Skeletal Features Research Articles

Effects of advanced maternal age and acute prenatal alcohol exposure on mouse offspring growth and craniofacial phenotype.

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. 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 10weeks); (2) control young dams; (3) EtOH-treated old dams (6 to 7months); 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. 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. 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.

Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome

Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFβ in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. In this study, we report homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families. Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). Invitro studies on proband-derived dermal fibroblasts indicate distinct molecular mechanisms depending on the position of the variant in LTBP1. C-terminal variants lead to an altered LTBP1 loosely anchored in the microfibrillar network and cause increased ECM deposition in cultured fibroblasts associated with excessive TGFβ growth factor activation and signaling. In contrast, N-terminal truncation results in a loss of LTBP1 that does not alter TGFβ levels or ECM assembly. Invivo validation with two independent zebrafish lines carrying mutations in ltbp1 induce abnormal collagen fibrillogenesis in skin and intervertebral ligaments and ectopic bone formation on the vertebrae. In addition, one of the mutant zebrafish lines shows voluminous and hypo-mineralized vertebrae. Overall, our findings in humans and zebrafish show that LTBP1 function is crucial for skin and bone ECM assembly and homeostasis.

Are the Reasons Why Patients Are Referred for an Orthodontic Visit Correct?

Who does refer patients for an orthodontic consultation? Which are the main reasons for the referral? Does the visit of the orthodontic specialist confirm these reasons or reveal undiagnosed problems? Is there the risk that only evident dental problems are addressed, while craniofacial malformations remain underdiagnosed? This cross-sectional epidemiologic study aims to answer these questions, analysing the clinical data collected during the orthodontic visits of 500 Caucasian young patients referred to a public health structure of northern Italy. All patients were visited by the same expert specialist in orthodontics. Clinical data were collected, analysing both dental and skeletal features. The reasons for the referral of the visit were analysed and compared with the specialistic diagnoses. In our sample, dentists, relatives/friends and paediatricians were the major source of the referrals, followed by family doctors and other facial specialists. In most cases, the reasons for the referral were dental irregularities, but approximately 80% of dental irregularities were associated with undiagnosed facial dysmorphism. Skeletal facial anomalies need an early diagnosis to prevent the development of severe facial malformations that would require invasive and expensive treatments. These findings reveal poor diagnostic skills regarding skeletal anomalies in dentists and paediatricians and the need for better specific training.

Compound heterozygous missense mutations in a Chinese mucopolysaccharidosis type VI patient: a case report

BackgroundMucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B (ARSB) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body.In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis.Case presentationA 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI.ConclusionsThis paper reports a case of MPS VI confirmed by genetic diagnosis.MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

Durnonovariaodus maiseyi gen. et sp. nov., a new hybodontiform shark-like chondrichthyan from the Upper Jurassic Kimmeridge Clay Formation of England.

A partial skeleton of a hybodontiform shark-like chondrichthyan from the Upper Jurassic Kimmeridge Clay Formation of Dorset, England, is described and designated as a new genus and species, Durnonovariaodus maiseyi gen. et sp. nov. The holotype and only known specimen, which is represented by disarticulated splanchnocranial elements with associated teeth, a single dorsal fin spine, the pelvic girdle, as well as unidentifiable cartilage fragments, plus countless dermal denticles, exhibits a puzzling combination of dental and skeletal features, providing important new insights into the morphological and ecological diversity of hybodontiforms. Durnonovariaodus gen. nov. displays a unique set of dental characters, showing close morphological resemblance to Secarodus from the Middle Jurassic of England, which was erected for distinctive, strongly labio-lingually compressed multicuspid cutting teeth originally described as Hybodus polyprion. Skeletally, Durnonovariaodus gen. nov. resembles Hybodus and Egertonodus in having a palatoquadrate with a palatobasal process and an ethmoidal articular surface, combined with the possession of dorsal fin spines ornamented with costae. Therefore, and given the absence of any conclusive phylogenetic framework, Durnonovariaodus maiseyi gen. et sp. nov. is here tentatively referred to Hybodontidae until more complete material becomes available in order to enable a more reliable suprageneric identification. The holotype of Durnonovariaodus maiseyi gen. et sp. nov. contains two separate pelvic half-girdles, a feature previously considered as evolutionarily primitive among hybodontiforms. However, unfused pelvic half-girdles also occur in the supposedly closely related species Hybodus hauffianus and may in fact have been more widely distributed among hybodontiforms than previously thought, thus rendering the phylogenetic utility of separated pelvic half-girdles for inferring hybodontiform interrelationships difficult and unresolved.

