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BACKGROUND: We previously determined a nonlinear relationship between connexin 43 (Cx43) function and craniofacial phenotypic variation in the mutant mouse model G60S/+, and that this variation was driven by nasal bone deviation. While nonlinearities in the genotype-phenotype map appear to be common, few studies have looked at the developmental processes that underlie this nonlinearity. Here, we investigated the potential tissue-level developmental determinants of the variation in nasal bone phenotype in G60S/+ mice through postnatal development. RESULTS: The deviated nasal bone phenotype arises by postnatal day 21 and becomes more severe by 3 months in G60S/+ mice. Measures of nasal bone remodeling including the number of osteoclasts, mineralizing surface, mineral apposition rate, and bone formation rate are significantly greater in G60S/+ mice compared to wild-type mice at 2 months, but these differences do not correspond with nasal bone deviation. The degree of nasal bone deviation does significantly and negatively correlate with the ratio between nasal bone and cartilaginous nasal septum length. CONCLUSIONS: Our findings indicate that the mean phenotypic changes observed between G60S/+ and wild-type mice are due to reduced bone growth, but the increased phenotypic variation found within mutant mice is due to discordant growth between nasal cartilage and bone.
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Cartilagens Nasais , Crânio , Camundongos , Animais , Septo Nasal , FenótipoRESUMO
PURPOSE: Although several different contouring instructional programs are available to radiation oncologists and trainees, very little is known about which methods and resources benefit learners most, and whether some learners may need alternate forms of instruction. This study aimed to determine the factors that were predictors of learners' success in anatomy, radiology, and contouring education. METHODS AND MATERIALS: Participants in the online and face-to-face Anatomy and Radiology Contouring (ARC) Bootcamp completed pre- and postintervention evaluations that assessed anatomy/radiology knowledge, contouring skills, self-confidence, and spatial ability. Baseline factors were assessed as predictors of outcomes across multiple educational domains. RESULTS: One hundred and eighty (face-to-face: n = 40; online: n = 140) participants enrolled in the ARC Bootcamp, and 57 (face-to-face: n = 30; online: n = 27) participants completed both evaluations. Of the participants enrolled, 37% were female, and most were radiation oncology residents (62%). In the anatomy/radiology knowledge testing, all quartiles (based on baseline performance) improved numerically; however, the largest improvements occurred in learners with the lowest baseline scores (P < .001). At the end of the Bootcamp, learners with lower-performing scores did not reach the level of learners with the highest baseline scores (Bonferroni-corrected P < .001). Regarding the contouring assessment, improvements were only evident for the participants with lower-performing baseline scores (P < .05). Spatial anatomy skills, as measured by the spatial anatomy task, were correlated to contouring ability. Overall, the greatest improvements were seen for learners in postgraduate year 1 to 3, those with no previous rotation experience in a given discipline, and those who attended from other programs (ie, medical physics residents and medical students). CONCLUSIONS: The ARC Bootcamp improved all levels of performers' anatomy and radiology knowledge but only lower-performers' contouring ability. The course alone does not help lower-performing learners reach the abilities of higher-performers. The ARC Bootcamp tends to be most beneficial for participants with less radiation oncology experience. Curriculum modifications can be made to help support ARC Bootcamp participants with lower performing scores.
