Methylation analysis of histone 4-related gene HIST1H4F and its effect on gene expression in bladder cancer.

Recently, aberrant DNA methylation of the HIST1H4F gene (encodes Histone 4 protein) has been shown in many types of cancer, which may serve as a promising biomarker for early cancer diagnosis. However, the correlation between DNA methylation of the HIST1H4F gene and its role in gene expression is unclear in bladder cancer. Therefore, the first objective of this study is to explore the DNA methylation pattern of the HIST1H4F gene and then further elucidate its effects on HIST1H4F mRNA expression in bladder cancer. To this end, the methylation pattern of the HIST1H4F gene was analyzed by pyrosequencing and the effects of the methylation profiles of this gene on HIST1H4F mRNA expression in bladder cancer were examined by qRT-PCR. Sequencing analysis revealed significantly higher methylation frequencies of the HIST1H4F gene in bladder tumor samples compared to normal samples (p < 0,0001). However, when we evaluated the correlations between hypermethylation of HIST1H4F and the clinicopathological parameters (tumor stage, tumor grade, lymph node metastasis, muscle-invasion), no significant difference was found between the groups (p > 0.05). In addition, we examined the role of hypermethylation of the HIST1H4F gene on HIST1H4F mRNA expression. We found that hypermethylation of HIST1H4F in the exon have no effect HIST1H4F mRNA expression in bladder cancer (p > 0.05). We also confirmed our finding in cultured T24 cell line which HIST1H4F gene is hypermethylated. Our results suggest that hypermethylation of the HIST1H4F seems to be a promising early diagnostic biomarker in bladder cancer patients. However, further studies are needed to determine the role of HIST1H4F hypermethylation in tumorigenesis.

Analysis of the effects of COHb, lactate, and troponin levels on the clinical process and outcome in patients who were admitted to the emergency service due to carbon monoxide poisoning.

OBJECTIVE: The aim of the present study was to determine the demographic, medical, and treatment characteristics of patients followed up with the diagnosis of carbon monoxide (CO) poisoning in emergency care and also to determine the relationship of these patients' clinical process and outcome between carboxyhemoglobin (COHb), lactate, and troponin levels. METHODS: The present study was conducted retrospectively between 01/01/2013 and 01/01/2016 by examining 450 patients who were referred to the emergency service for CO poisoning. The ages; sexualities; manners of application; clinical findings; levels of blood COHb, lactate, and troponin; applied oxygen treatment method; and outcome of patients were evaluated. Data analysis was done by Shapiro-Wilk, Student's t, Mann-Whitney U, and chi-square tests. RESULTS: A total of 450 patients were included in the study. The median age of the patients was 35 (interquartile range (IQR) 26.75-45.00) years. In the study where data are not homogeneously distributed, the median levels of COHb, lactate, and troponin were 11.80% (IQR 3-23), 1.60 (IQR 1.10-2.5) mmol/l, and 0.00 (IQR 0.000-0.003) ng/ml, respectively. The levels of lactate were detected to be statistically high in patients who had syncope and who received hyperbaric oxygen treatment (p<0.05). In addition, the levels of lactate and troponin were significantly higher in patients who were hospitalized (p<0.05). CONCLUSION: The levels of COHb, lactate, and troponin can provide an insight to the clinician about hospitalization and the type of treatment.

Sociodemographic and clinical characteristics of synthetic cannabinoid users in a large psychiatric emergency department in Turkey.

Synthetic cannabinoid (SC) use is a global concern and is creating new challenges for treatment services. Although some studies have been reported, there is a need for further research regarding the sociodemographic and clinical characteristics of SC users so that general and psychiatric emergency departments can provide more effective treatments. We aimed to investigate the sociodemographic and clinical characteristics in a cohort of patients using SC who presented to the psychiatric emergency department of the University of Health Sciences, Istanbul Erenköy Training and Research Hospital for Psychiatry and Neurology (ERSHEAH) in Istanbul, Turkey. This cross-sectional and retrospective medical record review examined 340 SC users who presented to the emergency department of ERSHEAH in a 3-month period. The mean age of the SC users was 26.8 ± 7.5 years and 92.6% were men. Psychotic symptoms were present in 247 SC users (78.8%). Severe intoxication was diagnosed in 26 SC users (7.6%), although SC was detectable in the samples of only 6 patients (13.6%). Impaired consciousness (42.3%) was the most common reason for referral to the general hospital and increased liver enzyme levels (15.9%) were the most common indication in the laboratory findings. We observed that the SC users in our sample presenting as psychiatric emergencies were mostly young men experiencing psychotic symptoms. Determining the sociodemographic and clinical properties of SC users may provide an important contribution to fast recognition and more effective management of acute symptoms of SC users in emergency departments.

Diagnostic value of CMR in young patients with clinically suspected acute myocarditis is determined by cardiac enzymes.

