The comparative and functional anatomy of the forelimb muscle architecture of Humboldt's woolly monkey (Lagothrix lagotricha).

Humboldt's woolly monkey (Lagothrix lagortricha) is a ceboid primate that more frequently engages in plantigrade quadrupedalism (~89%) but is, like most other members of the subfamily Atelinae, capable of suspensory postures and "tail assisted" brachiation. That taxon's decreased reliance on suspension is reflected in the skeletal anatomy of the upper limb which is less derived relative to more frequently suspensory atelines (Ateles, Brachyteles) but is in many ways (i.e., phalangeal curvature, enlarged joint surfaces, elongated diaphyses) intermediate between highly suspensory and quadrupedal anthropoids. Although it has been suggested that muscle may have morphogenetic primacy with respect to bone this has not been explicitly tested. The present study employs analyses of Lagothrix upper limb muscle fiber length, relative physiological cross-sectional area and relative muscle mass to test whether muscular adaptations for suspensory postures and locomotion in Lagothrix precede adaptive refinements in the skeletal tissues or appear more gradually in conjunction with related skeletal adaptations. Results demonstrate that Lagothrix upper limb musculature is most like committed quadrupeds but that limited aspects of the relative distribution of segmental muscle mass may approach suspensory hylobatids consistent with only a limited adaptive response in musculature prior to bone. Results specific to the shoulder were inconclusive owing to under-representation of quadrupedal shoulder musculature and future work should be focused more specifically on the adaptive and functional morphology of the muscular anatomy and microstructure of the scapulothoracic joint complex.

Dental tissue changes in juvenile and adult mice with osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a disorder of type I collagen, causes skeletal deformities as well as defects in dental tissues, which lead to increased enamel wear and smaller teeth with shorter roots. Mice with OI exhibit similar microstructural dentin changes, including reduced dentin tubule density and dentin cross-sectional area. However, the effects of these mutations on gross dental morphology and dental tissue volumes have never been characterized in the osteogenesis imperfecta murine (OIM) mouse model. Here we compare mineralized dental tissue measurements of OIM mice and unaffected wild type (WT) littermates at the juvenile and adult stages. The maxillary and mandibular incisors and first molars were isolated from microCT scans, and tissue volumes and root length were measured. OIM mice have smaller teeth with shorter roots relative to WT controls. Maxillary incisor volumes differed significantly between OIM and WT mice at both the juvenile and young adult stage, perhaps due to shortening of the maxilla itself in OIM mice. Additionally, adult OIM mice have significantly less crown enamel volume than do juveniles, potentially due to loss through wear. Thus, OIM mice demonstrate a dental phenotype similar to humans with OI, with decreased tooth size, decreased root length, and accelerated enamel wear. Further investigation of dental development in the OIM mouse may have important implications for the development and treatment of dental issues in OI patients.

Neurocranial growth in the OIM mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation. The OI craniofacial phenotype includes midfacial underdevelopment, as well as neurocranial changes (e.g., macrocephaly and platybasia) that may also affect underlying nervous tissues. This study aims to better understand how OI affects the integrated development of the neurocranium and the brain. Juvenile and adult mice with OI (OIM) and unaffected wild type (WT) littermates were imaged using in vivo micro-computed tomography (microCT). Virtual endocast models were used to measure brain volume, and 3D landmarks were collected from the cranium and brain endocasts. Geometric morphometric analyses were used to compare brain shape and integration between the genotypes. OIM mice had increased brain volumes (relative to cranial centroid size) only at the juvenile stage. No significant difference was seen in cranial base angle (CBA) between OIM and WT mice. However, CBA was higher in juvenile than in adult OIM mice. Brain shape was significantly different between OIM and WT mice at both stages, with OIM mice having more globular brains than WT mice. Neurocranial and brain morphology were strongly integrated within both genotypes, while adult OIM mice tended to have lower levels of skull-brain integration than WT mice. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Decreased skull-brain integration in adult mice suggests that compensatory mechanisms may exist during postnatal growth to maintain neurological function despite significant changes in neurocranial morphology.

