Body Donation Research Articles

Neuropathological evidence that the association between APOE‐e4 genotype and higher medial temporal lobe tau burden is mediated by higher local amyloid‐β levels

AbstractBackgroundEvidence from previous PET imaging studies suggests that increased neocortical tau seen in APOE‐ε4 carriers can be explained by the higher levels of neocortical amyloid‐β (Aβ) pathology also seen in this group. However, these studies also suggest an amyloid‐independent association between APOE‐ε4 and medial temporal lobe (MTL) tau. Using neuropathological data, we investigated whether amyloid‐β in the MTL, which is difficult to accurately measure with PET, may fully mediate the association between APOE‐ε4 carriership and MTL tau burden.MethodAmyloid‐β and tau pathology in MTL and neocortical areas have been measured in a total of 2,704 individuals from two independent neuropathological datasets (Arizona Study of Aging and Neurodegenerative Disorders, Brain and Body Donation Program, n=1,117 and ROSMAP, n=1,587; Table 1). Regression models were used to investigate the associations between APOE‐ε4 carriership and neocortical and local (MTL) amyloid‐β on MTL tau, adjusting for age, sex and presence of co‐pathologies. Based on these results, we also tested whether local (MTL) amyloid‐β mediated the association between APOE‐ε4 carriership and MTL tau.ResultSupporting results from previous studies, APOE‐e4 carriers showed higher tau burden in the MTL (p<0.001) when amyloid‐β was not included in the model in both datasets. In independent models, both local and neocortical amyloid‐β were associated with MTL tau, with local amyloid‐β showing a stronger association with MTL tau in both datasets (Arizona: βMTL=0.93 vs. βneoc=0.76; ROSMAP: βMTL=0.42 vs. βneoc=0.40). When both measures were included in the model, local amyloid‐β also showed a stronger association with MTL tau in ROSMAP (βMTL=0.28 vs. βneoc=0.19). In the Arizona dataset, neocortical amyloid‐β effect became non‐significant (p=0.252) when local amyloid‐β was also included in the model. Finally, with mediation analyses we observed that MTL amyloid‐β fully mediated the APOE‐ε4 effect on MTL tau in both datasets (Figure 1). All statistics are reported in Table 2.ConclusionIn two large neuropathological datasets, we showed that the association between APOE‐ε4 genotype and higher medial temporal lobe tau burden is mediated by higher local amyloid‐β levels. This finding contradicts some previous imaging literature, where only global amyloid‐β burden was considered.

Ex vivo models of corneal epithelial regeneration in bioreactor: Respective roles of limbal, conjunctival and corneal epithelia

AbstractPurpose: The corneas preserved in bioreactor (BR) had been shown to have not only a better endothelial viability, but also a more differentiated and stratified epithelium than corneas preserved in organoculture. Purpose: By using BR, we would analyse the respective contribution of corneal (C), limbal (L), and conjunctival (Conj) epithelia in corneal epithelial regeneration.Methods: Five pairs of corneas from body donation to Science were used with a death‐to‐collection time < 20 h. A 3‐ to 5‐mm‐wide conjunctival flange was kept intact. Five patterns were set up by fully mechanical removal of 1, 2, or 3 epithelia: C‐L + Conj+, C‐L‐Conj+, C‐L + Conj‐, C + L‐Conj‐, C‐L‐Conj‐ (control) n = 2 for each pattern. The limbus was destroyed by scraping and thermocoagulation. Corneas were then kept in BR (21 mmHg, 2.5 μl/min of Corneamax Eurobio, 31°C) for 3 weeks to allow epithelial regeneration. The epithelium was then analysed using immunofluorescence (IF) on flat mounted cornea by targeting CK12 (corneal epithelium) and CK15 (limbal epithelium). Cell nuclei were counterstained with DAPI. Corneal transparency was quantified using a transparometer.Results: No epithelium was reconstituted in the controls. In the other 4 models including the C‐L‐Conj+ group, the cornea was transparent and covered by a pluristratified corneal epithelium, characterized by CK12 expression.Conclusions: In this BR model, conjunctival epithelial cells allowed the regeneration of a typical corneal epithelium in model C‐L‐Conj+. The corneal epithelium can also migrate to the limbus and conjunctiva. We hypothesize that all 3 ocular surface epithelia (including the conj) contain stem cells or progenitors capable of migrating throughout the cornea and restoring the corneal epithelium independently of each other. The main difference between our ex vivo model and in vivo situation is absence of neovascularization. This suggests that the main cause of limbic insufficiency is due to the loss of the anti‐angiogenic barrier rather than the loss of limbic stem cells.

