CLINICAL AND GENETIC FEATURES OF PERSONALIZED ANTIPSYCHOTIC THERAPY OF PATIENTS WITH PARANOID SCHIZOPHRENIA OF THE KAZAKH ETHNIC GROUP IN THE REPUBLIC OF KAZAKHSTAN.

The problems of schizophrenia therapy occupy a leading place in both foreign and domestic clinical psychiatry. The paper presents the results of a study to identify reliable biomarkers for predicting antipsychotic therapy of patients with paranoid schizophrenia of the Kazakh ethnic group in the Republic of Kazakhstan, conducted within the framework of the project: "National program for the introduction of personalized and preventive medicine in the Republic of Kazakhstan" IRN ОР12165486. The effectiveness and tolerability of antipsychotic drugs used in the treatment of paranoid schizophrenia in the Republic of Kazakhstan according to clinical treatment protocols are analyzed. Gender and age-specific dynamics in the clinic of paranoid schizophrenia in antipsychotic therapy in persons of Kazakh ethnicity are described. Certain genetic features of representatives of the Kazakh ethnic group have been identified, which can influence the effectiveness and tolerability of antipsychotic drugs, which determines the basis of an innovative approach to personalized therapy of paranoid schizophrenia in patients of the Kazakh ethnic group in the Republic of Kazakhstan.

Carfentanil on the darknet: Potential scam or alarming public health threat?

BACKGROUND: In an age of global insecurity, highly potent synthetic drugs have become a major public health issue. Their online advertisement and sale are facilitated by surface web, darknet markets and social media fuelling substance abuse and addiction, as well as various types of new criminal activities and their growth in sophistication. This study presents a systematic analysis of the darknet sale of one of the most potent synthetic opioids: Carfentanil. With an equianalgesic potency of 10.000 times a unit of morphine, its toxicity is comparable to traditional nerve agents, and it has been previously used as a chemical weapon, causing human fatalities. METHODS: Digital trace data was collected retrospectively from all the darknet marketplaces, which have been active in the past five years. Data on vendors offering Carfentanil on Agartha, Empire and Yakuza marketplaces were analysed with regard to items sold and sellers' features as these were the only active markets at the time of search. Searches were carried out in the English language only. RESULTS: 63 Cartfentanil vendors operating on 19 darknet marketplaces were identified. Contacts and payments were facilitated with end-to-end encryption messaging mobile applications and content-expiring messages. Although it is known that Agartha is a scam market, and no operative sellers were found on Yakuza, several sellers promoting Carfentanil sales were active in the Empire marketplace with a number of transaction ranging from 4 to 1223. CONCLUSION: The availability of highly potent drugs such as Carfentanil on the darknet requires the urgent development of novel scientific methods and tools able to monitor and to predict such new threats, while informing policymaking and protecting the health and the security of citizens.

[Play behavior in people with various degrees of pathological gambling risk].

OBJECTIVE: We studied play behavior of customers of betting offices. MATERIAL AND METHODS: A study included 216 people who were surveyed using the Canadian problem gambling index. According to the results of the test, we stratified the sample by the risk of pathological gambling. RESULTS AND CONCLUSION: The high prevalence of people with medium and high risk of pathological gambling was identified. Significant differences in the characteristics of gambling behavior were found. We described the qualitative and quantitative indicators of gaming activity that proved the appearance of the addicted dominant in the high-risk group (changes in the motivational sphere, financial loss, using alternative forms of the game, the regular play activity and low level of the reflection of problems caused by the game).

Breast tumor contamination of PBSC harvests: tumor depletion by positive selection of CD34(+) cells.

