The association between lunar phase and intracranial aneurysm rupture: Myth or reality? Own data and systematic review

Abstract Background It is a common belief in medical community that lunar phases have an impact on human health. A growing body of evidence indicates that lunar phases can predict the risk to develop acute neurological and vascular disorders. The goal of present report was to present our institution data and to perform systematic review of studies examining the association of intracranial aneurysm rupture with moon phases. Methods We identified all patients admitted to our department for ruptured intracranial aneurysms in a period between November, 2011 and December, 2014. Patients with a known aneurysm rupture date were included. Lunar phases were determined by dividing lunar month (29.5 days) into eight equal parts, i.e., new moon, waxing crescent, first quarter, waxing gibbous, full moon, waning gibbous, last quarter and waning crescent. A systematic literature review was undertaken to identify studies that evaluated the association of lunar phases with the incident of intracranial aneurysm rupture. Result One hundred and eighty-six patients (62 men and 124 women, median age 56 years) were admitted to our department for treatment of ruptured intracranial aneurysms. The rate of intracranial aneurysm rupture was equally distributed across all phases of the lunar cycle (X 2 [7; 185] = 12.280, p = 0.092). We identified three studies that evaluated the association between incident intracranial aneurysm rupture and lunar phases with a total of 1483 patients. One study from Lebanon found that the incidence rate of intracranial aneurysm rupture was statistically significantly greater during the new moon phase (25% cases), relative to the other seven lunar phases (p < 0.001). Two subsequent studies from Austria and Germany in larger patient samples (n = 717 and n = 655, respectively) did not find an association between lunar phases and intracranial aneurysm rupture (p-values of 0.84 and 0.97, respectively). When analyzing all four studies together, we did not find an association between lunar phases and incidence of intracranial aneurysm rupture (X 2 [1668; 7] = 2.080, p = 0.955). Conclusions Moon phases are not associated with incidence of intracranial aneurysm rupture. Studies investigating the association of intracranial aneurysm rupture with lunar illumination defined using more sensitive approaches are encouraged

RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) Gene Variants with Predisposition to Age-Related Macular Degeneration

Background. Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of a central part of the neural retina (macula) and a leading cause of blindness in elderly people. While it is known that the AMD is a multifactorial disease, genetic factors involved in lipid metabolism, inflammation, and neovascularization are currently being widely studied in genome-wide association studies (GWAS). The aim of our study was to evaluate the impact of new single nucleotide polymorphisms (SNPs) in RAD51B, TRIB1, COL8A1, and COL10A1 genes on AMD development. Methods. Case-control study involved 254 patients diagnosed with early AMD, 244 patients with exudative AMD, and 942 control subjects. The genotyping of RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702, rs4351379, and rs4351376), COL8A1 (rs13095226), and COL10A1 (rs1064583) was carried out using TaqMan assays by a real-time polymerase chain reaction (RT-PCR) method. Results. Statistically significant difference was found in genotype (TT, TC, and CC) distribution of COL8A1 rs13095226 between exudative AMD and control groups (60.2%, 33.6%, and 6.1% vs. 64.9%, 32.3%, and 2.9%, respectively, p=0.036). Also, comparing with TT+TC, rs13095226 CC genotype was associated with 3.5-fold increased odds of exudative AMD development (OR = 3.540; 95% CI: 1.415-8.856; p=0.007). Conclusion. Our study revealed a strong association between a variant in COL8A1 (rs13095226) and exudative AMD development

Clinical and Biological Correlates of Preoperative Cognitive Functioning of Glioma and Meningioma Patients

Objectives. This study aimed to investigate the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-Btype natriuretic peptide (NT-proBNP) serum concentrations with cognitive functions of glioma and meningioma patients. Methods. 177 brain tumor patients awaiting for brain tumor surgery participated in the study. Patients were assessed preoperatively, using neuropsychological tests for verbal memory, psychomotor speed, mental flexibility, and verbal fluency. The functional status of patients was evaluated using the Karnofsky Performance Index. Blood samples were drawn for evaluation of serum hsCRP and NT-proBNP concentrations upon hospital admission. Results. The highest NT-proBNP concentration was observed in meningioma patients. Glioma and meningioma patients did not differ in hsCRB concentration. Patients in the highest hsCRP tertile were older and more frequently reported cardiovascular comorbidity. Patients in the highest NT-proBNP tertile were older, more frequently with cardiovascular comorbidity, females, and diagnosed with a meningioma. hsCRP was significantly related to slower psychomotor speed in high-grade glioma patients (rho = 0:30, p < 0:05). In meningioma sample, NT-proBNP correlated with decreased psychomotor speed (rho = 0:38, p < 0:01), mental flexibility (rho = 0:33, p < 0:01), worse cumulative learning (rho = −0:27, p < 0:05), and delayed recall (rho = 0:30, p < 0:01). However, the relationship between the NT-proBNP and cognitive functions became nonsignificant when demographic and clinical covariates were included into analysis. Higher hsCRP concentration remained significantly related to slower psychomotor speed (p = 0:02) and worse mental flexibility (p = 0:05) in glioma patients, independently from demographic and clinical covariates. Preoperative cognitive functioning was also predicted by older age, gender, side and location of the tumor, and tumor malignancy, and general functional status of a patient. Conclusions. NT-proBNP was not associated with memory, language, and attention/executive cognitive domains of glioma and meningioma patients. Increased hsCRP was related to slower psychomotor speed and worse mental flexibility in glioma patients, indicating that inflammation processes are important for cognitive functioning in glial tumors

