Mapping molar shapes on signaling pathways

A major challenge in evolutionary developmental biology is to understand how genetic mutations underlie phenotypic changes. In principle, selective pressures on the phenotype screen the gene pool of the population. Teeth are an excellent model for understanding evolutionary changes in the genotype-phenotype relationship since they exist throughout vertebrates. Genetically modified mice (mutants) with abnormalities in teeth have been used to explore tooth development. The relationship between signaling pathways and molar shape, however, remains elusive due to the high intrinsic complexity of tooth crowns. This hampers our understanding of the extent to which developmental factors explored in mutants explain developmental and phenotypic variation in natural species that represent the consequence of natural selection. Here we combine a novel morphometric method with two kinds of data mining techniques to extract data sets from the three-dimensional surface models of lower first molars: i) machine learning to maximize classification accuracy of 22 mutants, and ii) phylogenetic signal for 31 Murinae species. Major shape variation among mutants is explained by the number of cusps and cusp distribution on a tooth crown. The distribution of mutant mice in morphospace suggests a nonlinear relationship between the signaling pathways and molar shape variation. Comparative analysis of mutants and wild murines reveals that mutant variation overlaps naturally occurring diversity, including more ancestral and derived morphologies. However, taxa with transverse lophs are not fully covered by mutant variation, suggesting experimentally unexplored developmental factors in the evolutionary radiation of Murines. Author summary Teeth are found in almost all vertebrates, and they show many different morphologies. In mammals, especially the cheek teeth or molars are highly diverse in shape, reflecting a vast range of dietary habits and efficiency of occlusion. As teeth are the most durable part of the body, they preserve well in the fossil record. The diversity of molar fossils has been useful in reconstructing the diet and phylogeny of extinct mammals. Genetically modified mice (mutants) show diverse modifications of their molar morphology, but we lack computational tools to test to what extent mutant morphologies account for the natural diversity found in the wild. We developed data mining using machine learning and phylogeny-based methods to analyze three-dimensional molar shapes in mouse mutants and natural species. Although many mutants and species have comparable features, most of the mutant molar variation covers the more evolutionarily ancestral than the more evolutionary derived shapes. Yet to be explored developmental factors may underly the more extreme shapes.Peer reviewe

Sleep Duration and Overweight among Elementary Schoolchildren:A Population-based Study in Japan

Although a number of studies have investigated the relationship of sleep duration to overweight and obesity, studies conducted among population-based elementary schoolchildren have been limited in Japan. The aim of the present study was to investigate the relationship between sleep duration and overweight among elementary schoolchildren in Japan. The study subjects were all fourth-grade schoolchildren (9 or 10 years of age) in Ina-town, Saitama Prefecture, Japan from 1999 to 2008. Information concerning each subjectʼs sex, age, and lifestyle was obtained using a self-administered questionnaire, while measurements of his or her height and weight were carried out. Childhood overweight was determined according to the definition established by the International Obesity Task Force. Data from 3,433 children were analyzed. In logistic regression analysis, a statistically significant dose-response relationship was observed between sleep duration and overweight among boys (p for trend＝0.014) but not among girls (p for trend＝0.149). Short sleep duration was associated with childhood overweight, and the sex difference in the association was observed. These findings suggested that it is important to consider sleep duration as part of any program to prevent overweight among elementary schoolchildren, especially among boys

Median alveolar cleft and palatal mass without a median upper cleft lip

Median cleft is rare among facial clefts, including bilateral and unilateral clefts. Median upper cleft lip and median alveolar cleft correspond to Type 14 and Type 0, respectively, in Tessier's classification system. Some authors have reported surgical procedures for median cleft. In the case of median alveolar cleft, bone grafting to the cleft side and orthodontics are generally applied, similarly to bilateral or unilateral cleft. Median alveolar cleft is usually accompanied by median upper cleft lip, the degree of which differs in each case. The symptoms include, but are not limited to, median lip defect, wide philtrum, and vermilion notch. However, an isolated alveolar cleft is extremely rare. We encountered a patient with an isolated alveolar cleft who did not have a light median upper cleft lip, such as a wide philtrum or vermilion notch. We herein report this case and describe its treatment

Use of the duplication range concept for understanding morphology and predicting prognosis in thumb polydactyly

This study systematically and comprehensively analysed 129 thumb polydactylies in 122 patients using a duplicating range concept based on the level of skin and skeletal bifurcation. Numerical levels were defined along the longitudinal axis of the ulnar thumb duplicate from distal to proximal: level 0 (thumb tip) to level 6 (carpometacarpal joint). The relationships between duplication range and morphological parameters were evaluated. Nail asymmetry was associated with skin bifurcation levels 0 to 2. Proximal phalangeal asymmetry and interphalangeal joint deviation, associated with skin bifurcation levels were assigned scores of 1 to 2.5 and 1 to 2, respectively. Metacarpophalangeal joint deviation had a bimodal distribution, at levels 1.5 and 4 of the longitudinal axes. Morphological similarity was found in patients with the same duplication range. The duplication range concept could potentially improve our understanding of morphology variation and predicting prognoses in thumb polydactyly

Efficacy of gelatin gel sheets in sustaining the release of basic fibroblast growth factor for murine skin defects