BACKGROUND: Positive selection of CD34(+) cells may reduce or eliminate tumor cells contaminating PBSC harvests of breast cancer (BrCa) patients. However, to assess tumor purging accurately methods may be needed that are of higher sensitivity than standard immunocytochemistry (ICC) assays. METHODS: BrCa-cell depletion, resulting from CD34(+) cell selection, was evaluated using a novel, highly sensitive assay based upon immunomagnetic enrichment with ICC detection in 36 BrCa patients undergoing highdose chemotherapy with autologous PBSC support. RESULTS: The prevalence of BrCa-cell contamination was significantly lower (P = 0.0078) in selected CD34(+) cell fractions (17/35, 49%) from apheresis collections compared with CD34(-) cell fractions (25/35, 71%). In 8/34 (24%) patients, BrCa cells were detected in CD34(-) cell fractions, but not in paired CD34(+) cell fractions. Significantly lower total numbers (P < 0.0005) of BrCa cells were enumerable in CD34(+) cell fractions compared with corresponding apheresis harvests. The median total BrCa-cell content of selected CD34(+) cell fractions with measurable contamination was 22 BrCa cells (range, 6-73 BrCa cells), compared with 3297 BrCa cells (range, 10-98 400 BrCa cells) in apheresis harvests. The median log depletion of BrCa cells achieved by positive CD34(+) cell selection in specimens with detectable contamination both before and after selection was 2.2 (range, 1.7-4.0). Total pre-selection BrCa cell number was significantly predictive (P = 0.004) of residual detectable post-selection contamination. DISCUSSION: Positive CD34(+) cell selection is an effective tumor purging strategy. The prevalence of PBSC contamination in BrCa patients is substantially higher than formerly appreciated.

Breast tumor contamination of peripheral blood stem cell harvests: increased sensitivity of detection using immunomagnetic enrichment.

Contaminating tumor cells in peripheral blood stem cell (PBSC) grafts infused for hematopoietic rescue after high-dose chemotherapy could potentially contribute to relapse in BrCa patients. To date the prevalence of PBSC contamination in BrCa patients, as determined by standard immuno-cytochemistry (ICC) assays, has generally been found to be relatively low. However, assay sensitivity may have an important impact on the ability to detect contamination. In this investigation a novel and highly sensitive BrCa cell assay using immunomagnetic enrichment with a panel of antiBrCa monoclonal antibodies (MAbs) and detection by ICC has been characterized. The immunomagnetic enrichment with ICC detection (IE-ICC) assay was directly compared with standard ICC in ability to detect BrCa contamination of PBSC specimens from patients with high-risk stage II/III and metastatic disease. The sensitivity of the IE-ICC assay was approximately 50-fold greater than that of standard ICC. As determined by standard ICC assay, BrCa cells were present in 1/14 patients (7%) and 2/26 (8%) specimens. In contrast, with IE-ICC assay the proportions of positive findings in patients (12/14, 86%) and specimens (19/26, 73%) were significantly higher (p = 0.001 and p < 0.0005, respectively). These preliminary findings suggest that the prevalence of PBSC contamination may be substantially higher than previously appreciated. Consequently, measures to reduce tumor contamination in the graft may have the potential to improve patient outcomes. Higher sensitivity assays such as the IE-ICC assay may play an important role in assessing the risks associated with tumor contamination and the effectiveness of tumor-purging approaches such as positive selection of CD34+ cells and in monitoring patient response to therapy.

Mechanisms of unusually high antioxidant activity of RSV-SR-transformed cells and of its suppression by activated p21ras.

We have previously demonstrated that hamster embryo fibroblasts (HEFs) transformed by Rous Sarcoma virus, Schmidt-Ruppin strain (RSV-SR) are highly resistant to damage by H202 (H2O2R), (in contrast to HEFs transformed spontaneously, or by bovine adenovirus and SV40), while N-ras transfection of RSV-SR transformants leads to suppression of pp6Ov-scr and of H2O2R. In this study we have examined (1) mechanisms of antioxidant activity (AOA) of HEFs transformed by these agents and (2) the possible role of the v-src gene in unusually high AOA of RSV-SR transformants and of activated ras oncogenes in its suppression. All transformants exhibit increased catalase and glutathione peroxidase (GP) activities, while SOD, glutathione and glutathione reductase (GR) were reduced. As compared with other transformants, the significantly higher catalase and the low SOD activities were characteristic of RSV-SR-transformants, while an increase in GP was observed in all types of transformants. Correspondingly, RSV-SR-transformants showed an extremely high H202-catabolizing activity (H2O2CA) and no lipid peroxidation chain reaction (LPCR). N-ras-induced suppression of pp60v-scr of RSV-SR-transformed HEFs coincided with the suppression of catalase, GP, H202 and H202CA. However, suppression of catalase and GP was also observed in N-ras- and Ha-ras-transfected, spontaneously transformed HEFs. Thus, extremely high catalase activity and suppression of LPCR are apparently the main mechanisms of the unusually high H202R of RSV-SR transformants, while its suppression by activated ras oncogenes may also take place in some transformants, free of v-src activity.