Identification of the TTC26 Splice Variant in a Novel Complex Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations

Ciliopathies constitute heterogeneous disorders that result from mutations in ciliary proteins. These proteins play an important role in the development of organs, physiology, and signaling pathways, and sequence variations in the genes encoding these proteins are associated with multisystem disorders. In this study, we describe a severe ciliopathy disorder that segregates in an autosomal recessive manner in a nonconsanguineous Saudi family. The proband exhibited features such as cholestasis, cystic dilatation of intrahepatic biliary ducts, diabetes insipidus, dysmorphic facial features, optic atrophy, pituitary hypoplasia, hydrocephalus, aqueductal stenosis, hyperextensible knee joints, bilateral knee dislocation, polydactyly, and syndactyly. Whole-genome sequencing and Sanger sequencing revealed a homozygous splice site variant (c.4–1G>C; NM_024926.3) in the tetratricopeptide repeat domain 26 (TTC26) gene located in chromosome 7q34, which cosegregated perfectly with the disease phenotype. qRT-PCR revealed a substantial decrease in the expression of the TTC26 gene as compared to the normal control, suggesting the pathogenicity of the identified variant. This report further strengthens the evidence that homozygous variants in the TTC26 gene cause severe ciliopathies with diverse phenotypes. We named this newly characterized condition as BRENS syndrome, which stands for biliary, renal, neurological, and skeletal features.

Design and Baseline Demographics of a Five-Year, Multi-National Observational Cohort Study of Children With Achondroplasia (ACHieve Study)

Background: Achondroplasia (ACH) is the most common form of dwarfism occurring in 1 in 22,000 births (95% CI 18,500 to 26,000). This skeletal dysplasia is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 (FGFR3) gene located on chromosome 4p16.3 and results in sustained activation of the FGFR3 pathway leading to impaired chondrogenesis and endochondral bone formation. Both typical childhood growth patterns and the impaired linear growth of ACH are modulated by the delicate balance between growth-inhibiting FGFR3/mitogen-activated phosphokinase and growth-promoting c-type natriuretic peptide/natriuretic peptide receptor B.Individuals with ACH frequently develop clinically significant comorbidities, many with onset during childhood. Currently, there are no therapies addressing the underlying pathology. Most available treatments are surgical with goals to alleviate the symptoms from specific comorbidities (i.e. foramen magnum and spinal stenosis or recurrent otitis media). Since the available therapies do not address the underlying etiology, individuals with ACH often undergo multiple surgeries and myriad other forms of supportive care throughout their lives. The precise timing of comorbidity onset and the natural history of many of the skeletal dysplasia features are incompletely defined. This information is needed to inform the design and conduct of pathology-targeted intervention studies. Aim: The purpose of this study is to gather information about the precise timing of comorbidity onset, the longitudinal growth trajectory, and the evolution of body proportionality in children with ACH. Methods and Future Results: The ACHieve study (NCT03875534) is a multi-center, longitudinal, observational cohort study in children with ACH from birth up to 8 years at enrollment. In this non-therapeutic study, children are evaluated every six months for up to 5 years in 25 centers from North America, Europe and Oceania. The first patient was enrolled in 2019 and a total of 84 children have been enrolled to date. At each assessment, children undergo comprehensive anthropometric studies, (including body proportionality measurements and recumbent or standing height) and information on the timing and nature of ACH-related comorbidities and their treatments are collected. Additional information about the baseline demographics, including sex, age distribution, race/ethnicity, and height standard deviation scores will be presented at the time of conference. Conclusions: The ACHieve study will provide additional insight into the natural history of growth, body proportionality, and comorbidities in children with ACH. These observations will serve as a benchmark for future intervention trials targeting the pathology of the underlying skeletal dysplasia.

