The effect of typicality training on costly safety behavior generalization.

BACKGROUND AND OBJECTIVES: Typicality asymmetry in generalization refers to enhanced fear generalization when trained with typical compared to atypical exemplars. Typical exemplars are highly representative of their category, whereas atypical exemplars are less representative. Individual risk factors, such as trait anxiety, attenuate this effect, due to the high level of threat ambiguity of atypical exemplars. Although recent research provided evidence for generalization of safety behavior, it is unclear whether this generalization also follows typicality asymmetry. This study examined (1) whether participants exhibited typicality asymmetry in the generalization of safety behavior and (2) whether this effect would be attenuated by individual risk factors, such as intolerance of uncertainty and trait anxiety. METHODS: Participants were trained with either typical (Typical group, n = 53) or atypical (Atypical group, n = 55) exemplars in a fear and avoidance conditioning procedure. Participants acquired differential conditioned fear and costly safety behavior to the threat- and safety-related exemplars. In a following Generalization Test, the degree of safety behavior to novel exemplars of the same categories was tested. RESULTS: The Atypical group showed greater differential safety behavior responses compared to the Typical group. Higher trait anxiety was associated with lower differential safety behavior generalization, driven by an increase in generalized responding to novel safety-related exemplars. LIMITATIONS: This study used hypothetical cost instead of real cost. CONCLUSIONS: Training with atypical exemplars led to greater safety behavior generalization. Moreover, individuals with high trait anxiety show impaired safety behavior generalization.

Associating IDH and TERT Mutations in Glioma with Diffusion Anisotropy in Normal-Appearing White Matter.

BACKGROUND AND PURPOSE: IDH and TERT mutations might infiltratively manifest within normal-appearing white matter with specific phenotypes such as microstructural changes undetectable by standard MR imaging contrasts but potentially associable with DTI variables. The aim of this retrospective glioma study was to statistically investigate IDH and TERT associations and classifications with DTI reported microstructure in normal-appearing white matter. MATERIALS AND METHODS: Retrospective data from patients imaged between March 2012 and February 2016 were analyzed by grouping them as IDH-TERT subgroups and by IDH and TERT mutation status. DTI variables in the IDH-TERT subgroups were first identified by the Kruskal-Wallis test, followed by Dunn-Sidák multiple comparisons with Bonferroni correction. IDH and TERT mutations were compared with the Mann-Whitney U test. Classification by thresholding was tested using receiver operating characteristic analysis. RESULTS: Of 170 patients, 70 patients (mean age, 43.73 [SD, 15.32] years; 40 men) were included. Whole-brain normal-appearing white matter fractional anisotropy (FA) and relative anisotropy (RA) (P = .002) were significantly higher and the contralateral-ipsilateral hemispheric differences, ΔFA and ΔRA, (P < .001) were significantly lower in IDHonly patients compared with TERTonly, with a higher whole-brain normal-appearing white matter FA and RA (P = .01) and ΔFA and ΔRA (P = .002) compared to double positive patients. Whole-brain normal-appearing white matter ADC (P = .02), RD (P = .001), λ2 (P = .001), and λ3 (P = .001) were higher in IDH wild-type. Whole-brain normal-appearing white matter λ1 (AD) (P = .003), FA (P < .001), and RA (P = .003) were higher, but Δλ1 (P = .002), ΔFA, and ΔRA (P < .001) were lower in IDH mutant versus IDH wild-type. ΔFA (P = .01) and ΔRA (P = .02) were significantly higher in TERT mutant versus TERT wild-type. CONCLUSIONS: Axial and nonaxial diffusivities, anisotropy indices in the normal-appearing white matter and their interhemispheric differences demonstrated microstructural differences between IDH and TERT mutations, with the potential for classification methods.

Clinical and genetic features of 13 patients with mucopolysaccarhidosis type IIIB: Description of two novel NAGLU gene mutations.

