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Objectives The present study aimed to investigate whether exosomes derived from miR‐375‐overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration. Materials and Methods Exosomes enriched with miR‐375 (Exo [miR‐375]) were generated from hASCs stably overexpressing miR‐375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting. The construction efficiency of Exo (miR‐375) was evaluated with qRT‐PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR‐375) was investigated with ALP and ARS assays. Furthermore, dual‐luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR‐375 in osteogenic regulation. Finally, Exo (miR‐375) were embedded with hydrogel and applied to a rat model of calvarial defect, and μ‐CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR‐375) in bone regeneration. Results miR‐375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR‐375) at 50 μg/mL improved the osteogenic differentiation of hBMSCs. With miR‐375 absorbed by hBMSCs, insulin‐like growth factor binding protein 3 (IGFBP3) was inhibited by binding to its 3′UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR‐375). After incorporated with hydrogel, Exo (miR‐375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR‐375) enhanced the bone regenerative capacity in a rat model of calvarial defect. Conclusions Taken together, our study demonstrated that exosomes derived from miR‐375‐overexpressing hASCs promoted bone regeneration.

Background: Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment. Methods: Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe. Results: Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively. Conclusion: There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials.

The management of cerebrospinal fluid (CSF) fistulae after anterior cranial base fracture remains a surgical challenge. We reviewed our results in the repair of CSF fistulae complicating multiple anterior cranial base fractures via a combined intracranial extradural and intradural approach and describe a treatment algorithm derived from this experience. We retrospectively reviewed the files of 209 patients with an anterior cranial base fracture complicated by a CSF fistula who were admitted between 1980 and 2003 to Liège State University Hospital. Among those patients, 109 had a persistent CSF leak or radiological signs of an unhealed dural tear. All underwent the same surgical procedure, with combined extradural and intradural closure of the dural tear. Of the 109 patients, 98 patients (90%) were cured after the first operation. Persistent postoperative CSF rhinorrhea occurred in 11 patients (10%), necessitating an early complementary surgery via a transsphenoidal approach (7 patients) or a second-look intracranial approach (4 patients). No postoperative neurological deterioration attributable to increasing frontocerebral edema occurred. During the mean follow-up period of 36 months, recurrence of CSF fistula was observed in five patients and required an additional surgical repair procedure. The closure of CSF fistulae after an anterior cranial base fracture via a combined intracranial extradural and intradural approach, which allows the visualization and repair of the entire anterior base, is safe and effective. It is essentially indicated for patients with extensive bone defects in the cranial base, multiple fractures of the ethmoid bone and the posterior wall of the frontal sinus, cranial nerve involvement, associated lesions necessitating surgery such as intracranial hematomas, and post-traumatic intracranial infection. Rhinorrhea caused by a precisely located small tear may be treated with endoscopy.

Inflammatory myofibroblastic tumors (IMTs) represent rare neoplasms, particularly infrequent in the pediatric skull. We present a novel case of a newborn male with a 5 cm right temporal mass and discuss current diagnostic and treatment options for IMTs. A multidisciplinary effort to surgically remove the lesion was successful, and the patient’s skull defect healed without neurological deficits. The etiology of IMTs remains elusive, with proposed associations with chromosomal mutations in the anaplastic lymphoma kinase (ALK) gene. Surgical excision remains the primary treatment for IMTs. Promising pharmacological treatments, like Crizotinib, warrant further research into understanding potential alternatives in IMT management.

Background Growing skull fractures (GSF) represent a rare complication following linear traumatic skull fractures with an underlying dural tear, mainly occurring during infancy and early childhood. GSF can cause encephalocele, hydrocephalus, or encephalomalacia, potentially leading to long-term neurological sequelae. Therefore, prompt diagnosis and early treatment is paramount. Methods We outline our surgical reconstruction technique for managing GSF. Conclusion GSF is effectively treated with a dural and bony reconstruction, using a fast-resorbable polymer mesh.

The geometry and mechanical properties of infant skull bones differ significantly from those of adults. Over the past decades, debates surrounding whether fractures in infants come from deliberate abuse or accidents have generated significant impacts in both legal and societal contexts. However, the etiology of infant skull fractures remains unclear, which motivates this study with two main components of work. Firstly, we present and implement a progressive unidirectional fabric composite damage model for infant cranial vaults to represent ductile and anisotropic properties—two typical mechanical characteristics of infant skulls. Secondly, we hypothesize that these intrinsic material properties cause injuries perpendicular to the fiber direction to dominate infant skull fractures, resulting in fracture lines that align with the direction of mineralization in the infant skull. The material model and the finite element (FE) model were verified hierarchically, and this hypothesis was verified by reconstructing two legal cases with known fall heights and implementing the above damage model into CT-based subject-specific infant FE head models. We discovered that the infant skull is more susceptible to injuries within planes perpendicular to the mineralization direction because of the anisotropic mechanical property caused by the direction of mineralization, leading to infant skull fractures aligning with the mineralization direction. Our findings corroborated the several previously reported observations of fractures on cranial vaults, demonstrating that these fractures were closely associated with sutures and oriented along the mineralization direction, and revealed the underlying mechanisms of infant skull fracture pattern. The modeling methods and results of this study will serve as an anchor point for more rigorous investigations of infant skull fractures, ultimately aiming to provide convincing biomechanical evidence to aid forensic diagnoses of abusive head trauma.