Knowledge, Attitude and Practice Among the Medical And Dental Undergraduates Regarding On Whole Body Donation For Teaching Learning Purposes: A Perspectives From Bioethics- A Cross Sectional Study

Knowledge, Attitude and Practice Among the Medical And Dental Undergraduates Regarding On Whole Body Donation For Teaching Learning Purposes: A Perspectives From Bioethics- A Cross Sectional Study

PANDEMIC CHANGING ATTITUDE OF MEDICAL STUDENTS TOWARDS BODY DONATION

Between 2018 and 2020 we carried out a research project endorsed by the University Secretary of Science and Technology, based on different group’s surveys, to obtain supporting data for the creation of the Program for Body Procurement and Donation. As the pandemic COVID-19 stopped all face-to-face educational activities and seriously affected the reception of bodies for teaching and research, in 2021 we reiterated a survey on some similar data, with the aim of evaluating the impact the pandemic had had on the opinion of two of these groups (medical students). This survey included 1406 students from all years of the career, who were asked about their knowledge on body donation and the Program, their interest in collaborating with it, their willingness to donate their own body and reasons for doing or not doing so. Results showed a similar composition of the samples in relation to age, gender, geographic origin, religion and differences in each year of the career (compared with those of 2018). Specific aspects also evidenced similarities about knowledge of the possibility of donating (p=0.0812) and interest in collaborating with the Program (p=0.2460), but reached 72% (p=<0.0001) in willingness to donate their own body. We also analyzed the reasons to donate and not donate in the context of the pandemic and concluded that it positively influenced these results; directly, due to the increased appreciation of scientific research and indirectly, because the pandemic facilitated communications and access to scientific information online.

Topographic and Morphometric Study of the Foramen Spinosum of the Skull and Its Clinical Correlation.

Background and Objectives: The spinous foramen (FS) of the skull is an opening located in the greater wing of the sphenoid bone at the base of the skull, and it includes the middle meningeal vessels and the meningeal branch of the mandibular trigeminal nerve. The FS is commonly used as an anatomical landmark in neurosurgical procedures and neuroimaging of the middle cranial fossa because of its relationship with other cranial foramina and surrounding vascular and nervous structures. Thus, specific knowledge of its topography and possible anatomical variations is important regarding some surgical interventions and skull imaging. The aim of this study was to provide further details on the morphology of the FS of the skull by evaluating its topographic and morphometric relationships and correlating the findings with clinical practice. Materials and Methods: Thirty dried skulls of human skeletons from body donors from the collection of the Laboratory of Anatomical Microdissection at a medical school were used. The metric dimensions and variations of the FS and its relationship with adjacent bone structures were analyzed with an interface digital microscope. Results: The results showed the bilateral presence of the FS in all skulls; however, differences were observed in the shape, diameter, and topography in relation to the foramen ovale and the spine of the sphenoid. The FS was present in the greater wing of the sphenoid bone; however, in one skull, it was located in the lateral lamina of the pterygoid process. The FS was smaller than the foramen ovale. A round and oval FS shape was the most common (42.1% and 32.8% of the samples, respectively), followed by drop-shaped (12.5%) and irregular-shaped (12.5%) foramina. Conclusions: In conclusion, FS variations among individuals are common and must be considered by surgeons during skull base interventions in order to avoid accidents and postoperative complications.