Morphological variability in the inner ear of mice with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is known to cause hearing loss in ~60% of the affected human population. While OI-related pathologies have been studied in the middle ear, the development of cochlear pathologies is less well understood. In this study, we examine OI-related pathologies of the cochlea in a mouse model of OI to (1) document variation between OI and unaffected mice, and (2) assess the intrusion of the otic capsule onto the cochlea by analyzing differences in duct volumes. Juvenile and adult OIM C57BL/6mice were compared to unaffected wildtype (WT) mice using three-dimensional models of the cochlea generated from high resolution micro-CT scans. Two-tailed Mann-Whitney U tests were then used to investigate duct volume differences both within and between the OI and WT samples. Areas of higher ossification were observed at the cochlear base in the OI sample. OI mice also had significant intraindividual differences in duct volume between right and left ears (4%-15%), an effect not observed in WT mice. WT and OI duct volumes showed a large degree of overlap, although the OIM volumes were more variable. Our findings indicate that OIM mice are likely to exhibit more asymmetry and variation in cochlear volume despite minor differences in sample cochlear volumes, possibly due to bony capsule intrusion. This suggests a potential mechanism of hearing loss, and a high potential for cochlear and otic capsule alteration in OIM mice.

First patient project: Engaging pathology through the donor dissection experience and its role in professionalism.

The peer-reviewed anatomical education literature thoroughly describes the benefits and drawbacks of donor dissection. Gross anatomy laboratory environments utilizing donor dissection are generally considered to be a premier environment where students foster non-traditional discipline-independent skills (NTDIS), including the acquisition of professionalism, empathy, resilience, emotional intelligence, and situational awareness. Therefore, this IRB-approved study explored the impact of a formal humanism and pathology thread, the first patient project (FPP), on the personal and professional development of pre-professional undergraduate students in a gross anatomy dissection-based course. Five reflections from each student were collected across four cohorts (n = 74 students, 370 reflections). A post-course questionnaire collected data on student perceptions of the project. The framework method was used to analyze reflection and free response data and descriptive statistics were performed on Likert-style items using Excel. Three themes were identified to encompass the impacts of the FPP on professional development and include: Socialization (through collective dissection experience and pathology), Humanistic Qualities (respect for the donor and their history, and introspection), and Content and Skills (technical and NTDIS, anatomical knowledge). The end of course FPP survey was completed by 29 students across three cohorts (65%) and their perspectives were generally favorable regarding the promotion of respect, empathy, and humanization of their donors. This study underscores the value of incorporating humanism, pathology, and reflection, facilitated through formal curriculum for pre-professional undergraduate students. It provides evidence of the positive impact on their personal and professional development, supporting the integration of NTDIS in curricula across various disciplines.

Science Communication and Biomedical Visualization: Two Sides of the Same Coin.

Biomedical visualization has a long history as a tool for education around public health. However, recent advances in our understanding of how to be more effective at communicating complex scientific ideas to a public audience necessitate a re-examination of approaches to biomedical visualization. Scientific knowledge has expanded dramatically in the twenty-first century, as has its availability beyond the scientific arena. This chapter briefly discusses the historical approaches in biomedical visualization from the perspective of Western public health. It also outlines the approach that biomedical visualization should take according to best practices in effective science communication.

"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.

Anatomy Nights: An international public engagement event increases audience knowledge of brain anatomy.

