Skeletal Features Research Articles

Congenital Dyserythropoietic Anemia Type I Due to Biallelic CDAN1 mutations: Report from the Congenital Dyserythropoietic Anemia Registry (CDAR)

Congenital dyserythropoietic anemias (CDA) are rare hereditary diseases of abnormal erythropoiesis. The CDA Registry of North America (CDAR) (NCT02964494) was opened in 2016 to investigate the natural history and molecular biology of CDA. CDA type I (CDA-I) is a recessive form of CDA characterized by macrocytic anemia, hemolysis with inadequate reticulocytosis, and iron overload. The bone marrow shows binucleated erythroblasts with chromatin bridges by light microscopy and spongy heterochromatin in erythroblasts by electron microscopy. The phenotypic heterogeneity in presentation and course of CDA-I is remarkable. Most CDA-I cases are caused by biallelic mutations in CDAN1or C15orf41, and 10-20% do not have an identifiable mutation. Non-hematological features, especially skeletal features, were historically reported in 10-20% of patients (Wickramasinghe, 1998). Due to the rarity of CDA-I and its clinical overlap with several disorders, the diagnosis is often missed or delayed by up to 17 yrs (median) (Roy, 2019). We describe in this study the characteristics and clinical course of CDA-I patients due to CDAN1 mutations enrolled in CDAR. Patients with a phenotypic diagnosis of CDA and their family members were enrolled in CDAR. Clinical and demographic data were gathered from participants at study entry and updated periodically thereafter. Participants elect to give blood, bone marrow, and DNA samples to the biorepository associated with CDAR. Participants with a phenotypic diagnosis of CDA-I and confirmed mutations in CDAN1 were included in this study. Six participants had a diagnosis of CDA-I due to biallelic CDAN1 mutations, comprising 18% (6/33) of affected CDAR participants. CDAN1 mutations were found in 75% of cases diagnosed phenotypically as CDA-I. All six participants presented early in life with a variable degree of non-immune hemolysis, and the diagnosis was confirmed within a median of 2 years from presentation. The characteristics of participants are summarized in table 1. Two had family history of stillbirth or fetal demise in older siblings due to hydrops fetalis. One participant presented prenatally with fetal anemia and started intrauterine transfusions at 24 weeks of gestation; 2 presented with severe anemia and signs of hydrops, pulmonary hypertension, transaminitis, severe hyperbilirubinemia, and thrombocytopenia at birth; and 3 presented with neonatal jaundice and moderate anemia. All participants required blood transfusions in the neonatal period. Three had spontaneous improvement and did not require transfusions after the first year of life. One remained transfusion-dependent at last follow up at the age of 4 yrs. One became transfusion-independent after starting interferon-alpha at 1 yr of age and did not need further transfusions even after discontinuation at 3 yrs of age. One had splenectomy at 11 y.o because he was misdiagnosed to have a membrane disorder but presented in adulthood with hemolytic anemia and pulmonary hypertension and was diagnosed at that time with CDA-I by genetic sequencing. All participants had one or more non-hematological manifestations, including hypertrophic skin folds, onychocryptosis, curved toenails, syndactyly, café-au-lait spots, macrocephaly, spinal fusion, scoliosis, and short stature. One participant suffered a thalamic stroke in the postnatal period, 2 had transient neonatal pulmonary hypertension in the setting of severe anemia, and one had pulmonary hypertension post-splenectomy in adulthood. Ferritin was high in all participants at last follow up, and 4 received chelation therapy. In summary, mutations in CDAN1 are the most common identified mutations in CDAR. CDA-I causes early-onset macrocytic anemia, which may present prenatally, with variable severity of hemolysis ranging from hydrops to mild neonatal jaundice and anemia. Non-hematological manifestations, mainly skeletal, nail and skin abnormalities are more common in CDA-I than previously reported, and their presence in infants with unexplained anemia should raise suspicion for the diagnosis. The availability of molecular testing has significantly accelerated the diagnosis. Management of patients with CDA-I requires multidisciplinary approach from an early age to improve outcome. Collaboration between clinicians, scientists, patients, and families is needed to advance the understanding and treatment of this rare disease. Disclosures Chonat: Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Kalfa:Agios: Other: local PI of clinical research trial; FORMA: Other: sponsored research agreement.

Skeletal abnormalities are common features in Aymé-Gripp syndrome.