AIM: Mucopolysaccharidosis type III B (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the NAGLU gene which codes the lysosomal enzyme alpha-N-acetylglucosaminidase. The major symptoms of the disease are cognitive and neurological defects. In this study, the molecular spectrums of 13 MPS IIIB patients were evaluated. MATERIAL AND METHODS: Thirteen MPS IIIB patients from 11 families were included in this study. All patients were both clinically and molecularly diagnosed. NAGLU gene sequencing was performed using a next generation sequencing platform (Illumina MiSeq). Demographic, clinical and laboratory findings of the patients were obtained via the hospital records. RESULTS: Ten different mutations from the 13 MPS IIIB patients were identified. Eight of the 10 mutations were missense, one was splice site, and one large deletion was also observed. Two mutations c.509G>T (p.Gly170Val) and c.700C>G (p.Arg234Gly) have been defined for the first time in this study. CONCLUSION: Our study expanded the mutation spectrum of the NAGLU gene thereby contributing to the improved genetic counselling of MPS IIIB patients. Confirming the literature, missense mutations were also found to be the most common NAGLU mutations in our study.

Preoperative grading of supratentorial gliomas using high or standard b-value diffusion-weighted MR imaging at 3T.

PURPOSE: The goal of this study was to compare diffusion-weighted magnetic resonance imaging (DW-MRI) using high b-value (b=3000s/mm2) to DW-MRI using standard b-value (b=1000s/mm2) in the preoperative grading of supratentorial gliomas. MATERIALS AND METHODS: Fifty-three patients with glioma had brain DW-MRI at 3T using two different b-values (b=1000s/mm2 and b=3000s/mm2). There were 35 men and 18 women with a mean age of 40.5±17.1 years (range: 18-79 years). Mean, minimum, maximum, and range of apparent diffusion coefficient (ADC) values for solid tumor ROIs (ADCmean, ADCmin, ADCmax, and ADCdiff), and the normalized ADC (ADCratio) were calculated. A Kruskal-Wallis statistic with Bonferroni correction for multiple comparisons was applied to detect significant ADC parameter differences between tumor grades by including or excluding 19 patients with an oligodendroglioma. Receiver operating characteristic curve analysis was conducted to define appropriate cutoff values for grading gliomas. RESULTS: No differences in ADC derived parameters were found between grade II and grade III gliomas. Mean ADC values using standard b-value were 1.17±0.27×10-3mm2/s [range: 0.63-1.61], 1.05±0.22×10-3mm2/s [range: 0.73-1.33], and 0.86±0.23×10-3mm2/s [range: 0.52-1.46] for grades II, III and IV gliomas, respectively. Using high b-value, mean ADC values were 0.89±0.24×10-3mm2/s [range: 0.42-1.25], 0.82±0.20×10-3mm2/s [range: 0.56-1.10], and 0.59±0.17×10-3mm2/s [range: 0.40-1.01] for grades II, III and IV gliomas, respectively. ADCmean, ADCratio, ADCmax, and ADCmin were different between grade II and grade IV gliomas at both standard and high b-values. Differences in ADCmean, ADCmax, and ADCdiff were found between grade III and grade IV only using high b-value. CONCLUSION: ADC parameters derived from DW-MRI using a high b-value allows a better differential diagnosis of gliomas, especially for differentiating grades III and IV, than those derived from DW-MRI using a standard b-value.

Bruton's tyrosine kinase inhibition increases BCL-2 dependence and enhances sensitivity to venetoclax in chronic lymphocytic leukemia.

Although the BTK inhibitor ibrutinib has transformed the management of patients with chronic lymphocytic leukemia (CLL), it does not induce substantial apoptosis in vitro, and as such the mechanisms underlying its ability to kill CLL cells are not well understood. Acalabrutinib, a more specific BTK inhibitor now in development, also appears to be highly effective in CLL, but the connection of its mechanism with CLL cell death is also unclear. Using dynamic BH3 profiling, we analyzed alterations in the function of the mitochondrial apoptotic pathway induced by ibrutinib and acalabrutinib. We studied CLL patient samples treated ex vivo with both drugs, as well as primary samples from CLL patients on clinical trials of both drugs. We found that BTK inhibition enhances mitochondrial BCL-2 dependence without significantly altering overall mitochondrial priming. Enhancement of BCL-2 dependence was accompanied by an increase in the pro-apoptotic protein BIM. In contrast, treatment with the selective BCL-2 inhibitor venetoclax enhanced overall mitochondrial priming without increasing BCL-2 dependence. Pre-treatment of CLL cells with either BTK inhibitor, whether ex vivo or in vivo in patients, enhanced killing by venetoclax. Our data suggest that BTK inhibition enhances mitochondrial BCL-2 dependence, supporting the ongoing development of clinical trials combining BTK and BCL-2 inhibition.

