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In order to investigate the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in pulmonary immunological processes, leukocyte populations were stained immunohistochemically on cryostat lung sections of ICAM-1–/– and LFA-1–/– mice. A further group of ICAM-1–/– mice was exposed to Haemophilus influenzae type-b ( Hib) 24 h before being sacrificed. Comparison of the numbers of leukocytes in these groups revealed different behaviors of the leukocyte subsets: granulocytes were significantly increased in all three groups. Lymphocytes were increased in ICAM-1–/– mice, while there was no significant difference in LFA-1–/– and even a decrease in ICAM-1–/– mice after Hib exposure. Neither in ICAM-1–/– nor in LFA-1–/– mice did macrophages and dendritic cells (DCs) show significant differences to control animals. After Hib exposure, a significant elevation of DCs was observed. The following conclusions can be drawn: (1) all investigated leukocyte subsets can use ICAM-1- and LFA-1-independent pathways in the lungs of mice; (2) the pathways used by the leukocytes are cell-type specific; (3) ICAM-1 plays an important role in the enhanced recruitment of lymphocytes during Hib challenge in the lung; and (4) the alternative migratory mechanisms are able to compensate for the absence of ICAM-1 or LFA-1 or even lead to increased cell numbers. This overcompensation can be seen as a result of a balance between active alternative migratory mechanisms, which takes place in the absence of ICAM-1 or LFA-1. [ABSTRACT FROM AUTHOR]

The undergraduate medical curriculum has been modified or even totallyreorganized in many countries in recent years, and there are plans to makedepartmental budgets and the salaries of university professors partially dependenton the outcome of teaching. Questionnaires are often used in such situationsas a means of curriculum evaluation. Based on our own experience such evaluationsshould be done not only during and immediately after a course in the curriculum,but also at later time points, e.g., at the end of the undergraduate and alsothe postgraduate phase. The clinical relevance of lectures and courses canonly be graded adequately after some years of clinical experience. Gross anatomywas graded top at all time points evaluated and reached higher levels of ‘clinicalrelevance’ than other typical preclinical and even clinical subjects.Efforts should be made to obtain a high response rate for representative results.After modifying parts of a course detailed questionnaires should also includespace for students' suggestions. The results of such evaluations arenot only relevant to the head of department as feedback on the individuallecturers but also important for the curriculum committee and the dean. Anatomistsshould utilize these evaluations to improve teaching. [ABSTRACT FROM AUTHOR]

Background: Immune function is better preserved by laparoscopic versus conventional surgery. Numerous mediators of the systemic trauma response are synthesized and/or regulated by the liver. However, it has been stated that the advantages of laparoscopic surgery are no more obvious when conventional operations are performed via mini-laparotomy. We set out to compare the impact of laparoscopy and mini- and full laparotomy on the hepatic macrophage populations.Methods: Male Lewis rats were subjected to anesthesia alone (control), mini-laparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 min. Endpoints were the total protein in the peritoneal lavage fluid, hepatic ED-1 cells (recruited monocytes), hepatic ED-2 cells (Kupffer cells), the expression of OX-6 in the liver, and C-reactive protein (CRP) in plasma.Results: Protein in the peritoneal lavage fluid increased significantly after all interventions. Full laparotomy was accompanied by an enhancement in ED-1-positive monocytes in the liver parenchyma compared to all other groups (p < 0.001). Mini- and full laparotomy led to an increase in ED-2-positive Kupffer cells (p < 0.001). Laparoscopy did not affect the number of monocytes/macrophages. There was no significant alteration of OX-6 expression in either group. No change in the cellular composition in the periportal fields was observed. The CRP plasma levels did not significantly differ between groups.Conclusions: Laparoscopy completely prevents hepatic macrophage populations from expansion and normal cell disposition is preserved. Laparotomy, irrespective of incision size, increases the number of Kupffer cells. Moreover, full laparotomy, but not mini-laparotomy or laparoscopy, causes an increase in hepatic monocyte recruitment. The regulating pathways after surgery differ from other immunologic challenges, such as sepsis, in which immunocompetent cells accumulate and are stimulated in the periportal fields. [ABSTRACT FROM AUTHOR]

Objective The laryngeal mucosa starts to be exposed to infectious agents immediately after birth. The course of laryngeal infections in young children differs significantly from that in adults. The first line of defense encountered by an inhaled infectious agent is the mucosa-associated immune system, which includes immunocompetent cells and secretory components. The cellular elements are partially organized in a typical morphological pattern known as mucosa-associated lymphoid tissue (MALT). Differences in the ability of young children and adults to react to a laryngeal infection raise the questions of whether and to what extent immunocompetent cells are already present in the larynx at birth. These questions were investigated in this study. Material and Methods Dendritic cells, T lymphocytes, B lymphocytes, macrophages and glands were examined and detected in an (immuno-)histological study of 8 fetal larynges (14th-22nd week of gestation). Results Immunocompetent cells and glands were present mainly in the epi- and subglottic regions and ventricular folds, whereas the glottis was largely spared. The pattern of distribution was scattered and no organized MALT was seen. Conclusion Essential cell populations of a mucosa-associated immune system for the initiation of an immune response may exist in the human larynx at birth. [ABSTRACT FROM AUTHOR]

Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7–11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein. The mitochondrial Nnt-protein is one of several enzymes that catalyses the generation of NADPH, which in turn is important for the elimination of reactive oxygen species (ROS). As ROS is thought to contribute to the pathophysiology of hypoxia-ischemia, the lack of Nnt might indirectly increase ROS levels and therefore result in increased brain damage. We therefore hypothesize that lesion score and lesion size will increase in C57BL/6J mice as compared to C57BL/6N mice. Surprisingly, the results showed exactly the opposite: C57BL/6J mice showed a decrease in lesion score and size, associated with a reduced number of apoptotic cells and activated microglia. In contrast, the number of cells with ROS-induced DNA modifications (detected by 8OHdG) was higher in C57BL/6J than C57BL/6N mice. In conclusion, C57BL/6J mice showed reduced ischemic consequences after postnatal hypoxic-ischemic brain injury compared to C57BL/6N mice, with the exception of the amount of ROS-induced DNA-damage. These differences might relate to the lack of Nnt, but also to a modified metabolic setting (cardiovascular parameters, oxygen and glucose metabolism, immune function) in C57BL/6J mice. [ABSTRACT FROM AUTHOR]

Nicotinamide-nucleotide-transhydrogenase (Nnt) is a mitochondrial protein. It is altered and functionally lacking in the C57BL/6J sub-strain. This leads to the generation of more radical oxygen species than in the C57BL/6N sub-strain. During studies on the effect of Nnt in perinatal hypoxia the cerebral vasculature was investigated in postnatal day 9 mice using post mortem arterial filling with silicone rubber compounds. Surprisingly, the tiny vessels were no longer uniformly filled and a bleb-like pattern occurred in both sub-strains. Furthermore, considerably more bleb-like spots were observed in the C57Bl/6J sub-strain than in the C57Bl/6N sub-strain. These blebs might be the result of feathery vessels bursting. It remains unclear how the mechanisms in the used strains differ. Nnt might influence the vascular structure or its development and mechanisms and should be investigated further. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q®-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q®-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis. [ABSTRACT FROM AUTHOR]

The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation. [ABSTRACT FROM AUTHOR]

Cilomilast and tacrolimus as well as rapamycin are potential drugs for the treatment of allergic skin diseases like atopic dermatitis and allergic contact dermatitis. To compare the in vitro and in vivo immunomodulatory effects of the phosphodiesterase 4 inhibitor cilomilast with those of tacrolimus and rapamycin. The in vitro action of cilomilast, tacrolimus and rapamycin were tested in a mixed leucocyte reaction (MLR). In vivo, the inhibitory action of the immunomodulatory drugs was compared in the toluene-2,4-diisocyanate (TDI)-induced allergic inflammatory response with particular focus on dendritic cell (DC) function. Cilomilast, tacrolimus and rapamycin were all able to inhibit DC-mediated T-cell activation in a MLR. But it was demonstrated for cilomilast that the target cells are T cells rather than DC. In vivo, a combination of systemic and topical administration of each of these three substances significantly inhibited swelling in the murine ear 16 h after TDI challenge. There was also a reduction in the weight of the draining auricular lymph node, in lymphocyte cell count, and in the number of emigrated DC. The density of Langerhans cells in the epidermis was correspondingly higher in mice treated with cilomilast, tacrolimus and rapamycin than in those treated with vehicle. All three substances were found to inhibit DC migration ex vivo in a skin DC migration assay performed on ear tissue after TDI challenge. DC migration into the draining lymph node also takes place in the elicitation phase of allergic contact dermatitis and this migration can be influenced by tacrolimus and rapamycin, and, to a lesser extent, by cilomilast. [ABSTRACT FROM AUTHOR]

CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26– T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production. [ABSTRACT FROM AUTHOR]

Introduction: Several investigations over the past few years have shown that the importance of preserving the blood supply of the transport disc during segmental distraction has been overestimated. It was clearly demonstrated that distraction osteogenesis by local bone transportation could be achieved even with free bone grafts. So far, there have been no systematic investigations into how different types of free bone grafts vary in their function and suitability as transport discs in segmental craniofacial distraction. The aim of this study was to develop criteria to aid the clinician in selecting the most suitable free bone graft for distraction purposes. Materials and Methods: Under general anesthesia, calvarial defects measuring 6 x 5 cm were created in 12 adult black head sheep in order to reconstruct them by segmental distraction using two different types of bone grafts as transport discs. Group 1 (n=6) received autotopical membranous bone of the calvarium as the transport segment, while group 2 (n=6) received heterotopical enchondral material from the iliac crest. Distraction was started postoperatively after 5 days at 0.6 mm/day and continued for 7 weeks. After a further 6 weeks of consolidation, the animals were killed and specimens examined macroscopically, radiographically and histologically. Results: The significantly better quality of bone regenerates of group 1 was clearly influenced by the significantly better stability of the transport disc's connection to the distraction device, the calvaria grafts showing better volume stability and better mechanical resistance during transport than the iliac bone. The influence of both types of bone grafts on the macro- and microstructure of the newly formed bone was clearly evident. The mineralization density of group 2 regenerates was significantly lower than that of group 1 specimens. Conclusion: High mechanical stability of the bone graft is a very important point to consider when selecting a free graft for use as transport disc in local bone transport, especially if transport is necessary over long distances. [ABSTRACT FROM AUTHOR]

