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Journal of Structural Biology Dec 2020Craniosynostosis severity varies in patients with identical genetic mutations. To understand causes of this phenotypic variation, we backcrossed the FGFR2 mouse model of...
Craniosynostosis severity varies in patients with identical genetic mutations. To understand causes of this phenotypic variation, we backcrossed the FGFR2 mouse model of Crouzon syndrome onto congenic C57BL/6 and BALB/c backgrounds. Coronal suture fusion was observed in C57BL/6 (88% incidence, p < .001 between genotypes) but not in BALB/c FGFR2 mutant mice at 3 weeks after birth, establishing that that the two models differ in phenotype severity. To begin identifying pre-existing modifiers of craniosynostosis severity, we compared transcriptome signatures of cranial tissues from C57BL/6 vs. BALB/c FGFR2 mice. We separately analyzed frontal bone with coronal suture tissue from parietal bone with sagittal suture tissues because the coronal suture but not the sagittal suture fuses in FGFR2 mice. The craniosynostosis associated Twist and En1 transcription factors were down-regulated, while Runx2 was up-regulated, in C57BL/6 compared to BALB/c tissues, which could predispose to craniosynostosis. Transcriptome analyses under the GO term MAPK cascade revealed that genes associated with calcium ion channels, angiogenesis, protein quality control and cell stress response were central to transcriptome differences associated with genetic background. FGFR2 and HSPA2 protein levels plus ERK1/2 activity were higher in cells isolated from C57BL/6 than BALB/c cranial tissues. Notably, the HSPA2 protein chaperone is central to craniofacial genetic epistasis, and we find that FGFR2 protein is abnormally processed in primary cells from FGFR2 but not FGFR2 mice. Therefore, we propose that differences in protein quality control responses may contribute to genetic background influences on craniosynostosis phenotype severity.
Topics: Animals; Cranial Sutures; Craniosynostoses; Disease Models, Animal; Female; Genetic Background; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Phenotype; Receptor, Fibroblast Growth Factor, Type 2; Skull
PubMed: 32976998
DOI: 10.1016/j.jsb.2020.107629 -
Bone Reports Dec 2022Cortical porosity develops in chronic kidney disease (CKD) and increases with progressing disease. Cortical porosity is likely a prominent contributor to skeletal...
Cortical porosity develops in chronic kidney disease (CKD) and increases with progressing disease. Cortical porosity is likely a prominent contributor to skeletal fragility/fracture. The degree to which cortical porosity occurs throughout the skeleton is not fully known. In this study, we assessed cortical bone porosity via micro-computed tomography at multiple skeletal sites in rats with progressive chronic kidney disease. We hypothesized that cortical porosity would occur in long bones throughout the body, but to a lesser degree in flat bones and irregular bones. Porosity was measured, using micro-CT, at 17 different skeletal sites in 6 male rats with CKD. Varying degrees of porosity were seen throughout the skeleton with higher porosity in flat and irregular bone (i.e. parietal bone, mandible) vs. long bones (p = 0.01) and in non-weightbearing bones vs. weightbearing bones (p = 0.01). Porosity was also higher in proximal sites vs. distal sites in long bones (p < 0.01 in all comparisons). There was large heterogeneity in porosity within skeletal sites across rats and within the same rat across skeletal sites. Correlations showed cortical porosity of the proximal tibia was positively associated with porosity at the other sites with the strongest correlation to the parietal bone and the weakest to the ulna. Overall, our data demonstrates varying and significant cortical bone porosity across the skeleton of animals with chronic kidney disease. These data point to careful selection of skeletal sites to assess porosity in pre-clinical studies and the potential for fractures at multiple skeletal sites in patients with CKD.
PubMed: 36035656
DOI: 10.1016/j.bonr.2022.101612 -
Quantitative Imaging in Medicine and... Jun 2022To use conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to investigate the effects of long-term hypoxia on cranial bone marrow...