Latin American Anatomists’ views on human body dissection and donation

BackgroundStudies abound regarding the medical students' views on the importance of anatomy and the dissection of human bodies, but little is known about the views of Latin American Anatomists. MethodsA survey was carried out to test several hypotheses among anatomists of the Americas about how they perceive their professional identity, the use and role of dissection in their undergraduate courses, and the approval degree of bequeathing their body for anatomical teaching/research; another goal was ascertaining to what extent their attitude on these topics depended on gender, length of teaching experience and belief in the afterlife. ResultsOne hundred and forty-five anatomists from thirteen Latin American and Caribbean Countries took the survey; 79% stated the main role of an anatomist is teaching; 34% recorded their undergraduate students dissected human cadavers as part of their anatomy lab course—undergraduates dissecting less in the less experienced anatomists’ courses (p = 0.0002). Most anatomists said dissection was a training tool for undergraduate students, a tool for developing professional skills, and a tool to help control emotions—most experienced anatomists stood out from the rest saying dissection is only to teach anatomy (p < 0.001), even if such response was the least valued by them among all replies. Men differed from women in valuing dissection as a tool to help control emotions (p = 0.006); less experienced anatomists held the opposite (p < 0.0001). Approval of a close doctor-patient relationship diverged, being different between the most and the least experienced anatomists (p = 0.01). Anatomists said they would donate only their organs (44%), whole body (9%) and both organs and body (46%). Undecided anatomists about the belief in life after death were the least in favor of donation (p = 0.05).

Ethics of the use of dead human bodies in anatomy teaching in India.

The study of the human anatomy predominantly requires the use of remains of the dead. Unclaimed bodies are easily available in India; however, there is a lack of clear ethical guidelines governing their transport and exchange. We raise pertinent questions about the ethical implications of using unclaimed bodies in teaching anatomy, their transport, transfer and storage, ethical and legal issues regarding the voluntary donation of bodies and dry human bones, as well as the commercial aspects of body donation. We also examine existing practices in anatomy departments in India, and explore the available legal safeguards. We detail practical and ethical challenges in the existing practices and safeguards and attempt to provide solutions.

Anatomy acts concerning body and organ donations across the globe: past, present and future with a special emphasis on the indian scenario.

From the era of pre-historic times, the ancient Indians and the Greeks highlighted the importance of body and organ donations thereby emphasizing the need for anatomical sciences in medicine through the use of effective dissections for the same. However, after the Renaissance, there was a surge in dissections throughout the world, particularly in Europe, as a result of which various laws were enacted by governments concerning the procurement of bodies for the purpose of scientific dissections, which were later promulgated throughout the world through various anatomical acts. The situation in India was quite similar to that of Britain until its independence in 1947, after which different Indian states formulated their own anatomy acts that had their own merits and pitfalls. Hence, this literature review serves to highlight the various acts throughout history and would serve as a guide to emphasize the future perspectives of formulating a centralized unified anatomy act for the Indian nation that could possibly be the need of the hour.

"A whole new perspective on how the body fits together"-An evaluation of a cadaver laboratory experience for high school students.

The Center for Anatomy and Physiology Education has hosted interactive human cadaver laboratory tours for local high schools (ages 14-18) and undergraduate university students since 2014 to expose students to healthcare careers. Students receive information on the history of body donation and healthcare careers and observe human anatomy on prosections and with isolated organs. The goal of this study was to evaluate students' perceptions of the anatomy laboratory tours and their impact on students' interests in healthcare careers. Students completed pre- and post-tour questionnaires. Responses were analyzed using thematic analysis and linguistic inquiry. Of the 261 students who completed pre-tour questionnaires, 204 (78%) completed the post-tour questionnaire. Before the tour, students anticipated learning about human anatomy and expected to only see but not touch a cadaver. Most students expressed excitement and/or nervousness. A few students viewed the laboratory tour as an opportunity to test if they could see themselves in a healthcare career. After the tour, most students indicated that the tour either met or exceeded their expectations. Students found the laboratory tour to be educational and interesting and were surprised by the opportunity to interact with the donor. Numerous students expressed an increased interest in healthcare careers after the tour. Overall, students perceived the tour as an engaging experience that improved their anatomical knowledge and reinforced/increased their interest in healthcare careers. Academic institutions can positively impact local students by implementing an anatomy tour, sharing access to their in-house human cadaver laboratory, and recruiting instructors to share their anatomy expertise.