Aymé-Gripp syndrome (AYGRPS) is a recognizable condition caused by a restricted spectrum of dominantly acting missense mutations affecting the transcription factor MAF. Major clinical features of AYGRPS include congenital cataracts, sensorineural hearing loss, intellectual disability, and a distinctive flat facial appearance. Skeletal abnormalities have also been observed in affected individuals, even though these features have not been assessed systematically. Expanding the series with four additional patients, here we provide a more accurate delineation of the molecular aspects and clinical phenotype, particularly focusing on the skeletal features characterizing this disorder. Apart from previously reported malar flattening and joint limitations, we document that carpal/tarsal and long bone defects, and hip dysplasia occur in affected subjects more frequently than formerly appreciated.

Therapeutic management of ventricular arrhythmias in Andersen-Tawil syndrome

Andersen-Tawil Syndrome (ATS) is a rare periodic paralysis with typical skeletal and neuromuscular features. Cardiac involvement may range from asymptomatic ventricular arrhythmias to sudden death. Its management remains challenging and the choice between antiarrhythmic drug therapy and implantable cardioverter defibrillator (ICD) is not simple. We present a case of ATS patient with episodes of bidirectional ventricular tachycardia, well controlled by flecainide therapy initially, which in particular conditions of fever and hypokaliemia had a cardiac arrest with ventricular fibrillation, with neurological sequelae and need of an ICD implant. A review of the therapeutic management of this disease is presented.

Recognizing Normal and Hemiplegic Gait According to Human Skeletal Joints Distance Features

Recognizing Normal and Hemiplegic Gait According to Human Skeletal Joints Distance Features

The study of facial morphology in patients with vertical growth pattern (hyperdivergent) lacking or showing temporomandibular disorders symptoms

AimAccording to the large number of studies, there seems to be a significant relation between hyperdivergence growth pattern and temporomandibular disorders. However, it is not clearly scrutinized which morphological factors can contribute to the development of temporomandibular disorders. The aim of this study was to investigate the relation between some skeletal and facial morphologic features of hyperdivergent facial growth pattern patients and temporomandibular disorders. Materials and MethodsThis case-control study was performed on a population of 50 patients including 25 patients with temporomandibular disorder and 25 non- temporomandibular disorder individuals aged between 15–30 years with hyperdivergent growth pattern (Frankfurt Mandibualr plane angle between 28 and 35 degree). Two groups of symptomatic and asymptomatic patients (case and control) were matched for age and gender. In order to evaluate the skeletal and dental variables, lateral cephalometries was taken and traced after obtaining written consent from the patients. The measured variables were A point to Nasion to B point, Frankfurt plane to Nasion to Pogonion, Nasion to A point to Pogonion, Sella to Gnathion to Frankfurt plan, Articular point to Gonion-Menton, Sella to Articular point to Gonion, Palatal plane to Mandibular plane, and Articular point to Gonion angles. The intervals of Basion to Nasion, Sella to Basion, Gonion to Menton, and amounts of Anterior facial height meas, Upper Anterior facial height ratio to Lower Anterior facial height, posterior facial height, overjet, and overbite Data were analyzed by Chi2 test, t-test, and multivariate test. ResultsAccording to the descriptive statistics, the age of the control and case groups averaged 21.12±1.99 and 21.63±1.58 years respectively. Among the people referred to the dental school, the frequency of males and females in the control and case groups were 6, 7 and 19, 18 respectively. The results of t-test and multivariate tests indicated significant differences between the two variables of overbite and mandibular length. ConclusionThe present study revealed increased overbite (dental feature) and mandibular length (skeletal feature) is more likely to be associated with a higher risk of temporomandibular disorders joint disease in patients with hyperdivergent facial growth pattern. Clinical significanceTreatment of the deep bite condition can be helpful in improving temporomandibular disorder.

P6497Loeys-Dietz syndrome-5: phenotypic spectrum of TGFB3 mutations in an international cohort and first report of a homozygous patient

