Skeletal Features Research Articles

Design, synthesis, anti-inflammatory, cytotoxic and cell based studies of some novel side chain analogues of myrrhanones A & B isolated from the gum resin of Commiphora mukul

Myrrhanones A (1) and B (2), isolated from the gum resin of Commiphora mukul, were reported to exhibit anticancer and anti-inflammatory activities. In view of their interesting skeletal features and biological activities they have been chemically modified by exploiting their side chain functionalities to synthesise 29 diverse analogues. All the synthesized analogues were screened for their cytotoxic potential against a panel of five human cancer cell lines which include DU145 (Prostate), HT-29 (Colon), MCF-7 (Breast), Hela (Cervical) and U87MG (Glioblastoma) along with a normal cell line (L132). The synthesized analogues were also screened for anti-inflammatory activity against TNF-α and IL-1β using LPS induced inflammation model employing U937 cells. The biological screening results revealed that compounds 4b (piperidine analogue), 9d (linear aliphatic four member amide analogue) and 9i (N-methyl piperazine analogue) displayed significant cytotoxic activity against MCF-7, HT-29 and DU145 [IC50 (μM): 4.65 ± 1.28, 5.48 ± 0.13 and 6.63 ± 1.39] respectively. These analogues were further taken up for apoptotic assay, which confirmed that compounds 4b, 9d and 9i induced apoptosis in MCF-7, HT-29, DU145 cells and arrested in G0/G1 phase. Further, compounds 9c and 9g found to exhibit good anti-inflammatory activity against TNF-α with IC50 (μM) values of 10.02 ± 2.13 and 10.53 ± 0.48 respectively, while compound 2 exhibited strong inhibitory activity against both TNF-α (IC50: 9.39 ± 0.44 μM) and IL-1β (IC50: 12.15 ± 1.36 μM).

Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features

PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.

The Relation Between Morphometric Features and Susceptibility to Mandibular Angle Fractures.

The study was aimed to determine possible relations between skeletal morphologic parameters to mandibular angle fractures. Retrospective study of 100 patients suffering from mandibular fractures and treated in the Rambam Health Care Campus between the years 2013 and 2017 was conducted. Predictor variable was facial skeletal morphologic features as derived from the measurements. Outcome variable was mandibular angle fractures. About 42 patients suffered from angle fractures. Gonial angle (131.3° versus 118.1°), condylar neck width (8.3 mm versus 6.8 mm sagittaly and 7.1 mm versus 5.8 mm horizontally), and wisdom tooth prevalence and impaction were positively correlated to the fracture. Ramus height (48.3 mm versus 53.4 mm) was negatively correlated to angle fractures. Many reports in the literature show positive relations between impacted 3rd molars and angle fractures, yet only sporadic reports describe relations between facial fractures and facial features. Our results showed the predictable positive relation between angle fractures and 3rd molar prevalence and impaction. Yet surprisingly, we found unequivocal significant positive correlation between angle fractures to gonial angle and condylar neck width and negative correlation to ramus height. Based on the correlation to the gonial angle and ramal height, it is concluded that enlarged anterior vertical growth is a predictor for angle fractures, as are condylar neck width, and wisdom teeth.

Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome

To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.

Identification of an aquaculture poriferan "Pest with Potential" and its phylogenetic implications.

Correct identification and classification of sponges is challenging due to ambiguous or misleading morphological features. A particular case is a blue keratose sponge occasionally referred to as the “Blue Photo Sponge” among aquarists, which appears frequently (and in several cases unintended) in private aquaria. This spicule-less species, occasionally specified as Collospongia auris Bergquist, Cambie & Kernan 1990, not only displays a high phenotypic plasticity in growth form and colour, it also proliferates in aquacultures under standard conditions unlike most other sponges. Therefore, this species is regarded as a pest for most aquarists. In turn, the ease of cultivation and propagation in aquacultures qualifies this species as a model organism for a wide array of scientific applications. For these purposes, correct identification and classification are indispensable. We reconstructed ribosomal gene trees and determined this species as Lendenfeldia chondrodes (De Laubenfels, 1954) (Phyllospongiinae), distant to Collospongia auris, and corroborated by skeletal features. Additionally, the resulting phylogeny corroborated major shortcomings of the current Phyllospongiinae classification—its consequences are discussed.