AIMS: Cardiovascular magnetic resonance (CMR) has become a valuable diagnostic tool for non-invasive diagnosis of acute myocarditis. However, since CMR studies are time- and cost-intensive and its diagnostic accuracy still not perfect, additional parameters are warranted to preselect and identify those individuals in whom a CMR study is likely to add crucial information regarding correct and timely diagnosis of acute myocarditis. The diagnostic value of CMR was evaluated in a population of young patients with clinically suspected acute myocarditis in relation to ECG and serum cardiac enzyme findings. METHODS AND RESULTS: Only young patients aged ≤ 40 years in whom acute myocarditis was highly suspected based on their clinical symptoms, resting ECG findings and/or levels of cardiac enzymes (at presentation) were included to this study. After ruling out obstructive coronary artery disease, a multi-parametric CMR study was performed as part of the diagnostic work-up. The CMR protocol comprised cine sequences, T2-weighted edema imaging and late gadolinium enhancement (LGE) imaging on a 1.5-T MR scanner. 89 patients (28 ± 7 years, 89 % male) were included to this study presenting with symptoms of chest pain (85 %), dyspnea (26 %), fatigue (23 %) and/or palpitations (18 %). Pathological ECG changes were present in 72 patients (81 %). An elevated serum troponin level was measured in 45 patients (51 %). Pathological CMR findings (presence of edema and/or LGE) were detected in 35 patients (39 %). In detail, pathological CMR findings were detected in 36 % of patients with resting ECG changes and in 73 % of patients with troponin rise. In contrast, normal CMR results were obtained in 95 % of patients with negative troponin at presentation, but only in 41 % of patients with normal ECG. On multivariable analysis, a positive serum troponin was the only independent predictor for a pathological CMR finding (OR = 33.26, 95 % CI = 3.04-363.35, p = 0.004). CONCLUSIONS: The clinical use of non-invasive CMR in the work-up of clinically suspected "acute" myocarditis in young patients is only helpful and appropriately indicated in those ones with elevated cardiac enzymes. A pre-selection of such patients for CMR based on serum cardiac enzymes--but not on ECG recordings--may prevent a meaningless overuse of CMR.

Myocardial fibrosis imaging based on T1-mapping and extracellular volume fraction (ECV) measurement in muscular dystrophy patients: diagnostic value compared with conventional late gadolinium enhancement (LGE) imaging.

AIM: Cardiac involvement with progressive myocardial fibrosis leading to dilated cardiomyopathy is a major cause of death in muscular dystrophy patients. Extracellular volume fraction (ECV) measurement based on T1-mapping pre- and post-contrast promises the detection of early 'diffuse' myocardial fibrosis that cannot be depicted by conventional contrast-imaging based on late gadolinium enhancement (LGE). With this study, we evaluated the presence of diffuse myocardial fibrosis in regions of 'normal' (LGE-negative) and 'diseased' (LGE-positive) appearing myocardium as well as its relation to the extent of left ventricular (LV) dysfunction and the occurrence of arrhythmias in Becker muscular dystrophy (BMD) patients. METHODS AND RESULTS: Twenty-seven BMD patients (35 ± 12 years) and 17 matched male healthy controls (33 ± 8 years) underwent cardiovascular magnetic resonance (CMR) studies including ECV measurement and LGE-imaging. Ambulatory monitoring of arrhythmic events was performed by means of an external event loop recorder. Twenty BMD patients (74%) demonstrated cardiac involvement as detected by typical inferolateral presence of LGE. Twelve patients (44%) had an impaired LV ejection fraction-all being LGE-positive. Global myocardial ECV was significantly higher in the BMD group (29 ± 6%) compared with the control group (24 ± 2%, P = 0.001). Patients with cardiac involvement demonstrated higher global ECV (31 ± 6%) as well as significantly increased regional ECV not only in LGE-positive segments (34 ± 6%), but also in LGE-negative segments (28 ± 6%) compared with BMD patients without cardiac involvement and to controls, respectively (24 ± 3 and 24 ± 2%, P = 0.005). Global ECV in patients with cardiac involvement substantially correlated to LV ejection fraction (r = -0.629, P = 0.003) and to the number of LGE-positive segments (r = 0.783, P < 0.001). On univariable analysis, global ECV-but not the categorical presence of LGE per se--was significantly associated with arrhythmic events (OR: 1.97, CI: 32.22-1.21, P = 0.032). CONCLUSION: ECV measurement by CMR is a useful tool in assessing the total extent of myocardial fibrosis as well as in depicting subtle diffuse fibrosis in areas of normal appearing myocardium on LGE-images. Thus, myocardial ECV is a potential additional quantitative tool for accurate detection of cardiac involvement and risk stratification in muscular dystrophy patients.