Oncosuppressive role of RUNX3 in human astrocytomas

Background. Gliomas are the most common and aggressive among primary malignant brain tumours with significant inter- and intratumour heterogeneity in histology, molecular profile, and patient outcome. However, molecular targets that could provide reliable diagnostic and prognostic information on this type of cancer are currently unknown. Recent studies show that certain phenotypes of gliomas such as malignancy, resistance to therapy, and relapses are associated with the epigenetic alterations of tumour-specific genes. Runt-related transcription factor 3 (RUNX3) is feasible tumour suppressor gene since its inactivation was shown to be related to carcinogenesis. Aim. The aim of the study was to elucidate RUNX3 changes in different regulation levels of molecular biology starting from epigenetics to function in particular cases of astrocytic origin tumours of different grade evaluating significance of molecular changes of RUNX3 for patient clinical characteristics as well as evaluate RUNX3 reexpression effect to GBM cells. Methods. The methylation status and protein expression levels of RUNX3 were measured by methylation-specific PCR and Western blot in 136 and 72 different malignancy grade glioma tissues, respectively. Lipotransfection and MTT were applied for proliferation assessment in U87-MG cells. Results. We found that RUNX3 was highly methylated and downregulated in GBM. RUNX3 promoter methylation was detected in 69.4% of GBM (n=49) as compared to 0 to 17.2% in I-III grade astrocytomas (n=87). Weighty lower RUNX3 protein level was observed in GMB specimens compared to grade II-III astrocytomas. Correlation test revealed a weak but significant link among Runx3 methylation and protein level. Kaplan-Meier analysis showed that increased RUNX3 methylation and low protein level were both associated with shorter patient survival (p<0.05). Reexpression of RUNX3 in U87-MG cells significantly reduced glioma cell viability compared to control transfection. [...]

Brain MRI morphometric analysis in Parkinson’s disease patients with sleep disturbances

Abstract Background Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients. Methods Twenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software. Results PD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson’s disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons. Conclusions PD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas

Association of genetic variants at CETP, AGER, and CYP4F2 locus with the risk of atrophic age-related macular degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly individuals. The etiology of AMD includes environmental and genetic factors. Methods: We aimed to determine the association between CETP (rs5882; rs708272; rs3764261; rs1800775; rs2303790), AGER (rs1800624; rs1800625), and CYP4F2 (rs1558139) gene polymorphisms and development of atrophic AMD. About 52 patients with atrophic AMD and 800 healthy control subjects were evaluated. The genotyping of single-nucleotide polymorphisms in CETP, AGER, and CYP4F2 was carried out using the real-time-PCR method. Results: Genetic risk models in the analysis of CETP rs5882 revealed statistically significant variables with increased risk of atrophic AMD in the codominant (p < .001), dominant (p < .001), recessive (p < .001), and additive (p < .001) models with the highest 25.4-fold increased risk of atrophic AMD in the codominant model (p < .001). The AGER rs1800625 was associated with a highly increased risk of atrophic AMD in the codominant (p < .001), recessive (p < .001), and additive (p < .001) genetic models

<it>MGMT</it>, <it>GATA6</it>, <it>CD81</it>, <it>DR4</it>, and <it>CASP8</it> gene promoter methylation in glioblastoma

<p>Abstract</p> <p>Background</p> <p>Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome.</p> <p>Methods</p> <p>The methylation status of <it>MGMT</it>, <it>CD81</it>, <it>GATA6</it>, <it>DR4</it>, and <it>CASP8</it> in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis.</p> <p>Results</p> <p>The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: <it>MGMT</it> in 51.3%, <it>GATA6</it> in 68.4%, <it>CD81</it> in 46.1%, <it>DR4</it> in 41.3% and <it>CASP8</it> in 56.8% of tumors. Methylation of <it>MGMT</it> was associated with younger patient age (p < 0.05), while <it>CASP8</it> with older (p < 0.01). <it>MGMT</it> methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of <it>CASP8</it> was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> as independent predictors for glioblastoma patient outcome (p < 0.05). <it>MGMT</it> and <it>GATA6</it> were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy.</p> <p>Conclusions</p> <p>High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> genes methylation in glioblastoma patient outcome.</p