Background: Gelatin has been used as a material sustaining the release of basic fibroblast growth factor (bFGF), which promotes fibroblast proliferation and capillary formation and accelerates wound healing. In the application of these materials, bFGF is impregnated immediately before application, and it is difficult to conform the shape to the wound. In this study, we prepared a pliable and plastic gelatin gel sheet (GGS) that sustains bFGF and conforms to the shape of the wound as a result of cross-linking just before application. In addition, we examined the sustained release profile of bFGF from GGS and its effect on wound healing in murine skin defects. Materials and methods: A 13-wt% gelatin solution was mixed with bFGF before cross-linking with 1% glutaraldehyde solution. GGSs impregnated with 7 μg/cm2 of bFGF were incubated in phosphate-buffered saline and collagenase solution, and GGS degradation and bFGF release were evaluated. In the murine experiments, GGSs treated without bFGF and GGSs impregnated with 1, 3.5, 7, or 14 μg/cm2 of bFGF were applied to full-thickness skin defects created on the backs of C57BL/6JJcl mice, and the wound closure, epithelial length, extent of granulation tissue and capillary formation were compared. Results: bFGF was released according to the degradation of GGS in phosphate-buffered saline, and the remaining bFGF was released in collagenase solution. In the animal studies, epithelialization was accelerated in the GGSs treated with 1 and 3.5 μg/cm2 of bFGF, and granulation tissue formation and angiogenesis were promoted based on the amount of bFGF impregnated into the GGS. Conclusions: GGS impregnated with bFGF is capable of sustaining the release of bFGF, with consequent accelerated epithelialization, granulation tissue formation, and angiogenesis in vivo. GGS is a novel and promising wound dressing that sustains bFGF and can be adapted to the shape of various wounds in the treatment of both acute and chronic wounds

Fingerstall-type tissue oximetry reduced anxiety of nurses in postoperative nursing monitoring of free flaps

Background: Postoperative free flap monitoring is essential for immediately detecting obstruction of anastomosed vessels with successive recovery surgery for salvaging flaps. We performed postoperative nursing monitoring using handheld Doppler sonography, but nurses reported feeling anxious with this approach and demanded a clear-cut evaluation method. Therefore, we implemented monitoring with the fingerstall-type tissue oximeter Toccare, a noninvasive device that enables easy flap checking by simply touching the flap with a probe. Method: Handheld Doppler was used for nursing monitoring from April to October 2020, with anxiety associated with its use reported. We collected information via an anonymous questionnaire to determine the reason for the anxiety. Toccare was subsequently applied for postoperative free flap monitoring by nurses. The protocol involved measuring tissue oxygen saturation by touching the flap with a Toccare probe every 4 hours from 24 to 100 hours postoperatively. Seven months later, a second anonymous questionnaire was conducted, and results were compared. Result: Free deep inferior epigastric artery perforator flaps and anterolateral thigh flaps (n = 5 each) were included. The average tissue oxygen saturation values in the deep inferior epigastric artery perforator and anterolateral thigh flaps were 52.0% and 52.4%, respectively. According to the second questionnaire about Toccare, 7% felt anxious, 62% felt slightly anxious, and 31% did not feel anxious. Toccare was preferred by 89% of nurses who had used both methods. Conclusions: Flap monitoring using Toccare reduced nurses’ anxiety. A numerical evaluation method with easy handling and clear doctor call criteria is essential for low-anxiety nursing monitoring

Exploring metameric variation in human molars: A morphological study using morphometric mapping

Human molars exhibit a type of metameric variation, which is the difference in serially repeated morphology within an organism. Various theories have been proposed to explain how this variation is brought about in the molars. Actualistic data that support the theories, however, are still relatively scarce because of methodological limitations. Here we propose new methods to analyse detailed tooth crown morphologies. We applied morphometric mapping to the enamel-dentine junction of human maxillary molars and examined whether odontogenetic models were adaptable to human maxillary molars. Our results showed that the upper first molar is phenotypically distinct among the maxillary molars. The average shape of the upper first molar is characterized by four well-defined cusps and precipitous surface relief of the occlusal table. On the other hand, upper third molar is characterized by smooth surface relief of the occlusal table and shows greater shape variation and distinct distribution patterns in morphospace. The upper second molar represents an intermediate state between first and third molar. Size-related shape variation was investigated by the allometric vector analysis, and it appeared that human maxillary molars tend to converge toward the shape of the upper first molar as the size increases. Differences between the upper first molar and the upper second and third molar can thus be largely explained as an effect of allometry. Collectively, these results indicate that the observed pattern of metameric variation in human molars is consistent with odontogenetic models of molar row structure (inhibitory cascade model) and molar crown morphology (patterning cascade model). This study shows that morphometric mapping is a useful tool to visualize and quantify the morphological features of teeth, which can provide the basis for a better understanding of tooth evolution linking morphology and development

A Case of Giant Congenital Melanocytic Nevus Treated with Combination Therapy of Autologous Mesh-skin Grafts and Cultured Epithelial Autografts

Surgical excision of a giant congenital melanocytic nevus (GCMN) results in a full-thickness skin defect that is usually difficult to reconstruct even with tissue expansion or skin grafting. Here, we report the first case of GCMN treated with a combination of cultured epithelial autografts (CEAs) and mesh-skin grafts to reconstruct a large skin defect after surgical excision. A 14-month-old girl had a GCMN occupying 20% of the total body surface area of her neck and back. A 5-stage, full-thickness excision was performed between the age of 14 and 25 months. In each intervention, the wound after excision was covered with 1:6 mesh-skin grafts and CEAs, except for the neck, where patch skin grafts and CEAs were used. The skin grafts and CEAs were engrafted without shedding and epithelialization was completed within 3-4 weeks. Eighteen months after the last surgery, a mesh-like scar remained, with no recurrence or severe contracture observed. The cosmetic appearances of the donor sites (the scalp and lower abdomen) were acceptable. The application of CEAs with mesh-skin grafts has been established for the treatment of severe burns. This combined method also provides a possible option for the treatment of GCMNs