Anatomy Nights is an international public engagement event created to bring anatomy and anatomists back to public spaces with the goal of increasing the public's understanding of their own anatomy by comparison with non-human tissues. The event consists of a 30-minute mini-lecture on the anatomy of a specific anatomical organ followed by a dissection of animal tissues to demonstrate the same organ anatomy. Before and after the lecture and dissection, participants complete research surveys designed to assess prior knowledge and knowledge gained as a result of participation in the event, respectively. This study reports the results of Anatomy Nights brain events held at four different venues in the UK and USA in 2018 and 2019. Two general questions were asked of the data: 1) Do participant post-event test scores differ from pre-event scores; and 2) Are there differences in participant scores based on location, educational background, and career. We addressed these questions using a combination of generalized linear models (R's glm function; R version 4.1.0 [R Core Team, 2014]) that assumed a binomial distribution and implemented a logit link function, as well as likelihood estimates to compare models. Survey data from 91 participants indicate that scores improve on post-event tests compared to pre-event tests, and these results hold irrespective of location, educational background, and career. In the pre-event tests, participants performed well on naming structures with an English name (frontal lobe and brainstem), and showed signs of improvement on other anatomical names in the post-test. Despite this improvement in knowledge, we found no evidence that participation in Anatomy Nights improved participants' ability to apply this knowledge to neuroanatomical contexts (e.g., stroke).

Evolution of a discipline-The changing face of anatomy.

This special issue is unlike any other special issue published in this journal's history. You will not find the types of original research in anatomy and evolutionary biology that you are accustomed to seeing adorning the pages of The Anatomical Record. Instead, the articles included cover the past and future of the discipline of anatomy broadly and of the American Association for Anatomy (AAA) more narrowly, and through two specific rhetorical frames: ethics; and diversity, equity, and inclusion. The articles in this issue are divided into two sections. The first section traces the history of anatomy and addresses many of the ethical dilemmas we face as a result of that history. The second section sets the stage for how the discipline and the AAA move forward to create a more diverse, equitable, and inclusive future for students, teachers, colleagues, and everyone else we touch through our work as anatomists. While this is only the beginning of our reconciliation with our past, the future certainly looks bright.

It is essential to connect: Evaluating a Science Communication Boot Camp.

Scientific knowledge has expanded dramatically in the 21st century. Yet, even in science where there is large consensus among the studies-evolution by natural selection, for example, or the human basis of accelerated climate change-the public and policymakers are not always in agreement with the science. To bridge this gap, scientists and educators need to connect and engage with diverse audiences with varying levels of science literacy. Communication scholars have identified several effective tactics to communicate effectively with non-specialist audiences. However, our sometimes-siloed thinking in science and higher education discourages sharing this knowledge across disciplinary lines. Furthermore, many training programs focus on educating about which communication strategies work, but they fail to provide participants with the opportunity to develop the skills required to listen effectively and respond in an engaging way. To that end, we created the Science Communication Boot Camp (SCBC) with support from an American Association for Anatomy innovations grant. The 3-day program engaged and immersed participants in training designed to develop audience-centered communication, distill scientific concepts into meaningful narratives, and connect effectively with the public, collaborators, and policymakers. Based on participant surveys at three timepoints (preworkshop, postworkshop, and 2-year follow-up), the SCBC was effective in helping participants to increase their communication skills and willingness to engage with the public and other non-specialist audiences.

Craniofacial allometry in the OIM-/- mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a skeletal disorder characterized by the impaired synthesis of type I collagen (Col1). This study tests the hypothesis that the craniofacial phenotype of severe OI is linked to an overall reduction in body size. 3D landmark data were collected from µCT scans of adult OIM-/- and wild-type (WT) mice and used to calculate centroid sizes (CS) and interlandmark distances (ILDs). To remove the effect of body size, ILDs were scaled against craniomandibular lengths and CS. Mann-Whitney U tests were used to compare CS and absolute/scaled ILDs between genotypes. OIM-/- mice are smaller than their WT littermates in body mass, craniomandibular CS, and absolute ILDs including skull, basicranial, palatal, mandibular, and toothrow lengths. When linear distances are scaled to CS, OIM-/- mice have a relatively short midface, short nasal bones, tall mandibular corpora, and long mandibular toothrows. Results underscore the importance of size and scaling in morphometric analyses. The deleterious effect of Col1 mutations on global skeletal dimensions combined with localized morphometric changes may underlie the facial phenotype seen in human patients with severe OI. Attempts to identify these localized changes should first account for the restricted growth and small body sizes present in individuals with OI.

