Protein kinase a distribution differentiates human glioblastoma from brain tissue

Brain tumor glioblastoma has no clear molecular signature and there is no effective therapy. In rodents, the intracellular distribution of the cyclic AMP (cAMP)-dependent protein kinase (Protein kinase A, PKA) R2Alpha subunit was previously shown to differentiate tumor cells from healthy brain cells. Now, we aim to validate this observation in human tumors. The distribution of regulatory (R1 and R2) and catalytic subunits of PKA was examined via immunohistochemistry and Western blot in primary cell cultures and biopsies from 11 glioblastoma patients. Data were compared with information obtained from 17 other different tumor samples. The R1 subunit was clearly detectable only in some samples. The catalytic subunit was variably distributed in the different tumors. Similar to rodent tumors, all human glioblastoma specimens showed perinuclear R2 distribution in the Golgi area, while it was undetectable outside the tumor. To test the effect of targeting PKA as a therapeutic strategy, the intracellular cyclic AMP concentration was modulated with different agents in four human glioblastoma cell lines. A significant increase in cell death was detected after increasing cAMP levels or modulating PKA activity. These data raise the possibility of targeting the PKA intracellular pathway for the development of diagnostic and/or therapeutic tools for human glioblastoma

Bone lengthening osteogenesis, a combination of intramembranous and endochondral ossification: an experimental study in sheep

We evaluated the morphological features of the newly formed tissue in an experimental model of tibial callotasis lengthening on 24 lambs, aged from 2 to 3 months at the time of operation. A unilateral external fixator prototype Monotube Triax® (Stryker Howmedica Osteonics, New Jersey) was applied to the left tibia. A percutaneous osteotomy was performed in a minimally traumatic manner using a chisel. Lengthening was started 7 days after surgery and was continued to 30 mm. The 24 animals were randomly divided into three groups of 8 animals each: in Group 1, lengthening took place at a rate of 1 mm/day for 30 days; in Group 2, at a rate of 2 mm/day for 15 days; in Group 3, at a rate of 3 mm/day for 10 days. In each group, 4 animals were killed 2 weeks after end of lengthening, and the other 4 animals at 4 weeks after end of lengthening. To assess bony formation in the distraction area, radiographs were taken every 2 weeks from the day of surgery. To study the process of vascularization, we used Spalteholz’s technique. After killing, the tibia of each animal was harvested, and sections were stained with hematoxylin and eosin, Masson’s trichrome, and Safranin-O. Immunohistochemistry was performed, using specific antibodies to detect collagens I and II, S100 protein, and fibronectin. A combination of intramembranous and endochondral ossification occurred together at the site of distraction. Our study provides a detailed structural characterization of the newly formed tissue in an experimental model of tibial lengthening in sheep and may be useful for further investigations on callotasis

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Reproducible Disc Degeneration Scale in a Large Animal Model

IntroductionTo study the efficacy of novel regenerative strategies is necessary to develop new models that do not implement annulus fibrosus (AF) damage. We hypothesize an ideal preclinical model t..

Disc Regeneration Using MSC Transplanted via the Endplate Route

IntroductionStem cell based intervertebral disc (IVD) regeneration is quickly moving toward clinical applications.1 However, many aspects need to be investigated to routinely translate this therapy..

Rare Clinical Onset of Nontraumatic Intracavernous Aneurysm of the Internal Carotid Artery: A Diagnostic and Therapeutic Challenge

AbstractWhile the so-called pseudoaneurysms can result from arterial injury during trans-sphenoidal surgery or after a trauma, spontaneous aneurysms of cavernous–internal carotid artery (CICA) are rare. Symptoms vary and the differential diagnosis with other, more frequent, sellar lesions is difficult. We describe three cases of misdiagnosed CICA spontaneous aneurysm. In two cases the onset was with neuro-ophthalmological manifestations, classifiable as "cavernous sinus syndrome." The emergency computed tomography scan did not show CICA aneurysm and the diagnosis was made by surgical exploration. The third patient came to our attention with a sudden severe unilateral epistaxis; endonasal surgery revealed also in this case a CICA aneurysm, eroding the wall and protruding into the sphenoidal sinus. When the onset was with a cavernous sinus syndrome, misdiagnosis exposed two patients to potential serious risk of bleeding, while the patient with epistaxis was treated with embolization, using coils and two balloons. Intracavernous nontraumatic aneurysms are both a diagnostic and therapeutic challenge, because of their heterogeneous onset and risk of rupture, potentially lethal. Intracavernous aneurysms can be managed with radiological follow-up, if asymptomatic or clinically stable, or can be surgically treated with endovascular or microsurgical techniques