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Internato e Residência , Radioterapia (Especialidade) , Radiologia , Feminino , Humanos , Masculino , Radioterapia (Especialidade)/educação , Avaliação Educacional , Radiologia/educação , Currículo , RadiografiaRESUMO
PURPOSE: The Anatomy and Radiology Contouring (ARC) Bootcamp was a face-to-face (F2F) intervention providing integrated education for radiation oncology (RO) residents and medical physicists. To increase access, we launched an online offering in 2019. We evaluated the effect of the online course on participants' knowledge acquisition, contouring skills, and self-confidence by comparing it with the F2F course. METHODS AND MATERIALS: Using modules, the online course offers content similar to that of the F2F comparator. Participants from the 2019 F2F and the 2019-2020 online course completed pre- and postevaluations assessing anatomy and radiology knowledge, contouring skills, self-confidence, and course satisfaction. RESULTS: There were 180 individuals enrolled (F2F: n = 40; online: n = 140); 57 participants (F2F: n = 30; online: n = 27) completed both evaluations. The online course had a wider geographic participation (19 countries) than F2F (4 countries). F2F had primarily RO resident participation (80%), compared with online (41%). Both cohorts demonstrated similar improvements in self-confidence pertaining to anatomy and radiology knowledge, contouring skills, and interpreting radiology images (all P < .001). Both the online (mean ± SD improvement: 6.6 ± 6.7 on a 40-point scale; P < .001) and F2F (3.7 ± 5.7; P = .002) groups showed anatomy and radiology knowledge improvement. Only the F2F group demonstrated improvement with the contouring assessment (F2F: 0.10 ± 0.17 on a 1-point Dice scale; P = .004; online: 0.07 ± 0.16; P = .076). Both cohorts perceived the course as a positive experience (F2F: 4.8 ± 0.4 on a 5-point scale; online: 4.5 ± 0.6), stated it would improve their professional practice (F2F: 4.6 ± 0.5; online: 4.2 ± 0.8), and said they would recommend it to others (F2F: 4.8 ± 0.4; online: 4.4 ± 0.6). CONCLUSIONS: The online ARC Bootcamp demonstrated improved self-confidence, knowledge scores, and high satisfaction levels among participants. The offering had lower completion rates but was more accessible to geographic regions, provided a flexible learning experience, and allowed for ongoing education during the COVID-19 pandemic.
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Educação a Distância , Radioterapia (Especialidade)/educação , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: As new treatments and technologies have been introduced in radiation oncology, the clinical roles of radiation therapists (RTs) have expanded. However, there are few formal learning opportunities for RTs. An online, anatomy, radiology and contouring bootcamp (ARC Bootcamp) originally designed for medical residents was identified as a prospective educational tool for RTs. The purpose of this study was to evaluate an RT edition of the ARC Bootcamp on knowledge, contouring, and confidence, as well as to identify areas for future modification. METHODS: Fifty licensed RTs were enrolled in an eight-week, multidisciplinary, online RT ARC Bootcamp. Contouring practice was available throughout the course using an online contouring platform. Outcomes were evaluated using a pre-course and post-course multiple-choice quiz (MCQ), contouring evaluation and qualitative self-efficacy and satisfaction survey. RESULTS: Of the fifty enrolled RTs, 30 completed the course, and 26 completed at least one of the post-tests. Nineteen contouring dice similarity coefficient (DSC) scores were available for paired pre- and post-course analysis. RTs demonstrated a statistically significant increase in mean DSC scoring pooled across all contouring structures (mean ± SD improvement: 0.09 ± 0.18 on a scale from 0 to 1, p=0.020). For individual contouring structures, 3/15 reached significance in contouring improvement. MCQ scores were available for 26 participants and increased after RT ARC Bootcamp participation with a mean ± SD pre-test score of 18.6 ± 4.2 (46.5%); on a 40-point scale vs. post-test score of 24.5 ± 4.3 (61.4%) (p < 0.001). RT confidence in contouring, anatomy knowledge and radiographic identification improved after course completion (p < 0.001). Feedback from RTs recommended more contouring instruction, less in-depth anatomy review and more time to complete the course. CONCLUSIONS: The RT ARC Bootcamp was an effective tool for improving anatomy and radiographic knowledge among RTs. The course demonstrated improvements in contouring and overall confidence. However, only approximately half of the enrolled RTs completed the course, limiting statistical power. Future modifications will aim to increase relevance to RTs and improve completion rates.
