Endothelin B Receptor Mutant Exhibits Craniofacial Dysmorphology Resembling Domestication Syndrome

Author(s):  
Ko-Chin Chen ◽  
Allison Gee ◽  
Geoffrey Croaker

Abstract Background: ETB-/- mutation is a major cause of HSCR, a neurocristopathy known for its enteric nervous system failure. Other than regulating ENCC migration, ETB mediates ET-1 clearance. Consequently, ETB may indirectly affect ET-1/ETA signaling, which controls CNCC migration and craniofacial development. Interestingly, it was hypothesized that “domestication syndrome” arise from changes in neural crest determining genes, including ETA and ETB. While ETA-/- animals are known to suffer severe dysmorphology resembling CATCH22 syndrome, we hypothesize that sl/sl rat, an ETB-/- HSCR model animal, may exhibit subtle craniofacial changes through indirect control. These features may share resemblance to those of domestication syndrome. Methods: Ten rat pups with an average age of 88 hours were anaesthetized with 5% isoflurane and culled via exsanguination. Tail tips were removed for genotyping. Head tissue were stained in 1.5% iodine for two weeks prior to micro-CT scanning. In vivo micro-CT scanning of cranial specimen was performed followed by ex vivo micro-CT scanning of 2 samples for image quality control. 3D visualization and analyses were performed using open-source program, Drishti. Cephalometric measurements were made based on selected craniofacial landmarks. Comparisons were made between sl/sl rats and the control group, which consisted of wild-type and heterozygotes. Results: Subtle reductions in facial measurements were seen in sl/sl rats when compared with the control group, ranging from 1.4% to 15%. These changes were observed in cranial, maxillary and mandibular parameters: total skull length, nasal length, nasal width, nasal cavity width, interorbital width, interlens distance, inner and outer canthal distance, maximal skull height, cranial length, intracranial length and width, interorbital width, and interzygomatic width. Consistently, craniofacial ratio indices showed sl/sl rat has a flatter cranium (skull height/skull length: 0.393 vs 0.413) and a shorter but broader nose (nasal-width/nasal-length: 0.794 vs 0.874). Additionally, subtle dystopia canthorum may be presented in sl/sl rat based on increased W index. While there was no discrepancy in dental number and morphology between the control and sl/sl groups, dimensional difference was detected. Conclusions: This study demonstrated subtle craniofacial changes are presented in ETB-/- HSCR model, supporting the idea that ETB regulates CNCC migration. The findings also implicate HSCR patient may have predisposing risks for conditions such as obstructive sleep apnea, cleft palate, or dental malocclusion. Lastly, these changes share resemblance with described domestication syndrome, supporting NCC-determining gene, ETB, may play a role in the formation of domestication.

2011 ◽  
Vol 340 ◽  
pp. 241-247
Author(s):  
Ya Bo Yan ◽  
Jun Wang ◽  
Wei Qi ◽  
Yang Zhang ◽  
Wei Lei

To study whether the architectural parameters are sensitive to the shape of volume of interests in micro-CT scanning, six human C5 body samples were scanned by micro-CT. Cubic and cylindrical volumes of interests were acquired as the length of cubic samples was being changed continually. The nonlinear curve fitting method was employed to explore the correlation between the parameters and the volume of interests. The selected morphological indices showed a significantly variable tendency for the lengths of cubic and cylindrical regions of interests, except the Tb.Th and BS/BV. The Dunnett-t tests were performed to compare the architectural parameters of different region of interests against that of control group. There was no significant difference observed between the architectural parameters from cubic region of interests and that from the cylindrical region of interests.


2018 ◽  
Vol 47 (2) ◽  
pp. 694-706 ◽  
Author(s):  
Zengfa Huang ◽  
Cheng Cheng ◽  
Beibei Cao ◽  
Jing Wang ◽  
Hui Wei ◽  
...  

