Long-term treatment with olanzapine in hospital conditions: Prevalence and predictors of the metabolic syndrome

© 2015, Serbia Medical Society. All rights reserved. Introduction The risk of metabolic abnormalities is greatly increased in schizophrenic patients started on an atypical antipsychotic medication. Patients with psychiatric disorders exceed mortality ranges resulting from, among others, increased risk of cardiovascular events. Other factors contributing to the development of metabolic syndrome include prolonged duration of illness, increasing age, female sex and lifestyle factors. Objective This cross-sectional study was taken up to assess the prevalence of the metabolic syndrome (MetS) in schizophrenic patients receiving olanzapine monotherapy for at least six months and to determine the most important risk factors associated with metabolic syndrome presence in these patients. Methods A total of 93 long term hospitalized schizophrenic patients (71 men, 22 women), had a screening of the following: case-history data, psychiatric scales, anthropometric measures, blood (fasting glucose, lipid status, C-reactive protein – CRP) and urine samples (microalbuminuria). Results Prevalence of MetS according to International Diabetes Federation criteria in our study was 34.4%. The multivariate analysis distinguished the following significant predictors of MetS presence (in order of appearance): data about diabetes mellitus in family history (p=0.002), body mass index >25 kg/m2 (p=0.002), hyperlipidemia in family history (p=0.008), and elevated CRP value (p=0.042). Conclusion High rate of MetS in patients treated with olanzapine in this study exceeds MetS prevalence in general population. Among observed parameters, our study pointed to several “high risk” predictors associated with MetS presence. Regular monitoring of cardiometabolic risk factors is highly recommended. Positive heredity distress mentioned above may direct a psychiatrist to prescribe some other drug than olanzapine in the long term treatment of schizophrenia

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Charakterisierung des Vitamin D Rezeptor-DNA-Komplexes auf dem epsilon- Keimbahnpromotor

Recently an increased incidence of allergic diseases has been associated to vitamin D deficiency. It was previously demonstrated that calcitriol, the active form of vitamin D, inhibits epsilon germline transcription, a prerequisite for IgE production. However, the underlying mechanisms remained unexplored. The aim of this work was to investigate the epsilon germline promoter regarding vitamin D receptor (VDR)-DNA-complex formation, changes in the chromatin acetylation and its impact on the epsilon germline transcription in human B cells. The VDR binding to the epsilon germline promoter in human B cells, the composition of the VDR-recruited complex and the acetylation pattern were investigated by chromatin immunoprecipitation. The calcitriol mediated action on Iε were analysed using a reporter gene assay. The data demonstrate that calcitriol-activated VDR binds together with retinoid X receptor α to the Iε. The heterodimer interacts with silencing mediator for retinoid and thyroid hormone receptors (SMRT), which is recruiting histone deacetylase (HDAC) 1 and HDAC3. The inhibition of SMRT or HDACs reversed the site specific deacetylation of histone 3 and 4 and the Iε transrepression driven by calcitriol. These VDR-complex transrepressive actions on Iε were confirmed in a reporter assay. We show here that calcitriol-mediated inhibition of Iε involves the recruitment of VDR-heterodimers, which engage co-repressors and histone modifying enzymes. Our findings shed new light on mechanisms of VDR-transrepression in principal and understanding of IgE regulation in particular.Kürzlich wurde der Zusammenhang zwischen der gestiegenen Inzidenz allergischer Erkrankungen und Vitamin D-Defizienz beschrieben. Es wurde gezeigt, dass Calcitriol, als bioaktive Form von Vitamin D, die Epsilon- Keimbahntranskription, die Voraussetzung für den Klassenwechsel zu IgE, hemmt. Allerdings sind die zugrunde liegenden Mechanismen nicht aufgeklärt. Zielsetzung dieser Arbeit war die Untersuchung des epsilon-Keimbahnpromotors hinsichtlich Vitamin-D-Rezeptor(VDR)-DNA-Komplexbildung, Modifikation der Chromatin-Acetylierung, sowie deren Einfluss auf die Epsilon- Keimbahntranskription in humanen B-Zellen. Die Bindung des VDR an den epsilon- Keimbahnpromotor (Iε) in humanen B-Zellen, die Zusammensetzung des durch den VDR rekrutierten Komplexes sowie das Acetylierungsmuster wurden mittels Chromatin-Immunpräzipitation untersucht. Die Calcitriol-vermittelten Effekte am Iε wurden durch Reportergen-Untersuchungen analysiert. Die Daten zeigen hier, dass der Calcitriol-aktivierte VDR gemeinsam mit dem Retinsäure- XRezeptor an Iε bindet. Die Interaktion dieses Heterodimers mit SMRT (engl.: silencing mediator for retinoid and thyroid hormone receptors) führt weiter zur Rekrutierung von Histon-Deacetylase (HDAC) 1 und HDAC3. Die Hemmung von SMRT und HDACs führt zur Umkehrung der Calcitriol-vermittelten spezifischen Deacetylierung von Histon 3 und 4 sowie der Transrepression von Iε. Die transrepressiven Effekte des VDR-Komplexes auf Iε wurden in Reportergen- Analysen bestätigt. Es ist hier verdeutlicht, dass die Calcitriol-vermittelte Hemmung des epsilon-Keimbahntranskripts auf der Rekrutierung von VDR- Heterodimeren mit Einbindung von Co-Repressoren und Histon-modifizierenden Enzymen beruht. Diese Arbeit zeigt neue Aspekte der VDR-vermittelten Transrepression und Regulation des IgE-Klassenwechsels