Investigating Student Perceptions of a Dissection-Based Undergraduate Gross Anatomy Course Using Q Methodology.

The demand for upper-level undergraduate dissection-based anatomy courses is growing, as professional programs require more advanced anatomy training prior to matriculation. To address this need, Indiana University School of Medicine (IUSM) partnered with Indiana University-Purdue University Indianapolis-a large, urban, life science-focused campus nearby to IUSM-to offer an undergraduate, dissection-based course in regional gross anatomy. Because this is a new course, a deeper post-course evaluation of student perceptions was conducted using Q methodology. In this study, Q methodology was used to evaluate student views of the overall course structure, pre-laboratory materials and activities, assessments, and quality of instruction. Of the 15 students in the spring semester 2018 cohort, 80% (n = 12) participated in the evaluation, and 10 of those students followed up with written explanations for their rationale in selecting the four statements with which they most strongly agreed and disagreed. The Q methodology sorted the students into one of three statistically significant groups: Motivated Dissectors (n = 6), Traditional Students (n = 3), and Inspired Learners (n = 3). Motivated Dissectors and Inspired Learners felt strongly that the course did not encourage self-directed learning and that the pre-laboratory materials were not adequate to prepare them for quizzes. Traditional Students, however, disagreed, having a favorable opinion of the pre-laboratory materials, even though this group felt most strongly that the amount of material covered in the course was overwhelming. This study demonstrates the utility of Q methodology to evaluate courses to elucidate student perspectives and inform future course modifications.

Muscle contraction induces osteogenic levels of cortical bone strain despite muscle weakness in a mouse model of Osteogenesis Imperfecta.

Mechanical interactions between muscle and bone have long been recognized as integral to bone integrity. However, few studies have directly measured these interactions within the context of musculoskeletal disease. In this study, the osteogenesis imperfecta murine model (oim/oim) was utilized because it has both reduced bone and muscle properties, allowing direct assessment of whether weakened muscle is able to engender strain on weakened bone. To do so, a strain gauge was attached to the tibia of healthy and oim/oim mice, muscles within the posterior quadrant of the lower hind limb were stimulated, and bone strain during muscle contraction was measured. Results indicated that the relationship between maximum muscle torque and maximum engendered strain is altered in oim/oim bone, with less torque required to engender strain compare to wild-type and heterozygous mice. Maximum muscle torque at 150 Hz stimulation frequency was able to engender ~1500 µÉ› in oim/oim animals. However, even though the strain engendered in the oim/oim mice was high relative to historical bone formation thresholds, the maximum strain values were still significantly lower than that of the wild-type mice. These results are promising in that they suggest that muscle stimulation may be a viable means of inducing bone formation in oim/oim and potentially other disease models where muscle weakness/atrophy exist.

Mouse Hind Limb Skeletal Muscle Functional Adaptation in a Simulated Fine Branch Arboreal Habitat.

The musculoskeletal system is remarkably plastic during growth. The purpose of this study was to examine the muscular plasticity in functional and structural properties in a model known to result in significant developmental plasticity of the postcranial skeleton. Fifteen weanling C57BL/6 mice were raised to 16 weeks of age in one of two enclosures: a climbing enclosure that simulates a fine branch arboreal habitat and is traversed by steel wires crossing at 45° relative to horizontal at multiple intersections, and a control enclosure that resembles a parking deck with no wires but the same volume of habitable space. At killing, ex vivo contractility properties of the soleus (SOL) and extensor digitorum longus (EDL) muscles were examined. Our results demonstrate that EDL muscles of climbing mice contracted with higher specific forces and were comprised of muscle fibers with slower myosin heavy chain isoforms. EDL muscles also fatigued at a higher rate in climbing mice compared to controls. SOL muscle function is not affected by the climbing environment. Likewise, mass and architecture of both EDL and SOL muscles were not different between climbing and control mice. Our data demonstrate that functional adaptation does not require concomitant architectural adaptation in order to increase contractile force. Anat Rec, 301:434-440, 2018. © 2018 Wiley Periodicals, Inc.