Abstract Background Mutations in TGFB3 cause Loeys-Dietz syndrome-5 (LDS5), an autosomal dominantly inherited connective tissue disorder. LDS5 is characterized by aortic aneurysms and dissections associated with systemic features mainly involving the ocular and skeletal systems. Precise delineation of LDS5 phenotype is difficult because of the small number of identified cases. Purpose The purpose of this study was to further define LDS5 with an emphasis on cardiologic features by describing the genotype and phenotype in an international cohort of patients. Methods We performed a retrospective cross-sectional multicentre study. Genetic testing was performed as a part of standard medical care. Clinical data were collected by means of an anonymized questionnaire, which was sent to the referent physicians. Results Ten (7 novel) TGFB3 mutations were identified in 31 patients (16 index patients). The mean age at last evaluation was 32 years (range 4–60 years). Aortic root dilatation, varices, and mitral valve insufficiency were the most common cardiovascular findings, reported in 28%, 22%, and 21% of patients, respectively. Higher incidences (40%, 29%, and 25%) of these findings were observed in the index patients. Four patients (8%) underwent aortic surgery, all after age 40. Abdominal aortic aneurysms were reported in 2/26 (8%) patients. Extra aortic artery disease included iliac artery aneurysm (one index patient) and tortuosity of the internal carotid and vertebral arteries (one index patient and one relative). The most frequently reported systemic features were high-arched palate, arachnodactyly, pes planus, pectus deformity, and joint hypermobility. Interestingly, we identified an homozygous TGFB3 mutation in a patient who presented with aortic dilatation at age 17, splenic torsion, severe myopia, cleft palate, and other skeletal features. Her heterozygous parents, brother, and sister displayed signs of the disease, but to a milder degree. To the best of our knowledge, this is the first identification of homozygous TGFB3 mutation. Conclusions Our data are in line with previous research, showing that aortic root dilatation is the main cardiovascular feature of LDS5. No deaths related to cardiovascular events were reported in any of the presented families. The cardiovascular phenotype of LDS5 appears to be milder compared to other vascular connective tissue disorder, such as Marfan syndrome, although our findings suggest that homozygosity is associated with a more severe and early-onset phenotype.

Environmental and biological controls on Na∕Ca ratios in scleractinian cold-water corals

Abstract. Here we present a comprehensive attempt to correlate aragonitic Na∕Ca ratios from Desmophyllum pertusum (formerly known as Lophelia pertusa), Madrepora oculata and a caryophylliid cold-water coral (CWC) species with different seawater parameters such as temperature, salinity and pH. Living CWC specimens were collected from 16 different locations and analyzed for their Na∕Ca ratios using solution-based inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements. The results reveal no apparent correlation with salinity (30.1–40.57 g kg−1) but a significant inverse correlation with temperature (-0.31±0.04 mmolmol-1∘C-1). Other marine aragonitic organisms such as Mytilus edulis (inner aragonitic shell portion) and Porites sp. exhibit similar results highlighting the consistency of the calculated CWC regressions. Corresponding Na∕Mg ratios show a similar temperature sensitivity to Na∕Ca ratios, but the combination of two ratios appears to reduce the impact of vital effects and domain-dependent geochemical variation. The high degree of scatter and elemental heterogeneities between the different skeletal features in both Na∕Ca and Na∕Mg, however, limit the use of these ratios as a proxy and/or make a high number of samples necessary. Additionally, we explore two models to explain the observed temperature sensitivity of Na∕Ca ratios for an open and semi-enclosed calcifying space based on temperature-sensitive Na- and Ca-pumping enzymes and transport proteins that change the composition of the calcifying fluid and consequently the skeletal Na∕Ca ratio.

Can radiomics help to predict skeletal muscle response to chemotherapy in stage IV non-small cell lung cancer?

BackgroundMuscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss. MethodsA total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance. ResultsSixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss. ConclusionsThe present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features.

Regulation of mitochondrial activity controls the duration of skeletal muscle regeneration in response to injury

Thyroid hormone is a major regulator of skeletal muscle development and repair, and also a key regulator of mitochondrial activity. We have previously identified a 43 kDa truncated form of the nuclear T3 receptor TRα1 (p43) which stimulates mitochondrial activity and regulates skeletal muscle features. However, its role in skeletal muscle regeneration remains to be addressed. To this end, we performed acute muscle injury induced by cardiotoxin in mouse tibialis in two mouse models where p43 is overexpressed in or depleted from skeletal muscle. The measurement of muscle fiber size distribution at different time point (up to 70 days) upon injury lead us to unravel requirement of the p43 signaling pathway for satellite cells dependent muscle regeneration; strongly delayed in the absence of p43; whereas the overexpression of the receptor enhances of the regeneration process. In addition, we found that satellite cells derived from p43-Tg mice display higher proliferation rates when cultured in vitro when compared to control myoblasts, whereas p43−/− satellites shows reduced proliferation capacity. These finding strongly support that p43 plays an important role in vivo by controling the duration of skeletal muscle regeneration after acute injury, possibly through the regulation of mitochondrial activity and myoblasts proliferation.