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Radiologia , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: The Anatomy and Radiology Contouring (ARC) Bootcamp was a face-to-face (F2F) course designed to ensure radiation oncology residents were equipped with the knowledge and skillset to use radiation therapy techniques properly. The ARC Bootcamp was proven to be a useful educational intervention for improving learners' knowledge of anatomy and radiology and contouring ability. An online version of the course was created to increase accessibility to the ARC Bootcamp and provide a flexible, self-paced learning environment. This study aimed to describe the instructional design model used to create the online offering and report participants' motivation to enroll in the course and the online ARC Bootcamp's strengths and improvement areas. METHODS: The creation of the online course followed the analysis, design, development, implementation, and evaluation (ADDIE) framework. The course was structured in a linear progression of locked modules consisting of radiology and contouring lectures, anatomy labs, and integrated evaluations. RESULTS: The online course launched on the platform Teachable in November 2019, and by January 2021, 140 participants had enrolled in the course, with 27 participants completing all course components. The course had broad geographic participation with learners from 19 different countries. Of the participants enrolled, 34% were female, and most were radiation oncology residents (56%), followed by other programs (24%), such as medical physics residents or medical students. The primary motivator for participants to enroll was to improve their subject knowledge/skill (44%). The most common strength identified by participants was the course's quality (41%), and the most common improvement area was to incorporate more course content (41%). CONCLUSIONS: The creation of the online ARC Bootcamp using the ADDIE framework was feasible. The course is accessible to diverse geographic regions and programs and provides a flexible learning environment; however, the course completion rate was low. Participants' feedback regarding their experiences will inform future offerings of the online course.
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BACKGROUND: We compared skull shape and variation among genetically modified mice that exhibit different levels of connexin43 (Cx43) channel function, to determine whether Cx43 contributes to craniofacial phenotypic robustness. Specifically, we used two heterozygous mutant mouse models (G60S/+ and I130T/+) that, when compared to their wildtype counterparts, have an ~80% and ~50% reduction in Cx43 function, respectively. RESULTS: Both mutant strains showed significant differences in skull shape compared to wildtype littermates and while these differences were more severe in the G60S/+ mouse, shape differences were localized to similar regions of the skull in both mutants. However, increased skull shape variation was observed in G60S/+ mutants only. Additionally, covariation of skull structures was disrupted in the G60S/+ mutants only, indicating that while a 50% reduction in Cx43 function is sufficient to cause a shift in mean skull shape, the threshold for Cx43 function for disrupting craniofacial phenotypic robustness is lower. CONCLUSIONS: Collectively, our results indicate Cx43 can contribute to phenotypic robustness of the skull through a nonlinear relationship between Cx43 gap junctional function and phenotypic outcomes.
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Conexina 43/fisiologia , Dureza/fisiologia , Crânio/fisiologia , Animais , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Tamanho do Órgão/genética , Fenótipo , Gravidez , Crânio/anatomia & histologia , Crânio/diagnóstico por imagemRESUMO
BACKGROUND: Prenatal alcohol exposure (PAE) can result in developmental defects that include growth restriction, craniofacial anomalies, and cognitive behavioral deficits, though the presence and severity of these adverse outcomes can vary dramatically among exposed individuals. Preclinical animal models have demonstrated that the dose and timing of PAE account for much, but not all, of this phenotypic variation, suggesting that additional factors mitigate the effects of PAE. Here, we used a mouse model to investigate whether maternal age modulates the effects of PAE on the severity and variation in offspring growth and craniofacial outcomes. METHODS: Nulliparous C57BL/6N dams received either an intraperitoneal injection of ethanol (EtOH) or vehicle solution on gestational day 7.5. Dams were divided into four groups: (1) EtOH-treated young dams (6 to 10 weeks); (2) control young dams; (3) EtOH-treated old dams (6 to 7 months); and (4) old control dams. Neonate offspring growth restriction was measured through body mass and organ-to-body mass ratios, while skeletal craniofacial features were imaged using micro-CT and analyzed for size, shape, and variation. RESULTS: PAE and advanced maternal age each increased the risk of low birthweight and growth restriction in offspring, but these factors in combination changed the nature of the growth restriction. Similarly, both PAE and advanced maternal age individually caused changes to craniofacial morphology such as smaller skull size, dysmorphic skull shape, and greater skull shape variation and asymmetry. Interestingly, while the combination of PAE and advanced maternal age did not affect mean skull shape or size, it significantly increased the variation and asymmetry of those measures. CONCLUSION: Our results indicate that maternal age modulates the effects of PAE, but that the effects of this combination on offspring outcomes are more complex than simply scaling the effects of either factor.
