: Cerebral cavernous malformation (CCM) is a type of vascular malformations characterized by the absence of intervening brain parenchyma. Cerebral cavernous malformations are of two forms, sporadic and familial. About 0.4-0.8% of the population are affected as assessed based on Magnetic Resonance Imaging (MRI) findings and postmortem findings. Three genetic mutations have been identified: CCM1, CCM2, CCM3, with an incidence of 40%, 40% and 20%, respectively. : This study presents five members diagnosed with Familial CCM in a Filipino family. A 25-year-old male, from a low socio-economic background, was admitted due to a progressive generalized headache of 2 years’ duration, during which multiple brain lesions were observed on MRI. All members of the family became symptomatic before 30 years of age, and four out of the five members underwent surgery. However, molecular genetic testing was not performed as the patient could not afford it. The testing was not covered by the country’s insurance system, and it would have been an out-of-pocket expense. In patients diagnosed with cerebral cavernous malformations, a thorough clinical and family history is warranted accompanied by MRI-GRE (Magnetic Resonance Imaging Gradient Echo) and MRI T2 help establish final diagnosis. Confirmation with molecular genetic testing should be offered to all members of the family for proper neurological and genetic care.
Human ; Male,Female ; Adult: 25-44 yrs old ; Middle Aged: 45-64 yrs old ; Aged: 65-79 yrs old ; familial cerebral cavernous malformation

: This is a case of a 6-year-old male who had a motor vehicular accident, who initially presented without neurologic deficit immediately post injury but followed up with seizures and motor weakness. The aim of the study is to review the pathomechanism of traumatic aneurysm in blunt head trauma in pediatric patients. : The initial imaging done revealed a closed, depressed comminuted fracture in the left frontal bone. Three weeks post-injury, he had recurrent generalized tonic clonic seizures and angiogram showed saccular aneurysm of the left A2 with left frontal intracerebral hemorrhage (ICH). The patient underwent bifrontal craniotomy, clipping of aneurysm and evacuation of the ICH. Treatment options includes endovascular approach, wrapping and trapping the aneurysm. However, there is no single modality indicated for all lesions. Post operatively, the patient was aphasic with right hemiparesis (2/5). Speech improved the second week after the surgery. Rehabilitation was initiated after admission and unassisted ambulation noted after 2 months. Work up done for other possible causes of aneurysm in the pediatric population revealed unremarkable findings. Mechanism associated with blunt traumatic head injury in the development of aneurysm could be secondary to a shear or rotational injury damaging vessels in close proximity to dura, for instance in this case, close to the falx cerebri.
blunt head injury

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Cell Differentiation ; Cell Line ; DNA Methylation ; Embryonic Stem Cells ; cytology ; metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Myocytes, Cardiac ; cytology ; metabolism ; Transcription, Genetic