Skin-infiltrating T cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES (regulation on activation, normal T cell expressed and secreted; CCL5), TARC (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell attracting chemokine; CCL27).To investigate which T-cell-attracting chemokines are involved in allergic contact dermatitis in mice.Allergic contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid diflorasone diacetate were studied in mouse ears.RANTES and TARC were elevated in both models of allergic contact dermatitis 24 h after challenge, whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by diflorasone diacetate in the DNCB model but was highly induced in the TDI model; in contrast, TARC was not influenced by cilomilast.TARC and RANTES, but not CTACK, are involved in these two models of allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Background: The increased production of nerve growth factor (NGF) has been associated with allergen-induced airway hyperresponsiveness and enhanced airway inflammation in experimental models of asthma. The aim of this study was to investigate whether a local application of anti-NGF to the lungs may affect the allergen-specific early (EAR) and late (LAR) airway responses to ovalbumin (Ova) of Ova-sensitized brown Norway rats. Methods: Rats were sensitized systemically with Ova and were boosted twice intratracheally with Ova aerosol using a microsprayer. Two hours before every boost, the animals were pretreated either with aerosolized anti-NGF or with a control antibody. On day 21, all animals were challenged with inhalational Ova aerosol and pulmonary resistance was recorded in anesthetized, orotracheally intubated animals during the early and late asthmatic responses. In addition, differential cell counts from bronchoalveolar lavage and serum immunoglobulin E (IgE) levels were determined 48 h post-Ova challenge. Results: Pretreatment with anti-NGF significantly attenuated the EAR but had no significant effect on the LAR. Serum IgE levels and inflammatory cell influx into the lungs were not affected by anti-NGF pretreatment. Conclusion: The data from this study suggest that NGF is directly involved in the development of the EAR without affecting the inflammatory airway response or LAR. [ABSTRACT FROM AUTHOR]

The article presents a letter to the editor about postmortem effects of the expression of immunologically relevant surface molecules in the human tracheal mucosa.

Structured surgical education has become increasingly important in recent years. Intraventricular neuroendoscopic procedures have been widely established. However, training surgical skills with these techniques is crucial for young residents due to the potential harm to adjacent tissue. Therefore, we evaluated two different training models. Participants in two different international workshops were trained on a prefixed cadaver model and on a living murine intraabdominal model. Crucial neuroendoscopic techniques such as membrane perforation and tissue biopsy were performed. A blinded questionnaire evaluated both models. Sixty-three participants were trained on the animal model. Forty of these were trained on the cadaver model. The training effect was evaluated almost equally, with 8.5/10 for the animal model and 8.9/10 for the cadaver model. The tissue properties were rated higher regarding realism in the animal model, whereas the anatomic realism was rated higher in the cadaver model. The animal model is a valid alternative to cadaver models for teaching endoscopic neurosurgical skills. This model benefits from the simulation of real surgical tissue properties, including bleeding. The low costs and availability of this technique make it more ubiquitous and can help train further generations of neurosurgeons., Competing Interests: Declarations Ethics approval All animal experiments were performed under approval by the local governmental animal care committee (registration number TVA 11-2023). The education of physicians on cadavers were performed under approval by the local governmental ethic committee (registration number 245/22). Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches., Aims: This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries., Methods: Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres., Results: A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 μm [31-73], middle 38 μm [26-58], distal 31 μm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 μm [31-81]), followed by the LAD (42 μm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005)., Conclusions: Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.