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Animais Recém-Nascidos/crescimento & desenvolvimento , Etanol/administração & dosagem , Etanol/efeitos adversos , Ossos Faciais/patologia , Idade Materna , Crânio/patologia , Animais , Peso ao Nascer/efeitos dos fármacos , Índice de Massa Corporal , Anormalidades Craniofaciais/induzido quimicamente , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-NatalRESUMO
PURPOSE: Simulation-based medical education is an effective tool for medical teaching, but simulation-based medical education deployment in radiation oncology (RO) is limited. Flexible nasopharyngoscopy (FNP), an essential skill for RO residents, requires practice that typically occurs on volunteer patients, introducing the potential for stress and discomfort. We sought to develop a high-fidelity simulator and intervention that provides RO residents the opportunity to develop FNP skills in a low-pressure environment. METHODS AND MATERIALS: Computed tomography images were used to create an anatomically accurate 3-dimensional-printed model of the head and neck region. An intervention incorporating didactic instruction, multimedia content, and FNP practice on the model was designed and administered to RO residents attending the Anatomy and Radiology Contouring Bootcamp. Participants completed pre- and postintervention evaluations of the training session and model fidelity, and self-assessments of FNP skill and confidence performing FNP. Participants were video recorded performing FNP pre- and postintervention. Videos were scored by a blinded observer on a predefined rubric. Changes in scores were evaluated using the Wilcoxon signed-rank test. RESULTS: Twenty-four participants from 17 institutions and 4 countries completed the intervention, 50% were women, and most were senior residents. Postintervention, FNP confidence and FNP performance improved significantly (mean ± standard deviation on a 10-point scale: 1.8 ± 1.8, P < .001; 2.2 ± 2.0, P < .001, respectively). Participants felt the model was helpful (mean ± standard deviation on a 5-point scale: 4.2 ± 0.6), anatomically correct (4.1 ± 0.9), and aided in spatial comprehension (4.3 ± 0.8). Overall satisfaction for the intervention was high (4.3 ± 0.8). Participants strongly agreed the intervention should be integrated into RO training programs (4.3 ± 0.8). CONCLUSIONS: A 3-dimensional-printed model and associated intervention were effective at improving FNP performance and the teaching method was rated highly by participants. RO residents may benefit from broader dissemination of this technique to improve trainee performance.
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Cabeça , Internato e Residência , Modelos Anatômicos , Nariz/cirurgia , Faringe/cirurgia , Impressão Tridimensional , Radioterapia (Especialidade)/educação , Humanos , Nariz/anatomia & histologia , Faringe/anatomia & histologiaRESUMO
BACKGROUND & OBJECTIVES: Radical inguinal lymph node dissections (rILND) for penile cancer risk significant postoperative lymphocele and lymphedema. However, reducing the risk of lymphatic complications is limited by our understanding of lymphatic anatomy. Therefore, this study aims to elucidate the lymphatic anatomy within the current surgical borders of a rILND. METHODS: To visualize the position of the lymph nodes, tissue packets excised from the inguinal region of five fresh, male cadavers were imaged using microcomputed tomography (µCT). To standardize the position, rotation and size between specimens, each lymph node packet was aligned using a Generalized Procrustes analysis. RESULTS: There was a median of 13.5 lymph nodes (range = 8-18) per packet, with the majority (99%) clustered within a 6 cm radius of the saphenofemoral junction; a region 39%-41% smaller than current surgical borders. No difference existed between the number of nodes between sides, or distribution around the saphenofemoral junction. CONCLUSIONS: This study provides the first 3D, in situ, standardized characterization of lymph node anatomy in the inguinal region using µCT. By using knowledge of the normal lymphatic anatomy, this study can help inform the reduction in borders of rILND to limit disruption and ensure a complete lymphadenectomy.
