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Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes =1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

This corrects the article DOI: 10.1038/nature19356.

Blood plasma viscosity (PV) is an established biomarker for numerous diseases. Measurement of the shear PV using conventional rheological techniques is, however, time consuming and requires significant plasma volumes. Here, we show that Brillouin light scattering (BLS) and angle-resolved spectroscopy measurements of the longitudinal PV from microliter-sized plasma volumes can serve as a proxy for the shear PV measured using conventional viscometers. This is not trivial given the distinct frequency regime probed and the longitudinal viscosity, a combination of the shear and bulk viscosity, representing a unique material property on account of the latter. We demonstrate this for plasma from healthy persons and patients suffering from different severities of COVID-19 (CoV), which has been associated with an increased shear PV. We further show that the additional information contained in the BLS-measured effective longitudinal PV and its temperature scaling can provide unique insight into the chemical constituents and physical properties of plasma that can be of diagnostic value. In particular, we find that changes in the effective longitudinal viscosity are consistent with an increased suspension concentration in CoV patient samples at elevated temperatures that is correlated with disease severity and progression. This is supported by results from rapid BLS spatial-mapping, angle-resolved BLS measurements, changes in the elastic scattering, and anomalies in the temperature scaling of the shear viscosity. Finally, we introduce a compact BLS probe to rapidly perform measurements in plastic transport tubes. Our results open a broad avenue for PV diagnostics based on the high-frequency effective longitudinal PV and show that BLS can provide a means for its implementation. [ABSTRACT FROM AUTHOR]

Exact three-dimensional (3D) structural information of developing organoids is key for optimising organoid generation and for studying experimental outcomes in organoid models. We set up a 3D imaging technique and studied complexly arranged native and experimentally challenged cardioids of two stages of remodelling. The imaging technique we employed is S-HREM (Scanning High Resolution Episcopic Microscopy), a variant of HREM, which captures multiple images of subsequently exposed surfaces of resin blocks and automatically combines them to large sized digital volume data of voxels sizes below 1 μm3. We provide precise volumetric information of the examined specimens and their single components and comparisons between stages in terms of volume and micro- and macroanatomic structure. We describe the 3D arrangement and lining of different types of cavities and their changes between day 10 and day 14 and map the various cell types to their precise spatial and structural environment. Exemplarily, we conducted semiautomatic counts of nuclei. In cryo-injured cardioids, we examined the extension and composition of the injured areas. Our results demonstrate the high quality and the great potential of digital volume data produced with S-HREM. It also provides sound metric and structural information, which assists production of native and experimentally challenged left ventricle cardioids and interpretation of their structural remodelling. [ABSTRACT FROM AUTHOR]

OBJECTIVES This study aimed to provide comprehensive morphological descriptions of the morphology of the tricuspid valve and to evaluate if a novel echocardiography-based tricuspid valve nomenclature can also be understood anatomically. METHODS Tricuspid valves of 60 non-embalmed human body donors without a medical history of pathologies or macroscopic malformations of the heart were included. Length, height and surface area of leaflets were measured. The valves were morphologically classified according to a novel echocardiography-based classification, in which 6 types are distinguished: classic 3-leaflet configuration, bicuspid valves, valves with 1 leaflet split into 2 scallops or leaflets and valves with 2 leaflets divided into 2 scallops or leaflets. RESULTS We found a true 3-leaflet configuration in only 19 (31.7%) of valves. Five (8.3%) had a 2-leaflet configuration with a fused anterior and posterior leaflet. Of those, 3 had a divided septal leaflet. Four valves (6.7%) had a divided anterior leaflet, 17 (28.3%) had a divided posterior leaflet, 6 (10%) had a divided septal leaflet and 9 (15.0%) had 2 leaflets divided. Overall, 39 (65%) of valves have at least 1 leaflet that is divided. In 22 (36.7%) specimens, the leaflet was divided into true leaflets, and in 17 (28.3%) specimens, the leaflet was divided into scallops. In addition, we could identify 9 (15%) valves having 1 leaflet divided not only in 2 but 3 scallops or leaflets. CONCLUSIONS This study provides further anatomical insight for the significant variability in the morphology of the tricuspid valve. By updating the understanding of its morphological characteristics, this study equips clinicians with valuable insights to effectively advance surgical and interventional treatment of tricuspid valves. [ABSTRACT FROM AUTHOR]