BACKGROUND
To use conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to investigate the effects of long-term hypoxia on cranial bone marrow conversion in healthy people at high altitudes.
METHODS
A total of 1,130 individuals were selected from altitudinal areas of 2,000-3,000, 3,100-4,000, and >4,100 m. Each altitude range was divided into 5 age groups: 0-5, 6-14, 15-29, 30-49, and ≥50 years. Firstly, cranial bone marrow typing of the participants in each altitude range was performed on sagittal T1-weighted images (T1WI) according to the average diploe thickness and signal intensity of the normal skull, and the relationship between bone marrow conversion and age was analyzed. Secondly, the apparent diffusion coefficient (ADC) values of the frontal bone, parietal bone, occipital bone, and temporal bone were measured in the DWI post-processing workstation and statistical methods were used to analyze whether different altitudinal gradients and long-term hypoxic environment had any effect on cranial bone marrow conversion.
RESULTS
There was a positive correlation between bone marrow type and age in the healthy populations at all 3 levels of altitude (P<0.05). The average thickness of the cranial diploe also positively correlated with age (P<0.05); in the age ranges of 30-49 and ≥50 years, the ADC values of the occipital and temporal bone marrow positively correlated with increasing altitude (P<0.05).
CONCLUSIONS
The cranial bone marrow of normal people at high altitudes changes from Type I to Type IV with increasing age and under the influence of long-term chronic hypoxia. The bone marrow of the occipital and temporal bones of healthy people aged 30-49 and ≥50 years showed erythromedularization during the process of Type III and IV bone marrow conversion.
PubMed: 35655838
DOI: 10.21037/qims-21-740 -
Molecular Genetics and Metabolism... Dec 2023Mucopolysaccharidosis type II (MPS II, OMIM 309900) is an X-linked disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS). The clinical...
Mucopolysaccharidosis type II (MPS II, OMIM 309900) is an X-linked disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS). The clinical manifestations of MPS II involve cognitive decline, bone deformity, and visceral disorders. These manifestations are closely associated with IDS enzyme activity, which catalyzes the stepwise degradation of heparan sulfate and dermatan sulfate. In this study, we established a novel -deficient mice and further assessed the enzyme's physiological role. Using DNA sequencing, we found a genomic modification of the Ids genome, which involved the deletion of a 138-bp fragment spanning from intron 2 to exon 3, along with the insertion of an adenine at the 5' end of exon 3 in the mutated allele. Consistent with previous data, our -deficient mice showed an attenuated enzyme activity and an enhanced accumulation of glycosaminoglycans. Interestingly, we noticed a distinct enlargement of the calvarial bone in both neonatal and young adult mice. Our examination revealed that deficiency led to an enhanced osteoblastogenesis in the parietal bone, a posterior part of the calvarial bone originating from the paraxial mesoderm and associated with an enhanced expression of osteoblastic makers, such as and . In sharp contrast, cell proliferation of the parietal bone in these mice appeared similar to that of wild-type controls. These results suggest that the deficiency of could be involved in an augmented differentiation of calvarial bone, which is often noticed as an enlarged head circumference in MPS II-affected individuals.
PubMed: 38053930
DOI: 10.1016/j.ymgmr.2023.101021 -
Cureus Oct 2020Enlarged parietal foramina (PFM) are congenital calvarial defects characterized by bilateral parietal bone defects (>5 mm), occurring on each side of the sagittal suture...
Enlarged parietal foramina (PFM) are congenital calvarial defects characterized by bilateral parietal bone defects (>5 mm), occurring on each side of the sagittal suture along its posterior aspect. While often lacking underlying intracranial malformations, there has been increasing recognition of coexisting brain malformations in certain subtypes. We present a case of a 12-year-old girl presenting with new-onset grand mal seizure with developmental delay and a known family history of epilepsy. Brain MRI revealed large, bilateral parietal bone defects with underlying cortical malformation (polymicrogyria and ulegyria) and vascular abnormalities (persistent falcine sinus), related to PFM. This case report describes the genetic basis for recognized subtypes of PFM and the rare association of brain malformations associated with PFM due to mutations in the ALX4 homeobox gene.