Background: Canonical transient receptor potential channels play a crucial role in cancer cell proliferation. While TRPC6 subtype detection in submandibular glands and the relevance of some TRPC channels in this gland have been shown in animal models, its histological detection in human lacrimal and submandibular glands, as well as related tumors, lacks systematic study. Studying TRPC6 in humans could lead to new therapeutic options. This research aimed to immunohistochemically detect TRPC6 in human samples of physiological lacrimal and submandibular glands and of adenoid cystic carcinoma and mucoepidermoid carcinoma., Methods: Seven fixed body donors and samples of six cancer patients were examined. The ten tissue samples collected from the submandibular and lacrimal glands were then processed into histological slides and stained with hematoxylin-eosin. Tumor samples were provided as sections. TRPC6 presence was determined by immunohistochemistry, which was performed by indirect detection with a primary TRPC6 antibody, a secondary HRP-conjugated antibody and the chromogen diaminobenzidine., Results: Results confirm TRPC6 expression in all ten physiological gland samples: all samples showed a immunohistochemical signal with varying intensity. No significant gender-specific differences could be observed. TRPC6 was detected in four of six submandibular adenoid cystic carcinoma and the mucoepidermoid carcinoma samples, especially in tumor cells' cytoplasma and nuclei. Excretory ducts consistently showed TRPC6. Mucous tubules, their nuclei and the nuclei of adipocytes generally showed no signal while serous acini and their nuclei showed a weak TRPC6 signal., Conclusion: The discovery of TRPC6 in glandular tissue indicates a role in salivary gland function and calcium homeostasis is a basis for further research into its significance for tumor development in adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands. TRPC6 could be used as a target for treatment of these tumors. However, the correlation between TRPC6 and submandibular and lacrimal gland diseases requires further exploration., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Transient receptor potential canonical channel 6 (TRPC6) is a non-selective cation channel that is activated by diacylglycerol. It belongs to the TRP superfamily, is expressed in numerous tissues and has been shown to be associated with diseases, such as focal segmental glomerulosclerosis, idiopathic pulmonary arterial hypertension and cardiac hypertrophy. The investigation of the channel in human lymphoid tissues has thus far been limited to mRNA analysis or the western blotting of isolated lymphoid cell lines. The present study aimed to detect the channel in human lymphoid tissue using immunohistochemistry. For this purpose, lymphatic tissues were obtained from body donors. The lymphatic organs analyzed included the lymph nodes, spleen, palatine tonsil, gut-associated lymphoid tissues (ileum and vermiform appendix) and thymus. A total of 102 samples were obtained and processed for hematoxylin and eosin (H&E) staining. The H&E staining method was employed to identify five samples with good morphology. In total, three samples of the palatine tonsil of patients were included. Immunostaining was carried out using a knockout-validated anti-TRPC6 antibody. As shown by the results, using immunohistochemical staining, the presence of TRPC6 was confirmed in all the analyzed lymphatic tissue samples. Lymphocytes in lymph nodes, spleen, palatine tonsil, thymus, and gut-associated lymphatic tissues in ileum and vermiform appendix exhibited a positive staining signal. The follicle-associated epithelium of the palatine tonsil, ileum and appendix also demonstrated staining. Vessels of the lymphatic organs, particularly the trabecular arteries of the spleen, the submucosal vessels of the appendix and ileum, as well as the high endothelial venules in the palatine tonsils and lymphatic vessels of the lymph nodes expressed TRPC6 protein. TRPC6 in follicles may be involved in the immune response. TRPC6 in high endothelial venules suggests a role in leukocyte migration. The role of TRPC6 and other channels of the TRP family in lymphatic organs warrant further investigations to elucidate whether TRP channels are a pharmacological target., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Daum et al.)

Background: Expression and function of TRPC3 and TRPC6 in the pancreas is a controversial topic. Investigation in human tissue is seldom. We aimed to provide here a detailed description of the distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas., Methods: We collected healthy samples from cadavers (n = 4) and visceral surgery (n = 4) to investigate the respective expression profiles using immunohistochemical tracing with knockout-validated antibodies., Results: TRPC3- and TRPC6-proteins were detected in different pancreatic structures including acinar cells, as well as epithelial ductal cells from intercalate, intralobular, and interlobular ducts. Respective connective tissue layers appeared unstained. Endocrine islets of Langerhans were clearly and homogenously immunolabeled by the anti-TRPC3 and anti-TRPC6 antibodies. Insular α, β, γ, and δ cells were conclusively stained, although no secure differentiation of cell types was performed., Conclusions: Due to aforementioned antibody specificity verification, protein expression in the immunolabeled localizations can be accepted. Our study in human tissue supports previous investigations especially with respect to acinar and insular α and β cells, while other localizations are here reported for the first time to express TRPC3 and TRPC6, ultimately warranting further research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Transient receptor potential channel canonical 5 (TRPC5) is a non-selective ion channel; ion influx through TRPC5 causes activation of downstream signaling pathways. In addition, TRPC5 has been identified as having a potential role in pathological processes, particularly in diseases caused by cellular cation homeostasis dysregulation, such as bronchial asthma or pulmonary hypertension. However, the expression and distribution of TRPC5 in the human lung remain unclear. To date, TRPC5 has only been detected in a few cell types in the human lung, such as airway, pulmonary venous and arterial smooth muscle cells. The present study therefore aimed to investigate the protein expression of TRPC5 in the human lung and to evaluate its histological distribution. Human lung samples were obtained from six preserved body donors. After processing, both hematoxylin & eosin staining, as well as immunohistochemistry were performed. Microscopic analysis revealed medium to strong immunostaining signals in all lung structures examined, including the pleura, pulmonary arteries and veins, bronchioles, alveolar septa, type 1 and 2 pneumocytes, as well as alveolar macrophages. Current research suggests that TRPC5 may be involved in various pathological processes in the human lung and some pharmacological compounds have already been identified that affect the function of TRPC5. Therefore, TRPC5 may present a novel drug target for therapeutic intervention in various lung diseases. The results of the present study indicate that the TRPC5 protein is expressed in all examined histological structures of the human lung. These findings suggest that TRPC5 may be more important for physiological cell function and pathophysiological cell dysfunction in the lung than is currently known. Further research is needed to explore the role and therapeutic target potential of TRPC5 in the human lung., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Umlauf et al.)