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

Brillouin light scattering (BLS) spectroscopy is a label-free method of measuring the GHz-frequency viscoelastic properties. The measured longitudinal modulus is acutely sensitive to the degree of hydration, crosslinking, and temperature, which can be indicative of tissue health. As such, performing in situ measurements on humans is particularly desirable for exploring potential clinical translation, however, is not possible with existing designs which are coupled to bench-top microscopes. Here we introduce a robust fiber coupled hand-held BLS probe and demonstrate its reliability for measuring excised human tissue. We verify its accuracy using confocal BLS microscopy and further show that it is possible to distinguish veins, arteries, nerves and muscles based on their BLS-measured viscoelasticity. This provides a necessary first step towards in situ clinical BLS viscoelasticity studies of human tissue.

Genetically engineered mouse models have the potential to unravel fundamental biological processes and provide mechanistic insights into the pathogenesis of human diseases. We have previously observed that germline genetic variation at the TULP4 locus influences clinical characteristics in patients with myeloproliferative neoplasms. To elucidate the role of TULP4 in pathological and physiological processes in vivo, we generated a Tulp4 knockout mouse model. Systemic Tulp4 deficiency exerted a strong impact on embryonic development in both Tulp4 homozygous null (Tulp4−/−) and heterozygous (Tulp4+/−) knockout mice, the former exhibiting perinatal lethality. High‐resolution episcopic microscopy (HREM) of day 14.5 embryos allowed for the identification of multiple developmental defects in Tulp4−/− mice, including severe heart defects. Moreover, in Tulp4+/− embryos HREM revealed abnormalities of several organ systems, which per se do not affect prenatal or postnatal survival. In adult Tulp4+/− mice, extensive examinations of hematopoietic and cardiovascular features, involving histopathological surveys of multiple tissues as well as blood counts and immunophenotyping, did not provide evidence for anomalies as observed in corresponding embryos. Finally, evaluating a potential obesity‐related phenotype as reported for other TULP family members revealed a trend for increased body weight of Tulp4+/− mice. Research Highlights: To study the role of the TULP4 gene in vivo, we generated a Tulp4 knockout mouse model.Correlative analyses involving HREM revealed a strong impact of Tulp4 deficiency on murine embryonic development. [ABSTRACT FROM AUTHOR]

Connective or muscular tissue crossing the axilla is named axillary arch (of Langer). It is known to complicate axillary surgery and to compress nerves and vessels transiting from the axilla to the arm. Our study aims at systematically researching the frequency, insertions, tissue composition and dimension of axillary arches in a large cohort of individuals with regard to gender and bilaterality. In addition, it aims at evaluating the ability of axillary arches to cause compression of the axillary neurovascular bundle. Four hundred axillae from 200 unembalmed and previously unharmed cadavers were investigated by careful anatomical dissection. Identified axillary arches were examined for tissue composition and insertion. Length, width and thickness were measured. The relation of the axillary arch and the neurovascular axillary bundle was recorded after passive arm movements. Twenty‐seven axillae of 18 cadavers featured axillary arches. Macroscopically, 15 solely comprised muscular tissue, six connective tissue and six both. Their average length was 79.56 mm, width 7.44 mm and thickness 2.30 mm. One to three distinct insertions were observed. After passive abduction and external rotation of the arm, 17 arches (63%) touched the neurovascular axillary bundle. According to our results, 9% of the Central European population feature an axillary arch. Approximately 50% of it bilaterally. A total of 40.74% of the arches have a thickness of 3 mm or more and 63% bear the potential of touching or compressing the neuromuscular axillary bundle upon arm movement. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini‐pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex‐vivo aerodynamic and acoustic analysis. Methods: Feasibility testing and prototype implantation were performed using in‐vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS‐Implant. Results: The prototype showed in the in‐vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar "distance S" as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p =.0187), phonation threshold flow (p =.0001) and phonation threshold power (p =.0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p =.2976; p =.1771) but not significant. Conclusions: Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long‐term implantation. Level of Evidence: N/A [ABSTRACT FROM AUTHOR]