GNAS Heterozygous Inactivation Differentially Affects Osteoclast-Specific Calcitonin Receptor Bioactivity in a Mouse Model of Albright Hereditary Osteodystrophy Based Upon Parental Inheritance

Abstract Albright hereditary osteodystrophy (AHO) is caused by the heterozygous inactivation of GNAS, encoding the α-stimulatory subunit (Gαs) of G protein-coupled receptors. Skeletal manifestations of AHO include adult short stature, brachydactyly and subcutaneous ossifications. AHO patients with maternally-derived GNAS mutations develop pseudohypoparathyroidism type 1A (PHP1A) and are obese with resistance to hormones requiring Gαs (eg., PTH, TSH and GHRH) due to tissue-specific GNAS imprinting. Paternally-derived GNAS mutations cause pseudopseudohypoparathyroidism (PPHP) in which patients have AHO skeletal features but do not develop severe obesity or hormonal resistance. Mouse models have shown loss of Gα s signaling in osteoblasts or osteoclasts leads to osteopenia, and suggest AHO patients would display a reduced bone mineral density (BMD). Interestingly, PHP1A patients have been shown to have normal to increased BMD without any correlation to body mass index or serum PTH measurement. Based on the differences observed clinically and hormonally between PHP1A and PPHP, we hypothesize that there may also be distinctions in overall bone remodeling between these two disorders due to GNAS imprinting. This study addressed whether the heterozygous inactivation of Gnas differentially affects Gα s-receptor bioactivity within osteoclasts (OCs) based upon parental inheritance. Bone Marrow Macrophages (BMMs) were harvested from our laboratory’s AHO mouse model with either maternally-inherited (Gnas+/-m) mutations correlating to PHP1A or paternally-inherited (Gnas+/-p) mutations correlating to PPHP. BMMs were exposed to 10-7M salmon calcitonin (sCT), 10-5M forskolin or PBS for 6 hrs. OC receptor activity was measured by fluorescent microscopy to visualize actin ring morphology and RT-PCR analysis of Gα s-PKA signaling transcripts Crem and Ramp3. Forskolin treatment displayed no significant variations in OC ring morphology or Crem and Ramp3 mRNA expression between Gnas+/-m, Gnas+/-p and WT cultures. Both WT and Gnas+/-p OCs displayed appropriate responses to sCT, as indicated by a significant disruption in actin ring morphology and increased Crem and Ramp3 mRNA expression when compared to vehicle-treated controls. SCT-treated Gnas+/-m OCs, however, displayed only mild disruptions in actin ring morphology, and we observed significant reductions in Ramp3 expression compared to WT as well as reductions in Crem compared to WT and Gnas+/-p. These data suggest evidence of partial calcitonin resistance within Gnas+/-m OCs due to impaired Gα s- signaling. These data correlate with previous clinical observations of calcitonin resistance in PHP1A patients. Because these findings were observed only within Gnas+/-m cultures, future work is warranted to determine whether this impaired receptor activity may be attributed to partial Gnas imprinting within OCs or the myeloid lineage.

