EphrinA5 regulates cell motility by modulating Snhg15/DNA triplex-dependent targeting of DNMT1 to the Ncam1 promoter.

Cell-cell communication is mediated by membrane receptors and their ligands, such as the Eph/ephrin system, orchestrating cell migration during development and in diverse cancer types. Epigenetic mechanisms are key for integrating external "signals", e.g., from neighboring cells, into the transcriptome in health and disease. Previously, we reported ephrinA5 to trigger transcriptional changes of lncRNAs and protein-coding genes in cerebellar granule cells, a cell model for medulloblastoma. LncRNAs represent important adaptors for epigenetic writers through which they regulate gene expression. Here, we investigate a lncRNA-mediated targeting of DNMT1 to specific gene loci by the combined power of in silico modeling of RNA/DNA interactions and wet lab approaches, in the context of the clinically relevant use case of ephrinA5-dependent regulation of cellular motility of cerebellar granule cells. We provide evidence that Snhg15, a cancer-related lncRNA, recruits DNMT1 to the Ncam1 promoter through RNA/DNA triplex structure formation and the interaction with DNMT1. This mediates DNA methylation-dependent silencing of Ncam1, being abolished by ephrinA5 stimulation-triggered reduction of Snhg15 expression. Hence, we here propose a triple helix recognition mechanism, underlying cell motility regulation via lncRNA-targeted DNA methylation in a clinically relevant context.

Role of DNMTs in the Brain.

DNA methyltransferases (DNMTs) are widely expressed in the brain, dictating the transcriptional activity of genes through various epigenetic mechanisms. Functional irregularities, alterations in the activity, and aberrant expression levels of DNMTs have been linked to various neurodevelopmental abnormalities, neuropsychiatric disorders, neurodegenerative diseases, and brain cancer. A continuously increasing number of studies address the roles DNMTs have in the brain, to reach a better understanding of their involvement in disease-related pathophysiologies, which in turn is required to dissect their applicability as potential therapeutic targets. This chapter provides an overview of DNMT function in the developing and the adult brain, putting a spotlight on their role in orchestrating diverse aspects of brain development, memory, and aging, followed by a discussion of associated neurodevelopmental and neurodegenerative disorders, and the implications in brain cancer.

The evaluation of intracranial pressure evaluation by optic nerve sheath diameter measurement on bedside ultrasonography after ischemic stroke.

INTRODUCTION: We aimed to predict intracranial pressure(ICP)after cerebral ischemic stroke by measuring diameter of the optic nerve sheath(ONSD)with bedside ultrasonography(US). In order to see the ICP changes,it was planned to record delta ICP changes at the 3rd and 5th day follow-up of the patients METHOTS: Patients aged 18 years or older who were admitted to the emergency department(ED)with stroke symptoms for one year were included.Demographic data,time elapsed since the onset of symptoms,neurogical status assesment scales,ONSD values measured by US in three time periods(the day the patient was admitted to the ED,the 3rd and 5th days of hospitalization),MDCT findings when the patient was admitted,ONSD values in MDCT,whether they received tissue plasminogen activator(tPA)and whether they underwent decompression surgery were recorded. RESULTS: The average age of the 82 patients was 67.5(range 33-89)years.Forty-two patients(51.2%)were male.On both the right and left sides,ONSD on the 3rd day was larger(>5 mm)than on first day(p < 0.05). ONSD on the 5th day was larger than on the first day(p > 0.05). All ONSD results measured using both US and MDCT showed a positive correlation between the same eye and contralateral eye measurements(p < 0.05). DISCUSSION: CT is the most critical radiological method for stroke patients.Transport to radyology unit in unstable patients carries risk and is not recommended.Optic nerve US can be used in the early diagnosis of ICP increase and provides early treatment.The ease of use and safety in unstable patients have increased its popularity. CONCLUSION: We believe that measuring ONSD using US is an appropriate choice on ICP management in stroke patients.

Alterations in inflammatory markers and clinical outcome after spontaneous intracerebral hemorrhage - Preliminary results.

OBJECTIVE: After an intracerebral hemorrhage, there is an immunological reaction, the specific mechanism of which is not fully understood, that seems to contribute to secondary brain injury. In this study, we investigated alterations of inflammatory markers in the blood and clinical outcome after an intracerebral hemorrhage. METHODS: Between July 2013 and February 2016, we performed a prospective study for which we recruited patients who had suffered an intracerebral hemorrhage. Using various scoring scales we evaluated the neurological state upon admission and discharge, and at one and three months following the ICH. During the hospital stay, various inflammatory markers were examined in blood samples. RESULTS: Out of 132 screened patients, 27 were included (48.2% male, mean age 68 years). We found significantly elevated serum concentrations of interleukin-6 (p=0.006) at the time of admission and throughout days three and five. There were also elevated c-reactive protein and granulocyte-colony stimulating factor concentrations found. The concentrations of these immune parameters showed significant monotonic relationships. The ROC analyses showed a better discrimination for mortality with regard to the percentage of T helper cells than with regard to the ICH volume alone. CONCLUSION: Our results may be regarded as preliminary evidence of the occurrence of inflammation after intracerebral hemorrhage. If there is a relationship between inflammation and clinical outcome remains speculative.

The reno-protective effects of atorvastatin in crush syndrome and rhabdomyolysis:is there a dilemma?