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Canal Inguinal/patologia , Canal Inguinal/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Neoplasias Penianas/patologia , Neoplasias Penianas/cirurgia , Idoso , Cadáver , Seguimentos , Humanos , Canal Inguinal/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Masculino , Neoplasias Penianas/diagnóstico por imagem , Prognóstico , Microtomografia por Raio-XRESUMO
Mutations in the gene encoding the gap-junctional protein connexin43 (Cx43) are the cause of the human disease oculodentodigital dysplasia (ODDD). The mandible is often affected in this disease, with clinical reports describing both mandibular overgrowth and conversely, retrognathia. These seemingly opposing observations underscore our relative lack of understanding of how ODDD affects mandibular morphology. Using two mutant mouse models that mimic the ODDD phenotype (I130T/+ and G60S/+), we sought to uncover how altered Cx43 function may affect mandibular development. Specifically, mandibles of newborn mice were imaged using micro-CT, to enable statistical comparisons of shape. Tissue-level comparisons of key regions of the mandible were conducted using histomorphology, and we quantified the mRNA expression of several cartilage and bone cell differentiation markers. Both G60S/+ and I130T/+ mutant mice had altered mandibular morphology compared to their wildtype counterparts, and the morphological effects were similarly localized for both mutants. Specifically, the biggest phenotypic differences in mutant mice were focused in regions exposed to mechanical forces, such as alveolar bone, muscular attachment sites, and articular surfaces. Histological analyses revealed differences in ossification of the intramembranous bone of the mandibles of both mutant mice compared to their wildtype littermates. However, chondrocyte organization within the secondary cartilages of the mandible was unaffected in the mutant mice. Overall, our results suggest that the morphological differences seen in G60S/+ and I130T/+ mouse mandibles are due to delayed ossification and suggest that mechanical forces may exacerbate the effects of ODDD on the skeleton.
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Conexina 43 , Anormalidades Craniofaciais/patologia , Anormalidades do Olho/patologia , Deformidades Congênitas do Pé/patologia , Mandíbula/patologia , Osteogênese , Sindactilia/patologia , Anormalidades Dentárias/patologia , Animais , Conexina 43/metabolismo , Junções Comunicantes , CamundongosRESUMO
Oculodentodigital dysplasia (ODDD) is a disease caused by mutations in the GJA1 gene that encodes the gap-junctional protein connexin43 (Cx43). ODDD affects multiple organs, but craniofacial anomalies are typical. However, details on the timing of phenotypic presentation of these abnormalities and their correspondence with potential cellular changes are incomplete. Here, we perform the first assessment of the development of the ODDD craniofacial phenotype in the Cx43I130T/+ mouse model and show that the phenotypic features commonly found in patients with the disorder arise in mice between E17.5 and birth and become more profound with age. Using mice heterozygous for the I130T mutation of Gja1, we provide a detailed analysis of the craniofacial phenotype in this ODDD model using shape analyses based on micro-CT images. Results show that in addition to differences in facial bone morphology, there are significant shape differences in the cranial base. Mutant mice display delayed ossification at E17.5 and birth, particularly in bones of the face and cranial vault but ossification is normal at three months. Our immunohistochemical analyses of the palatine bone indicate that osteoblast differentiation is delayed in Cx43I130T/+ mice compared to their wildtype littermates, which likely contributes to the phenotypic variations observed in the facial bones. Our histological and immunohistochemical analyses of the synchondroses of the cranial base show no differences in molecular indicators of chondrocyte differentiation in mutant mice, suggesting that the differences to cranial base morphology displayed by Cx43I130T/+ mice are not due to differences in chondrocyte proliferation or differentiation. Together, our findings suggest that Cx43I130T/+ mice represent a surrogate model to not only inform about the craniofacial anomalies found in ODDD patients but also to show that reduced Cx43 function leads to phenotypic changes that are largely due to osteoblast defects.