Ontogeny of hallucal metatarsal rigidity and shape in the rhesus monkey (Macaca mulatta) and chimpanzee (Pan troglodytes).

Life history variables including the timing of locomotor independence, along with changes in preferred locomotor behaviors and substrate use during development, influence how primates use their feet throughout ontogeny. Changes in foot function during development, in particular the nature of how the hallux is used in grasping, can lead to different structural changes in foot bones. To test this hypothesis, metatarsal midshaft rigidity [estimated from the polar second moment of area (J) scaled to bone length] and cross-sectional shape (calculated from the ratio of maximum and minimum second moments of area, Imax /Imin ) were examined in a cross-sectional ontogenetic sample of rhesus macaques (Macaca mulatta; n = 73) and common chimpanzees (Pan troglodytes; n = 79). Results show the hallucal metatarsal (Mt1) is relatively more rigid (with higher scaled J-values) in younger chimpanzees and macaques, with significant decreases in relative rigidity in both taxa until the age of achieving locomotor independence. Within each age group, Mt1 rigidity is always significantly higher in chimpanzees than macaques. When compared with the lateral metatarsals (Mt2-5), the Mt1 is relatively more rigid in both taxa and across all ages; however, this difference is significantly greater in chimpanzees. Length and J scale with negative allometry in all metatarsals and in both species (except the Mt2 of chimpanzees, which scales with positive allometry). Only in macaques does Mt1 midshaft shape significantly change across ontogeny, with older individuals having more elliptical cross-sections. Different patterns of development in metatarsal diaphyseal rigidity and shape likely reflect the different ways in which the foot, and in particular the hallux, functions across ontogeny in apes and monkeys.

Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

Glucocorticoids Induce Bone and Muscle Atrophy by Tissue-Specific Mechanisms Upstream of E3 Ubiquitin Ligases.

Glucocorticoid excess, either endogenous with diseases of the adrenal gland, stress, or aging or when administered for immunosuppression, induces bone and muscle loss, leading to osteopenia and sarcopenia. Muscle weakness increases the propensity for falling, which, combined with the lower bone mass, increases the fracture risk. The mechanisms underlying glucocorticoid-induced bone and muscle atrophy are not completely understood. We have demonstrated that the loss of bone and muscle mass, decreased bone formation, and reduced muscle strength, hallmarks of glucocorticoid excess, are accompanied by upregulation in both tissues in vivo of the atrophy-related genes atrogin1, MuRF1, and MUSA1. These are E3 ubiquitin ligases traditionally considered muscle-specific. Glucocorticoids also upregulated atrophy genes in cultured osteoblastic/osteocytic cells, in ex vivo bone organ cultures, and in muscle organ cultures and C2C12 myoblasts/myotubes. Furthermore, glucocorticoids markedly increased the expression of components of the Notch signaling pathway in muscle in vivo, ex vivo, and in vitro. In contrast, glucocorticoids did not increase Notch signaling in bone or bone cells. Moreover, the increased expression of atrophy-related genes in muscle, but not in bone, and the decreased myotube diameter induced by glucocorticoids were prevented by inhibiting Notch signaling. Thus, glucocorticoids activate different mechanisms in bone and muscle that upregulate atrophy-related genes. However, the role of these genes in the effects of glucocorticoids in bone is unknown. Nevertheless, these findings advance our knowledge of the mechanism of action of glucocorticoids in the musculoskeletal system and provide the basis for novel therapies to prevent glucocorticoid-induced atrophy of bone and muscle.