Background/aim: We aim to determine the effects of low-dose atorvastatin treatment together with crush fluid resuscitation on renal functions and muscle enzyme levels in a rat model of crush syndrome. Materials and methods: The study involved female Wistar Albino rats weighing 250-300 g that were housed with free access to food and water. The crush model was obtained by compression. Rats were randomly divided into four groups: control (C) group, atorvastatin + crush fluid (ACF) group, crush fluid (CF) group, and hypertonic saline (%3) + mannitol + sodium bicarbonate (SM) group. Blood was obtained at 24, 48, and 72 h, and serum creatinine kinase, myoglobin, urea, creatinine, and lactate dehydrogenase levels were studied.Results: All parameters were statistically significantly higher in the control group than in the treatment groups at all hours. However, there was no statistically significant difference among treatment groups regarding any of the parameters.Conclusion: This is the first study determining the role of atorvastatin in the treatment of renal ischemia/reperfusion injury in a crush syndrome and rhabdomyolysis model setting. Larger studies with different atorvastatin doses are required to define the role of this drug in the treatment of renal ischemia/reperfusion injury during crush syndrome.

Spontaneous rupture of intracranial dermoid tumor in a patient with vertigo. Computed tomography and magnetic resonance imaging findings.

BACKGROUND: Congenital dermoid cysts are very rare, constituting less than 1% of intracranial tumors. Spontaneous rupture of dermoid tumor is a potentially serious complication that can lead to meningitis, seizures, cerebral ischemia and hydrocephalus. Occasionally, dermoid tumors are incidentally discovered on computed tomography (CT) of the brain or magnetic resonance imaging (MRI) following unrelated clinical complaints. They are also discovered during radiologic investigations of unexplained headaches, seizures, and rarely olfactory delusions. CASE REPORT: In this report we describe a patient complaining of vertigo caused by spontaneous rupture of dermoid cyst, preoperatively diagnosed by CT and MRI. Cranial CT revealed a dense fatty lesion adjacent to the posterolateral parasellar region on the left with multiple small, dense fat droplets scattered in the subarachnoid space corresponding to a dermoid cyst rupture. Cranial MRI sections revealed a lesion with mixed-signal-intensity and multiple hyperintense droplets scattered through the cerebellar surface on the left. No enhancement was found on axial T1-weighted MRI after intravenous Gadolinium administration. Diffusion weighted image (DWI) and apparent diffusion coefficient map studies exhibited explicit restricted diffusion. DISCUSSION: Many studies and literature case reports concerning the rupture of dermoid cyst have been reported. However, multimodal imaging of this rare pathology in the same patient is uncommon. Although dermoid cysts are pathognomonic in appearance on a CT examination, the MRI is also of value in helping to understand the effect of extension and pressure of the mass. DWI is also important for support of the diagnosis and patient follow-up.

Direct venous spinal reabsorption of cerebrospinal fluid: a new concept with serial magnetic resonance cisternography in rabbits.

OBJECT: For nearly 100 years it has been believed that the main reabsorption of CSF occurs in arachnoid projections into the superior sagittal sinus, but a significant number of experiments and cases conflict with this hypothesis. According to recently published studies, CSF is permanently produced and absorbed in the whole CSF system. Clusters of arachnoidal villi, which are speculated to have a role in the reabsorption of CSF, have recently been revealed in the dorsal root of the spinal nerves. Huge absorptive surface areas of microvessels have been suggested to serve a putative role in reabsorption. The authors' aim was to observe direct venous connections between the subarachnoid space and the perispinal veins. METHODS: Eleven adult (6 months old) New Zealand white male rabbits weighing approximately 3.0 kg each were used in this experiment. After obtaining precontrast MR cisternography images, subarachnoid access was gained percutaneously via a cisternal approach by using a 20-gauge intravenous indwelling cannula. One rabbit died as a result of brainstem trauma during percutaneous cannulation before contrast administration, but contrast agent was still injected to see the possible MR imaging results of spinal CSF reabsorption after death. Magnetic resonance imaging was performed at 15, 60, 120, and 180 minutes after the administration of contrast agent. After intramuscular injections of anesthetic, 2 rabbits died 120 and 150 minutes after contrast injection, but the MR imaging study at 180 minutes after contrast injection was still performed. RESULTS: Direct connections between the subarachnoid space and the perispinal veins were observed in all rabbits during serial MR cisternography. The enhancement power was not affected by the amount of injected contrast agent or by cervical or lumbar penetration but was increased at higher contrast concentrations or upon seizure (physical activity). CONCLUSIONS: Extracranial reabsorption of CSF has been finally proved with direct radiological confirmation of spinal venous reabsorption of CSF using serial MR cisternography. The authors believe that this study can help to develop a more accurate model of CSF dynamics, which will allow understanding of many CSF-related diseases, as well as the development of new strategies for treatment.

Language, foreign nationality and ethnicity in an English prison: implications for the quality of health and social research.

BACKGROUND: More than one in 10 of all prisoners in England and Wales are Foreign Nationals. This article discusses whether the research applications to one London prison are aimed at understanding a prisoner population characterised by significant multinational and multilingual complexity. METHODS: We studied all accessible documents relating to research undertaken at a women's prison between 2005 and 2009 to assess the involvement of Foreign National prisoners and women with limited English. The source of information was prison research applications and protocols. We also looked at available final research reports and journal articles. RESULTS: Two key findings emerged from this study. First, studies at this prison frequently excluded Foreign National prisoners and women with limited English. Second, Foreign National prisoners were often clustered as a homogeneous category in the research reports reviewed. This is despite their diverse cultural backgrounds, their variable immigration status and their differing competence in English, all of which affect their lives. CONCLUSIONS: The failure to include and/or identify social subgroups of the population can undermine the value of research, including, in the case of the study prison, funded health research. This can compromise associated needs assessments and service delivery, particularly important in already disadvantaged populations; this may encourage and/or perpetuate a range of health inequalities. There is a pressing need to examine cultural exclusion in other health and criminal justice settings, to assess the ways in which-and the extent to which-such exclusion may compromise the merit of proposed and completed health and social research.