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Anormalidades Craniofaciais , Anormalidades Dentárias , Animais , Conexina 43/genética , Anormalidades Craniofaciais/genética , Anormalidades do Olho , Deformidades Congênitas do Pé , Junções Comunicantes , Humanos , Camundongos , Crânio , Sindactilia , Anormalidades Dentárias/genéticaRESUMO
Background: Distal radius fracture reduction by internal fixation is most commonly achieved using volar locking plates (VLPs). Many standard VLP designs make little point contact with radius anatomy, and most postsurgical complications following fixation are attributed to poor implant fit. Sex differences may require consideration in implant design, as females more commonly require VLP removal. Therefore, the purpose of this research was to determine whether the relationships between measures of radius shape are proportional between the sexes. Methods: Three-dimensional radius bone geometries were created from 40 male and 34 female (mean age = 72.04 years) forearm computed tomographic scans in Mimics (Materialise NV, Leuven, Belgium). Eleven measures of radius shape were collected from each scan. Principal components analysis was performed on these measures to determine which shape variables account for the greatest differences in radius shape among individuals and between the sexes. Results: Principal component scores representing isometric radius size separated the sexes. Six anthropometric measures significantly correlated with isometric radius size for all specimens, whereas 3 and 1 measures significantly correlated with isometric radius size in males and females, respectively. Conclusions: Anthropometrics of male and female radii vary by different proportions. Using anthropometrics from both sexes to create a single implant system may not result in optimal patient fit for either sex.
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Rádio (Anatomia)/anatomia & histologia , Caracteres Sexuais , Idoso , Antropometria , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Imageamento Tridimensional , Masculino , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgiaRESUMO
Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory spondyloarthropathy identified radiographically by calcification of the ligaments and/or entheses along the anterolateral aspect of the vertebral column. The etiology and pathogenesis of calcifications are unknown, and the diagnosis of DISH is currently based on radiographic criteria associated with advanced disease. To characterize the features of calcifications associated with DISH, we used micro-computed tomographic imaging to evaluate a cohort of 19 human cadaveric vertebral columns. Fifty-three percent of the cohort (n = 10; 3 females, 7 males, mean age of death = 81 years, range 67-94) met the radiographic criteria for DISH, with calcification of four or more contiguous vertebral segments. In almost all cases, the lower thoracic regions (T8-12) were affected by calcifications, consisting primarily of large, horizontal outgrowths of bony material. In contrast, calcifications localized to the upper thoracic regions demonstrated variability in their presentation and were categorized as either "continuous vertical bands" or "discontinuous-patchy" lesions. In addition to the variable morphology of the calcifications, our analysis demonstrated remarkable heterogeneity in the densities of calcifications, ranging from internal components below the density of cortical bone to regions of hyper-dense material that exceeded cortical bone. These findings establish that the current radiographic criteria for DISH capture heterogeneous presentations of ectopic spine calcification that can be differentiated based on morphology and density. These findings may indicate a naturally heterogenous disease, potential stage(s) in the natural progression of DISH, or distinct pathologies of ectopic calcifications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Calcinose/classificação , Calcinose/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Masculino , Microtomografia por Raio-XRESUMO
OBJECTIVES: Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (VP ) and additive genetic (VA ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? MATERIALS AND METHODS: We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. RESULTS: Covariates account for 1.2-91% of craniofacial VP . EID VA decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. DISCUSSION: Because a relatively large proportion of EID VA is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual VP patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes.
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Tamanho Corporal , Face/anatomia & histologia , Variação Genética , Papio , Crânio/anatomia & histologia , Animais , Antropologia Física , Evolução Biológica , Tamanho Corporal/genética , Tamanho Corporal/fisiologia , Cefalometria , Feminino , Variação Genética/genética , Variação Genética/fisiologia , Genética Populacional , Masculino , Papio/anatomia & histologia , Papio/genética , Papio/fisiologiaRESUMO
Pannexins form single-membrane channels that allow passage of small molecules between the intracellular and extracellular compartments. Of the three pannexin family members, Pannexin3 (Panx3) is the least studied but is highly expressed in skeletal tissues and is thought to play a role in the regulation of chondrocyte and osteoblast proliferation and differentiation. The purpose of our study is to closely examine the in vivo effects of Panx3 ablation on long bone morphology using micro-computed tomography. Using Panx3 knockout (KO) and wildtype (WT) adult mice, we measured and compared aspects of phenotypic shape, bone mineral density (BMD), cross-sectional geometric properties of right femora and humeri, and lean mass. We found that KO mice have absolutely and relatively shorter diaphyseal shafts compared with WT mice, and relatively larger areas of muscle attachment sites. No differences in BMD or lean mass were found between WT and KO mice. Interestingly, KO mice had more robust femora and humeri compared with WT mice when assessed in cross-section at the midshaft. Our results clearly show that Panx3 ablation produces phenotypic effects in mouse femora and humeri, and support the premise that Panx3 has a role in regulating long bone growth and development.