A Cephalometric Comparative Study for Upper Airway Dimensions in Different Craniofacial Growth Patterns

AIM AND OBJECTIVES: To compare different craniofacial patterns with pharyngeal widths. In OSA (Obstructive Sleep Apnea) patients, a mutual association between the pharyngeal structures and the dentofacial patterns has been suggested. The present study was performed to compare the nasopharynx, oropharynx and hypopharynx dimensions of persons with hypodivergent, normodivegent and hyperdivergent facial types and to predict and to facilitate treatment for OSA patients.Hypothesis: The Null hypothesis for the study was that there is no difference between the upper airway for patients with different growth pattern.MATERIALS AND METHODS: The sample comprised 60 patients divided into three groups: hypodivergent (n=20), normodivergent (n=20), and hyperdivergent (n=20) according to Jarabak’s ratio and FH-MP angle, which were used to compare the soft tissue airway dimensions. The statistical analysis was performed using Student’s t-Test, one way ANOVA (analysis of variance) and LSD (Least significant difference) test.RESULT: Overall narrower anteroposterior pharyngeal dimension was found in the hyperdivergent group as compared to the normodivergent group. Whereas, the superior part of upper pharyngeal width in the subjects with hypodivergent growth pattern was significantly narrower than in normal growth pattern groups.CONCLUSION: In hyperdivergent patients, the narrower anterioposterior dimension of the airway may be due to the skeletal features common to such patients, i.e., posterior vertical maxillary excess, posterior position and decreased mandibular size. The variations of the upper airway may be attributed to the horizontal and vertical growth patterns. Upper airway obstruction and later on OSA may be predisposed by skeletal deficiency.

A Scene Recognition and Semantic Analysis Approach to Unhealthy Sitting Posture Detection during Screen-Reading.

Behavior analysis through posture recognition is an essential research in robotic systems. Sitting with unhealthy sitting posture for a long time seriously harms human health and may even lead to lumbar disease, cervical disease and myopia. Automatic vision-based detection of unhealthy sitting posture, as an example of posture detection in robotic systems, has become a hot research topic. However, the existing methods only focus on extracting features of human themselves and lack understanding relevancies among objects in the scene, and henceforth fail to recognize some types of unhealthy sitting postures in complicated environments. To alleviate these problems, a scene recognition and semantic analysis approach to unhealthy sitting posture detection in screen-reading is proposed in this paper. The key skeletal points of human body are detected and tracked with a Microsoft Kinect sensor. Meanwhile, a deep learning method, Faster R-CNN, is used in the scene recognition of our method to accurately detect objects and extract relevant features. Then our method performs semantic analysis through Gaussian-Mixture behavioral clustering for scene understanding. The relevant features in the scene and the skeletal features extracted from human are fused into the semantic features to discriminate various types of sitting postures. Experimental results demonstrated that our method accurately and effectively detected various types of unhealthy sitting postures in screen-reading and avoided error detection in complicated environments. Compared with the existing methods, our proposed method detected more types of unhealthy sitting postures including those that the existing methods could not detect. Our method can be potentially applied and integrated as a medical assistance in robotic systems of health care and treatment.

Franklin expedition lead exposure: New insights from high resolution confocal x-ray fluorescence imaging of skeletal microstructure.