The impact of vitamin E supplementation on semen parameters and pregnancy rates after varicocelectomy: a randomised controlled study.

In this study, we aimed to investigate the impact of vitamin E supplementation on semen parameters and pregnancy after varicocelectomy. Forty-five infertile male patients who were diagnosed with varicocele and underwent subinguinal varicocelectomy were included in the study. After performing subinguinal varicocelectomy, the patients were randomised into two groups: 22 receiving vitamin E for 12 months, and 23 as the control group without receiving any supplementation. The pre-operative parameters of semen analyses and pregnancy rates of both groups were compared with those of post-operative parameters. There were no statistically significant differences between the groups in terms of sperm count and motile sperm percentage, in pre-operative, post-operative 3rd month, post-operative 6th month and post-operative 12th month periods. Repeated-measures anova was performed, and sperm count, percentage of change in sperm count, motile sperm count and percentage of change in motile sperm count of the groups were compared. The administration of vitamin E increased all of these parameters; however, they were not found to be statistically significant. In conclusion, vitamin E supplementation might improve the sperm parameters after varicocelectomy; however, further studies including larger number of samples are needed to make a proper decision on vitamin E supplementation after varicocelectomy.

Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method.

PURPOSE: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. METHODS: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann-Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using Spearman correlation analysis. RESULTS: There was a statistically significant difference between low and high-grade tumors for all parameters. Correlation analyses revealed significant positive correlations between rCBV and rCBF-ASL (r=0.81, p<0.001). However correlation between rCBF and rCBF-ASL was weaker (r=0.64, p<0.001). CONCLUSION: Arterial spin labeling is an employable imaging technique for evaluating tumor perfusion non-invasively and may be useful in differentiating high and low grade gliomas.

Self expandable polytetrafluoroethylene stent for carotid blowout syndrome.

Carotid blowout syndrome (CBS) is an emergency complication in patients undergoing treatment for head and neck cancers. The classical management of CBS is the ligation of the common carotid artery, because suturing is not be possible due to infection and necrosis of the field. In this case report, we present a patient with CBS, in whom we applied a self-expandable polytetrafluoroethylene (PTFE) stent and observed no morbidity. Endovascular stent is a life-saving technique with minimum morbidity that preserves blood flow to the brain. We believe that this method is preferable to ligation of the artery in CBS.

Comparison of spermatic vein histology in patients with and without varicocele.

The aim of this study was to investigate and compare histological characteristics of spermatic veins in patients with and without varicocele. Between February 2009 and July 2009, spermatic veins were obtained from 13 patients with varicocele. Microsurgical subinguinal low ligation was performed in all patients. Spermatic veins of patients without varicocele were obtained from 12 patients who underwent radical nephrectomy. Histologically, sections of veins were stained with haematoxylin and eosin. Mean tunica adventitia thickness size of the spermatic veins was 0.35 ± 0.08 mm and 0.22 ± 0.1 mm respectively in patients with varicocele and control group (P = 0.001). Similarly, mean tunica media thickness size of the spermatic veins was 0.25 ± 0.05 mm and 0.09 ± 0.04 mm respectively in patients with varicocele and control group (P < 0.001). No significant differences were detected regarding the tunica adventitia and tunica media thicknesses when patients with grade 2 varicocele were compared with patients with grade 3 varicocele (P > 0.05). No significant differences were detected between the tunica adventitia and tunica media thicknesses of patients with varicocele and sperm parameters (P > 0.05). Our study demonstrated that tunica adventitia and tunica media thicknesses seem to be increased in patients with varicocele compared with normal subjects.

Hypertension in leather tanning workers working in Istanbul, Turkey.