Background/Aims: Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. Methods: In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARγ was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. Results: In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARγ than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. Conclusions: ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ko-Chin Chen ◽  
Zan-Min Song ◽  
Geoffrey D. Croaker

Abstract Background ETB has been reported to regulate neurogenesis and vasoregulation in foetal development. Its dysfunction was known to cause HSCR, an aganglionic colonic disorder with syndromic forms reported to associate with both small heads and developmental delay. We therefore asked, "is CNS maldevelopment a more general feature of ETB mutation?" To investigate, we reviewed the micro-CT scans of an ETB−/− model animal, sl/sl rat, and quantitatively evaluated the structural changes of its brain constituents. Methods Eleven neonatal rats generated from ETB+/− cross breeding were sacrificed. Micro-CT scans were completed following 1.5% iodine-staining protocols. All scans were reviewed for morphological changes. Selected organs were segmented semi-automatically post-NLM filtering: TBr, T-CC, T-CP, OB, Med, Cer, Pit, and S&I Col. Volumetric measurements were made using Drishti rendering software. Rat genotyping was completed following analysis. Statistical comparisons on organ volume, organ growth rate, and organ volume/bodyweight ratios were made between sl/sl and the control groups based on autosomal recessive inheritance. One-way ANOVA was also performed to evaluate potential dose-dependent effect. Results sl/sl rat has 16.32% lower body weight with 3.53% lower growth rate than the control group. Gross intracranial morphology was preserved in sl/sl rats. However, significant volumetric reduction of 20.33% was detected in TBr; similar reductions were extended to the measurements of T-CC, T-CP, OB, Med, and Pit. Consistently, lower brain and selected constituent growth rates were detected in sl/sl rat, ranging from 6.21% to 11.51% reduction. Lower organ volume/bodyweight ratio was detected in sl/sl rats, reflecting disproportional neural changes with respect to body size. No consistent linear relationships exist between ETB copies and intracranial organ size or growth rates. Conclusion Although ETB−/− mutant has a normal CNS morphology, significant size reductions in brain and constituents were detected. These structural changes likely arise from a combination of factors secondary to dysfunctional ET-1/ET-3/ETB signalling, including global growth impairment from HSCR-induced malnutrition and dysregulations in the neurogenesis, angiogenesis, and cerebral vascular control. These changes have important clinical implications, such as autonomic dysfunction or intellectual delay. Although further human study is warranted, our study suggested comprehensive managements are required for HSCR patients, at least in ETB−/− subtype.


2020 ◽  
Vol 45 (2) ◽  
pp. 143-150
Author(s):  
G Demirel ◽  
IH Baltacioglu ◽  
ME Kolsuz ◽  
M Ocak ◽  
B Bilecenoglu ◽  
...  

SUMMARY Objectives: The aim of this study was to measure the volumetric cuspal deflection of premolars restored with different paste-like bulk-fill resin composites using microcomputed tomography (micro-CT). Methods and Materials: A total of 35 freshly extracted human maxillary second premolars were selected for this study. Standardized large MOD cavities were prepared in each premolar with a bucco-lingual width of 4 mm and a cavity depth of 4 mm measured from the palatal cusp tip. After cavity preparation, all samples were scanned immediately using a micro-CT system. After the initial micro-CT scanning, restorative procedures were performed. Four groups received different paste-like bulk-fill composites—Beautifil-Bulk Restorative (BBR), Admira Fusion x-tra (AFX), x-tra fill, and Sonic Fill—and the control group received a conventional universal composite and Clearfil Majesty Esthetic (CME). Immediately after the restorative procedure, each tooth was scanned by micro-CT in the same manner as the initial scanning. The buccal and palatal regions of each restoration were evaluated separately in terms of cuspal deflection. One-way analysis of variance was used to compare the effect of the composite resin, and multiple comparisons were performed by the Tukey test with a level of significance of α = 0.05. Results and Discussion: Multiple comparisons showed that teeth restored with the conventional paste-like composite and CME (control) had significantly different cuspal deflection from those filled with paste-like bulk-fill composites (p<0.05). Among the bulk-fill composites, a significant difference was observed between BBR and AFX (p<0.05). Conclusions: Paste-like bulk-fill resin composites had significantly lower cuspal deflection than the conventional paste-like resin composite tested.


Author(s):  
Ke Yu ◽  
Wenjia Liu ◽  
Naichuan Su ◽  
Helin Chen ◽  
Hang Wang ◽  
...  