In the summer of 1845, under the command of Sir John Franklin, 128 officers and men aboard Royal Navy ships HMS Erebus and HMS Terror sailed into Lancaster Sound and entered the waters of Arctic North America. The goal of this expedition was to complete the discovery of a northwest passage by navigating the uncharted area between Barrow Strait and Simpson Strait. Franklin and his crew spent the first winter at Beechey Island, where three crewmen died and were buried. In September 1846, the ships became stranded in ice off the northwest coast of King William Island, where they remained until April 1848. At that time, the crew, reduced to 105, deserted the ships and retreated south along the island’s western and southern shores in a desperate attempt to reach the mainland and via the Back River, to obtain aid at a Hudson’s Bay Company Post. Sadly, not one individual survived. Previous analyses of bone, hair, and soft tissue samples from expedition remains found that crewmembers’ tissues contained elevated lead (Pb) levels, suggesting that Pb poisoning may have contributed to their demise; however, questions remain regarding the timing and degree of exposure and, ultimately, the extent to which the crewmembers may have been impacted. To address this historical question, we investigated three hypotheses. First, if elevated Pb exposure was experienced by the crew during the expedition, we hypothesized that those sailors who survived longer (King William Island vs. Beechey Island) would exhibit more extensive uptake of Pb in their bones and vice versa. Second, we hypothesized that Pb would be elevated in bone microstructural features forming at or near the time of death compared with older tissue. Finally, if Pb exposure played a significant role in the failure of the expedition we hypothesized that bone samples would exhibit evidence of higher and more sustained uptake of Pb than that of a contemporary comparator naval population from the 19th century. To test these hypotheses, we analyzed bone and dental remains of crew members and compared them against samples derived from the Royal Navy cemetery in Antigua. Synchrotron-based high resolution confocal X-ray fluorescence imaging was employed to visualize Pb distribution within bone and tooth microstructures at the micro scale. The data did not support our first hypothesis as Pb distribution within the samples from the two different sites was similar. Evidence of Pb within skeletal microstructural features formed near the time of death lent support to our second hypothesis but consistent evidence of a marked elevation in Pb levels was lacking. Finally, the comparative analysis with the Antigua samples did not support the hypothesis that the Franklin sailors were exposed to an unusually high level of Pb for the time period. Taken all together our skeletal microstructural results do not support the conclusion that Pb played a pivotal role in the loss of Franklin and his crew.

ERAP1 deficient mice have reduced Type 1 regulatory T cells and develop skeletal and intestinal features of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a prototypical sero-negative autoimmune disease that affects millions worldwide. Single nucleotide polymorphisms in the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) gene have been linked to AS via GWAS studies, however, the exact mechanism as to how ERAP1 contributes to pathogenesis of AS is not understood. We undertook µCT imaging and histologic analysis to evaluate bone morphology of the axial skeletons of ERAP1−/− mice and discovered the hallmark skeletal features of AS in these mice, including spinal ankylosis, osteoporosis, and spinal inflammation. We also confirmed the presence of spontaneous intestinal dysbiosis and increased susceptibility to Dextran Sodium Sulfate (DSS)-induced colitis in ERAP1−/− mice, however the transfer of healthy microbiota from wild type mice via cross-fostering experiments did not resolve the skeletal phenotypes of ERAP1−/− mice. Immunological analysis demonstrated that while ERAP1−/− mice had normal numbers of peripheral Foxp3+ Tregs, they had reduced numbers of both “Tr1-like” regulatory T cells and tolerogenic dendritic cells, which are important for Tr1 cell differentiation. Together, our data suggests that ERAP1−/− mice may serve as a useful animal model for studying pathogenesis of intestinal, skeletal, and immunological manifestations of Ankylosing Spondylitis.

Dimorphism throughout the European eel's life cycle: are ontogenetic changes in head shape related to dietary differences?

A well-known link exists between an organism's ecology and morphology. In the European eel, a dimorphic head has been linked to differences in feeding ecology, with broad-headed eels consuming harder prey items than narrow-headed ones. Consequently, we hypothesized that broad-heads should exhibit a cranial musculoskeletal system that increases bite force and facilitates the consumption of harder prey. Using 3D-reconstructions and a bite model, we tested this hypothesis in two life stages: the sub-adult yellow eel stage and its predecessor, the elver eel stage. This allowed us to test whether broad- and narrow-headed phenotypes show similar trait differences in both life stages and whether the dimorphism becomes more pronounced during ontogeny. We show that broad-headed eels in both stages have larger jaw muscles and a taller coronoid, which are associated with higher bite forces. This increased bite force together with the elongated upper and lower jaws in broad-headed eels can also improve grip during spinning behavior, which is used to manipulate hard prey. Head shape variation in European eel is therefore associated with musculoskeletal variation that can be linked to feeding ecology. However, although differences in muscle volume become more pronounced during ontogeny, this was not the case for skeletal features.