During routine dissections of cadavers as part of the medical curriculum, we identified a rare unilateral variation in the brachial plexus on the right side of a female body donor. This variation consisted of four unusual changes to the regular pattering of nerve bundles and the dorsal scapular artery permeating the complex neural network. The variation included contributions of root C4 to the plexus by a root C4/C5 anastomosis, a rare fusion of the superior and middle trunks to a 'superomiddle' trunk, a preliminary, proximal branching of the suprascapular nerve off the C5 root. We further observed an accessory 'medial anterior division' branching off the fused upper and middle trunks merging with the anterior division of the inferior trunk forming the medial cord. The latter event potentially introduced nerve fibers from C5 to C7, which are absent in common patterns. We aim to relate these observations to previous categorizations and quantifications of brachial plexus patterns. We believe that the combination of different variations in this case resulted in a unique pattern. Since this observation was made in the dissection class, we further aim to raise awareness among medical students and anatomical instructors for the likelihood of variations to textbook patterns. This will hopefully foster an appreciation of uniqueness and individuality in the interaction with future patients demonstrating that proper preparation prior to surgical interventions is always a necessary prerequisite.

Micro- and nanoplastics (MNPs) are ubiquitous in the environment, resulting in the uptake of MNPs by a variety of organisms, including humans, leading to particle-cell interaction. Human macrophages derived from THP-1 cell lines take up Polystyrene (PS), a widespread plastic. The question therefore arises whether primary human macrophages also take up PS micro- and nanobeads (MNBs) and how they react to this stimulation. Major aim of this study is to visualize this uptake and to validate the isolation of macrophages from peripheral blood mononuclear cells (PBMCs) to assess the impact of MNPs on human macrophages. Uptake of macrophages from THP-1 cell lines and PBMCs was examined by transmission electron microscopy (TEM), scanning electron microscopy and live cell imaging. In addition, the reaction of the macrophages was analyzed in terms of metabolic activity, cytotoxicity, production of reactive oxygen species (ROS) and macrophage polarization. This study is the first to visualize PS MNBs in primary human cells using TEM and live cell imaging. Metabolic activity was size- and concentration-dependent, necrosis and ROS were increased. The methods demonstrated in this study outline an approach to assess the influence of MNP exposure on human macrophages and help investigating the consequences of worldwide plastic pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors declare no competing interests regarding the publication of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug phenylephrine., Methods: Cadavers were included after body donors gave written informed consent during lifetime. Exclusion criteria were known eye disease, or a postmortem interval exceeding 26 hours. A pupillometer with a minimum measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 minutes after the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction., Results: 30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was in median 3.5 mm (interquartile range [IQR]: 3.0-4.5 mm) and progressed to 4.0 mm (IQR: 3.5-5.0 mm) 20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR: 0.0-1.0 mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the initial and the reactive pupil (P = 0.0002)., Conclusion: Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the application of a third agent with a sympathomimetic mechanism of action could provide additional information. Further studies assessing such a triple approach in the compound method in comparison with the current gold standard for estimation of time since death are mandatory to ensure reliable results., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Posterior fixation of the subaxial cervical spine (SCS) commonly relies on the application of lateral mass screws (LMS), with pedicle screws being a less prevalent alternative. The present study provides another option: A recently introduced novel approach, the Attallah screw, intended to ensure a safety profile comparable to that of LMS, combined with a strength profile similar to that of pedicle screws. The focus of the present study is the comparative analysis of peak insertion torques for these three screw types. Employing standard surgical techniques and instruments, Attallah screws were scheduled for insertion on the right side of the SCS in 15 cadavers, pedicle screws on the left side in 8 cadavers, and LMS on the left side in the remaining 7 cadavers. The peak insertion torque was recorded using an electronic torque screwdriver. The results revealed that the peak insertion torques were similar in the pedicle and the Attallah screw at C3, C4 and C7, but differed at C5 (mean ± SD; pedicle, 79.5±19.6 cNm; Attallah, 56.7±18.5 cNm; P=0.029) and C6 (pedicle, 85.4±28.7 cNm; Attallah, 49.8±17.9 cNm; P=0.004) in favor of the superior pedicle screw measurements. The peak insertion torques of the pedicle screw were superior to the corresponding data from the LMS from C4 to C7. By contrast, the peak insertion torques of the Attallah screw were only superior to those of the LMS at C7 (Attallah, 69.5±24.5 cNm; lateral mass, 40.5±21.4 cNm; P=0.030), although similar trends were observed at the other cervical levels. On the whole, the findings presented herein indicate the level-dependent superior robustness of the Attallah screw as a posterior cervical fixation method compared to the LMS. However, from a biomechanical perspective, the pedicle screw remains the preeminent choice for fixation within the C5-C6 range., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Hasanain et al.)

Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.

Introduction: The management of fractured bones is a key domain within orthopedic trauma surgery, with the prevention of delayed healing and non-unions forming a core challenge. This study evaluates the efficacy of the AO Fracture Monitor in conjunction with biomechanical simulations to better understand the local mechanics of fracture gaps, which is crucial for comprehending mechanotransduction, a key factor in bone healing. Through a series of experiments and corresponding simulations, the study tests four hypotheses to determine the relationship between physical measurements and the predictive power of biomechanical models. Methods: Employing the AO Fracture Monitor and Digital Image Correlation techniques, the study demonstrates a significant correlation between the surface strain of implants and interfragmentary movements. This provides a foundation for utilizing one-dimensional AO Fracture Monitor measurements to predict three-dimensional fracture behavior, thereby linking mechanical loading with fracture gap dynamics. Moreover, the research establishes that finite element simulations of bone-implant systems can be effectively validated using experimental data, underpinning the accuracy of simulations in replicating physical behaviors. Results and Discussion: The findings endorse the combined use of monitoring technologies and simulations to infer the local mechanical conditions at the fracture site, offering a potential leap in personalized therapy for bone healing. Clinically, this approach can enhance treatment outcomes by refining the assessment precision in trauma trials, fostering the early detection of healing disturbances, and guiding improvements in future implant design. Ultimately, this study paves the way for more sophisticated patient monitoring and tailored interventions, promising to elevate the standard of care in orthopedic trauma surgery., Competing Interests: TP is president and board member of the AO Foundation, Switzerland, and extended board member of the German Society of Orthopedic Trauma Surgery (DGU), the German Society of Orthopedic Surgery and Traumatology (DGOU), and the German Society of Surgery (DGCH). TP is also the speaker of the medical advisory board of the German Ministry of Defense. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wickert, Roland, Andres, Diebels, Ganse, Kerner, Frenzel, Tschernig, Ernst, Windolf, Müller, Pohlemann and Orth.)

Several reports previously investigated the Transient Receptor Potential Canonical subfamily channel 3 (TRPC3) in the kidney. However, most of the conclusions are based on animal samples or cell cultures leaving the door open for human tissue investigations. Moreover, results often disagreed among investigators. Histological description is lacking since most of these studies focused on functional aspects. Nevertheless, the same reports highlighted the potential key-role of TRPC3 in renal disorders. Hence, our interest to investigate the localization of TRPC3 in human kidneys. For this purpose, both healthy mouse and human kidney samples that were originated from tumor nephrectomies have been prepared for immunohistochemical staining using a knockout-validated antibody. A blocking peptide was used to confirm antibody specificity. A normalized weighted diaminobenzidine (DAB) area score between 0 and 3 comparable to a pixelwise H-score was established and employed for semiquantitative analysis. Altogether, our results suggest that glomeruli only express little TRPC3 compared to several segments of the tubular system. Cortical and medullary proximal tubules are stained, although intracortical differences in staining exist in mice. Intermediate tubules, however, are only weakly stained. The distal tubule was studied in three localizations and staining was marked although slightly varying throughout the different subsegments. Finally, the collecting duct was also immunolabeled in both human and mouse tissue. We therefore provide evidence that TRPC3 is expressed in various localizations of both human and mouse samples. We verify results of previous studies and propose until now undescribed localizations of TRPC3 in the mouse but especially and of greater interest in the human kidney. We thereby not only support the translational concept of the TRPC3 channel as key-player in physiology and pathophysiology of the human kidney but also present new potential targets to functional analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.g., by regulating mucociliary clearance, remained largely elusive., Methods: We performed immunohistochemistry, RT-PCR and immunoblotting analyses for various tuft cell markers to confirm the presence of this cell type in human tracheal samples. Immunohistochemistry was conducted to study the distribution of tuft cells along the intrapulmonary airways in humans. We assessed the influence of bitter substances and the taste transduction pathway on mucociliary clearance in mouse and human tracheal samples by measuring particle transport speed., Results: Tuft cells identified by the expression of their well-established marker POU class 2 homeobox 3 (POU2F3) were present from the trachea to the bronchioles. We identified choline acetyltransferase in POU2F3 expressing cells as well as the transient receptor potential melastatin 5 (TRPM5) channel in a small population of tracheal epithelial cells with morphological appearance of tuft cells. Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the regulation of mucociliary clearance., Conclusions: We were able to detect tuft cells in the tracheobronchial tree down to the level of the bronchioles. Moreover, taste transduction and cholinergic signalling occur in the same cells and regulate mucociliary clearance. Thus, tuft cells are potentially involved in the regulation of innate immunity in human airways., (© 2023. The Author(s).)