Development of dentofacial characteristics related to Incontinentia Pigmenti syndrome: A repeated cross-sectional study

This research aimed to investigate the dentofacial characteristics of patients with Incontinentia Pigmenti (IP) (or Bloch-Sulzberger) syndrome in childhood, juvenile, and adulthood developmental stages. Fifteen female patients with a clinical diagnosis of IP, genetically confirmed by molecular testing, were included in this study. The records of 25 nonsyndromic females with Class I occlusion and lateral cephalograms obtained at similar developmental stages were selected from the American Association of Orthodontists Foundation Legacy Collection as a control group. Dentofacial features of subjects with IP and those in the control group were compared statistically using t test and Mann-Whitney rank-sum test (significance was defined as P<0.05). In general, patients with IP had shorter maxillary and mandibular length, straight skeletal profile, hypodivergent growth pattern with a tendency to mandibular protrusion, shorter anterior facial height, Class III compensatory positioning of incisors, more retruded lips, and smaller maxillary incisor exposure. The degree of hypodontia severity had a significant impact on skeletal, dental, and soft-tissue features in patients with IP. The results of this study showed that, since childhood, the dentofacial characteristics of patients with IP were progressively distancing from those of nonsyndromic patients with Class I occlusion, presenting their own orthodontic needs.

Correlation of the human pubic symphysis surface with age-at-death: a novel quantitative method based on a bandpass filter.

Age-at-death estimation from skeletal remains typically utilizes the roughness of pubic symphysis articular surfaces. This study presents a new quantitative method adapting a tool from geometric morphometrics, bandpass filtering of partial warp bending energy to extract only age-related changes of the surfaces. The study sample consisted of 440 surface-scanned symphyseal pubic bones from men between 14 and 82years of age, which were landmarked with 102 fixed and surface semilandmarks. From the original sample, 371 specimens within Procrustes distance of 0.05 of the side-specific average were selected. For this subsample, age was correlated with total bending energy (calculated as summed squared partial warps amplitudes) for a wide range of plausible bandpass filters. For our subsample's 188 right-side surfaces, the correlation between age and bandpass filtered versions of bending energy peaks relatively sharply at r = -0.648 for ages up through 49years against the first seven partial warp amplitudes only. The finding for left symphyses is similar. The results demonstrate that below the age 50, the symphyseal surface form changes most systematically related to age may be best detected by a lowpass-filtered version of bending energy: signals at the largest geometric scales of roughness rather than its full spectrum. Combining this method with information from other skeletal features could further improve age-at-death estimation based on the symphyseal pubic surface.

Comparative evaluation of Skeletal, Dental, and Soft Tissue Changes in Class II Division 1 Malocclusion Cases Treated with Twin Block and innovative Clear Block Appliance - A Prospective Interventional Study

The present study was undertaken to evaluate and compare the skeletal, dental, and soft tissue changes in skeletal Class II division 1 cases treated with Twin Block and Clear Block appliances using a cephalogram. A total of 40 patients of age between 12-14 years were randomly divided into two equal groups. Group 1: treated with Twin Block appliance and Group 2: treated with Clear Block appliance. The pre-treatment lateral cephalogram was taken and skeletal, dental, and soft tissue parameters were evaluated and the appliance was delivered. After 8 months, another lateral cephalogram of all the cases was taken and analyzed. The pre and post-treatment values were compared between the two groups. The pre-treatment cases were almost comparable in skeletal, dental, and soft tissue features in both groups. There was a significant change in mandibular growth by SNB angle. The retrusion and extrusion of maxillary incisors as well as a proclination and extrusion of mandibular incisors were seen in group 1 while no change was observed in group 2. Treatment with Clear Block appliances has shown significant and favorable Skeletal, Dental and Soft tissue changes which are similar to already proven by the Twin Block appliance. Clear Block provides an esthetic and less bulky option for growth modification with similar results as compared to conventional Twin Block with the additional benefit of preventing lower incisor proclination.

Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results

Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients. Retrospective cohort study. The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded. Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes ofuveitis. SpA patients with older age (P < .001), a smoking history (P=.004), delayed diagnosis (P=.001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both). Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA.