The Effects of Experimental Whole-Body Burning on Histological Age-at-Death Estimation from Human Cortical Bone and Dental Cementum.

Whole-body donations (n = 6) were placed in various experimental fire-death scenarios to understand the histological effects of thermal alteration on bones and teeth. Midshaft samples of the femur, 6th rib, and metatarsal were removed from each donor pre- and post-burning to examine histomorphometric differences and test established age-at-death estimation methods. Dental samples were taken post-burning to test the applicability of dental cementum analysis for age-at-death estimation. Significant differences in osteon area or Haversian canal area between some pre- and post-burn samples were found although no patterns related to temperature or element were observable. The femoral age estimates across pre- and post-burn samples were 91% accurate across all donors. The point age estimates from the ribs compared to known age were significantly different (t(10) = 6.88, p &lt; 0.001) with an average difference of -18.53 years. Dental age estimates of post-burn samples were not significantly different from the known donor age (t(3) = -0.74, p = 0.512) with an average difference of -3.96 years. Overall, the results of this study show that thermally altered remains can be used for histologic age-at-death analysis of cortical bone and dental cementum, within certain burning parameters.

Fewer medical students are open to body donation after dissecting human cadavers.

Cadaver dissection has long been hailed as a vital component of medical education. Although most physicians acknowledge positive impacts of cadaver dissection on their learning, they are less likely to will their bodies for anatomical dissection than the general public. This study aims to determine whether the proportion of medical students open to willed body donation changes after completing cadaver dissection. We conducted a longitudinal study surveying 323 medical students across three cohorts before and after anatomical dissection of human cadavers. Through the survey, students indicated whether they would will their body for anatomical dissection. Additionally, students responded to items regarding the rationale underlying their decision, demographics and perceived effects of anatomical dissection on medical education. The proportion of students who expressed openness to willed body donation decreased by 25% after cadaver dissection. Of the 171 students who initially stated they would will their body, 61 (35%) changed their response after completing cadaver dissection. Those who cited religion as a motivating factor were less likely to show openness to body donation, whereas those who cited ethical factors were more likely. This study documents a substantial decrease in the proportion of students open to willed body donation after completion of cadaver dissection. Despite this, students almost universally report educational benefits of cadaver dissection. This raises interesting questions regarding the emotional impact of cadaver dissection and the ethical implications of willed body donation.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

An Exploration of Death Anxiety of Family Members of Silent Mentor Body Donation Program.

Background: This study assesses the level of death anxiety among the family members of the Silent Mentor Programme (SMP) and determines whether their participation in various ceremonies during the training session impacted their death anxiety. Methods: The revised Collett-Lester Fear of Death Scale (CL-FODS) was administered to the study participants before the opening ceremony and after the sending-off ceremony of the programme. Results: All the four subscales that measure fear of one's own death, fear of the process of one's own dying, fear of the death of others and fear of the process of others dying in the CL-FODS showed significant reduction after the sending-off ceremony compared with before the opening ceremony. Younger family members reported significantly higher mean total death anxiety scores compared to the older members. Conclusion: The SMP not only nurtures doctors with humanity but also helps the family members to cope with grief and loss.

Spinal cord from body donors is suitable for multicolor immunofluorescence

Immunohistochemistry is a powerful tool for studying neuronal tissue from humans at the molecular level. Obtaining fresh neuronal tissue from human organ donors is difficult and sometimes impossible. In anatomical body donations, neuronal tissue is dedicated to research purposes and because of its easier availability, it may be an alternative source for research. In this study, we harvested spinal cord from a single organ donor 2 h (h) postmortem and spinal cord from body donors 24, 48, and 72 h postmortem and tested how long after death, valid multi-color immunofluorescence or horseradish peroxidase (HRP) immunohistochemistry is possible. We used general and specific neuronal markers and glial markers for immunolabeling experiments. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24 h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High-contrast multicolor images of the 24-h spinal cords allowed accurate automated quantification of different neuronal elements in the same sample. Although there was antibody-specific signal reduction over postmortem intervals, the signal quality for most antibodies was acceptable at 48 h but no longer at 72 h postmortem. In conclusion, our study has defined a postmortem time window of more than 24 h during which valid immunohistochemical information can be obtained from the body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research.