FEM and Von Mises analysis on prosthetic crowns structural elements: evaluation of different applied materials

The aim of this paper is to underline the mechanical properties of dental single crown prosthodontics materials in order to differentiate the possibility of using each material for typical clinical condition and masticatory load. Objective of the investigation is to highlight the stress distribution over different common dental crowns by using computer-aided design software and a three-dimensional virtual model. By using engineering systems of analyses like FEM and Von Mises investigations it has been highlighted the strength over simulated lower first premolar crowns made by chrome cobalt alloy, golden alloy, dental resin, and zirconia. The prosthodontics crown models have been created and put on simulated chewing stresses. The three-dimensional models were subjected to axial and oblique forces and both guaranteed expected results over simulated masticatory cycle. Dental resin presented the low value of fracture while high values have been recorded for the metal alloy and zirconia. Clinicians should choose the better prosthetic solution for the teeth they want to restore and replace. Both prosthetic dental crowns offer long-term success if applied following the manufacture guide limitations and suggestions

Thalamopeduncular Tumors in Pediatric Age: Advanced Preoperative Imaging to Define Safe Surgical Planning: A Multicentric Experience

Background: Thalamopeduncular tumors are challenging lesions arising at the junction between the thalamus and the cerebral peduncle. They represent 1-5% of pediatric brain tumors, are mainly pilocytic astrocytoma and occur within the first two decades of life. To date, the optimal treatment remains unclear. Methods: We retrospectively reviewed pediatric patients who underwent surgery for thalamopeduncular tumors in the Academic Pediatric Neurosurgery Unit of Padova and Verona from 2005 to 2022. We collected information on age, sex, symptoms, preoperative and postoperative neuroradiological studies, histological specimens, surgical approaches, and follow-up. Results: We identified eight patients with a mean age of 9 years. All lesions were pilocytic astrocytoma. The main symptoms were spastic hemiparesis, cranial nerve palsy, headache, and ataxia. The corticospinal tract was studied in all patients using diffusion-tensor imaging brain MRI and in two patients using navigated transcranial magnetic stimulation. The transsylvian approach was the most frequently used. A gross total resection was achieved in two patients, a subtotal resection in five and a partial resection in one. In three patients, a second treatment was performed due to the regrowth of the tumor, performing an additional surgery in two cases and a second-look surgery followed by adjuvant therapy in one. After the surgery, four patients maintained stability in their postoperative neurological exam, two patients improved, and two worsened but in one of them, an improvement during recovery occurred. At the last follow-up available, three patients were disease-free, four had a stable tumor residual, and only one patient died from the progression of the disease. Conclusions: Advanced preoperative tools allow one to define a safe surgical strategy. Due to the indolent behavior of thalamopeduncular tumors, surgery should be encouraged

Metastatic osteosarcoma of craniovertebral junction with cervicalgia and torticollis an a pediatric patient

Abstract Background Primary osteosarcoma of craniovertebral junction is extremely rare and reports in paediatric patients are limited. The symptoms are subtle and mostly underestimated. Case presentation. We present an unusual case of a 11-years old girl affected by an extensive and metastatic osteosarcoma of the atlas presented with cervicalgia and right torticollis refractory to medical treatment. The patient underwent open biopsy confirming the malignant histology. Conclusions Cervicalgia with or without a torticollis refractory to medical treatment, in absence of history of fell or trauma, is highly suspicious and should be considered as a warning sign for a severe pathology and it should not be neglected