Since the discovery of TRP proteins in 1969, during studies of the fruit fly Drosophila melanogaster, interest around them and the subfamily of TRPC channels has remained high. TRPC3 was able to be detected in a number of organs in rodents, such as rats and mice, and also in various human tissues. For the most part, these investigations were carried out using gene expression of TRPC3. Further work has already confirmed the relevance of TRPC3 in the context of neurodegenerative diseases, such as spinocerebellar ataxia, and carcinogenic entities, such as ovarian carcinoma. An association with TRPC3 has also been demonstrated for diseases that affect the liver. In order to confirm the expression of TRPC3 in the human liver, this study uses samples taken from eight (n = 8) fixated human body donors and analyzed with immunohistochemistry. In accordance with the macroscopic anatomy of the organs, six samples (n = 6) of liver tissue and three (n = 3) of gallbladder tissue were obtained. TRPC3 was clearly detected in all liver and gallbladder samples examined. Thus, it is not unlikely that TRPC3 plays a role in the extensive metabolic processes of the liver and could also serve as a target for pharmacological interventions in an imbalance of calcium homeostasis., Competing Interests: Declaration of Competing Interest Authors declare that they have no disclosures., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Renal denervation is optimised when guided by knowledge of nerve distribution., Aims: We aimed to assess sympathetic nerve distribution along the renal arteries, especially in post-bifurcation vessel segments., Methods: Renal arteries and surrounding tissue from 10 body donors were collected and examined histologically. Immunohistochemical staining was used to analyse nerve distribution and to identify afferent and efferent sympathetic nerves., Results: A total of 6,781 nerves surrounding 18 renal arteries were evaluated. The mean lumen-nerve distance of the left renal artery (2.32±1.95 mm) was slightly greater than the right (2.29±2.03 mm; p=0.161); this varied across the arteries' courses: 3.7±2.3 mm in proximal segments, 2.5±2.0 mm in middle segments, 1.9±1.6 mm in distal prebifurcation segments and 1.3±1.0 mm in post-bifurcation segments (p<0.001). The number of nerves per quadrant was highest in the proximal segments (13.7±18.6), followed by the middle (9.7±7.9), distal prebifurcation (8.0±7.6), and distal post-bifurcation (4.3±4.0) segments (p<0.001). Circumferentially, the number of nerves was highest in the superior (7.8±9.4) and the ventral (7.6±13.1) quadrants (p=0.638). The mean tyrosine hydroxylase (TH) to calcitonin gene-related peptide (CGRP) ratio increased from proximal (37.5±33.5) to distal (72.0±7.2 in the post-bifurcation segments; p<0.001). Thirty-eight neuroganglia were identified along 14 (78%) renal arteries., Conclusions: Nerves converge to the renal arteries' lumen in the distal segments and along branches, resulting in the lowest number of nerves per quadrant and the shortest lumen-nerve distance in the distal post-bifurcation segments. Efferent nerves occur predominantly, and the ratio of efferent to afferent nerves continues to increase in the vessels' course.

Background : Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. Materials and Methods : In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty. Utilizing computed tomography scans of the patients' pelvis and 3D templates of the implants (Aesculap Plasmafit, B. Braun; Aesculap Plasmafit Revision, B. Braun; Avantage Acetabular System, Zimmerbiomet, EcoFit 2M, Implantcast; Tritanium Revision, Stryker), we performed 3D templating and positioned the acetabular cup implants accordingly. To evaluate accuracy, we compared the planned sizes of the acetabular cups in 2D and 3D with the sizes implanted during surgery. Results : An analysis was performed to examine potential influences on templating accuracy, specifically considering factors such as gender and body mass index (BMI). Significant statistical differences ( p < 0.001) in the accuracy of size prediction were observed between 3D and 2D templating. Personalized 3D templating exhibited an accuracy rate of 66.7% for the correct prediction of the size of the acetabular cup, while 2D templating achieved an exact size prediction in only 26.7% of cases. There were no statistically significant differences between the 2D and 3D templating methods regarding gender or BMI. Conclusion : This study demonstrates that 3D templating improves the accuracy of predicting acetabular cup sizes in revision arthroplasty when compared to 2D templating. However, it should be noted that the predicted implant size generated through 3D templating tended to overestimate the implanted implant size by an average of 1.3 sizes.

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., (© 2023 The Authors. Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: Flexor hallucis longus (FHL) transfer is a well-established method for treating chronic Achilles tendon ruptures and tendinopathy. Harvesting of the FHL tendon in zone 2 results in greater length but is also associated with an increased risk of injury to the medial plantar nerve and requires an additional plantar incision. Because of the anatomic proximity of the FHL tendon to the tibial neurovascular bundle in zone 2, the purpose of this study was to investigate the risk of vascular or nerve injury with arthroscopic assisted percutaneous tenotomy in zone 2 of the FHL tendon., Methods: Endoscopically assisted percutaneous FHL transfer was performed on 10 right lower extremities from 10 cadaveric human specimens. The FHL tendon lengths and the relationship between FHL tendon and the tibial neurovascular bundle at zone 2 was analyzed., Results: We observed a complete transection of the medial plantar nerve in 1 case (10%). The mean length of the FHL tendon was 54.7 ± 9.5 mm and the mean distance from the distal stump of the FHL tendon to local neurovascular structures was 1.3 ± 0.7 mm., Conclusion: There is a risk of neurovascular injury after endoscopic FHL tenotomy in zone 2. The tenotomy site is within 2 mm of the local neurovascular structures in the majority of cases. The additional length gained from this technique is unlikely to be required for the majority of FHL tendon transfer procedures. If additional length is needed, we would recommend the use of intraoperative ultrasonography or a mini-open approach to minimize injury risk., Level of Evidence: Level V, expert opinion.