Novel anatomical findings with implications on the etiology of the piriformis syndrome

PurposeThe cause of the piriformis-related pelvic and extra-pelvic pain syndromes is still not well understood. Usually, the piriformis syndrome is seen as extra-pelvic sciatica caused by the entrapment of the sciatic nerve by the piriformis in its crossing through the greater sciatic foramen. However, the piriformis muscle may compress additional nerve structures in other regions and cause idiotypic pelvic pain, pelvic visceral pain, pudendal neuralgia, and pelvic organ dysfunction. There is still a lack of detailed description of the muscle origin, topography, and its possible relationships with the anterior branches of the sacral spinal nerves and with the sacral plexus. In this research, we aimed to characterize the topographic relationship of the piriformis with its surrounding anatomical structures, especially the anterior branches of the sacral spinal nerves and the sacral plexus in the pelvic cavity, as well as to estimate the possible role of anatomical piriformis variants in pelvic pain and extra-pelvic sciatica.MethodsHuman cadaveric material was used accordingly to the Swiss Academy of Medical Science Guidelines adapted in 2021 and the Federal Act on Research involving Human Beings (Human Research ACT, HRA, status as 26, May 2021). All body donors gave written consent for using their bodies for teaching and research. 14 males and 26 females were included in this study. The age range varied from 64 to 97 years (mean 84 ± 10.7 years, median 88).Resultsthree variants of the sacral origin of the piriformis were found when referring to the relationship between the muscle and the anterior sacral foramen. Firstly, the medial muscle origin pattern and its complete covering of the anterior sacral foramen by the piriformis muscle is the most frequent anatomical variation (43% in males, 70% in females), probably with the most relevant clinical impact. This pattern may result in the compression of the anterior branches of the sacral spinal nerves when crossing the muscle.ConclusionsThese new anatomical findings may provide a better understanding of the complex piriformis and pelvic pain syndromes due to compression of the sacral spinal nerves with their somatic or autonomous (parasympathetic) qualities when crossing the piriformis.

Anatomical study of the carotid-trigeminal interface: The missing link in the trigeminovascular system?

The trigeminal system is considered a prominent actor in brain nociceptive innervation. The trigeminovascular system is mainly composed of pseudounipolar neurons located within the trigeminal ganglion, whose dendrites originate in cerebral blood vessels. Anatomical studies demonstrating anatomical continuity between perivascular fibers and the trigeminal system are lacking. This issue is addressed in this study. Eleven cadaveric heads obtained from a body donation program were fixed in formalin. We performed a microanatomical study of the cavernous carotid-trigeminal interface and a histological examination of the tissue bridges crossing the virtual space between the medial aspect of the trigeminal ganglion and ophthalmic nerve and the lateral aspect of the cavernous segment of the internal carotid artery. Very strong adhesion was observed between the horizontal segment of the artery and the ophthalmic nerve in all specimens. The virtual space in this interface was crossed by a web of delicate filaments. Histological examination demonstrated the presence of nerve fibers in all samples. In this study, the carotid-trigeminal interface has been described in greater detail than ever before and could provide insight into disorders related to the trigeminovascular system. As the present results do not allow the exact nature of the axons to be affirmed, further investigation is necessary.