Airway and cephalometric changes in adult orthodontic patients after premolar extractions.

To examine changes in the airway and cephalometric measurements associated with orthodontic treatment of adults with and without premolar extractions. The study investigated whether extractions had a direct or indirect effect on the airway and examined selected skeletal and dental features. This retrospective study used pre- (T1) and posttreatment (T2) cone-beam computed tomography scans of 83 adult patients matched for age and sex. A total of 15 airway and 10 skeletal and dental measures were analyzed by means of repeated-measures analysis of variance. There were no results showing that extractions affected airway dimensions that could not be accounted for as reflections of measurement error. There was no evidence that extractions affected the airway indirectly through skeletal and dental changes. There were strong and consistent findings that patients with small airways showed larger ones after treatment and that patients with large airways showed smaller ones later. These effects were independent of whether or not extractions were part of treatment. The measurement phenomena of regression toward the mean and of differential unfolding of natural changes over time could have accounted for the results observed. There was no evidence that extractions in nongrowing patients have negative consequences on the size of various airway measures in the nasopharynx, retropalatal, or retroglossal regions.

Corrosion Resistance Behavior of GTAW Welded AISI type 304L Stainless Steel

Stainless steel (SS) has broad application in nuclear and several industries as structural material attributed to the desirable mechanical and suitable corrosion resistance properties. Corrosion resistance behaviors and microstructural evolutions of type 304L SS gas tungsten arc welded (GTAW) joint of different thickness were investigated using optical microscopy, scanning electron microscopy, X-ray diffraction, micro-Vickers hardness test and electrochemical techniques. Microscopic analsis reveals the weld microstrcture, interdendritic δ-ferrite of lathy and skeletal features along with austenite structure. Hardness is more in 6-mm-thick welded sample attributed to δ-ferrite contents. The measured corrosion rate in boiling HNO3 increases with the increase in the thickness of the welded specimen, and base metal shows a marginally higher corrosion rate compared to weld metals. The corrosion rate of the base and weld metals of the AISI type 304L SS in 65% nitric acid is in the acceptable range. However, as the delta ferrite with a higher amount of chromium is present, the austenite matrix in the microstructure results in a lower corrosion rate of the weldment compared to its base material. The electrochemical corrosion behaviors of type 304L SS base metal and weldments in 6 M HNO3 solution at 25 ± 1 °C are evaluated using potentiodynamic polarization and electrochemical impedance spectroscopy methods. The corrosion resistance, hardness and microstructure behavior of GTAW welded AISI type 304L SS are elaborated and discussed.

Distinction of Arvernoceros ardei and Cervus perrieri (Cervidae, Mammalia) from the late Pliocene site of Perrier (France) based on the postcranial skeleton: taxonomic and phylogenetic conclusions

Characteristics of the postcranial skeleton of Arvernoceros ardei and Cervus perrieri from Perrier (France, late Pliocene, 2.78 ± 0.01 Ma BP, MNQ 16b) are described and distinguished. This was made possible by using the skeletal remains of A. ardei from Kaltensundheim (Germany, Thuringia, late Pliocene age) as identification keys. C. perrieri did not occur in Kaltensundheim. Twenty-five skeletal differences of A. ardei and C. perrieri are detected, and are compared to the genera Eucladoceros, Cervus, Praemegaceros and Megaloceros. The results demonstrate a high level of conformity of A. ardei with Eucladoceros in predominantly plesiomorphic features; major differences exist between A. ardei and Cervus, and A. ardei and Megaloceros. C. perrieri shows several similarities with Cervus elaphus, in which both differ from A. ardei and Eucladoceros. An association of C. perrieri to the genus Cervus is indicated by the postcranial skeleton, as has been discussed in the literature based on antler characteristics. By the findings of Kaltensundheim, a precise association of dental and skeletal characteristics to A. ardei is possible now. The allocation of E. giulii from Untermasfeld (Germany, Thuringia, Jaramillo event) to the genus Arvernoceros appears doubtful based on the dental and skeletal features of A. ardei from Kaltensundheim and Perrier. The original classification within the genus Eucladoceros is considered probable.

