An in vitro and finite element study of load redistribution in the midfoot

A good knowledge of midfoot biomechanics is important in understanding the biomechanics of the entire foot,but it has never been investigated thoroughly in the literature.This study carried out in vitro experiments and finite element analysis to investigate the midfoot biomechanics.A foot-ankle finite element model simulating the mid-stance phase of the normal gait was developed and the model validated in in vitro experimental tests.Experiments used seven in vitro samples of fresh human cadavers.The simulation found that the first principal stress peaks of all midfoot bones occurred at the navicular bone and that the tensile force of the spring ligament was greater than that of any other ligament.The experiments showed that the longitudinal strain acting on the medial cuneiform bone was-26.2±10.8μ-strain,and the navicular strain was-240.0±169.1μ-strain along the longitudinal direction and 65.1±25.8μ-strain along the transverse direction.The anatomical position and the spring ligament both result in higher shear stress in the navicular bone.The load from the ankle joint to five branches of the forefoot is redistributed among the cuneiforms and cuboid bones.Further studies on the mechanism of loading redistribution will be helpful in understanding the biomechanics of the entire foot.     

<Emphasis Type="Italic">Hoxa3</Emphasis> regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice

Genetic disruption of Hoxa3 results in bilateral defects of the common carotid artery, which is derived from the third branchial arch artery. The tunica media of the great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells. The expression of -galactosidase in these mouse embryos was examined by both whole-mount X-gal staining and immunohistochemistry with the monoclonal -galactosidase antibody on sections. The migration of neural crest cells from the neural tube to the third branchial arch was not affected in the Hoxa3 homozygotes. The initial formation of the third arch artery was also not disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when differentiation of the third pharyngeal arch began. The internal and external carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed an abnormal persistence of the ductus caroticus. The third pharyngeal arch of wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3 null mutants, however, the fusion was delayed, and the hypoplastic third pharyngeal arch was still discerned at E12.5. Moreover, the number of proliferating cells in the third arch of the null mutants was small compared with that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation of the third pharyngeal arch. The defective development of the third pharyngeal arch may induce the anomalies of the carotid artery system. This work was supported in part by a grant (no. 14570026) from the Ministry of Education of Japan to Y.K.     

A three‐dimensional placoderm (stem‐group gnathostome) pharyngeal skeleton and its implications for primitive gnathostome pharyngeal architecture

The pharyngeal skeleton is a key vertebrate anatomical system in debates on the origin of jaws and gnathostome (jawed vertebrate) feeding. Furthermore, it offers considerable potential as a source of phylogenetic data. Well‐preserved examples of pharyngeal skeletons from stem‐group gnathostomes remain poorly known. Here, we describe an articulated, nearly complete pharyngeal skeleton in an Early Devonian placoderm fish, Paraplesiobatis heinrichsi Broili, from Hunsrück Slate of Germany. Using synchrotron light tomography, we resolve and reconstruct the three‐dimensional gill arch architecture of Paraplesiobatis and compare it with other gnathostomes. The preserved pharyngeal skeleton comprises elements of the hyoid arch (probable ceratohyal) and a series of branchial arches. Limited resolution in the tomography scan causes some uncertainty in interpreting the exact number of arches preserved. However, at least four branchial arches are present. The final and penultimate arches are connected as in osteichthyans. A single median basihyal is present as in chondrichthyans. No dorsal (epibranchial or pharyngobranchial) elements are observed. The structure of the pharyngeal skeleton of Paraplesiobatis agrees well with Pseudopetalichthys from the same deposit, allowing an alternative interpretation of the latter taxon. The phylogenetic significance of Paraplesiobatis is considered. A median basihyal is likely an ancestral gnathostome character, probably with some connection to both the hyoid and the first branchial arch pair. Unpaired basibranchial bones may be independently derived in chondrichthyans and osteichthyans.     