Identification and characterization of a novel FBN1 gene variant in an extended family with variable clinical phenotype of Marfan syndrome

ABSTRACTMarfan syndrome (MFS) is a multi-systemic autosomal dominant condition caused by mutations in the gene (FBN1) coding for fibrillin-1. Mutations have been associated with a wide range of overlapping phenotypes. Here, we report on an extended family presenting with skeletal, ocular and cardiovascular clinical features. The 37-year-old male propositus, who had chest pain, dyspnea and shortness of breath, was first diagnosed based on the revised Ghent criteria and then subjected to molecular genetic analyses. FBN1 sequencing of the proband as well as available affected family members revealed the presence of a novel variant, c.7828G>C (p.Glu2610Gln), which was not present in any of the unaffected family members. In silico analyses demonstrated that the Glu2610 residue is part of the conserved DINE motif found at the beginning of each cbEGF domain of FBN1. The substitution of Glu2610 with Gln decreased fibrillin-1 production accordingly. Despite the fact that this variation appears to be primarily responsible for the etiology of MFS in the present family, our findings suggest that variable clinical expressions of the disease phenotype should be considered critically by the physicians.

Establishment of a prediction method for the mid-facial region of unknown human Mongoloid skeletal remains

Forensic facial approximation is a technique used to estimate the antemortem facial features of unknown skeletal remains. In recent years, many researchers have reported nasal tip predictions with positive results. However, the morphological nasal features of the skull can vary widely, and it is hard to obtain accurate values using facial approximation techniques. We assumed that these variations are due to an over-dependence on the values obtained from a single distance metric factor in an anatomical area. Measurements were acquired using cephalometric radiographic images obtained from 190 Japanese individuals (90 men, aged 18–36 years and 100 women, aged 18–46 years). Soft tissue and skeletal features were traced onto acetate sheets. The orbitale (Or), porion (Po), and the Frankfurt Horizontal Plane (FHP) were plotted in addition to the rhinion (Rhi), anterior nasal spine (ANS), subnasale (Sn), prosthion, and point-A (A). From these, the following were measured: a length from rhinion to prosthion; b length from rhinion to the intersection of a line perpendicular to the anterior nasal spine; c length from the prosthion to the intersection of a line perpendicular to the anterior nasal spine; g the proportion of d/b; and f the proportion of c/b. A calculation was generated from these measurements and from proportions of a–h, and applied to the samples. An R-squared (RSQ) test and standard error (SE) were used to compare the actual and predicted values. The errors observed between the predicted and actual values were not greater than 5mm in any of the samples; 91.3% and 71.2% of predicted Sn had an error lower than 2.5 and 1.5mm respectively, from the actual. Reliable results were obtained using the method in the present study.In addition, in the process of obtaining the measurements, we found reliable proportional differences between the sexes in the piriform and axillary alveolar regions.