Primary intraosseous meningioma of the skull (PIMS) is a rare type of primary extradural meningioma (PEM) involving cranial bone. The existing literature strongly suggest the importance of radiological feacures in pathological diagnosis of PIMS. Thereby, the aim of this study is to investigate the association between imaging classification and histopathological grading in PIMS. In this retrospective study, we retrospectively analyzed the computed tomography scan/magnetic resonance imaging and pathological data pertaining to patients with pathologically proven PIMS. The association between radiological features, imaging classification, and histopathological grading was analyzed using logistic regression analysis. In this study, data of 25 patients with PIMS were assessed. The univariate logistic regression analysis results showed significant correlation between histopathological grading and imaging classification (OR: 22.5; 95% CI: 2.552–198.378; p = 0.005), intra- and extracalvarial extension (OR: 7.2; 95% CI: 1.066–48.639; p = 0.043), and tumor margin (OR: 7.19; 95% CI: 1.06–47.61; p = 0.043). According to the results of multivariate logistic regression analysis, imaging classification was the strongest independent risk factor for high-grade PIMS, and the risk of aggressiveness of osteoblastic type of PIMS was 16.664 times higher than that of osteolytic type of PIMS (OR: 16.664; 95% CI: 1.15–241.508; p = 0.039). Imaging classification is an independent risk factor for high-grade PIMS. ●Standardized nomenclature of the rare meningioma in cranial bone.●Enhancement in our understanding of primary intraosseous meningioma in the skull.●Imaging classification is correlated to histological grade.●Osteoblastic type tumor calls for a more aggressive clinical management.

Regeneration of critical bone defects requires the use of biomaterials. The incorporation of osteoinductive agents, such as bone morphogenetic proteins (BMPs), improves bone formation. This study aimed to compare the efficacy of rhBMP-2 in combination with different materials for bone regeneration in critical-sized rat calvarial defects. This was an experimental animal study using 30 rats. In each rat, two 5-mm critical-size defects were made in the calvaria (60 bone defects in total) using a trephine. All rats were randomized to one of the six groups: control (C), autograft + rhBMP-2 (A), absorbable collagen sponge + rhBMP-2 (ACS), β-tricalcium phosphate + rhBMP-2 (B-TCP), bovine xenograft + rhBMP-2 (B), and hydroxyapatite + rhBMP-2 (HA). The outcome was assessed after 4 and 8 weeks using histological description and the histological bone healing scale. Statistical analysis was performed using the Kruskal-Wallis and Mann–Whitney U tests, with a p-value set at 0.05. The average bone healing scores per group were as follows: C group, 12.5; A group, 26.5; ACS group, 18.8; B-TCP group, 26.2; HA group, 20.9; and B group, 20.9. The C group showed a significant difference between weeks 4 and 8 (p=0.032). Among the 4-week groups, the C group showed a significant difference compared to A (p=0.001), ACS (p=0.017), and B-TCP (p=0.005) groups. The 8-week experimental group did not show any significant differences between the groups. The 5-mm critical size defect in rat calvaria requires the use of bone biomaterials to heal at 4 and 8 weeks. rhBMP-2, as applied in this study, showed no difference in new bone formation when combined with bovine, B-TCP, or HA biomaterials.

To characterise the symptomatic phenotype of Chiari-like malformation (CM), secondary syringomyelia (SM) and brachycephaly in the Cavalier King Charles Spaniel using morphometric measurements on mid-sagittal Magnetic Resonance images (MRI) of the brain and craniocervical junction. This retrospective study, based on a previous quantitative analysis in the Griffon Bruxellois (GB), used 24 measurements taken on 130 T1-weighted MRI of hindbrain and cervical region. Associated brachycephaly was estimated using 26 measurements, including rostral forebrain flattening and olfactory lobe rotation, on 72 T2-weighted MRI of the whole brain. Both study cohorts were divided into three groups; Control, CM pain and SM and their morphometries compared with each other. Fourteen significant traits were identified in the hindbrain study and nine traits in the whole brain study, six of which were similar to the GB and suggest a common aetiology. The Control cohort had the most elliptical brain (p = 0.010), least olfactory bulb rotation (p = 0.003) and a protective angle (p = 0.004) compared to the other groups. The CM pain cohort had the greatest rostral forebrain flattening (p = 0.007), shortest basioccipital (p = 0.019), but a greater distance between the atlas and basioccipital (p = 0.002) which was protective for SM. The SM cohort had two conformation anomalies depending on the severity of craniocervical junction incongruities; i) the proximity of the dens (p <0.001) ii) increased airorhynchy with a smaller, more ventrally rotated olfactory bulb (p <0.001). Both generated 'concertina' flexures of the brain and craniocervical junction. Morphometric mapping provides a diagnostic tool for quantifying symptomatic CM, secondary SM and their relationship with brachycephaly. It is hypothesized that CM pain is associated with increased brachycephaly and SM can result from different combinations of abnormalities of the forebrain, caudal fossa and craniocervical junction which compromise the neural parenchyma and impede cerebrospinal fluid flow.

Introduction Melanotic neuroectodermal tumor of infancy (MNT1) is a rare congenital pigmented neoplasm of neural crest origin, locally aggressive, and rapidly growing that develops during the first year of life. It most commonly arises from the maxilla, the cranial vault, and the mandible. Early diagnosis and radical surgery are critical for a long-term outcome. Methods A literature search through PUBMED revealed 43 cases of MNT1 arising in the skull. We reviewed the available literature and studied the presenting symptoms, diagnostic procedures, treatment, rates of recurrences, malignancy, and data of follow-up. We report two further cases of infants aged 4 and 10 months, respectively, with MNT1 arising from the cranial vault who underwent radical excision of the lesion. Conclusion Melanotic neuroectodermal tumor of infancy should be included in the differential diagnosis of skull lesions in infants. Radical surgery must be considered as the treatment of choice and close follow-up for at least 2 years is necessary.