Retinoic acid affects craniofacial patterning by changing Fgf8 expression in the pharyngeal ectoderm

Retinoic acid signaling plays important roles in establishing normal patterning and cellular differentiation during embryonic development. In this study, we show that single administration of retinoic acid at embryonic day 8.5 causes homeotic transformation of the lower jaw into upper jaw-like structures. This homeosis was preceded by downregulation of Fgf8 and Sprouty expression in the proximal domain of the first pharyngeal arch. Downregulation of mesenchymal genes such as Dlx5, Hand2, Tbx1 and Pitx2 was also observed. The oropharynx in retinoic acid-treated embryos was severely constricted. Consistent with this observation, Patched expression in the arch endoderm and mesenchyme was downregulated. Thus, retinoic acid affects the expression of subsets of epithelial and mesenchymal genes, possibly disrupting the regional identity of the pharyngeal arch.     

Anti-apoptotic gene Bcl2 is required for stapes development and hearing

In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2^−/− mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2^−/− mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2^−/−Bim^−/− mice and partially rescued in Bcl2^−/−Bim^+/− mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2^−/− defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.     

不同颌间牵引固定方案治疗单纯髁状突骨折的临床疗效比较

目的:研究不同颌间牵引固定方案治疗单纯髁状突骨折的临床疗效,为临床治疗提供依据。方法:选取2010年1月到2015年1月我院收治的单纯髁状突骨折患者50例,按照随机数字表法将患者分为A组和B组,A组给予牵引钉植入牵引固定方案治疗,B组给予牙弓夹板行颌间牵引固定方案治疗,比较两组操作时间、术后最大开口度、五个时间点软垢指数(DI)、牙龈指数(GI)以及社区牙周需要治疗指数(CPITN),并比较两组临床疗效。结果:A组操作时间显著短于B组(P0.05);术后最大开口度和颞下颌关节情况无显著差异(P0.05);A组第2次、3次、4次以及5次的DI、GI和CPITN均显著优于B组(P0.05);两组面型偏斜、咀嚼良好、咬合关系、关节弹性、开口偏斜以及关节牙痛比较均无显著差异(P0.05)。结论:牵引钉植入与牙弓夹板颌间牵引固定均可以较好改善患者骨折情况,但牵引钉植入术对患者伤害小,操作时间短,术后患者软垢和牙龈情况均较好。     

Roles of the Foxj1 and Inv genes in the left-right determination of internal organs in mice

In Foxj1 knockout mice, half show situs solitus while the other half show situs inversus, which means a random determination of the left-right axis. In contrast, the inv mutant mice show a mirror-image configuration of the internal organs, which means a reversal of the left-right axis. Although these two mutant mice have primary cilia on the nodal cells, their phenotypes are different in laterality determination. We thus made Foxj1/inv double mutant mice and analyzed their phenotype. We found the phenotypes of Foxj1/inv double mutant mice to be more similar to those of the Foxj1 mutant mice than those of the inv mutant mice. We also found right pulmonary isomerism to be a major phenotype of the Foxj1 mutant mice and the Foxj1/inv double mutant mice, which is likely due to the absence of the Pitx2 expression at both lateral plate mesoderms. These results indicate that a random signal of laterality (Foxj1) is dominant over the reversal signal of laterality (Inv).     

<Emphasis Type="Italic">Hoxa3</Emphasis> and signaling molecules involved in aortic arch patterning and remodeling

Anomalies of the aortic arch have long been of anatomicoclinical interest. Recent studies on gene-targeted mice have identified the candidate genes that are involved in the patterning and remodeling of the pharyngeal arch arteries. In this review, we discuss our present knowledge with regard to the signaling molecules that regulate specific aspects of arch artery development. We focus first on Hoxa3, because it plays a critical role in the regulation of the differentiation of the third pharyngeal arch. Hoxa3 is expressed by the neural crest cells that originate from the rhombomeres, viz., (r)5, r6, and r7, and populate the third pharyngeal arch; it is also expressed in the third pharyngeal pouch. In Hoxa3 homozygous null mutant mice, the third arch artery degenerates bilaterally at embryonic day 11.5, resulting in the malformation of the carotid artery system. Complex combinatorial signals among the neural crest cells, pharyngeal mesoderm, ectoderm, and pouch endoderm are required for the proper development of the arch arterial system. Therefore, we highlight the numerous signaling pathways and individual genes expressed by the ectomesenchymal neural crest cells and also by the other epithelial and mesodermal cells of the pharynx. Defects in these genes result in malformations of the arch artery derivatives. This review should deepen our understanding of congenital human syndromes with abnormal patterns of pharyngeal arch arteries.