Caustic Skeleton & Cosmic Web

We present a general formalism for identifying the caustic structure of a dynamically evolving mass distribution, in an arbitrary dimensional space. The identification of caustics in fluids with Hamiltonian dynamics, viewed in Lagrangian space, corresponds to the classification of singularities in Lagrangian catastrophe theory. On the basis of this formalism we develop a theoretical framework for the dynamics of the formation of the cosmic web, and specifically those aspects that characterize its unique nature: its complex topological connectivity and multiscale spinal structure of sheetlike membranes, elongated filaments and compact cluster nodes. Given the collisionless nature of the gravitationally dominant dark matter component in the universe, the presented formalism entails an accurate description of the spatial organization of matter resulting from the gravitationally driven formation of cosmic structure. The present work represents a significant extension of the work by Arnol'd et al. [1], who classified the caustics that develop in one- and two-dimensional systems that evolve according to the Zel'dovich approximation. His seminal work established the defining role of emerging singularities in the formation of nonlinear structures in the universe. At the transition from the linear to nonlinear structure evolution, the first complex features emerge at locations where different fluid elements cross to establish multistream regions. Involving a complex folding of the 6-D sheetlike phase-space distribution, it manifests itself in the appearance of infinite density caustic features. The classification and characterization of these mass element foldings can be encapsulated in caustic conditions on the eigenvalue and eigenvector fields of the deformation tensor field. In this study we introduce an alternative and transparent proof for Lagrangian catastrophe theory. This facilitates the derivation of the caustic conditions for general Lagrangian fluids, with arbitrary dynamics. Most important in the present context is that it allows us to follow and describe the full three-dimensional geometric and topological complexity of the purely gravitationally evolving nonlinear cosmic matter field. While generic and statistical results can be based on the eigenvalue characteristics, one of our key findings is that of the significance of the eigenvector field of the deformation field for outlining the entire spatial structure of the caustic skeleton emerging from a primordial density field. In this paper we explicitly consider the caustic conditions for the three-dimensional Zel'dovich approximation, extending earlier work on those for one- and two-dimensional fluids towards the full spatial richness of the cosmic web. In an accompanying publication, we apply this towards a full three-dimensional study of caustics in the formation of the cosmic web and evaluate in how far it manages to outline and identify the intricate skeletal features in the corresponding N-body simulations.

Shape variation and modularity of skull and teeth in domesticated horses and wild equids

BackgroundIn horses, the morphological changes induced by the process of domestication are reportedly less pronounced than in other species, such as dogs or pigs – although the horses’ disparity has rarely been empirically tested. We investigated shape differences and modularity of domesticated horses, Przewalski’s horses, donkeys and zebras. Mandibular and tooth shape have been shown to be valuable features for differentiating wild and domesticated forms in some mammals.ResultsBoth mandible and teeth, show a pattern of shape space occupation analogous to that of the cranium, with domesticated horses occupying a similar extension in shape space to that of wild equids. Only cranial shape data exhibit a tendency to separate domesticated horses and Przewalski’s horses from donkeys and zebras. Maximum likelihood model-based tests confirm the horse cranium is composed of six developmental modules, as reported for placental mammals in general. The magnitude of integration in domesticated horse skull was lower than in wild equids across all six cranial modules, and lower values of integration were associated with higher disparity values across all modules.ConclusionThis is the first study that combines different skeletal features for the description and comparison of shape changes in all living equid groups using geometric morphometrics. We support Darwin’s hypothesis that the shape variation in the skull of domesticated horses is similar to the shape variation of all wild equid species existing today. Lower magnitudes of module integration are recovered in domesticated horses compared to their wild relatives.

Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7

Frontometaphyseal dysplasia 2 (FMD2) is a skeletal dysplasia with supraorbital hyperostosis combined with undermodeling of the bones, joint contractures and some extraskeletal features. It is caused by heterozygous mutations in MAP3K7, encoding the Mitogen-Activated Protein 3-Kinase 7. MAP3K7 is activated by TGF-β and plays an important role in osteogenesis. Less than 20 patients with FMD2 and MAP3K7 mutations have been described thus far. The majority of the patients harbor a recurrent missense mutation, NM_003188.3: c.1454C > T [NP_003179.1: p.(Pro485Leu)], which leads to a more severe phenotype than mutations in other domains. Here we describe an additional patient with FMD2 caused by the recurrent c.1454C > T MAP3K7 mutation, identified as a de novo variant by whole-genome sequencing. The 17-year-old boy has the characteristic skeletal and facial features of FMD2. However, some novel features were also observed, including growth retardation and spina bifida occulta. In line with other patients harboring the same mutation he also showed keloid scars and had no intellectual disability. This report expands the clinical spectrum of FMD2 caused by the recurrent c.1454C > T [p.(Pro485Leu)] mutation in MAP3K7.