The aim of this research was to evaluate the resorption and osseointegration of an autogenous bone ring, which was grafted in a local vertical alveolar defect with simultaneous implant placement. Six Beagle dogs were enrolled in the study; their four nonadjacent mandibular premolars were extracted, and the buccal plate was removed to create bone defects in two of the four sites. Three months after extraction, Straumann implants (Ø 3.3 mm, length of 8 mm) were placed in the bone defect sites with simultaneous autogenous bone ring grafting and in the conventional extraction sites. After a 3-month healing period and a 3-month loading period, the animals were euthanized. The harvested samples were analyzed using micro-CT scanning and histological analysis. From the micro-CT measurements, the average vertical bone resorption of the bone ring was 0.23±0.03 mm, which was not significantly different from that around the conventional implant, 0.24±0.12 mm (P > 0.05). The ratio of the bone volume to the total volume of the bone ring group was 91.11±0.02, which was higher than that of the control group, 88.38±2.34 (P < 0.05). From the hard tissue section, the bone rings developed fine osseointegration with the implants and the base alveolar bone. The results suggest autogenous bone ring grafting with simultaneous implant placement can survive in a local vertical bone defect with little bone resorption and good osseointegration in dogs with strict management. A bone ring graft must be compared with guided bone generation (GBR), and a larger and longer observation must be confirmed in clinical patients.


2014 ◽  
pp. 77-86
Author(s):  
Anh Tien Hoang ◽  
Thi Y Nhi Nguyen ◽  
Luu Trinh Nguyen ◽  
Thi Hong Diep Phan ◽  
Huu Cat Nguyen ◽  
...  

Background : Sleep Apnea Syndrome (SAS) is a cause of hypertension, increasingcardiovascular risk and cardiovascular disease such as stroke, coronary artery disease, myocardial infarction, arrhythmias, heart failure, increasing the risk of death in patients with heart disease, independent of other causative factors. So far, in Vietnam there are very few studies on Obstructive Sleep Apnea Syndrome (OSAS) and cardiovascular risk factors . Self-making SASD07 is trustly for detecting OSAS with statistical significiant in comparision with StarDustII (gold criteria). Subjects and Methods: Cross sectional study, comparision with control group: 136 peoples (68 in disease group and 68 in control group). Patients were parallelly measured with StarDustII and SASD07 to detect OSAS and find the corellation with cardiovascular risk factors. Results: There is a positive correlation between SBP with the severity of OSAS (r = 0.459, p < 0.001), positive correlation between DBP with the severity of OSAS (r = 0.352, p < 0.003). No statistically significant differences between severe OSAS and fasting blood glucose, cholesterol, HDL Cholesterol, Non - HDL Cholesterol, LDL Cholesterol and TG median (p > 0.05). There is a positive correlation between AHI and neck circumference (r = 0.511, p < 0.001), waist circumference (r = 0.585, p < 0.001), BMI (r = 0.380, p < 0.01). SASD07 diagnostic value of detecting OSAS compared with StarDustII have Kappa = 0.72, (standard error 0.06, p <0.001). Conclusion: The risk factors related to OSAS in our study is neck circumference, waist circumference, systolic blood pressure, diastolic blood pressure. SASD07 have a good value in diagnosing of OSAS compared with polysomnography StarDustII. Key words: Sleep Apnea Syndrome, cardiovascular risk factor, SASD07.


2013 ◽  
Vol 82 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Ana Ivanović ◽  
Gregor Aljančič ◽  
Jan W. Arntzen

We performed an exploratory analysis of the morphology of the cranium in the white olm (Proteus anguinus anguinus) and the black olm (P. a. parkelj) with micro-CT scanning and geometric morphometrics. The mudpuppy (Necturus maculosus) was used as an outgroup. The black olm falls outside the white olm morphospace by a markedly wider skull, shorter vomers which are positioned further apart and by laterally positioned squamosals and quadrates relative to the palate (the shape of the buccal cavity). On account of its robust skull with more developed premaxillae a shorter otico-occipital region, the black olm is positioned closer to Necturus than are the studied specimens of the white olm. The elongated skull of the white olm, with an anteriorly positioned jaw articulation point, could be regarded as an adaptation for improved feeding success, possibly compensating for lack of vision. As yet, the alternative explanations on the evolution of troglomorphism in Proteus are an extensive convergence in white olms versus the reverse evolution towards less troglomorphic character states in the black olm. To further understand the evolutionary trajectories within Proteus we highlight the following hypotheses for future testing: i) morphological differentiation is smaller within than between genetically differentiated white olm lineages, and ii) ontogenetic shape changes are congruent with the shape changes between lineages. We anticipate that the morphological detail and analytical power that come with the techniques we here employed will assist us in this task.