INTRODUCTION: Leather tanning may result in various occupational diseases. The aim of this study was to compare the relation between blood pressure levels and vocations in leather tanning. METHODS: Our study was conducted in Turkey's leading leather process plant located in Tuzla organised industry zone, between March 11 and May 30, 2005. All leather plants that consented to participate in our study were included. The blood pressure, height and weight of the workers were measured. Their ages, educational levels, smoking habits and hypertension history were obtained via interviewing the subjects. The relation between three main factors, i.e. age, body mass index (BMI), working period, and hypertension were analysed through multiple logistic regression analysis. RESULTS: 40.4 percent (295) of 730 workers' blood pressure values were found to be within normal limits. 59.6 percent (435) were found to be hypertensive. The hypertension correlation remained significant, along with BMI and their working period (p-values were 0.0001 and 0.035, respectively). CONCLUSION: Our study demonstrated that BMI and working period have a key influence on the increased risk of hypertension, which leads us to consider the importance of occupational exposure. Different hypertension studies to be conducted in various occupational fields would likely be able to confirm our findings.

Confirmed prevalence of food allergy and non-allergic food hypersensitivity in a Mediterranean population.

BACKGROUND: Until the present, no comprehensive studies evaluating the prevalence of food allergy and non-allergic food hypersensitivity (FA/NAFH) in adults have been done in Turkey or its surrounding countries. OBJECTIVE: This large population-based study was planned to identify the confirmed prevalence of adverse reactions to food in adults in Istanbul. METHODS: A total of 17 064 telephone numbers were randomly selected from both the European and Asian sides of Istanbul, and the 11 816 subjects who agreed to participate in the study were addressed with a questionnaire of eight items. Those who disclosed food-related complaints in this survey were called again and a similar questionnaire was repeated. The respondents who were suspected of having food allergy or food hypersensitivity were invited for a personal clinical investigation that included double-blind, placebo-controlled food challenge tests. RESULTS: The lifetime prevalence of self-reported FA/NAFH was found to be 9.5% [1118/11 816; 95% confidence interval (CI): 8.94-10.00%]. After the clinical investigations, the point prevalence of FA/NAFH, which also included the 'possible FA/NAFH group', was found to be as low as 0.3% (30/11 816; 95% CI: 0.17-0.36%), and the FA/NAFH rates assessed by double-blind, placebo-controlled food challenge tests were 0.1% (12/11 816; 95% CI: 0.05-0.18%) and 0.1% (11/11 816; 95% CI: 0.05-0.17%), respectively. The most significant factor influencing FA/NAFH was familial atopy (adjusted OR 4.3; 95% CI: 3.67-4.99), and the most related atopic disease was itching dermatitis/urticaria (adjusted OR: 3.9; 95% CI: 3.31-4.54). CONCLUSION: We may conclude that FA/NAFH in the Turkish population seems to be low when compared with Northern and Western European countries. This may be due to genetic, cultural or dietary factors, and further studies evaluating the reasons for this low prevalence of FA/NAFH in our population are needed.

Bilateral coronary-pulmonary artery fistulae associated with severe aortic insufficiency: an interesting association causing myocardial ischemia.

BACKGROUND: Coronary artery fistula (CAF) is defined as a direct communication of a coronary artery with a cardiac chamber, great vessel or other vascular structure, bypassing the myocardial capillary bed. Congenital CAFs joining into the pulmonary artery are rare cardiac anomalies. CAFs arising from two coronary arteries are even more rare especially when combined with valvular heart disease. The coincidence of CAFs with aortic insufficiency is relatively rare and sometimes might cause myocardial ischemia. RESULTS: We present a case of bilateral coronary-pulmonary artery fistula combined with severe aortic insufficiency causing myocardial ischemia and who subsequently underwent fistula ligation during aortic valve surgery.

Primary chylopericardium.

Primary chylopericardium is a rare entity. Here we describe a 36-year-old, asymptomatic male in whom pericardial effusion was detected by chest X-ray and echocardiography on routine health control. After pericardiocentesis that revealed the chylous nature of the fluid, partial pericardiectomy without duct ligation was carried out. In the follow-up period, there was no evidence of pericardial fluid on chest X-ray and echocardiography, at three months after the procedure.

Brain natriuretic peptide and the severity of aortic regurgitation: is there any correlation?