Significance of the anatomical relationship between the flexor digitorum longus and sustentaculum tali for reconsideration of the talocalcaneonavicular joint stability mechanism

The talocalcaneonavicular joint (TCN-j) is supported by the spring ligament, which has recently been revealed to be part of the joint capsule complex, along with the tendinous sheath of the tibialis posterior and flexor digitorum longus (FDL). Nonetheless, the FDL’s role in TCN-j stability has received limited attention. This study aimed to elucidate the positional relationships between the FDL and sustentaculum tali, which comprises the TCN-j. We hypothesized that the FDL runs medial to the sustentaculum tali, and its course significantly changes from the sitting to the standing position. Six ankles from six body donors were investigated, and seven ankles from seven volunteers were assessed using ultrasonography. The FDL was three-dimensionally located inferomedial to the sustentaculum tali. The FDL tendinous sheath was attached to the sustentaculum tali or connected by the tibialis posterior via the tendinous sheath. Based on the in vivo ultrasound image, the FDL location relative to the sustentaculum tali was maintained; however, the curvature of the FDL course was significantly more prominent in standing than in sitting. The FDL force against the bending moment may prevent the excessive eversion of the foot and aid the conventional spring ligament’s contribution to TCN-j stability for maintaining the longitudinal arch.

A rare bifurcation of the external iliac artery into femoral and deep femoral arteries

The current cadaveric report describes a quite rare unilateral bifurcation of the external iliac artery (EIA) into two femoral arteries (FAs) of almost equal diameter and parallel course, at the level of the inguinal ligament (IL). The variant FAs were identified on a 75-year-old formalin-embalmed female cadaver, derived from a body donation program after a signed informed consent. The EIA bifurcated into a FA and a deep femoral artery (DFA). The DFA extremely high origin was identified at the IL level. Both lateral and medial circumflex femoral arteries originated from the DFA. The in-depth knowledge of the FA variant origin is of paramount importance to vascular surgeons and interventional radiologists during vessel catheterization and attempts to interpret the angiographic findings. In particular, the DFA's high origin from the EIA and the coexistence of two FAs in a parallel course may pose problems to clinicians during angiographic procedures leading to diagnostic errors. The DFA high origin may also complicate femoral arterial and venous puncture and femoral nerve blocks, due to the close neurovascular relationship. There is a possibility for the FA to be mistaken for a vein leading to accidental intra-arterial injection and consequently thrombosis. Thus, variable arterial pattern is important to be identified preoperatively using Doppler ultrasound imaging.

Brain Donation Decisions as Disease Specific Behaviors: An Elucidation of the Donation Process in the Context of Essential Tremor.

Brain donation is a challenging process, comprising four sequential stages: (1) the brain donation decision, (2) pre-mortem arrangements and follow up, (3) specimen collection and (4) tissue processing. It is important to understand the factors that are pertinent to each stage. Currently, there is extensive information on factors that involve donor’s personal and cultural backgrounds and how these could affect the process. However, little is known about disease-specific factors that influence the process. The Essential Tremor Centralized Brain Repository was established in 2003, and after nearly 20 years of collecting essential tremor (ET) brain tissue, we are well-positioned to discuss the brain donation process from a disease-specific standpoint. In the current manuscript, we discuss ET disease-specific factors that influence the first two stages of the brain donation process. We center our discussion around three points: (1) factors that influence the patient’s decision to donate, (2) the involvement of next of kin in the donation, and (3) the rationale for enrolling patients prospectively and evaluating them longitudinally before the anatomical gift takes place. This discussion shares our understanding of the background from which our repository operates and may be of value for other brain banks that study similar neurodegenerative diseases.

Negotiating humanity: an ethnography of cadaver-based simulation.

Human body donation (HBD) serves an essential function in many medical schools, particularly in institutions where people engage in cadaver-based simulation (CBS) as a pedagogical approach. The people who facilitate HBD and CBS have a highly specialized skill set, yet their expertise remains largely unacknowledged, and takes place out of sight from the broader medical school community. This manuscript, based on a two-year practice-based ethnography (Structured Observations n = 68 h, Unstructured Observations n = 150 + hours; Interviews n = 24; and Document/Policy Analysis n = 14) illuminates the complex work of HBD. We identify three primary functions of HBD and CBS (1. Cadaver Intake & Administration, 2. Cadaver Preparation, and 3. Cadaver-Based Pedagogy). We describe how medical educators involved in CBS have developed a skillset specific to their role: negotiating humanity.