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Conexinas/deficiência , Fêmur/anatomia & histologia , Úmero/anatomia & histologia , Animais , Densidade Óssea/fisiologia , Estudos Transversais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Microtomografia por Raio-XRESUMO
BACKGROUND: Radiation therapy treatment planning has advanced over the past 2 decades, with increased emphasis on 3-dimensional imaging for target and organ-at-risk (OAR) delineation. Recent studies suggest a need for improved resident instruction in this area. We developed and evaluated an intensive national educational course ("boot camp") designed to provide dedicated instruction in site-specific anatomy, radiology, and contouring using a multidisciplinary (MDT) approach. METHODS: The anatomy and radiology contouring (ARC) boot camp was modeled after prior single-institution pilot studies and a needs-assessment survey. The boot camp incorporated joint lectures from radiation oncologists, anatomists, radiologists, and surgeons, with hands-on contouring instruction and small group interactive seminars using cadaveric prosections and correlative axial radiographs. Outcomes were evaluated using pretesting and posttesting, including anatomy/radiology multiple-choice questions (MCQ), timed contouring sessions (evaluated relative to a gold standard using Dice similarity metrics), and qualitative questions on satisfaction and perceived effectiveness. Analyses of pretest versus posttest scores were performed using nonparametric paired testing. RESULTS: Twenty-nine radiation oncology residents from 10 Canadian universities participated. As part of their current training, 29%, 75%, and 21% receive anatomy, radiology, and contouring instruction, respectively. On posttest scores, the MCQ knowledge scores improved significantly (pretest mean 60% vs posttest mean 80%, P<.001). Across all contoured structures, there was a 0.20 median improvement in students' average Dice score (P<.001). For individual structures, significant Dice improvements occurred in 10 structures. Residents self-reported an improved ability to contour OARs and interpret radiographs in all anatomic sites, 92% of students found the MDT format effective for their learning, and 93% found the boot camp more effective than educational sessions at their own institutions. All of the residents (100%) would recommend this course to others. CONCLUSIONS: The ARC boot camp is an effective intervention for improving radiation oncology residents' knowledge and understanding of anatomy and radiology in addition to enhancing their confidence and accuracy in contouring.
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Anatomia/educação , Internato e Residência , Órgãos em Risco/anatomia & histologia , Órgãos em Risco/diagnóstico por imagem , Radioterapia (Especialidade)/educação , Canadá , Competência Clínica , Avaliação Educacional/métodos , Feminino , Humanos , Masculino , Radioterapia (Especialidade)/organização & administração , Radiografia , Radiologia/educaçãoRESUMO
The development, function, and integration of morphological characteristics are all hypothesized to influence the utility of traits for phylogenetic reconstruction by affecting the way in which morphological characteristics evolve. We use a baboon model to test the hypotheses about phenotypic and quantitative genetic variation of traits in the cranium that bear on a phenotype's propensity to evolve. We test the hypotheses that: 1) individual traits in different functionally and developmentally defined regions of the cranium are differentially environmentally, genetically, and phenotypically variable; 2) genetic covariance with other traits constrains traits in one region of the cranium more than those in others; 3) and regions of the cranium subject to different levels of mechanical strain differ in the magnitude of variation in individual traits. We find that the levels of environmental and genetic variation in individual traits are randomly distributed across regions of the cranium rather than being structured by developmental origin or degree of exposure to strain. Individual traits in the cranial vault tend to be more constrained by covariance with other traits than those in other regions. Traits in regions subject to high degrees of strain during mastication are not any more variable at any level than other traits. If these results are generalizable to other populations, they indicate that there is no reason to suppose that individual traits from any one part of the cranium are intrinsically less useful for reconstructing patterns of evolution than those from any other part.