PubMed: 33269135
DOI: 10.7759/cureus.11204 -
Journal of Maxillofacial and Oral... Jul 2022Melioidosis is a potentially fatal, life-threatening infection caused by the gram-negative saprophytic organism Burkholderia. It is a disease endemic to Southeast Asia...
Melioidosis is a potentially fatal, life-threatening infection caused by the gram-negative saprophytic organism Burkholderia. It is a disease endemic to Southeast Asia and Northern Australia. This infection transmits through direct contact, cutaneous inoculation, inhalation, or ingestion, and patients clinically exhibit abscesses in single or multiple organs. It is clinically under-reported due to a low index of suspicion, lack of diagnostic facilities, and misdiagnosis as tuberculosis. Infections of the musculoskeletal system are exceedingly rare, and clinical presentation may vary from the involvement of femoral bone, palmar tenosynovitis, and parietal bone osteomyelitis secondary to central nervous system involvement. The rarity of the melioidosis to secondarily infect a developmental odontogenic cyst leading to focal osteomyelitis of mandible prompts the clinician toward thorough evaluation for early diagnosis and treatment.
PubMed: 35891942
DOI: 10.1007/s12663-022-01763-w -
BMC Veterinary Research Apr 2021The authors report a case of keratinized squamous cell carcinoma (SCC) in a 14-year-old dog with extensive cranial bone invasion. To our knowledge, this is the first...
BACKGROUND
The authors report a case of keratinized squamous cell carcinoma (SCC) in a 14-year-old dog with extensive cranial bone invasion. To our knowledge, this is the first description of such a case of cranial keratinized SCC with aggressive generalized osteolysis described in a dog.
CASE PRESENTATION
The 14-year-old dog was referred for radiological examination with suspicion of head trauma with clinical signs of head deformation, exophthalmos and nasal discharge. The skull radiographs showed a large osteolytic defect of the frontal bone and parietal bone in the region of the external sagittal crest. Findings from the skull CT scan included generalized osteolysis in the region of parietal bone, frontal bones, maxilla on the right side and the nasal bone including the dorsal nasal concha. In the area of bone loss, new soft tissue formation with multifocal foci of mineralization was visible. The ultrasound examination revealed hypoechogenic changes with hyperechoic foci consistent with mineralization and poor vascularization. The brain and ocular structures were without visible changes. Fine needle aspiration cytology (FNAC) was performed, and squamous cell carcinoma was suspected. After 3 months, the re-presented to the clinic. The dog became progressively listless, his appetite was decreased, and he became acutely blind. Follow-up skull CT scan revealed significant osteolysis, which affected a significant aspect of the cranium. All bone defects had been replaced by new 3.5 cm-thick soft tissue formations with multifocal small 1-2 mm areas of mineralization. There was no evidence of metastasis. Histological examination confirmed the suspicion of squamous cell carcinoma.
CONCLUSIONS
This paper is the first report of cranial SCC in a dog causing extensive bone osteolysis. The lesions in this dog originated from the frontal and parietal bones including frontal sinuses. There are variants of tumors that arise from squamous epithelium or resemble SCC in the skull. These examples include adenosquamous carcinoma and proliferating trichilemmal tumours. In addition, there is possible malignant transformation caused by papilloma viruses. In the veterinary literature, there is only one similar description of adenosquamous carcinoma in a cat with similar clinical manifestations. It is justified to suspect a process of neoplastic epithelial origin in all cases of aggressive and extensive skull bone lysis. This issue should be subject to further investigation.
Topics: Animals; Bone Neoplasms; Carcinoma, Squamous Cell; Dog Diseases; Dogs; Male; Skull
PubMed: 33823849
DOI: 10.1186/s12917-021-02843-8 -
Acta Cirurgica Brasileira 2021This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.
PURPOSE
This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.
METHODS
Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.