Positive effect of intravenous iron-oxide administration on left ventricular remodelling in patients with acute ST-elevation myocardial infarction - a cardiovascular magnetic resonance (CMR) study.

OBJECTIVES: This study investigated the safety profile and potential "therapeutic" effect of intravenous ultrasmall superparamagnetic iron-oxide (USPIO)-based iron administration regarding infarct healing in patients with ST-elevation myocardial infarction (STEMI). USPIO-administration was recently shown to enable an improved characterization of myocardial infarct pathology in acute STEMI patients. MATERIALS AND METHODS: Seventeen study patients (IRON, 54 ± 9 yrs, 88% male) and 22 matched controls (CONTROL, 57 ± 9 yrs, 77% male) both with primary reperfused STEMI underwent multi-parametric CMR studies in the first week and three months after acute MI. Only IRON patients received a single intravenous bolus of 510 mg elemental iron as ferumoxytol (Feraheme(TM)) within four days following acute MI. RESULTS: Three months later, all patients were alive and there were no adverse cardiac events. Significant improvement in left ventricular (LV) ejection fraction (IRON: 53 ± 10% to 59 ± 9%, p=0.002; CONTROL: 54 ± 6% to 57 ± 10%, p=0.005) as well as shrinkage of infarct size were seen in both groups at follow-up. There was a more pronounced decrease in infarct size in the IRON group (IRON: -10.3 ± 5.4% vs. CONTROL: -7.0 ± 8.4%, p=0.050) in addition to a significant decrease in both endocardial extent and prevalence of transmural infarctions in IRON but not in CONTROL patients. A significant decrease in LV end systolic volume was only seen in the IRON group (71 ± 25 mL to 59 ± 25 mL, p=0.002). CONCLUSIONS: Intravenous iron administration in acute STEMI patients seems to be associated with an improved infarct healing and a beneficial global left ventricular remodelling. These findings together with the good safety profile make USPIO-based iron administration a promising future candidate as a "diagnostic" and "therapeutic" adjunctive solution in acute MI management.

Assessment of opioid receptor µ1 gene A118G polymorphism and its association with pain intensity in patients with fibromyalgia.

Fibromyalgia may present with widespread pain and tenderness, fatigue, anxiety, and depression and is associated with a low pain threshold. The etiology of fibromyalgia is yet to be ascertained, although both genetic and environmental factors may play a role in the susceptibility of patients to fibromyalgia. Various genetic variations have been investigated to explain fibromyalgia susceptibility and differences in pain sensitivity, pain threshold, and tolerance. The A118G rs1799971 polymorphism in the opioid receptor µ1 gene (OPRM1) is one of the candidate genes. We hypothesized that the OPRM1 polymorphism may play a role in fibromyalgia susceptibility and impact the pain intensity and pain-related symptoms in fibromyalgia patients. This study comprised of 108 patients with fibromyalgia and 100 healthy controls. Overall, the 118G allele frequency was 16.3 % and was significantly lower in patients with fibromyalgia than in the control group (13.9 and 19 %, respectively). No difference was observed between fibromyalgia patients with and without the A118G allele with regard to the Beck Depression Inventory, widespread pain index, symptom severity, and Fibromyalgia Impact Questionnaire scores. All body parts of patients with fibromyalgia demonstrated lower pressure pain thresholds (PPT) compared to controls. The PPTs were higher in the 118 A/A genotype carrier fibromyalgia patients than in 118*/G carriers; however, the differences were not significant. As the A118G polymorphism frequency was lower in fibromyalgia patients, this polymorphism may exert a protective effect against fibromyalgia in Turkish women. However, the OPRM1 polymorphism does not have a significant effect on pressure pain and fibromyalgia severity.

Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach.

AIMS: The purpose of this clinical trial was to investigate whether cardiovascular magnetic resonance imaging (CMR) using ferumoxytol (Feraheme™, FH), an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO), allows more detailed characterization of infarct pathology compared with conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction. METHODS AND RESULTS: Fourteen patients who had experienced an acute ST-elevation myocardial infarction were included in this study. Following coronary angiography, a first baseline study (pre-FH) was performed followed by subsequent CMR studies (post-FH) 48 h after intravenous ferumoxytol administration. The CMR studies comprised cine-CMR, T(2)-weighted short tau inversion recovery spin echo imaging, T(2)-mapping, and T(1)-weighted late gadolinium enhancement (LGE) imaging. The median extent of short-axis in-plane LGE was 30% [inter-quartile range (IQR) 26-40%]. The median in-plane extent of T(2)-weighted 'hypoenhancement' in the region of myocardial infarction, which was not present prior to ferumoxytol administration in any patient, was 19% (IQR 14-22%; P < 0.001 compared with the extent of LGE). The median in-plane extent of areas showing signal void in T(2)-mapping images post-FH in the region of myocardial infarction was 16% (IQR 12-18%; P < 0.001 compared with the extent of LGE; P = 0.34 compared with the extent of T(2)-weighted hypoenhancement). A substantial drop in absolute T(2)-values was observed not only in the infarct core and peri-infarct zone, but also in the remote 'healthy' myocardium, although there was only a minor change in the skeletal muscle. Substantial ferumoxytol uptake was detected only in cultured macrophages, but not in peripheral blood monocytes from study patients. CONCLUSION: We could demonstrate in humans that USPIO-based contrast agents enable a more detailed characterization of myocardial infarct pathology mainly by detecting infiltrating macrophages. Considering the multi-functionality of USPIO-based particles and their superior safety profile compared with gadolinium-based compounds, these observations open up new vistas for the clinical application of USPIO.