Introduction: In human and experimentally induced asthma, a dysfunction of the intra-alveolar-surface active agent (surfactant) has been demonstrated. Type II alveolar epithelial cells (AEII) synthesize, secrete and recycle surfactant. Prior to secretion, intracellular surfactant is stored in specific secretory organelles of AEII. The lamellar bodies (Lb) represent its ultrastructural correlate. The aim of this study was to investigate whether disturbances of the intra-alveolar surfactant are accompanied by alterations in the intracellular surfactant. Material and Methods: Brown-Norway rats were sensitized twice with ovalbumin (OVA) and heat killed Bordetella pertussis bacilli. During airway challenge, an aerosol of 5% ovalbumin/saline solution (0.25 l/min) was nebulized. 24 h after airway challenge, lungs were fixed by vascular perfusion. AEII and their Lb were characterized stereologically by light and electron microscopy. Results: In both groups, AEII were structurally intact. The number of AEII per lung and their number-weighted mean volume did not differ (controls: 49 × 10 6 , 393 µm 3 ; asthmatics: 44 × 10 6 , 390 µm 3 ). A mean of 90 Lb in AEII of asthmatics and of 93 Lb in AEII of controls were evaluated. The Lb mean total volume was 59 µm in asthmatics and 68 µm in controls. Values of both parameters did not reach significance. Also, the size distribution and mean volume of Lb was not influenced by asthma induction, because the volume weighted mean volume of Lb (2.18 µm in asthmatics compared to 1.87 µm in controls) and the numerical weighted mean volume (0.96 µm in asthmatics and 0.75 µm in controls) were comparable in both groups. Conclusion: The obtained results suggest that asthma-induced surfactant dysfunction is not related to disturbances in the intracellular surfactant´s ultrastructural correlates.

Background: Advanced core decompression (ACD) is a relative new technique for treatment of early stages of avascular femoral head necrosis. Although it is a promising treatment option, there is a need to modify this technique for achieving higher hip survival rates. An idea was to combine this technique with the lightbulb procedure in order to get a complete removal of the necrosis. This study aimed at evaluating the fracture risk of the femora treated by the combined Lightbulb-ACD technique as the basis for clinical application., Methods: Subject-specific models were generated from CT scan data of five intact femora. Several treated models were then created from each intact bone and simulated during normal walking activity. Biomechanical testing was additionally performed on 12 pairs of cadaver femora to confirm the simulation results., Findings: The finite element results revealed that the risk factor of the treated models with a 8 mm-drill increased, but was not significantly greater than that of their corresponding intact models. However, for the femur treated with a 10 mm-drill, the risk factor increased significantly. Fracture always initiated on the femoral neck, i.e. it was either subcapital or transcervical fracture. Our biomechanical testing results correlated well with the simulation data which confirmed the usefulness and effectiveness of the bone models., Interpretation: The combined Lightbulb-ACD technique using a 10 mm drill increased the fracture risk of femur postoperatively. A drill of up to 8 mm at the anterior head-neck junction did not however lead to the weakening of the femur so that full load bearing may be possible., Competing Interests: Declaration of Competing Interest Stefan Landgraeber received honoraria for lectures by Wright Medical., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease which has been suggested in previous rodent experiments.

Both particular myocardial locations in the human heart and the canonical transient receptor potential 6 (TRPC6) cation channel have been linked with cardiac pathophysiologies. Thus, the present study mapped TRPC6-protein distribution in select anatomic locations associated with cardiac disease in the context of an orienting pathological assessment. Specimens were obtained from 5 body donors (4 formalin fixation, 1 nitrite pickling salt-ethanol-polyethylene glycol (NEP) fixation; median age 81 years; 2 females) and procured for basic histological stains and TRPC6-immunohistochemistry. The latter was analyzed descriptively regarding distribution and intensity of positive signals. The percentage of positively labelled myocardium was also determined (optical threshold method). Exclusively exploratory statistical analyses were performed. TRPC6-protein was distributed widespread and homogenously within each analyzed sample. TRPC6-immunoreactive myocardial area was comparable regarding the different anatomic regions and sex. A significantly larger area of TRPC6-immunoreactive myocardium was found in the NEP-fixed donor compared to the formalin fixed donors. Two donors with more severe heart disease showed smaller areas of myocardial TRPC6-immunoreactivity overall compared to the other 3 donors. In summary, in the elderly, TRPC6-protein is widely and homogenously distributed, and severe cardiac disease might be associated with less TRPC6-immunoreactive myocardial area. The tissue fixation method represents a potential confounder.