Concise total synthesis of (±)-aspidospermidine and computational study: FT-IR, NMR, NBO, NLO, FMO, MEP diagrams

Aspidospermidine is a member of the compound class known as aspidospermaten-type alkaloids. Aspidospermidine is among the most highly sought aspidosperma alkaloid targets because it comprises the basic skeletal features of this family of natural products, particularly the complex and characteristic pentacyclic ABCDE framework. In this study, we used a new strategy developed to synthesize (±)aspidospermidine. The key steps involve a novel cyclization in a single step through an indoline substructure, leading to a versatile pentacyclic intermediate. The power of this concept has been demonstrated through the expedient, total syntheses of well-known alkaloid natural products including limaspermidine, vincadifformine, minovincine and cylindrocarine. Additionally, the PES scan has been performed to determine the stable conformers of the aspidospermidine compound at B3LYP/6-31G(d,p) level of theory in the gas phase and the stable conformers have been used to further analyses. The 1H and 1C NMR chemical shifts of the aspidospermidine compound have been observed by NMR spectroscopy and compared with the simulated by the GIAO (Gauge-Independent Atomic Orbital) approach. The vibrational modes determined by the FT-IR spectroscopy has been compared to the simulated vibrational modes of the aspidospermidine. The NBO analysis has been employed to elucidate the important intra-molecular interactions causing the molecular stability and the optical properties of the aspidospermidine have been investigated by NLO analysis. The FMO analysis and MEP diagrams have been used to predict the physicochemical and quantum chemical properties being important to explore the chemical reactivity behavior of the aspidospermidine.

367 Role of Pressure Magnitude in Compression Garment Therapy

Pressure garments are commonly employed to reduce scarring following burn injury, with varying efficacy rates reported. A possible mechanism for this variability is the range of pressures utilized. The optimum magnitude of pressure necessary to achieve the greatest benefit is unknown, though it has been suggested that pressure should exceed capillary pressure, 25–30 mmHg. Unfortunately, higher pressures are associated with increased risk of side effects such as deformation of skeletal features or constricted breathing. To better understand the role of pressure magnitude on therapy efficacy, pressure garment therapy and scar development was studied in a porcine model. Full-thickness burns (1 x 1 in) were created on female, red Duroc pigs (8 burns per pig), excised, and autografted with split-thickness autografts. Custom adjustable pressure garments were applied 1 wk after grafting and maintained at either 10, 20, or 30 mm Hg for 11 wks. Scar properties were monitored over time, including contraction, scar height, erythema, and biomechanics. All pressure-treated groups were significantly less contracted than controls. Scars in the 30 mm Hg group were 46% larger than controls and 13% larger than the 20 mm Hg group 6 wks post-grafting (p < 0.05). This trend persisted throughout the study with a 56% greater scar area in 30 mm Hg treated group vs. controls and 16% increase vs. the 20 mm Hg group (p < 0.05). Pressure therapy, at all magnitudes, significantly improved the scar elasticity and pliability. Pressure garment therapy, delivered at 30 mm Hg, was the most effective at reducing scar contraction compared to 20 or 10 mm Hg. In addition, all levels of pressure (10, 20 and 30 mm Hg) resulted in statistically significant benefits to scar pliability and elasticity with the greatest improvement observed when scars were treated with 30 mm Hg. Fabrication of garments to apply 30 mm Hg pressure to underlying scars results in scars that are thinner, more pliable and less contracted than garments exerting lower pressures. While higher pressures led to superior outcomes in our study, we did note that higher pressures led to increased garment fatigue and were overall less comfortable. If higher pressures cannot be tolerated or begin to cause detrimental effects, scar improvements can still be obtained with lower pressures.