Shikonin derivatives from onsoma visianii decrease expression of phosphorylated stat3 in leukemia cells and exert antitumor activity

Antitumor effects of shikonins on chronic lymphocytic leukemia (CLL) and B-cell pro-lymphocytic leukemia (B-PLL) are mostly unexplored. The antitumor activity of shikonins, isolated from Onosma visianii Clem (Boraginaceae), in BCL1, mouse CLL cells and JVM-13, human B-PLL cells was explored in this study. The cytotoxicity of shikonin derivatives was measured by an MTT test. Cell death, proliferation, cell cycle, and expression of molecules that control these processes were analyzed by flow cytometry. Expression of STAT3-regulated genes was analyzed by real-time q-RT-PCR (Quantitative Real-Time Polymerase Chain Reaction). The antitumor effects of shikonin derivatives in vivo were analyzed, using flow cytometry, by detection of leukemia cells in the peripheral blood and spleens of mice intravenously injected with BCL1 cells. The two most potent derivatives, isobutyrylshikonin (IBS) and α-methylbutyrylshikonin (MBS), induced cell cycle dis-turbances and apoptosis, inhibited proliferation, and decreased expression of phospho-STAT3 and downstream-regulated molecules in BCL1 and JVM-13 cells. IBS and MBS decreased the percentage of leukemia cells in vivo. The link between the decrease in phosphorylated STAT3 by MBS and IBS and BCL1 cell death was confirmed by detection of enhanced cell death after addition of AG490, an inhibitor of Jak2 kinase. It seems that IBS and MBS, by decreasing STAT3 phosphorylation, trigger apoptosis, inhibit cell proliferation, and attenuate leukemia cell stemness

Analysis of Risk Factors for Development of Cognitive Disorders in Maintenance Hemodialysis Patients – Pilot Study

Prevalence of cognitive disorders is high in maintenance hemodialysis patients. Montreal cognitive assessment (MoCA) is used for detecting and evaluation of cognitive disorder degree in this patient population. In examined patient population, only 5 (12.5%) of them had normal cognitive function (MoCA ≥26). Mild cognitive impairment (MoCA 18-26) was found in 65.9% (29) patients, while moderate cognitive disorder (MoCA 10-17) was detected in 6 (21.6%) patients. Major cognitive disorder wasn’t detected in examined population. Statistically significant correlation was not established between laboratory parameters and overall MoCA score. Statistically significant correlation, however, was established between MoCA item that evaluates space and time orientation and intermediate secondary hyperparathyroidism and space and time orientation and severe secondary hyperparathyroidism. Hemodynamic instability during hemodialysis and silent ischemia of the brain are increasing risk of appearance of cognitive disorders in maintenance hemodialysis patients

Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

The design of platinum based drugs is not a new field of interest. Platinum complexes are widely used as anticancer agents and currently, approximately 30 platinum(II) and platinum(IV) entered into some of the phases of clinical trials. A special place in today’s research belongs to platinum complexes with diammine ligands. A large number of edda (ethylenediamine- N, N’-diacetate)-type ligands and their corresponding metal complexes has been successfully synthesized. This article summarizes recent progress in research on edda-type-platinum complexes. Some of these agents achieves better effect compared to the gold standard (cisplatin). It has been shown that there is a possible relationship between the length of the ligand ester group carbon chain and its cytotoxic effect. In most cases the longer the ester chain is the greater is the antitumor activity. Of particular interest are the noticeable effects of some new platinum compound with edda-type ligand on cell lines that are known to have a high level of cisplatin-resistance. Exanimate complexes appear to have a different mode of mechanism of action compared with cisplatin which includes apoptotic and necrotic cell death. There are indications that further investigations of these compounds may be very useful in overcoming the problems associated global cancer statistic