RESULTS
There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.
CONCLUSIONS
Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.
Topics: Animals; Bone Regeneration; Mesenchymal Stem Cells; Parietal Bone; Platelet-Rich Plasma; Rats; Rats, Wistar
PubMed: 33503214
DOI: 10.1590/ACB351201 -
Journal of Lasers in Medical Sciences 2022The application of low-level laser therapy (LLLT) and some medications have been shown to accelerate bone formation in rapid palatal expansion (RPE). A combination of...
Effect of Simvastatin and Low-Level Laser Therapy on Sutural Bone Formation After Expansion in Rats: Biomechanical, Computed Tomography and Immunohistochemical Assessment.
The application of low-level laser therapy (LLLT) and some medications have been shown to accelerate bone formation in rapid palatal expansion (RPE). A combination of these two therapeutic modalities may reduce the time required for the retention period. This study sought to assess the effects of simvastatin and LLLT, alone and combined, on sutural bone formation in rats. Sixty male Wistar rats averagely weighing 150 g were divided into five groups (n=12) of control (group 1), 5 mg simvastatin (group 2), 10 mg simvastatin (group 3), LLLT (group 4), and LLLT plus 10 mg simvastatin (group 5). The expansion appliance was placed in the parietal bone in all groups. One week after placing the appliance, the spring was fixed with Duralay acrylic resin to serve as a retainer during the rest of the experiment. The rats were sacrificed after 30 (for biomechanical and computed tomography [CT] assessments) or 60 days (for biomechanical, CT and immunohistochemical [IHC] assessments). Groups 3 and 4 showed a significant improvement in osteogenesis (confirmed by CT findings, histological analysis and biomechanical test) compared to the control group. Group 5 was significantly superior to all other groups in terms of all parameters ( < 0.001). Group 2 and the control group were not significantly different (>0.05). Although LLLT, simvastatin treatment and the combination of both significantly improved sutural bone formation in rats compared to the control group, the combined treatment showed significantly superior clinical results compared to other interventions.
PubMed: 35996495
DOI: 10.34172/jlms.2022.21 -
Cureus Dec 2022Introduction Animal attacks cause a considerable number of injuries and lead to morbidity and mortality among children and adults. Bull gore injuries following...
Introduction Animal attacks cause a considerable number of injuries and lead to morbidity and mortality among children and adults. Bull gore injuries following bullfighting and other provoked attacks have been frequently described in literature. Our study describes the pattern of injuries and the unique mechanisms and management of blunt and penetrating trauma associated with unprovoked bull attacks. Methods In this retrospective study, we collected the data of 36 patients presenting to our emergency department with a history of bullhorn injury. The data comprised age, sex, location of injury, type and description of the injury, surgical procedure performed if any, requirement of postoperative intensive care unit (ICU) admission, and mortality. The data were then compiled and analyzed with MS Excel. Results Among the 36 patients, blunt injuries constituted 58.3% of cases, whereas penetrating injuries were seen in 41.7%. Men were commonly injured with a mean age of 39.1 years. Thorax (36%) and abdomen (33%) were the common sites of injury followed by perineum (17%), head (5%), spine (6%), and extremity (2%). Fall following the impact of bull led to indirect injuries, such as intracranial hemorrhage, parietal bone fracture, cervical spine injuries, and tibial fracture. More than half of the patients (n=19, 52.8%) required some form of surgery under local or general anesthesia. Among the operated patients, seven required postoperative ICU care and two expired. Conclusion Animal attack injuries represent a less explored niche of surgical conditions. Management in the emergency department includes prompt resuscitation to achieve hemodynamic stability, thorough wound wash to remove the contaminants, and appropriate imaging, if indicated. Wound exploration is recommended for penetrating injuries and on a case-to-case basis for blunt injuries. The complications of these wounds are due to multiple wound paths, muscle tearing, evisceration of internal organs, and high risk of wound infection.
PubMed: 36721567
DOI: 10.7759/cureus.33075