Cephalometric comparison of dentofacial parameters between Yemeni and Caucasian adults

Objective: The purposes of this research were to establish cephalometric standards for Yemeni adults and to compare them with those of the Caucasians. Material and Methods: 100 Yemeni students (fifty males, mean age of 23.6 ± 2.1 years, and fifty female, mean age of 21.5 ± 3.1 years) with normal occlusions and wellbalanced faces were involved in the study. Inclusion criteria were a class I malocclusion with minor or no crowding, the whole teeth is present except third molars and no previous orthodontic, orthopedic or maxillofacial surgery treatment. Five angular and eighteen linear measurements were used for the skeletal, dental and soft tissue analysis. All participant’s lateral cephalometric radiographs were evaluated. The average values and standard deviations for all the angles and linear measurements were determined. The differences for each measurement between the Yemeni and Caucasian participants were calculated using unpaired t–tests. Results: Yemeni subjects had a more retrognathic mandibular positions (P&lt; 0.05), protrusive mandibular incisors (P&lt; 0.01), more protruded lip positions (P &lt; 0.01), deeper mentolabial sulci (P&lt; 0.01) and a steeper mandibular planes (P&lt; 0.001) compared to the Caucasians. Yemeni females had a larger lower face height than Caucasian females (P&lt; 0.001). Conclusions: The study provides specific standards for Yemeni adults and shows that the Yemenis had different skeletal and dentoalveolar cephalometric standards in comparison with Caucasians. Keywords Cephalometric comparison; Skeletal and dental features; Yemeni norms.

Further delineation of van den Ende‐Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome

Van den Ende-Gupta syndrome (VDEGS) is a rare autosomal recessive condition characterized by distinctive facial and skeletal features, and in most affected persons, by biallelic pathogenic variants in SCARF2. We review the type and frequency of the clinical features in 36 reported individuals with features of VDEGS, 15 (42%) of whom had known pathogenic variants in SCARF2, 6 (16%) with negative SCARF2 testing, and 15 (42%) not tested. We also report three new individuals with pathogenic variants in SCARF2 and clinical features of VDEGS. Of the six persons without known pathogenic variants in SCARF2, three remain unsolved despite extensive genetic testing. Three were found to have pathogenic ABL1 variants using whole exome sequencing (WES) or whole genome sequencing (WGS). Their phenotype was consistent with the congenital heart disease and skeletal malformations syndrome (CHDSKM), which has been associated with ABL1 variants. Of the three unsolved cases, two were brothers who underwent WGS and targeted long-range sequencing of both SCARF2 and ABL1, and the third person who underwent WES and RNA sequencing for SCARF2. Because these affected individuals with classical features of VDEGS lacked a detectable pathogenic SCARF2 variant, genetic heterogeneity is likely. Our study shows the importance of performing genetic testing on individuals with the VDEGS "phenotype," either as a targeted gene analysis (SCARF2, ABL1) or WES/WGS. Additionally, individuals with the combination of arachnodactyly and blepharophimosis should undergo echocardiography while awaiting results of molecular testing due to the overlapping physical features of VDEGS and CHDSKM.

Comparison of the skeletal features of two sympatric tree frogs (Hylidae:Hyla)—Hyla japonica and Hylasuweonensis—using three-dimensional micro-computed tomography

We used three-dimensional micro-computed tomography to compare the skeletal features of two species of male tree frogs with similar morphologies: the globally prevalent Hyla japonica and critically endangered Hyla suweonensis. One of the most prominent differences between the two species was the angle of the alary processes of the premaxilla. In H. suweonensis, the alary processes were inclined posteriorly at an angle of 77.05°, whereas in H. japonica, they were deflected at an angle of 93.27° (a difference of more than 16°). This difference accounts for the more protruded shape of H. suweonensis compared with that of H. japonica. Sizes and proportions related to skeletal compartments (e.g. skull, forelimb, vertebrae, and hindlimb) also differed between the two species, which is consistent with the general exterior observation that compared with H. japonica, H. suweonensis has a more acuminate snout and a more slender body. The full skeletal configuration could provide classification keys for the two sympatric species that will be applicable to ecological field surveys and conservation activities.

