscopy with a variable-view rigid endoscope: an anatomical study.

AIM: To test the versatility and usefulness of a prototype rigid endoscope with a continuously variable-view-angle tip (Endochamaeleon, Karl Storz, Tuttlingen, Germany) with regard to field of vision and applicability for endoscopic assisted neurosurgery. METHODS: In five formaldehyde fixed specimens frontolateral and retrosigmoid approaches were prepared on both sides and five target positions of the endoscopes tip were defined. A rigid 4mm endoscope, which offers in one plane a viewing range of approximately -10 degrees to +120 degrees by turning a proximal knob coupled to fine distal optomechanics was compared to 0 degrees , 45 degrees , and 70 degrees rigid endoscopes. The visualizable neuroanatomical structures were assessed for each position, endoscope angle, and plane of view as well as the over-all visibility of neuroanatomical structures and the time factor. RESULTS: 1905 recorded images of 1800 different views were analyzed. The EC offers a variable angle of view in one plane without need to change the endoscope position. This feature is well suited for inspection of functionally delicate areas at the skull base. The maximum number of visible structures for each position was only seen with the EC. Endoscopic exploration was significantly less time consuming with the EC than with the other endoscopes. CONCLUSION: The EC provided superior usability and visualization potential compared to standard rigid endoscopes with fixed angulation. It combines the ergonomic and safety advantage of not having to insert endoscopes with different angles with the opportunity to "scan" the surgical field with a variable angle of 0 degrees -120 degrees within one plane of view.

The subcellular distribution of aquaporin 5 in the cochlea reveals a water shunt at the perilymph-endolymph barrier.

Aquaporins are membrane water channel proteins that have also been identified in the cochlea. Auditory function critically depends on the homeostasis of the cochlear fluids perilymph and endolymph. In particular, the ion and water regulation of the endolymph is essential for sensory transduction. Within the cochlear duct the lateral wall epithelium has been proposed to secrete endolymph by an aquaporin-mediated flow of water across its epithelial tight junction barrier. This study identifies interspecies differences in the cellular distribution of aquaporin 5 (AQP5) in the cochlear lateral wall of mice, rats, gerbils and guinea pigs. In addition the cellular expression pattern of AQP5 is described in the human cochlea. Developmental changes in rats demonstrate longitudinal and radial gradients along the cochlear duct. During early postnatal development a pancochlear expression is detected. However a regression to the apical quadrant and limitation to outer sulcus cells (OSCs) is observed in the adult. This developmental loss of AQP5 expression in the basal cochlear segments coincides with a morphological loss of contact between OSCs and the endolymph. At the subcellular level, AQP5 exhibits polarized expression in the apical plasma membrane of the OSCs. Complementary, the basolateral membrane in the root processes of the OSCs exhibits AQP4 expression. This differential localization of AQP5 and AQP4 in the apical and basolateral membranes of the same epithelial cell type suggests a direct aquaporin-mediated transcellular water shunt between the perilymph and endolymph in the OSCs of the cochlear lateral wall. In the human cochlea these findings may have pathophysiological implications attributed to a dysfunctional water regulation by AQP5 such as endolymphatic hydrops (i.e. in Meniere's disease) or sensorineural hearing loss (i.e. in Sjögren's syndrome).

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells.

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 microm ("thin" or "thick" dendrites, respectively). Three cells (4.5%) were bistratified, having thick dendrites, and the others (95.5%) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40%) and 2 groups with inner (50-100%) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat beta-cells, whereas one group of cells with thick dendrites includes cells that resemble cat alpha-cells.

The minute virus of mice capsid specifically recognizes the 3' hairpin structure of the viral replicative-form DNA: mapping of the binding site by hydroxyl radical footprinting.

The terminal hairpin structures of the DNA of minute virus of mice (MVM) are essential for viral replication. Here we show that the hairpin 3' terminus of MVM replicative-form DNA binds specifically to empty MVM capsids. Binding of the same terminal DNA sequence in its linear double-stranded (extended) conformation was not observed. After heat denaturation and quick cooling of 3'-terminal extended-form fragments, not only the virion strand but also the complementary strand was found to bind to the capsid, presumably because each strand re-formed a similar hairpin structure. No binding affinity for the capsid was found to be associated with hairpin or extended 5' termini or with any other region of the viral DNA. Hydroxyl radical footprinting analyses revealed three protected nucleotide stretches forming a binding site at the branch point of the two 3'-terminal hairpin arms looping out from the DNA stem (T structure). Single base changes within this site did not affect the binding. In band shift experiments, specific binding to the T structure was demonstrated for VPI but not for VP2.

The major capsid protein VP2 of minute virus of mice (MVM) can form particles which bind to the 3'-terminal hairpin of MVM replicative-form DNA and package single-stranded viral progeny DNA.

The capsids of minute virus of mice (MVM) consist of two closely related proteins, VP1 and VP2. We inactivated the VP1 gene in an infectious clone of MVM DNA by frameshift mutation. After transfection of mutated DNA, capsids consisting of VP2 only were made. They can package negative-strand DNA, and they specifically bind MVM 3'-terminal hairpin DNA.

A transcriptional promoter of the human parvovirus B19 active in vitro and in vivo.

The human parvovirus B19 causes aplastic crises in sickle cell anemia patients and the disease erythema infectiosum. So far, it has not been possible to grow B19 virus in cultured cells. Here we report the use of in vitro transcription in HeLa cell extracts and transient expression of cloned DNA transfected into HeLa cells to detect and map a strong transcriptional promoter on the B19 genome. The promoter is located near the left end of the B19 genome, at position 6 map units in the clone pYT103 (approximately 280 bp upstream of the first HindIII site), and directs transcription to the right. These results suggest that the strictly limited host range of B19 does not operate at the level of transcription from the promoter at the left end of the genome.