Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

The effect of psychological support for the relatives of intensive care unit patients on cadaveric organ donation rate.

We searched to see whether psychological support for relatives of intensive care unit patients helps them to donate organs of their brain-dead relatives. After receiving ethics committee permission, first-degree relatives of 200 general intensive care unit patients were enrolled in the study. The participants were divided into 2 groups randomly: an interview group (n = 100) and a control group (n = 100). Participants were asked to complete a questionnaire. Interviews with the psychologist and patients' relatives in the interview group were therapeutic in nature and were conducted according to the relatives' psychosocial needs in an unstructured format. In the control group, the psychologist and patients' relatives were not interviewed. The study utilized demographic data, the questionnaire for relatives of patients to mention their attitude on organ donation and the reasons for this choice, and the Participant Information Form to record demographic data and relatives' degree of relationship with the patient. There was no statistically significant difference between the 2 groups when compared according to sex ratio, patient age, and duration of patients' hospital stay. Whereas in the interview group, 75% agreed to allow their relatives to be organ donors, only 32% in the control group agreed (P < .0001). Of the 200 patients enrolled in the study, 93 lost their lives: 50 from the interview group and 43 from the control group. Among the relatives whose patients had lost their lives, 78% belonging to the interview group accepted to donate the organs of their patients, whereas in the control group 13.9% accepted (P < .0001). We hope that psychological support for the relatives of the potential brain-dead donor to cope with the psychological problems to be faced can improve the rate of organ donation.

Influence of tip wear of piezoelectric ultrasonic scalers on root surface roughness at different working parameters. A profilometric and atomic force microscopy study.

Roughness on tooth surfaces is reported to facilitate the reestablishment of microbial dental plaque. Hence, the main goal of dental scaling is to remove bacterial plaque and obtain smoother tooth surfaces. This study was aimed to assess the influence of tip wear of ultrasonic scaler inserts on root surface roughness at different working parameters. Twenty piezoelectric ultrasonic scaler inserts (10 worn/10 new) were selected to examine the erosion ratio (ER) on the scaler tips and to assess the influence of tip wear on root surface roughness. Erosion on the tip surfaces was evaluated under atomic force microscopy (AFM). Root samples were prepared and instrumented by new (Group I) and worn (Group II) inserts at different working parameters. Roughness change (Rc) on root surfaces after instrumentation was examined under profilometer and compared between and within the groups. Statistically significant differences were found between the mean ERs of new and worn tips (P < 0.01). The results of this study showed that tip angulation and instrument power strongly influenced the Rc values on instrumented samples (P < 0.05). It was also revealed that tip wear influenced the Rc values on root surfaces especially at 45° tip angulation (P < 0.05). Therefore, tip wear should also be considered as much as the other parameters to minimize the surface roughness during ultrasonic treatment.

The diagnostic value of beta-human chorionic gonadotropin, progesterone, CA125 in the prediction of abortions.

This study was conducted to investigate the effectiveness of serum levels of free beta-hCG, progesterone, CA125 and their combined use in the prediction of first trimester abortions. A total of 140 singleton pregnant women between 5 and 13 weeks' gestational age were included as Group I (n = 21) who resulted in abortion including missed abortion, incomplete abortion, complete abortion and inevitable abortion; Group II (n = 129) included normal pregnancies. When using the free beta-hCG level of <20 ng/ml as a cut off point, the sensitivity, specificity, PPV and NPV were 91%, 82%, 46% and 98%, when using a progesterone of <15 ng/ml as a cut off point, they were 91%, 89%, 59%, 98%. The single measurement of free beta-hCG or progesterone levels can be useful in the prediction of first trimester spontaneous abortions, but using progesterone may be recommended since it has high availability and low cost.

A simple technique to open the posterior wall of the third ventricle.

Third ventriculostomy is an operating technique which is mostly used in benign adult aqueductal stenosis. The most important stage of this operation is the manipulation of the basal membrane of the third ventricle. A technique which facilitates the opening of the posterior wall of the third ventricle is presented.