Potential impact of pediatric obstructive sleep apnea on mandibular cortical width dimensions.

To analyze differences in mandibular cortical width (MCW) among children diagnosed with obstructive sleep apnea (OSA) or at high- or low-risk for OSA. A total of 161 children were assessed: 60 children with polysomnographically diagnosed OSA, 56 children presenting symptoms suggestive of high-risk for OSA, and 45 children at low risk for OSA. Children at high- and low-risk for OSA were evaluated through the Pediatric Sleep Questionnaire. MCW was calculated using ImageJ software from panoramic radiograph images available from all participants. Differences between MCW measurements in the 3 groups were evaluated using analysis of covariance and Bonferroni post-hoc tests, with age as a covariate. The association between MCW and specific cephalometric variables was assessed through regression analysis. The participants' mean age was 9.6 ± 3.1 years (59% male and 41% female). The mean body mass index z-score was 0.62 ± 1.3. The polysomnographically diagnosed OSA group presented smaller MCW than the group at low-risk for OSA (mean difference = -0.385 mm, P = .001), but no difference with the group at high-risk for OSA (polysomnographically diagnosed OSA vs high-risk OSA: P = .085). In addition, the MCW in the group at high-risk for the OSA was significantly smaller than the group at low-risk for the OSA (mean difference = -0.301 mm, P = .014). The cephalometric variables (Sella-Nasion-A point angle (SNA) and Frankfort - Mandibular Plane angle (FMA)) explained only 8% of the variance in MCW. Reductions in MCW appear to be present among children with OSA or those at high-risk for OSA, suggesting potential interactions between mandibular bone development and/or homeostasis and pediatric OSA. Fernandes Fagundes NC, d'Apuzzo F, Perillo L, et al. Potential impact of pediatric obstructive sleep apnea on mandibular cortical width dimensions. J Clin Sleep Med. 2021;17(8):1627-1634.

On the matter of phytoplankton: A novel method using 3D computer models to calculate biovolume of microorganisms

AbstractWe develop a new method that allows for more accurate biovolume calculations of microorganisms. This method also allows the volume of individual skeletal features of microorganisms to be analyzed separately so that estimates of the resource cost per evolutionary adaptations may be assessed. We also provide a means to link community changes to alterations in nutrient cycles, ecosystem function, and rock‐forming processes by plankton. This method integrates computer‐aided design software from engineering and architecture into biological applications. Our method substantially improves the accuracy of biovolume estimates for species which currently rely upon simple geometric models that preclude the presence of ultrastructure in microorganism skeletons. In addition, using simple shapes to represent the skeletal form of microorganisms prohibits the exploration of resource cost that various adaptations, for example, spines for protection from grazers, have imposed upon plankton. Thus, integrating architectural and engineering approaches more broadly into biovolume estimations produces new insight into the physiology of microorganisms that can turn speculations into quantitative analyses.

Feet first: Adaptive growth in magellanic penguin chicks.

Growing animals should allocate their limited resources in ways that maximize survival. Seabird chicks must balance the growth of features and fat reserves needed to survive on land with those needed to successfully fledge and survive at sea. We used a large, 34‐year dataset to examine energy allocation in Magellanic penguin chicks. Based on the temporal trends in the selective pressures that chicks faced, we developed predictions relating to the timing of skeletal feature growth (Prediction 1), variation in skeletal feature size and shape (Prediction 2), and responses to periods of high energetic constraint (Prediction 3). We tested our predictions using descriptive statistics, generalized additive models, and principal component analysis. Nearly all of our predictions were supported. Chicks grew their feet first, then their flippers. They continued to grow their bill after fledging (Prediction 1). Variance in feature size increased in young chicks but declined before fledging; this variance was largely driven by overall size rather than by shape (Prediction 2). Chicks that died grew slower and varied more in feature size than those that fledged (Prediction 2). Skeletal features grew rapidly prior to thermoregulation and feet and flippers were 90% grown prior to juvenile feather growth; both thermoregulation and feather growth are energetically expensive (Prediction 3). To avoid starvation, chicks prioritized storing mass during the first 10 days after hatching; then, the body condition of chicks began to decline (Prediction 3). In contrast to our prediction of mass prioritization in young chicks, chicks that were relatively light for their age had high skeletal size to mass ratios. Chicks did not show evidence of reaching physiological growth limits (Prediction 3). By examining energy allocation patterns at fine temporal scales and in the context of detailed natural history data, we provide insight into the trade‐offs faced by growing animals.