677C>T and 1298A>C polymorphisms of methylenetetrahydropholate reductase gene and biochemical parameters in Turkish population with spina bifida occulta.

AIM: This study aimed to investigate the 677C > T and 1298A > C MTHFR gene polymorphisms and their metabolic effects on the levels of folate, vitamin B12 and homocysteine in the serum of Turkish spina bifida occulta (SBO) patients and healthy individuals in disease. MATERIAL AND METHODS: A case-control study was performed to detect 677C > T and 1298A > C MTHFR gene polymorphisms in 39 SBO patients and 34 healthy individuals. The folate, vitamin B12 and homocysteine concentrations in the serum of SBO and healthy individuals were evaluated and compared with MTHFR gene polymorphisms. RESULTS: 677 CC/CT/TT MTHFR genotype frequency differences between the SBO patients and controls were not significant (x(2)=3.325, P=0.068; x(2)=1.479, P=0.224; x(2)=0.275, P=0.600; respectively). 1298A > C MTHFR genotype frequency differences between the SBO patients and controls were significant (x(2)=8.477, P=0.004). The frequencies of the Aand C alleles of the 1298A > C polymorphism did not differ in a statistically significant manner between the groups (x(2)=0.576, P=0.448). The biochemical parameters were not significantly different between SBO patients and healthy individuals (P > 0.05). CONCLUSION: The 677C > T and 1298A > C polymorphisms of the MTHFR gene cannot be regarded as major risk factors for SBO in the Turkish patients 677TT homozygosity may affect the metabolism of homocysteine.

Evidence of association of vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis.

The vitamin D receptor (VDR) was the first candidate gene to be studied in relation to osteoporosis, and most attention has focused on polymorphisms situated near the 3' flank of VDR. The aim of this study was to investigate the association about VDR gene Apa I polymorphism with bone mineral density (BMD) in postmenopausal women with osteoporosis. We studied a total of 136 postmenopausal women with a mean age of 56.36 +/- 10.29 years. Among them, a total of 75 had osteoporosis, 37 had osteopenia, and 24 had normal BMD. Venous blood samples were obtained for evaluation of bone metabolism and genotyping. The VDR Apa I genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. BMDs at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry. Postmenopausal women with aa genotype had significantly lower BMD values (grams per centimeter square) at lumbar spines compared to persons with AA genotype. Also, postmenopausal women with AA genotype had significantly higher serum Ca level than the subjects with aa genotype. In conclusion, our result may indicate that VDR Apa I gene polymorphism may be responsible for a important part of the heritable component of lumbar spine BMD in postmenopausal women, possibly related to impaired calcium absorption from the bowel.

Genotyping for Cx26 and Cx30 mutations in cases with congenital hearing loss.

Hearing loss is the most frequent sensory defect in human being. The 13q11-q12 region contains the GJB2 and GJB6 genes, which code connexin 26 (CX26) and connexin 30 (CX30) proteins, respectively. The 35delG, 167delT, and 235delC mutations in the Cx26 gene are the main cause for sporadic nonsyndromic hearing loss (NSHL) in many populations. The 342-kb deletion [del(GJB6-D13S1830)] of the Cx30 gene is the second most common connexin mutation after the 35delG mutation in some NSHL populations. In our study 47 hearing-impaired students were included. The Cx26 gene and the Cx30 gene were analyzed for presence of the 35delG, 167delT, and 342-kb deletion [del(GJB6-D13S1830)]. Genotyping were performed for detecting 35delG, 167delT, and del(GJB6-D13S1830) mutations using the PCR-ELISA techniques. According to the results obtained from 47 cases, the 35delG mutation was detected in 7 cases ( approximately 14.9%). Four of these mutations were determined as homozygote mutant ( approximately 8.5%), and three were determined as heterozygote mutant ( approximately 6.4%). However, 167delT and del(GJB6-D13S1830) mutations were not detected in the study group. These results support the overwhelming majority of 35delG in our study group from deafness school in our study. In conclusion, the 35delG mutation was determined as the most frequently shown mutation that leads to congenital hearing loss as in previous studies from Turkey.