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome \u2013 new data and literature review

BackgroundHajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bone formation and resorption. The skeletal features of HCS include acro-osteolysis of the digits and osteoporosis commonly affecting vertebrae and long bones. Fractures are a prominent feature and are associated with significant morbidity. There is no specific treatment, but with both acro-osteolysis and generalized osteoporosis, it is possible that anti-resorptive treatment might be of benefit. However, to date only a few case reports have evaluated the effectiveness of bisphosphonate treatment.MethodsWe describe the clinical features, treatment regimens and response to bisphosphonate treatment in 7 newly described patients aged 6–39 with HCS, and pooled the data with that from 8 previously published cases (a total of 17 courses of treatment in 15 individuals).ResultsThe mean lumbar spine bone mineral density (BMD) z-score before treatment was − 2.9 (SD 1.2). In 14 courses of treatment (82%), there was an increase in BMD with bisphosphonate treatment, but the impact (in terms of change in spinal BMD z-score) appeared to be less with advancing age (p = 0.01). There was no evidence that acro-osteolysis was prevented.ConclusionsAlthough individual response is variable and age-related, the data support a role for bisphosphonates in preventing or treating spinal osteoporosis in HCS, but bone loss from the lumbar spine may be rapid after cessation.

Craniofacial structures' development in prenatal period: An MRI study.

The development of skeletal structures (cranial base, upper and lower) and upper airways spaces (oropharyngeal and nasopharyngeal) of the skull has always been an issue of great interest in orthodontics. Foetal MRI images obtained as screening exam during pregnancy can help to understand the development of these structures using a sample cephalometric analysis. A total of 28 MRI images in sagittal section of foetuses from 20th to 32th weeks of gestation were obtained to dispel doubts about the presence of skeletal malformations. Cephalometric measurements were performed on MRI T2-dependent images acquired with a 1.5 T scanner. The Software Osirix 5 permits to study sagittal and vertical dimensions of the skull analysing linear measurements, angles and areas of the skeletal structures. Vertical and sagittal dimension of cranial base, maxilla and mandible grow significantly (P<.01) between the second and third trimester of gestational period as well as nasopharyngeal and oropharyngeal spaces (P<.05). High correlation between the development of anterior cranial base and functional areas devoted to speech and swallow is demonstrated (r: .97). The development of craniofacial structures during foetal period seems to show a close correlation between skeletal features and functional spaces with a peak between the second and third trimester of gestation. MRI images result helpful for the clinician to detect with a sample cephalometric analysis anomalies of skeletal and functional structures during prenatal period.

Heritability of the airway structure and head posture using twin study.

Inherited traits of obstructive sleep apnoea (OSA) may have link to the heritability of the airway anatomy. The aim of this study was to investigate heritability of the airway anatomy by comparing skeletal and soft tissue features of Korean monozygotic twins (MZ) and dizygotic twins (DZ). In total, 72 participants (mean age, 41.5±5.9years; 40 males, 32 females) including 48 MZ (24 pairs) and 24 DZ (12 pairs) with same sex were participated. The craniofacial, craniovertebral, hyoideal and pharyngeal parameters were measured using lateral cephalograms. The genetic analysis was performed using Falconer's method. High heritability was detected in the hyoid position and inclination of the cervical column. The velopharyngeal and hypopharyngeal dimensions showed higher heritability compared to those of the nasopharynx and oropharynx. The body mass index (BMI) had interactions with the nasopharyngeal and hypopharyngeal dimensions and length of the tongue and soft palate. The mandibular growth had correlations with the nasopharyngeal and hypopharyngeal dimensions. The vertical skeletal relationships appeared to have interaction with the nasopharyngeal, velopharyngeal and hypopharyngeal dimensions, as well as length of the tongue and soft palate. A forwarded inclination of the cervical columns was seen in connections with BMI and the nasopharyngeal and hypopharyngeal dimensions. The airway structures and head postures seemed to be under strong genetic controls. The airway dimensions had associations with BMI, head postures and skeletal structures which showed high heritability. Forwarded head postures would be physiological adaptations of compromised airway adequacy by increased BMI and retrognathia.