We aimed to evaluate the correlation between aortic regurgitation severity and brain natriuretic (BNP) levels as a marker for left ventricular dysfunction. Sixty consecutive male patients (mean age 22 +/- 3 years) with isolated chronic aortic regurgitation were enrolled in the study together with a control group of 30 age-matched healthy volunteers (group A). Patients were classified with regard to aortic regurgitation vena contracta width as follows: group B, < 3 mm, mild (n = 16); group C, > or = 3 and < 6 mm, moderate (n = 26); group D, > or = 6 mm, severe (n = 18). BNP measurements were performed with a fluorescence immunoassay kit. BNP levels were increased in patients with aortic regurgitation, and severity of regurgitation had a significant influence on BNP levels. This effect can be explained by the volume loading effect of aortic regurgitation.

Spironolactone does not prevent restenosis after coronary stenting in humans.

INTRODUCTION: In animal studies, aldosterone enhanced neointimal proliferation by increasing extracellular accumulation of collagen and potentiating the effects of angiotensin II. Spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal proliferation. We conducted a placebo-controlled, double-blind, randomised study to assess the effect of spironolactone on angiographic 6-month in-stent restenosis. MATERIALS AND METHODS: Of the 310 randomised patients with significant coronary artery disease, 258 patients were available for analysis: 128 constituted the placebo group and 130 were assigned to receive spironolactone. Eligible patients were randomly assigned to receive a dose of 50 mg spironolactone or placebo orally twice a day for 6 months. The primary endpoint was the angiographic restenosis (>50% stenosis) rate at follow-up angiography. RESULTS: At 6-month follow-up angiography after stenting, there was no difference between the 2 groups in minimal lumen diameter, percent diameter stenosis, late loss, and net gain. Angiographic restenosis occurred in 46 (35.4%) of 130 patients receiving spironolactone and 50 (39.0%) of 128 in the placebo group with an odds ratio (OR) of 0.85 with a 95% confidence interval (CI) of 0.49 to 1.46 (P = 0.62). Restenosis rate was found in 60 (32.9%) of 182 lesions in the spironolactone group, and 61 (35.5%) of 172 lesions in the placebo group with an OR of 0.89 with a 95% CI of 0.56 to 1.42 (P = 0.89). CONCLUSIONS: Spironolactone did not reduce the incidence of in-stent restenosis as compared with placebo in human, contrary to the fact that reduction of neointimal formation in animal models has been observed upon administration of spironolactone.

Technetium-99m-HMPAO brain SPECT in anorexia nervosa.

Eating disorders have been redefined in recent years. Brain imaging techniques are useful in demonstrating the association between the morphologic and the functional cerebral changes in these cases. We report 99mTc-HMPAO brain SPECT findings in two patients with anorexia nervosa, before and after the treatment. While the detailed neurologic and laboratory examinations, including EEG and cranial CT, were within normal limits before therapy, SPECT study revealed diffuse bilateral hypoperfusion in frontal, parietal and frontotemporal areas which was more prominent in the left hemisphere. Post-treatment SPECT studies obtained after a clinical remission period of 3 mo showed normal brain perfusion in both patients. The pre- and post-treatment SPECT studies accurately reflect the functional state of the patients, and this technique may be used to follow-up the effect of treatment and predict the clinical response to therapy in patients with eating disorders.

Clozapine-induced myoclonic seizures and valproic acid.

Within a 3-year period, in 220 patients receiving clozapine, we observed myoclonic seizures in two who had no previous epileptic history. Seizures appeared at the titration phase at relatively low doses, and resolved with the addition of valproic acid, allowing further increases of the clozapine dose to therapeutic levels.

Suicide attempts among Turkish psychiatric patients.

OBJECTIVES: The aim of this study was to investigate the sociodemographic characteristics of those who attempt suicide in an Islamic country, the effect of religion on suicide attempts, and the frequency of DSM-III-R diagnoses in suicide attempters referred to the Gazi Medical School Psychiatry Department. METHOD: Medical records of 185 cases of suicide attempts were reviewed. RESULTS: There was a predominance of single, female subjects. Students, housewives, and employees represented the 3 largest groups. Drug overdose was the most common method of suicide attempt, and the most common DSM-III-R diagnosis was depression. The rate of repetition of suicide attempt was 43.3%. CONCLUSION: Suicide is one of the major problems among Turkish psychiatric patients, although the Islamic religion strongly disapproves of it.