Effects of dietary L‐ascorbyl‐2‐polyphosphate on growth performance, haematological parameters, biochemical characteristics, and skeletal features of juvenile hybrid grouper (♀Epinephelus fuscoguttatus × ♂E. lanceolatus)

A 14-week feeding trial was conducted to determine the effects of dietary L-ascorbyl-2-polyphosphate on the growth performance, haematological parameters, biochemical characteristics, and skeletal features of juvenile hybrid grouper (♀Epinephelus fuscoguttatus × ♂E. lanceolatus). Eight experimental diets containing graded vitamin C (VC) levels (0, 18, 45, 78, 144, 245, 386, and 762 mg/kg) were prepared and fed to triplicate groups of fish (initial body weight: 10.41 ± 0.06 g). The final body weight, weight gain rate, specific growth rates, and fish survival increased when fed with diets supplemented with VC regardless of the supplementation level. Total feed intake reduction was observed in fish fed non-VC diet. Whereas no significant differences were detected in the feed conversion ratios and protein efficiency ratios among fish treatments. The hepatic VC concentration was positively correlated with dietary VC supplementation and reached a plateau when supplemented with more than 386 mg/kg diet. Higher total protein and alkaline phosphatase levels in blood serum and incidence of skeletal deformities were recorded in the fish fed with a control diet compared to other treatments. The results indicate that adding 18 mg/kg of VC is optimum and further increase does not provide any significant benefit to fish growth and health.

Type 1 diabetic Akita mice have low bone mass and impaired fracture healing.

Type 1 diabetes (T1DM) impairs bone formation and fracture healing in humans. Akita mice carry a mutation in one allele of the insulin-2 (Ins2) gene, which leads to pancreatic beta cell dysfunction and hyperglycemia by 5-6weeks age. We hypothesized that T1DM in Akita mice is associated with decreased bone mass, weaker bones, and impaired fracture healing. Ins2±(Akita) and wildtype (WT) males were subjected to femur fracture at 18-weeks age and healing assessed 3-21days post-fracture. Non-fractured left femurs were assessed for morphology (microCT) and strength (bending or torsion) at 19-21weeks age. Fractured right femurs were assessed for callus mechanics (torsion), morphology and composition (microCT and histology) and gene expression (qPCR). Both Akita and WT mice gained weight from 3 to 18weeks age, but Akita mice weighed less starting at 5weeks (-5.2%, p<0.05). At 18-20weeks age Akita mice had reduced serum osteocalcin (-30%), cortical bone area (-16%), and thickness (-17%) compared to WT, as well as reduced cancellous BV/TV (-39%), trabecular thickness (-23%) and vBMD (-31%). Mechanical testing of non-fractured femurs showed decreased structural (stiffness, ultimate load) and material (ultimate stress) properties of Akita bones. At 14 and 21days post fracture Akita mice had a significantly smaller callus than WT mice (~30%), with less cartilage and bone area. Assessment of torsional strength showed a weaker callus in Akita mice with lower stiffness (-42%), maximum torque (-44%) and work to fracture (-44%). In summary, cortical and cancellous bone mass were reduced in Akita mice, with lower bone mechanical properties. Fracture healing in Akita mice was impaired by T1DM, with a smaller, weaker fracture callus due to decreased cartilage and bone formation. In conclusion, the Akita mouse mimics some of the skeletal features of T1DM in humans, including osteopenia and impaired fracture healing, and may be useful to test interventions.