Evidence‐based criteria for palaeopathological recognition: New methodology suggests that the rotator cuff condition will be amenable to reliable identification in the archeologic record

AbstractPurpose/research questionPitting or new bone formation on or around tendon insertions, marginal osteophytes, eburnation, cystic changes, and altered contours have been utilized by some palaeopathologists for recognition of the rotator cuff condition, with the purpose of this paper to evaluate the reliability for diagnosis (sensitivity and specificity) of these criteria as documented in the clinical literature.Materials and methodsThe spectrum of medical literature is examined without time limitation, utilizing the phrase “rotator cuff” to assess criteria utilized for diagnosis of a rotator cuff conditions, the reliability of those criteria, and the relationship to symptoms and limitations/disability.ResultsNone of the skeletal features previously referred to by palaeopathologists have reliable indicators for recognition and may simply be age‐related phenomena. New methodology is described, offering the opportunity for confident diagnosis.ConclusionsThere have been no validated evidence‐based criteria applicable for recognizing rotator cuff conditions in skeletons, in the absence of soft tissue structures. Greater tuberosity osteopenia has been noted but not yet evaluated for specificity. Rotator cuff conditions may actually be unrelated to lifestyle but may simply represent the accumulation/culmination of lifetime stresses (aging). The ratio of acromial lateral extension and height provides greater opportunity for confident diagnosis.Given the disconnection between presence or extent of pathology and clinical symptoms and limitations/disability, identification of any of the components utilized in previous consideration of rotator cuff disease diagnosis does not permit extrapolation to confidently hypothesize lifestyle or occupation.Contribution to knowledge/originality/valueDocuments a methodology for confident diagnosis of rotator cuff disease and the challenge of confident attribution of skeletal conditions and clinical/lifestyle implicationsLimitations of this studyEvidence, rather than conjecture/consensus‐based.Suggestions for further researchPopulation survey utilizing ratio of acromial length extension and height.

Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia.

Proteoglycans have a core polypeptide connected to glycosaminoglycans (GAGs) via a common tetrasaccharide linker region. Defects in enzymes that synthesize the linker result in a group of autosomal recessive conditions called "linkeropathies". Disease manifests with skeletal and connective tissue features, including short stature, hyperextensible skin, and joint hypermobility. We report a family with three affected pregnancies showing short limbs, cystic hygroma, and perinatal death. Two spontaneously aborted; one survived 1 day after term delivery, and had short limbs, bell-shaped thorax, 11 ribs, absent thumbs, and cleft palate. Exome sequencing of the proband and one affected fetus identified compound heterozygous missense variants, NM_007255.3: c.808C>T (p.(Arg270Cys)) and NM_007255.3: c.398A>G (p.(Gln133Arg)), in B4GALT7, a gene required for GAG linker biosynthesis. Homozygosity for p.(Arg270Cys), associated with partial loss of B4GALT7 function, causes Larsen of Reunion Island syndrome (LRS), however no previous studies have linked p.(Gln133Arg) to disease. The p.(Gln133Arg) and p.(Arg270Cys) variants were transfected into CHO pgsB-618 cells. High protein expression of p.(Gln133Arg) was found, with mislocalization, compared to p.(Arg270Cys) that had a normal Golgi-like pattern. The p.(Gln133Arg) had almost no enzyme activity and little production of heparan sulfate GAGs, while p.(Arg270Cys) only had 17% of wild-type activity. These findings expand the phenotype of B4GALT7-related linkeropathies to include lethal skeletal dysplasia due to more severe loss of function.

Sleep apnea and the impact on cardiovascular risk in patients with Marfan syndrome.

BackgroundMarfan syndrome (MFS) is an inherited connective tissue disorder characterized by ectopia lentis, aortic root dilation and dissection and specific skeletal features. Obstructive sleep apnea (OSA) in MFS has been described earlier but the prevalence and its relation with the cardiovascular risk is still controversial. This study aimed to further investigate these aspects.MethodsIn this prospective longitudinal study, we performed an attended polysomnography in 40 MFS patients (60% women, 37 ± 12.8 years) and evaluated several cardiovascular parameters through echocardiography, resting electrocardiogram, 24 hr‐Holter monitoring and serum NT‐ProBNP measurements.ResultsWe found that OSA was present in 42.5% of the patients and that higher body mass index was the most important factor associated with the presence of OSA. We observed that overweight was present in 27.5% of the patients in the whole cohort and in 55.6% if >40 years. Furthermore, when evaluating the impact of OSA on the cardiovascular system, we observed that patients with OSA tended to have higher systolic blood pressure, larger distal aortic diameters and a higher prevalence of ventricular arrhythmia. These differences were, however, not significant after adjusting for confounders.ConclusionsOur study shows a high prevalence of OSA and a high prevalence of overweight in MFS patients. We found some trends between OSA and cardiovascular features but we could not establish a solid association. Our study, however might be underpowered, and a multicenter collaborative study could be very useful to answer some important open questions.