2021 ◽  
Vol 11 (11) ◽  
pp. 5086
Author(s):  
Mazen F. Alkahtany ◽  
Saqib Ali ◽  
Abdul Khabeer ◽  
Shafqat A. Shah ◽  
Khalid H. Almadi ◽  
...  

This study aimed to investigate variations in the root canal morphology of maxillary second premolar (MSP) teeth using microcomputed tomography (micro-CT). Sixty (N = 60) human extracted MSPs were collected and prepared for micro-CT scanning. The duration for scanning a single sample ranged between 30 and 40 min and a three-dimensional (3-D) image was obtained for all the MSPs. The images were evaluated by a single observer who recorded the canal morphology type, number of roots, canal orifices, apical foramina(s), apical delta(s), and accessory canals. The root canal configuration was categorized in agreement with Vertucci’s classification, and any configuration not in agreement with Vertucci’s classification was reported as an “additional canal configuration”. Descriptive statistics (such as mean percentages) were calculated using SPSS software. The most common types agreeing with Vertucci’s classification (in order of highest to lowest incidence) were types I, III, V, VII, II, and VI. The teeth also exhibited four additional configurations that were different from Vertucci’s classification: types 2-3, 1-2-3, 2-1-2-1, and 1-2-1-3. A single root was found in 96.7% and the majority of the samples demonstrated two canals (73.3%). Further, 80% of the teeth showed one canal orifice. The number of apical foramina’s in the teeth was variable, with 56.7% having solitary apical foramen. The accessory canal was found in 33.3%, and apical delta was found in only 20% of the samples. Variable morphology of the MSPs was detected in our study. The canal configuration most prevalent was type 1; however, the results also revealed some additional canal types.


OTO Open ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 2473974X2198959
Author(s):  
Ahmed Yassin Bahgat

Objective Plasma is formed by creating a high-density energy field within an electrically conductive fluid such as saline. Sometimes ablated bits of tissue get stuck between the electrodes of the wand, obstructing the suction channel. The purpose of this study is to investigate the effect of cooling the irrigating saline during ablation of the hypertrophied tongue base in patients with obstructive sleep apnea. Study Design Prospective randomized controlled trial. Setting An otorhinolaryngology department in Main University hospitals. Methods Sixty adult patients with obstructive sleep apnea and tongue base hypertrophy underwent tongue base ablation surgery. Patients were randomly divided into 2 groups of 30 patients each: cooled saline and room temperature saline. The Coblation wand used was the EVac 70 Xtra HP (Smith & Nephew). Results In this study, a significant difference in operative time (mean ± SD) was seen between groups: 21.2 ± 5.5 minutes in the cold group and 47 ± 9.5 minutes in the control group ( P = .001). The wands in the cold group did not obstruct, while all the wands in the control group were obstructed by tissue clogs with variable degrees, hence wasting more time to clean the wands’ tips. Conclusion Cooling the irrigating saline overcame the problem of wand clogs, and the wand tip did not occlude at all during the procedures, thus saving time lost in wand cleaning and demonstrating a faster and safer surgical procedure. Further studies are needed to identify the hemostatic effect of the cooled saline over the regular one.


Author(s):  
Melek Cihanbeylerden ◽  
Melike Bağnu Yüceege

Abstract Introduction Obstructive sleep apnoea (OSA) is a cause of hypoxia, and the correlation between hypoxia and microvascular complications is well known. Microalbuminuria (MAU) is a marker for endovascular dysfunction and an indicator of cardiovascular events and all-cause mortality in the general population. The aim of this study was to investigate the relationship between microvascular damage and the metabolic complications of OSA based on the presence of MAU. Material and method Urinary albumin/creatinine ratio (ACR) and microalbumin level were examined in patients with an apnoea-hypopnoea index (AHI) greater than 5/h (study group) and in patients with an AHI less than 5/h (control group). The exclusion criteria were other possible causes of MAU (hypertension, nephropathy, coronary artery disease, and severe thyroid dysfunction). Results Of 103 patients enrolled, 80 formed the group with OSA and 23 served as controls. According to the AHI values, the patients were divided into four groups as normal, mild, moderate and severe. There was no significant difference between the four groups in terms of the microalbumin level and urinary albumin/creatinine ratio. Conclusion In this study, no significant relationship was found between MAU and sleep apnoea.


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