Assuntos
Meio Ambiente , Papio/anatomia & histologia , Papio/genética , Crânio/anatomia & histologia , Análise de Variância , Animais , Antropologia Física , Cefalometria , Variação Genética , Modelos Genéticos , Fenótipo , Filogenia , Especificidade da EspécieRESUMO
Sexual dimorphism is a widespread phenomenon and contributes greatly to intraspecies variation. Despite a long history of active research, the genetic basis of dimorphism for complex traits remains unknown. Understanding the sex-specific differences in genetic architecture for cranial traits in a highly dimorphic species could identify possible mechanisms through which selection acts to produce dimorphism. Using distances calculated from three-dimensional landmark data from CT scans of 402 baboon skulls from a known genealogy, we estimated genetic variance parameters in both sexes to determine the presence of gene-by-sex (G x S) interactions and X-linked heritability. We hypothesize that traits exhibiting the greatest degree of sexual dimorphism (facial traits in baboons) will demonstrate either stronger G x S interactions or X-linked effects. We found G x S interactions and X-linked effects for a few measures that span the areas connecting the face to the neurocranium but for no traits restricted to the face. This finding suggests that facial traits will have a limited response to selection for further evolution of dimorphism in this population. We discuss the implications of our results with respect to the origins of cranial sexual dimorphism in this baboon sample, and how the genetic architecture of these traits affects their potential for future evolution.
Assuntos
Variação Genética , Papio hamadryas/genética , Caracteres Sexuais , Crânio/anatomia & histologia , Animais , Evolução Biológica , Feminino , Genes Ligados ao Cromossomo X , MasculinoRESUMO
In this study we compare patterns of mandibular integration between mice and baboons using both phenotypic and quantitative genetic data. Specifically, we test how well each species fits with the mosaic model of mandibular integration suggested by Atchley and Hall (Biol Rev Camb Philos Soc 66:101-157, 1991) based on developmental modules. We hypothesize that patterns of integration will be similar for mice and baboons and that both species will show strong integration within developmental modules and weaker integration between modules. Corresponding landmark data were collected from the hemi-mandibles of an advanced intercross mouse sample (N = 1239) and mandibles from a baboon sample of known pedigree from the Southwest Foundation for Biomedical Research (N = 430). We used four methods of analysis to quantify and compare the degree of mandibular integration between species including two methods based on a priori assumptions, and two a posteriori analyses. We found that patterns of integration are broadly similar for baboon and mouse mandibles, with both species displaying a modular pattern of integration. While there is a general trend of similarity in integration patterns between species, there were some marked differences. Mice are strongly correlated among distances within the coronoid process and the incisive alveolar region, whereas baboons are strongly integrated within the condylar process. We discuss the potential evolutionary implications of the similar patterns of integration between these species with an emphasis on the role of modularity.
RESUMO
The mammalian skull performs a variety of functions and its growth and development mirrors this complexity. Cranial growth and development have been actively studied for many years. Despite this interest, the variation in the patterns and processes of skull growth has attracted little attention. An important and unanswered question is the extent to which patterns of cranial covariation and variation are dynamically reworked throughout postnatal growth. To address this question, we examine patterns of variability in random-bred mouse skulls aged 35, 90, and 150 days. Using a battery of both Procrustes coordinate and Euclidean distance-based methods, we measure mean shape, canalization, developmental stability, and morphological integration in these skulls. We predict that the patterns of variability are dynamic, particularly between the youngest and the two oldest age groups due to the influence of functional effects such as postweaning mastication. We also hypothesize that patterns of variability are structured by the same functional and developmental factors that have been shown to influence cranial growth in primates. Our results indicate that contrary to our predictions, patterns of canalization, developmental stability, and morphological integration are stabilized before 35 days. The mean shape, however, changed significantly with growth. We found that only the facial region showed significant integration as predicted by the functional matrix model used in other studies of integration. These results indicate that phenotypic integration in these mice does not closely match those found for primate species, suggesting that comparisons between species should be made with care.