The Utility of Skeletal and Surgical Features for the Personal Identification Process: A Pilot Study.

This pilot study provides a conceptual framework for the application of the anthropological analysis of skeletal features and surgical interventions for the purpose of identification in cases of unknown deceased individuals with unavailable fingerprint, genetic or odontological antemortem data. The study sample includes 276 individuals with known demographic and clinical information from the Italian CAL Milano Cemetery Skeletal Collection. In the sample, 124 (45%) individuals showed one or more skeletal features that may be potentially individualizing. Of these, 79% showed two and more features, which occurred in a multitude of different combinations. Skeletal findings may provide useful postmortem information that can be compared with antemortem witness statements and clinical imaging. However, more research into the utility of dry bone findings and the availability of comparative material, including imaging, and epidemiological data needs to be undertaken before skeletal features can be implemented into identification protocols and databases.

The Comparative Skeletal Structure of Blenniella bilitonensis (Skippers) and Bathygobius fuscus (Remainers)

Intertidal Zone is an area with high biological diversity including vertebrates. In order to survive in area with rapid change of environmental condition, animals need to be adapted accordingly. One type of adaptations that mostly employed is structural adaptation specifically ones that related to locomotor performances. Differences on how to navigate during high tides or when the water level subsided as well as types of locomotion between skippers and remainers suggested that there might also be structural differences in their skeleton. This research is aimed to study the skeletal structure of two species that use different strategy in their locomotion. Two species of fish from two main groups of intertidal fish (skippers and remainers) were caught and preserved in 96% Ethanol. The skeletal preparation was made using Inouye’s Alizarin Red Alcyan Blue Method. Data were collected by comparing skeletal structure between two species particularly the axial (vertebrae) and appendicular (pelvic, pectoral, caudal fin) skeleton. Based on the observation, skippers and remainers skeletal features has been adapted to different function during locomotion. Modifications on pelvic, pectoral and caudal bones were found in skippers and remainers. In B. bilitonensis, there are fusion of bones, reduction of some structures and also smaller bone area to provide agility. In remainers, modification mostly found in pelvic and pectoral fin. Pelvic fins possess larger and more rigid basal lepidotrichia as it was used as an attachment apparatus while fish cling to the substrate during high tide. In B. fuscus, pectoral fins are used as main propellers during swimming instead of caudal fins, hence larger bones area to provide more muscle attachment are observed in this species

Correlation Between Mandible and External Ear in Patients with Treacher-Collins Syndrome.

Patients with Treacher-Collins syndrome (TCS) are frequently affected by congenital ear deformities. The external ear in patients with TCS tends to have both abnormal morphology and reduced overall volume. Previous studies considered a correlation exists between TCS mandibular skeletal features and external ear volume. The purpose of this study was to assess the external ear volume in patients with TCS 3-dimensionally. Furthermore, this study evaluated the relationship between mandibular morphology, external ear profile, and external ear volume. A total of 36 nonoperated patients with TCS were compared to 39 age- and gender-matched normal controls. Morphologic variables of the mandible and the external ear were compared between TCS group and controls by 3-dimensional cephalometrics. The external ear volume and morphologic variables were analyzed with independent sample T-tests and Pearson correlation coefficient analyses (level of evidence: level III). The external ear volume was reduced by approximately 50% in patients with TCS compared to controls (P < 0.001). External ear length and width were positively correlated with external ear volume (length: r = 0.809, P < 0.001 on left and r = 0.732, P < 0.001 on right; width: r = 0.518, P = 0.001 on left and r = 0.447, P < 0.010 on right). A negative correlation of right ear inclination angle and external ear volume was shown in patients with TCS (r = -0.396, P = 0.027). However, no correlation was shown for the mandibular anatomic variables. Three-dimensional analysis confirmed that external ear volume is significantly reduced in patients with TCS. The external ear dimensions and orientation correlated significantly with ear volume. There was no intrinsic association between the severity of mandibular deformity and external ear volume.

Gaucher Disease in Bone: From Pathophysiology to Practice.

ABSTRACTGaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years’ of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X‐ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow‐up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.